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Sullivan, Keith Michael

Overview:

Research areas


Late effects of cancer treatment and stem cell transplantation 
Chronic graft-versus-host disease 
Transplantation for sickle cell and autoimmune diseases 
Knowledge engineering

Overview
Early on, Dr. Sullivan and the team at Fred Hutchinson Cancer Research Center developed a systematic investigative approach for the diagnosis and treatment of chronic graft-versus-host disease (GVHD), the major cause of late morbidity and non-relapse mortality following allogeneic stem cell transplantation (SCT). As a result of this work, it became clear that blood and marrow transplant recipients require systematic long-term follow-up to evaluate and treat late complications of high-dose chemoradiotherapy and SCT.

The program grew into a large multidisciplinary team, resulting in improvement in patient outcome and quality of life. Through the late events project, he also contributed to outcomes research, computer decision support systems, and knowledge engineering for follow-up care. With quality of life as a focus, research pursued the application of SCT to diseases with high morbidity but little immediate mortality. For young patients with advanced, symptomatic sickle cell disease, myeloablative conditioning and SCT from an HLA-identical sibling has led to an 86% long-term survival free of sickle cell disease. For individuals with autoimmune diseases such as multiple sclerosis, scleroderma, and systemic lupus erythematosus, current therapy is often incomplete and significant morbidity from the disease or its treatment is observed.

Recent preclinical and clinical data suggest that high-dose immunosupression and SCT can halt the progression and, in some settings, reverse the course of autoimmune diseases. Since his arrival at Duke University, over 30 centers nationwide are participating in Duke-led phase II and III trials to test the toxicity, efficacy, and quality of life following autologous and allogeneic stem cell transplantation for autoimmune diseases.

These trials will also serve as platforms to study the immune repertoire and mechanistic pathways before and after SCT to gain greater insight into the basic mechanisms of autoimmunity.

A national repository of tissue and cell specimens is also part of these NIH-supported trials to further promote scientific study from these unique patients.

Positions:

James B. Wyngaarden Professor of Medicine, in the School of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1971

M.D. — Indiana University at Indianapolis

Grants:

Transfusion Medicine and Hematology

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Preceptor
Start Date
July 01, 1975
End Date
June 30, 2021

Transplant Infectious Diseases Interdisciplinary Research Training Grant

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Advisor
Start Date
September 01, 2013
End Date
August 31, 2018

GSK Study 115523 (Zoster 002)

Administered By
Duke Cancer Institute
AwardedBy
GlaxoSmithKline
Role
Principal Investigator
Start Date
June 01, 2013
End Date
May 31, 2018

Scleroderma Cyclophosphamide or Transplantation (SCOT) Trial-Option 6

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 2011
End Date
October 31, 2017

Training Program in Inflammatory and Immunological Diseases

Administered By
Medicine, Rheumatology and Immunology
AwardedBy
National Institutes of Health
Role
Preceptor
Start Date
September 30, 1980
End Date
August 31, 2017

Marrow transplant compared to supportive care in adolescents and young adults with sickle cell disease

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
Emory University
Role
Principal Investigator
Start Date
August 01, 2016
End Date
July 31, 2017

Marrow transplant compared to supportive care in adults with sickle cell disease

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
Emory University
Role
Principal Investigator
Start Date
September 01, 2015
End Date
July 31, 2016

Marrow transplant compared to supportive care in adults with sickle cell disease

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
Emory University
Role
Principal Investigator
Start Date
May 15, 2014
End Date
April 30, 2016

14th Annual Southeastern Fellows Research Skills & Training Workshop

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
Jazz Pharmaceuticals
Role
Principal Investigator
Start Date
October 01, 2014
End Date
September 30, 2015

Home-Based Tablet Computer Pain Coping Skills Following Stem Cell Transplant

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 10, 2013
End Date
August 31, 2015

Hematopoietic Cell Therapy for Young Adults with Severe Sickle Cell Disease

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
University of Pittsburgh
Role
Principal Investigator
Start Date
September 01, 2011
End Date
April 30, 2014

Scleroderma Cyclophosphamide or Transplantation (SCOT) Trial-Option 2

Administered By
Duke University
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
November 01, 2012
End Date
October 31, 2013

Scleroderma Cyclophosphamide or Transplantation (SCOT) Trial

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
November 01, 2011
End Date
October 31, 2012

National Collaborative Study of Stem Cell Transplantation for Autoimmune Disease

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 2011
End Date
October 31, 2011

National Collaborative Study of Stem Cell Transplantation for Autoimmune Disease

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 22, 2000
End Date
September 30, 2011

Immunotherapy with Renal Tumor RNA Transfected Dendritic Cells

Administered By
Surgery, Urology
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
February 14, 2001
End Date
January 31, 2005

Computerized Decision Support for Posttransplant Care

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1999
End Date
September 29, 2000
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Awards:

Elected Fellow. American Association for the Advancement of Science.

Type
National
Awarded By
American Association for the Advancement of Science
Date
January 01, 2003

Highly Cited Researcher, Clinical Medicine Category. Institute for Scientific Information (ISI).

Type
National
Awarded By
Institute for Scientific Information (ISI)
Date
January 01, 2002

Electee. Association of American Physicians.

Type
National
Awarded By
Association of American Physicians
Date
January 01, 2001

Publications:

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases.

To ensure comparable grafts for autologous hematopoietic cell transplantation (HCT) in the National Institute of Allergy and Infectious Diseases-sponsored Investigational New Drug protocols for multiple sclerosis (HALT-MS) and systemic sclerosis (SCOT), a Drug Master File approach to control manufacture was implemented, including a common Master Production Batch Record and site-specific standard operating procedures with "Critical Elements." We assessed comparability of flow cytometry and controlled rate cryopreservation among sites and stability of cryopreserved grafts using hematopoietic progenitor cells (HPCs) from healthy donors. Hematopoietic Progenitor Cells, Apheresis-CD34+ Enriched, for Autologous Use (Auto-CD34+HPC) graft specifications included ≥70% viable CD34+ cells before cryopreservation. For the 2 protocols, 110 apheresis collections were performed; 121 lots of Auto-CD34+HPC were cryopreserved, and 107 of these (88.4%) met release criteria. Grafts were infused at a median of 25 days (range, 17 to 68) post-apheresis for HALT-MS (n = 24), and 25 days (range, 14 to 78) for SCOT (n = 33). Subjects received precryopreservation doses of a median 5.1 × 106 viable CD34+ cells/kg (range, 3.9 to 12.8)  for HALT-MS and 5.6 × 106 viable CD34+ cells/kg (range, 2.6 to 10.2) for SCOT. Recovery of granulocytes occurred at a median of 11 days (range, 9 to 15) post-HCT for HALT-MS and 10 days (range, 8 to 12) for SCOT, independent of CD34+ cell dose. Subjects received their last platelet transfusion at a median of 9 days (range, 6 to 16) for HALT-MS and 8 days (range, 6 to 23) for SCOT; higher CD34+/kg doses were associated with faster platelet recovery. Stability testing of cryopreserved healthy donor CD34+ HPCs over 6 months of vapor phase liquid nitrogen storage demonstrated consistent 69% to 73% recovery of viable CD34+ cells. Manufacturing of Auto-CD34+HPC for the HALT-MS and SCOT protocols was comparable across all sites and supportive for timely recovery of granulocytes and platelets.

Authors
Keever-Taylor, CA; Heimfeld, S; Steinmiller, KC; Nash, RA; Sullivan, KM; Czarniecki, CW; Granderson, TC; Goldstein, JS; Griffith, LM
MLA Citation
Keever-Taylor, CA, Heimfeld, S, Steinmiller, KC, Nash, RA, Sullivan, KM, Czarniecki, CW, Granderson, TC, Goldstein, JS, and Griffith, LM. "Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 23.9 (September 2017): 1463-1472.
PMID
28602891
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
9
Publish Date
2017
Start Page
1463
End Page
1472
DOI
10.1016/j.bbmt.2017.05.018

Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit.

Authors
Anand, S; Thomas, S; Hyslop, T; Adcock, J; Corbet, K; Gasparetto, C; Lopez, R; Long, GD; Morris, AK; Rizzieri, DA; Sullivan, KM; Sung, AD; Sarantopoulos, S; Chao, NJ; Horwitz, ME
MLA Citation
Anand, S, Thomas, S, Hyslop, T, Adcock, J, Corbet, K, Gasparetto, C, Lopez, R, Long, GD, Morris, AK, Rizzieri, DA, Sullivan, KM, Sung, AD, Sarantopoulos, S, Chao, NJ, and Horwitz, ME. "Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 23.7 (July 2017): 1151-1157.
PMID
28392378
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
7
Publish Date
2017
Start Page
1151
End Page
1157
DOI
10.1016/j.bbmt.2017.04.001

Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma.

Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015. Maintenance with bortezomib was initiated between 60 and 90 days after ASCT as a single agent 1.3 mg/m2 once every 2 weeks (n = 92) or in combination with lenalidomide (10 mg/day) (n = 10). The median age at ASCT was 64 (range, 31 to 78). Of the 99 patients with molecular data available, 42% had high-risk cytogenetics (including d17p, t(4;14), +1q, and t(14;16) by fluorescein in situ hybridization). Overall, 46% of patients experienced side effects from maintenance therapy, with 31% of all patients experiencing peripheral neuropathy. In total, 2% of patients required discontinuation of bortezomib maintenance because of adverse events. No secondary malignancies were reported from the therapy. The median progression-free survival (PFS) for patients receiving maintenance therapy with bortezomib after ASCT was 36.5 months (95% confidence interval [CI], 21.3 to not available) and median overall survival was 72.7 months (95% CI, 63.9 to not available). The PFS of patients with high-risk cytogenetics was not statistically significantly different from those with standard-risk cytogenetics, suggesting that maintenance with bortezomib may help overcome the impact of high-risk cytogenetics on early progression. These results indicate that maintenance therapy with bortezomib represents a safe, well-tolerated, and efficacious option for patients with high-risk cytogenetics, renal insufficiency, an inability to tolerate lenalidomide, or a previous history of another cancer.

Authors
Sivaraj, D; Green, MM; Li, Z; Sung, AD; Sarantopoulos, S; Kang, Y; Long, GD; Horwitz, ME; Lopez, RD; Sullivan, KM; Rizzieri, DA; Chao, NJ; Gasparetto, C
MLA Citation
Sivaraj, D, Green, MM, Li, Z, Sung, AD, Sarantopoulos, S, Kang, Y, Long, GD, Horwitz, ME, Lopez, RD, Sullivan, KM, Rizzieri, DA, Chao, NJ, and Gasparetto, C. "Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 23.2 (February 2017): 262-268.
PMID
27856369
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
2
Publish Date
2017
Start Page
262
End Page
268
DOI
10.1016/j.bbmt.2016.11.010

Efficacy and safety of high-dose chemotherapy with autologous stem cell transplantation in senior versus younger adults with newly diagnosed multiple myeloma.

We retrospectively studied 340 fit patients with multiple myeloma (MM) who underwent autologous stem cell transplantation (ASCT). We hypothesized that progression-free survival (PFS) of older patients was non-inferior to that of younger patients after ASCT. Our null hypothesis was that the PFS hazard ratio (HR) for a 5-year increase in age was ≥1.05; the alternative (non-inferiority) hypothesis was that the HR was ≤1. The observed HR was 0.94 (95% confidence interval [CI] 0.86-1.03); since the CI upper bound was <1.05, we reject the null hypothesis and conclude that PFS in older patients was at least as good as in younger patients. We cannot reject an analogous null hypothesis for overall survival (HR 1.06 [95% CI 0.94-1.19]), since the CI upper bound >1.05. Toxicity was similar across ages and transplant-related mortality was minimal. 28% of subjects <65 versus 45% of those ≥65 received maintenance therapy. In summary, ASCT prolongs PFS equally well in older vs. younger adults. Although we cannot exclude maintenance as a confounder, these data support ASCT for fit seniors with MM.

Authors
Huang, L-W; Bacon, W; Cirrincione, C; Peterson, B; Long, G; Rizzieri, D; Sullivan, KM; Corbet, K; Horwitz, M; Chao, N; Gasparetto, C; Tuchman, SA
MLA Citation
Huang, L-W, Bacon, W, Cirrincione, C, Peterson, B, Long, G, Rizzieri, D, Sullivan, KM, Corbet, K, Horwitz, M, Chao, N, Gasparetto, C, and Tuchman, SA. "Efficacy and safety of high-dose chemotherapy with autologous stem cell transplantation in senior versus younger adults with newly diagnosed multiple myeloma." Hematological oncology (January 19, 2017).
PMID
28105753
Source
epmc
Published In
Hematological Oncology
Publish Date
2017
DOI
10.1002/hon.2379

Review: Hematopoietic Stem Cell Transplantation for Scleroderma: Effective Immunomodulatory Therapy for Patients With Pulmonary Involvement.

Authors
Sullivan, KM; Shah, A; Sarantopoulos, S; Furst, DE
MLA Citation
Sullivan, KM, Shah, A, Sarantopoulos, S, and Furst, DE. "Review: Hematopoietic Stem Cell Transplantation for Scleroderma: Effective Immunomodulatory Therapy for Patients With Pulmonary Involvement." Arthritis & rheumatology (Hoboken, N.J.) 68.10 (October 2016): 2361-2371. (Review)
Website
http://hdl.handle.net/10161/12558
PMID
27213276
Source
epmc
Published In
Arthritis and Rheumatology
Volume
68
Issue
10
Publish Date
2016
Start Page
2361
End Page
2371
DOI
10.1002/art.39748

Universal Mask Usage for Reduction of Respiratory Viral Infections After Stem Cell Transplant: A Prospective Trial.

Respiratory viral infections (RVIs) are frequent complications of hematopoietic stem cell transplant (HSCT). Surgical masks are a simple and inexpensive intervention that may reduce nosocomial spread.In this prospective single-center study, we instituted a universal surgical mask policy requiring all individuals with direct contact with HSCT patients to wear a surgical mask, regardless of symptoms or season. The primary endpoint was the incidence of RVIs in the mask period (2010-2014) compared with the premask period (2003-2009).RVIs decreased from 10.3% (95/920 patients) in the premask period to 4.4% (40/911) in the mask period (P < .001). Significant decreases occurred after both allogeneic (64/378 [16.9%] to 24/289 [8.3%], P = .001) and autologous (31/542 [5.7%] to 16/622 [2.6%], P = .007) transplants. After adjusting for multiple covariates including season and year in a segmented longitudinal analysis, the decrease in RVIs remained significant, with risk of RVI of 0.4 in patients in the mask group compared with the premask group (0.19-0.85, P = .02). In contrast, no decrease was observed during this same period in an adjacent hematologic malignancy unit, which followed the same infection control practices except for the mask policy. The majority of this decrease was in parainfluenza virus 3 (PIV3) (8.3% to 2.2%, P < .001).Requiring all individuals with direct patient contact to wear a surgical mask is associated with a reduction in RVIs, particularly PIV3, during the most vulnerable period following HSCT.

Authors
Sung, AD; Sung, JAM; Thomas, S; Hyslop, T; Gasparetto, C; Long, G; Rizzieri, D; Sullivan, KM; Corbet, K; Broadwater, G; Chao, NJ; Horwitz, ME
MLA Citation
Sung, AD, Sung, JAM, Thomas, S, Hyslop, T, Gasparetto, C, Long, G, Rizzieri, D, Sullivan, KM, Corbet, K, Broadwater, G, Chao, NJ, and Horwitz, ME. "Universal Mask Usage for Reduction of Respiratory Viral Infections After Stem Cell Transplant: A Prospective Trial." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 63.8 (October 2016): 999-1006.
PMID
27481873
Source
epmc
Published In
Clinical Infectious Diseases
Volume
63
Issue
8
Publish Date
2016
Start Page
999
End Page
1006
DOI
10.1093/cid/ciw451

Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery.

The binding of CXCR4 with its ligand (stromal-derived factor-1) maintains hematopoietic stem/progenitor cells (HSPCs) in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT) promotes hematopoiesis by inducing HSC proliferation.We conducted a phase I/II trial of plerixafor on hematopoietic cell recovery following myeloablative allogeneic HSCT. Patients with hematologic malignancies receiving myeloablative conditioning were enrolled. Plerixafor 240 μg/kg was administered subcutaneously every other day beginning day +2 until day +21 or until neutrophil recovery. The primary efficacy endpoints of the study were time to absolute neutrophil count >500/μl and platelet count >20,000/μl. The cumulative incidence of neutrophil and platelet engraftment of the study cohort was compared to that of a cohort of 95 allogeneic peripheral blood stem cell transplant recipients treated during the same period of time and who received similar conditioning and graft-versus-host disease prophylaxis.Thirty patients received plerixafor following peripheral blood stem cell (n = 28) (PBSC) or bone marrow (n = 2) transplantation. Adverse events attributable to plerixafor were mild and indistinguishable from effects of conditioning. The kinetics of neutrophil and platelet engraftment, as demonstrated by cumulative incidence, from the 28 study subjects receiving PBSC showed faster neutrophil (p = 0.04) and platelet recovery >20 K (p = 0.04) compared to the controls.Our study demonstrated that plerixafor can be given safely following myeloablative HSCT. It provides proof of principle that blocking CXCR4 after HSCT enhances hematopoietic recovery. Larger, confirmatory studies in other settings are warranted.ClinicalTrials.gov NCT01280955.

Authors
Green, MMB; Chao, N; Chhabra, S; Corbet, K; Gasparetto, C; Horwitz, A; Li, Z; Venkata, JK; Long, G; Mims, A; Rizzieri, D; Sarantopoulos, S; Stuart, R; Sung, AD; Sullivan, KM; Costa, L; Horwitz, M; Kang, Y
MLA Citation
Green, MMB, Chao, N, Chhabra, S, Corbet, K, Gasparetto, C, Horwitz, A, Li, Z, Venkata, JK, Long, G, Mims, A, Rizzieri, D, Sarantopoulos, S, Stuart, R, Sung, AD, Sullivan, KM, Costa, L, Horwitz, M, and Kang, Y. "Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery." Journal of hematology & oncology 9.1 (August 17, 2016): 71-.
PMID
27535663
Source
epmc
Published In
Journal of Hematology and Oncology
Volume
9
Issue
1
Publish Date
2016
Start Page
71
DOI
10.1186/s13045-016-0301-2

The Diagnostic Yield of Site and Symptom-Based Biopsies for Acute Gastrointestinal Graft-Versus-Host Disease: A 5-Year Retrospective Review.

Graft-versus-host disease (GVHD) complicates half of hematopoietic stem cell transplants (HCT), and the gastrointestinal tract is commonly affected. Endoscopic biopsies have a key role in the diagnosis. The optimal procedure(s) to perform and site(s) to biopsy remain unclear.We retrospectively analyzed the charts of all adult patients who underwent allogeneic HCT at Duke University Medical Center between 1/1/05 and 1/1/11 and extracted data from those who underwent endoscopic biopsy for suspected GVHD. All histology was re-evaluated by blinded pathologists using 2006 NIH diagnostic criteria and then compared to the original clinical diagnosis of GVHD.A total of 169 adult patients underwent 250 endoscopic procedures to evaluate GVHD. The sensitivity of biopsies for clinical GVHD was 76 and 72% for upper and lower tract sites, respectively. In the presence of nausea, upper tract biopsies were positive for GVHD in 65%, 70% while lower tract biopsies were positive in 61-70%. In the presence of diarrhea, lower tract biopsies were positive in 65%, while upper tract sites were positive in 64-69%. Twenty six (40%) of the sixty-five endoscopies that simultaneously sampled upper and lower tract sites had discordant results. All were histologically positive for GVHD, yet 15% of upper tract biopsies and 25% of lower tract biopsies were negative.In this large review, the overall sensitivity of biopsies taken during EGD and Flex-Sig was 76 and 72%, respectively. A symptom-driven biopsy approach was not clearly supported as upper tract and lower tract biopsies were similarly diagnostic for GVHD regardless of symptoms.

Authors
Wild, D; Sung, AD; Cardona, D; Cirricione, C; Sullivan, K; Detweiler, C; Shealy, M; Balmadrid, B; Rowes, KL; Chao, N; Piryani, S; Karimabad, HM; Martin, P; Poleski, M
MLA Citation
Wild, D, Sung, AD, Cardona, D, Cirricione, C, Sullivan, K, Detweiler, C, Shealy, M, Balmadrid, B, Rowes, KL, Chao, N, Piryani, S, Karimabad, HM, Martin, P, and Poleski, M. "The Diagnostic Yield of Site and Symptom-Based Biopsies for Acute Gastrointestinal Graft-Versus-Host Disease: A 5-Year Retrospective Review." Digestive diseases and sciences 61.3 (March 2016): 806-813.
PMID
26537485
Source
epmc
Published In
Digestive Diseases and Sciences
Volume
61
Issue
3
Publish Date
2016
Start Page
806
End Page
813
DOI
10.1007/s10620-015-3938-8

Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease.

Although a number of published trials exist of HLA-identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) that span 2 decades, when and for whom this therapy should be pursued is a subject of debate. Assessments of the risks of transplant-related complications that include infertility and debilitating graft-versus-host disease and long-term quality of life after successful HCT are difficult to perform without prospective trials in transplant and nontransplant cohorts. However, it is possible to assess the risk of mortality and to compare published rates of survival in individuals with SCD treated and not treated by HCT. In this brief review, projections about mortality risk based on recent published reports are reviewed and summarized. The published data show overall survival and event-free survival rates of 95% and 92%, respectively, in children treated by HLA-identical sibling HCT. The overall survival rates in the Center for International Blood and Marrow Transplant Research (N = 412) and European Blood and Marrow Transplant (N = 487) registries were 91% and 95%, respectively. These results provide broad support for the therapeutic value of HLA-identical sibling HCT for children with SCD and serve as the basis for a strong recommendation in favor of the option of HCT when a suitable donor is available. The experience of HLA-identical sibling HCT in adults with SCD is limited but appears to be similar to results in children. These preliminary observations, however, warrant further investigation.

Authors
Walters, MC; De Castro, LM; Sullivan, KM; Krishnamurti, L; Kamani, N; Bredeson, C; Neuberg, D; Hassell, KL; Farnia, S; Campbell, A; Petersdorf, E
MLA Citation
Walters, MC, De Castro, LM, Sullivan, KM, Krishnamurti, L, Kamani, N, Bredeson, C, Neuberg, D, Hassell, KL, Farnia, S, Campbell, A, and Petersdorf, E. "Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 22.2 (February 2016): 207-211. (Review)
PMID
26500093
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
2
Publish Date
2016
Start Page
207
End Page
211
DOI
10.1016/j.bbmt.2015.10.017

Results of a Multicenter Pilot Investigation of Bone Marrow Transplantation in Adults with Sickle Cell Disease (STRIDE)

Authors
Krishnamurti, L; Sullivan, KM; Kamani, NR; Waller, EK; Abraham, A; Campigotto, F; Zhang, W; Smith, S; Hassell, KL; Decastro, L; Wu, CJ; Neuberg, DS; Walters, MC
MLA Citation
Krishnamurti, L, Sullivan, KM, Kamani, NR, Waller, EK, Abraham, A, Campigotto, F, Zhang, W, Smith, S, Hassell, KL, Decastro, L, Wu, CJ, Neuberg, DS, and Walters, MC. "Results of a Multicenter Pilot Investigation of Bone Marrow Transplantation in Adults with Sickle Cell Disease (STRIDE)." December 3, 2015.
Source
wos-lite
Published In
Blood
Volume
126
Issue
23
Publish Date
2015

Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma.

High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10(6) CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.

Authors
Tuchman, SA; Bacon, WA; Huang, L-W; Long, G; Rizzieri, D; Horwitz, M; Chute, JP; Sullivan, K; Morris Engemann, A; Yopp, A; Li, Z; Corbet, K; Chao, N; Gasparetto, C
MLA Citation
Tuchman, SA, Bacon, WA, Huang, L-W, Long, G, Rizzieri, D, Horwitz, M, Chute, JP, Sullivan, K, Morris Engemann, A, Yopp, A, Li, Z, Corbet, K, Chao, N, and Gasparetto, C. "Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma." Journal of clinical apheresis 30.3 (June 2015): 176-182.
PMID
25293363
Source
epmc
Published In
Journal of Clinical Apheresis
Volume
30
Issue
3
Publish Date
2015
Start Page
176
End Page
182
DOI
10.1002/jca.21360

A HYBRID IN-PERSON AND MHEALTH PAIN COPING SKILLS INTERVENTION FOR STEM CELL TRANSPLANT PATIENTS

Authors
Kelleher, SA; Fisher, HM; Shelby, RA; Sullivan, KM; Abernethy, AP; Keefe, FJ; Somers, TJ
MLA Citation
Kelleher, SA, Fisher, HM, Shelby, RA, Sullivan, KM, Abernethy, AP, Keefe, FJ, and Somers, TJ. "A HYBRID IN-PERSON AND MHEALTH PAIN COPING SKILLS INTERVENTION FOR STEM CELL TRANSPLANT PATIENTS." ANNALS OF BEHAVIORAL MEDICINE 49 (April 2015): S216-S216.
Source
wos-lite
Published In
Annals of Behavioral Medicine
Volume
49
Publish Date
2015
Start Page
S216
End Page
S216

Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma

© 2014 Wiley Periodicals, Inc. High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10 < sup > 6 < /sup > CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54] ). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.

Authors
Tuchman, SA; Bacon, WA; Huang, LW; Long, G; Rizzieri, D; Horwitz, M; Chute, JP; Sullivan, K; Engemann, AM; Yopp, A; Li, Z; Corbet, K; Chao, N; Gasparetto, C
MLA Citation
Tuchman, SA, Bacon, WA, Huang, LW, Long, G, Rizzieri, D, Horwitz, M, Chute, JP, Sullivan, K, Engemann, AM, Yopp, A, Li, Z, Corbet, K, Chao, N, and Gasparetto, C. "Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma." Journal of Clinical Apheresis 30.3 (January 1, 2015): 176-182.
Source
scopus
Published In
Journal of Clinical Apheresis
Volume
30
Issue
3
Publish Date
2015
Start Page
176
End Page
182
DOI
10.1002/jca.21360

A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients.

Recombinant herpes zoster (HZ) vaccines may be an alternative to the live-attenuated HZ vaccine for immunocompromised individuals. This was a phase 1/2, randomized, observer-blind, placebo-controlled study in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous hematopoietic stem-cell transplant 50 to 70 days earlier. Subjects (N = 121) were randomized 1:1:1:1 to receive (at months 0, 1, 3) three doses of 50 μg varicella-zoster virus glycoprotein E (gE) adjuvanted with AS01B, 3 doses of gE adjuvanted with AS01E, 1 dose of saline followed by 2 doses of gE/AS01B, or 3 doses of saline. One month after the last dose (6 months after transplant), frequencies of CD4(+) T cells expressing ≥2 activation markers after induction with gE and anti-gE antibody concentrations were higher with all gE/AS01 regimens than with saline. Both responses persisted up to 1 year in subjects vaccinated with gE/AS01. Immune responses were higher in the gE/AS01B 3-dose group than in the gE/AS01B 2-dose group but not higher than in the gE/AS01E 3-dose group. One serious adverse event (pneumonia) was considered vaccine related. Both formulations and both schedules were immunogenic and well tolerated in this population. This study was registered at www.clinicaltrials.gov as #NCT00920218.

Authors
Stadtmauer, EA; Sullivan, KM; Marty, FM; Dadwal, SS; Papanicolaou, GA; Shea, TC; Mossad, SB; Andreadis, C; Young, J-AH; Buadi, FK; El Idrissi, M; Heineman, TC; Berkowitz, EM
MLA Citation
Stadtmauer, EA, Sullivan, KM, Marty, FM, Dadwal, SS, Papanicolaou, GA, Shea, TC, Mossad, SB, Andreadis, C, Young, J-AH, Buadi, FK, El Idrissi, M, Heineman, TC, and Berkowitz, EM. "A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients." Blood 124.19 (November 2014): 2921-2929.
PMID
25237196
Source
epmc
Published In
Blood
Volume
124
Issue
19
Publish Date
2014
Start Page
2921
End Page
2929
DOI
10.1182/blood-2014-04-573048

Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment.

Delayed hematopoietic recovery is a major drawback of umbilical cord blood (UCB) transplantation. Transplantation of ex vivo-expanded UCB shortens time to hematopoietic recovery, but long-term, robust engraftment by the expanded unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell product consisting of stem cells expanded for 21 days in the presence of nicotinamide and a noncultured T cell fraction (NiCord) can accelerate hematopoietic recovery and provide long-term engraftment.In a phase I trial, 11 adults with hematologic malignancies received myeloablative bone marrow conditioning followed by transplantation with NiCord and a second unmanipulated UCB unit. Safety, hematopoietic recovery, and donor engraftment were assessed and compared with historical controls.No adverse events were attributable to the infusion of NiCord. Complete or partial neutrophil and T cell engraftment derived from NiCord was observed in 8 patients, and NiCord engraftment remained stable in all patients, with a median follow-up of 21 months. Two patients achieved long-term engraftment with the unmanipulated unit. Patients transplanted with NiCord achieved earlier median neutrophil recovery (13 vs. 25 days, P < 0.001) compared with that seen in historical controls. The 1-year overall and progression-free survival rates were 82% and 73%, respectively.UCB-derived hematopoietic stem and progenitor cells expanded in the presence of nicotinamide and transplanted with a T cell-containing fraction contain both short-term and long-term repopulating cells. The results justify further study of NiCord transplantation as a single UCB graft. If long-term safety is confirmed, NiCord has the potential to broaden accessibility and reduce the toxicity of UCB transplantation.Clinicaltrials.gov NCT01221857.Gamida Cell Ltd.

Authors
Horwitz, ME; Chao, NJ; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; McDonald, C; Waters-Pick, B; Stiff, P; Wease, S; Peled, A; Snyder, D; Cohen, EG; Shoham, H; Landau, E; Friend, E; Peleg, I; Aschengrau, D; Yackoubov, D; Kurtzberg, J; Peled, T
MLA Citation
Horwitz, ME, Chao, NJ, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, McDonald, C, Waters-Pick, B, Stiff, P, Wease, S, Peled, A, Snyder, D, Cohen, EG, Shoham, H, Landau, E, Friend, E, Peleg, I, Aschengrau, D, Yackoubov, D, Kurtzberg, J, and Peled, T. "Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment." The Journal of clinical investigation 124.7 (July 2014): 3121-3128.
PMID
24911148
Source
epmc
Published In
Journal of Clinical Investigation
Volume
124
Issue
7
Publish Date
2014
Start Page
3121
End Page
3128
DOI
10.1172/jci74556

Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies.

We present a comparative study on 124 patients with hematologic malignancies who had undergone reduced-intensity conditioning and then received a transplant from an HLA-matched related (MRD), an HLA-matched unrelated (MUD), or an HLA-haploidentical related (HAPLO) donor. The conditioning regimen, which consisted of fludarabine, melphalan or busulfan, and alemtuzumab was administered to patients with lymphoid (n = 62) or myeloid disease (n = 62). Mycophenolate mofetil was used as prophylaxis for graft-versus-host disease (GVHD), and 38, 58, and 33 patients received transplants from MRD, MUD, and HAPLO donors, respectively. Only 2 patients experienced primary graft failure (GF) after melphalan-based regimen, whereas 8 of the 17 patients who received a transplant from HAPLO donors experienced a primary GF after busulfan-based regimen. The cumulative incidence of grade III to IV acute GVHD in engrafted patients who had received transplants from MRD, MUD, or HAPLO donors was 3%, 11%, and 27%, respectively, and the 2-year overall survival (OS) rates were 51%, 22%, and 23%, respectively. According to multivariate analysis, transplantation from either MUD or HAPLO donors compared with MRD were adverse factors that affected the OS (P = .006 and P = .002, respectively). In conclusion, the reduced-intensity regimen that included fludarabine, busulfan, or melphalan and alemtuzumab using only mycophenolate mofetil as the GVHD prophylaxis conferred favorable outcomes in the MRD group but lower survival rates in the MUD and HAPLO groups. The busulfan-based regimen led to a high incidence of GF in the HAPLO group, suggesting the need for modification or intensification of immunosuppression.

Authors
Kanda, J; Long, GD; Gasparetto, C; Horwitz, ME; Sullivan, KM; Chute, JP; Morris, A; Shafique, M; Li, Z; Chao, NJ; Rizzieri, DA
MLA Citation
Kanda, J, Long, GD, Gasparetto, C, Horwitz, ME, Sullivan, KM, Chute, JP, Morris, A, Shafique, M, Li, Z, Chao, NJ, and Rizzieri, DA. "Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies." Biol Blood Marrow Transplant 20.2 (February 2014): 257-263.
PMID
24269380
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
257
End Page
263
DOI
10.1016/j.bbmt.2013.11.010

Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment.

High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (≥ 12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (≥ 13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (≥ 38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66-88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation.

Authors
Kanda, J; Kaynar, L; Kanda, Y; Prasad, VK; Parikh, SH; Lan, L; Shen, T; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; Winkel, S; McPherson, J; Kurtzberg, J; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Kaynar, L, Kanda, Y, Prasad, VK, Parikh, SH, Lan, L, Shen, T, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, Winkel, S, McPherson, J, Kurtzberg, J, Chao, NJ, and Horwitz, ME. "Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment." Bone Marrow Transplant 48.7 (July 2013): 926-931.
PMID
23334274
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
48
Issue
7
Publish Date
2013
Start Page
926
End Page
931
DOI
10.1038/bmt.2012.279

Gastric antral vascular ectasia and its clinical correlates in patients with early diffuse systemic sclerosis in the SCOT trial.

OBJECTIVE: To describe the prevalence and clinical correlates of endoscopic gastric antral vascular ectasia (GAVE; "watermelon stomach") in early diffuse systemic sclerosis (SSc). METHODS: Subjects with early, diffuse SSc and evidence of specific internal organ involvement were considered for the Scleroderma: Cyclophosphamide Or Transplant (SCOT) trial. In the screening procedures, all patients underwent upper gastrointestinal endoscopy. Patients were then categorized into those with or without endoscopic evidence of GAVE. Demographic data, clinical disease characteristics, and autoantibody data were compared using Pearson chi-square or Student t tests. RESULTS: Twenty-three of 103 (22.3%) individuals were found to have GAVE on endoscopy. Although not statistically significant, anti-topoisomerase I (anti-Scl70) was detected less frequently among those with GAVE (18.8% vs 44.7%; p = 0.071). Similarly, anti-RNP antibodies (anti-U1 RNP) showed a trend to a negative association with GAVE (0 vs 18.4%; p = 0.066). There was no association between anti-RNA polymerase III and GAVE. Patients with GAVE had significantly more erythema or vascular ectasias in other parts of the stomach (26.1% vs 5.0%; p = 0.003). CONCLUSION: Endoscopic GAVE was present on screening in almost one-fourth of these highly selected patients with early and severe diffuse SSc. While anti-Scl70 and anti-U1 RNP trended toward a negative association with GAVE, there was no correlation between anti-RNA Pol III and GAVE. Patients with GAVE had a higher frequency of other gastric vascular ectasias outside the antrum, suggesting that GAVE may represent part of the spectrum of the vasculopathy in SSc.

Authors
Hung, EW; Mayes, MD; Sharif, R; Assassi, S; Machicao, VI; Hosing, C; St Clair, EW; Furst, DE; Khanna, D; Forman, S; Mineishi, S; Phillips, K; Seibold, JR; Bredeson, C; Csuka, ME; Nash, RA; Wener, MH; Simms, R; Ballen, K; Leclercq, S; Storek, J; Goldmuntz, E; Welch, B; Keyes-Elstein, L; Castina, S; Crofford, LJ; Mcsweeney, P; Sullivan, KM
MLA Citation
Hung, EW, Mayes, MD, Sharif, R, Assassi, S, Machicao, VI, Hosing, C, St Clair, EW, Furst, DE, Khanna, D, Forman, S, Mineishi, S, Phillips, K, Seibold, JR, Bredeson, C, Csuka, ME, Nash, RA, Wener, MH, Simms, R, Ballen, K, Leclercq, S, Storek, J, Goldmuntz, E, Welch, B, Keyes-Elstein, L, Castina, S, Crofford, LJ, Mcsweeney, P, and Sullivan, KM. "Gastric antral vascular ectasia and its clinical correlates in patients with early diffuse systemic sclerosis in the SCOT trial." J Rheumatol 40.4 (April 2013): 455-460.
PMID
23418384
Source
pubmed
Published In
The Journal of rheumatology
Volume
40
Issue
4
Publish Date
2013
Start Page
455
End Page
460
DOI
10.3899/jrheum.121087

Stem cell transplantation in systemic sclerosis

PURPOSE OF REVIEW: The purpose of this review is to discuss recent published clinical and mechanistic studies on stem cell transplantation for systemic sclerosis and their implications for clinical practice. RECENT FINDINGS: Retrospective analyses of independent cohorts of systemic sclerosis patients treated with autologous stem cell transplantation showed significant improvement of skin thickening, lung function and quality of life, but at the expense of 6-17% treatment-related mortality. Right heart catheterization was employed in one study to identify and exclude patients at risk of serious cardiopulmonary toxicity. The superior efficacy of stem cell transplantation versus intravenous pulses cyclophosphamide was demonstrated in a small randomized, controlled phase 2 trial in 19 systemic sclerosis patients and a large randomized phase 3 trial in 156 patients with severe diffuse cutaneous systemic sclerosis. The latter also showed a survival benefit of transplanted patients despite a 10% transplant-related mortality. Mechanistic studies in transplanted patients have shown major shifts in circulating natural killer cells, T and B lymphocytes immediately after stem cell transplantation, similar to those observed in other autoimmune conditions. Stem cell transplantation of systemic sclerosis patients with lung involvement resulted in demonstrable attenuation of thoracic high-resolution CT (HRCT) abnormalities and serum markers of lung fibrosis. SUMMARY: Stem cell transplantation is an effective treatment option for patients with severe systemic sclerosis, but is associated with toxicity and treatment-related mortality. The available data suggest that patient selection and comprehensive cardiopulmonary screening are critical factors in determining outcome. VIDEO ABSTRACT AVAILABLE: See the Supplementary Digital content 1 (http://links.lww.com/COR/A7) © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Authors
Laar, JMV; Sullivan, K
MLA Citation
Laar, JMV, and Sullivan, K. "Stem cell transplantation in systemic sclerosis." Current Opinion in Rheumatology 25.6 (2013): 719-725.
PMID
24047607
Source
scival
Published In
Current Opinion in Rheumatology
Volume
25
Issue
6
Publish Date
2013
Start Page
719
End Page
725
DOI
10.1097/01.bor.0000434669.32150.ac

Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: Risk factors and response to treatment

High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (≥12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (≥13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (≥38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66-88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation. © 2013 Macmillan Publishers Limited All rights reserved.

Authors
Kanda, J; Kaynar, L; Kanda, Y; Prasad, VK; Parikh, SH; Lan, L; Shen, T; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; Winkel, S; McPherson, J; Kurtzberg, J; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Kaynar, L, Kanda, Y, Prasad, VK, Parikh, SH, Lan, L, Shen, T, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, Winkel, S, McPherson, J, Kurtzberg, J, Chao, NJ, and Horwitz, ME. "Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: Risk factors and response to treatment." Bone Marrow Transplantation 48.7 (2013): 926-931.
Source
scival
Published In
Bone Marrow Transplantation
Volume
48
Issue
7
Publish Date
2013
Start Page
926
End Page
931
DOI
10.1038/bmt.2012.279

Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation.

Immunologic reconstitution after allogeneic hematopoietic cell transplantation is a critical component of successful outcome. Umbilical cord blood (UCB) transplantation in adult recipients is associated with slow and often inadequate immune recovery. We characterized the kinetics and extent of immune recovery in 95 adult recipients after a dual UCB (n = 29) and matched sibling donor (n = 33) or matched unrelated donor (n = 33) transplantation. All patients were treated with myeloablative conditioning. There were no differences in the immune recovery profile of matched sibling donor and matched unrelated donor recipients. Significantly lower levels of CD3+, CD4+, and CD8+ T cells were observed in UCB recipients until 6 months after transplantation. Lower levels of regulatory T cells persisted until 1 year after transplantation. Thymopoiesis as measured by TCR rearrangement excision circle was comparable among all recipients by 6 months after transplantation. In a subset of patients 1 year after transplantation with similar levels of circulating T cells and TCR rearrangement excision circle, there was no difference in TCR diversity. Compared to HLA-identical matched sibling donor and matched unrelated donor adult hematopoietic cell transplantation recipients, quantitative lymphoid recovery in UCB transplantation recipients is slower in the first 3 months, but these differences disappeared by 6 to 12 months after transplantation.

Authors
Kanda, J; Chiou, L-W; Szabolcs, P; Sempowski, GD; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; McPherson, J; Hale, J; Livingston, JA; Broadwater, G; Niedzwiecki, D; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Chiou, L-W, Szabolcs, P, Sempowski, GD, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, McPherson, J, Hale, J, Livingston, JA, Broadwater, G, Niedzwiecki, D, Chao, NJ, and Horwitz, ME. "Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation." Biol Blood Marrow Transplant 18.11 (November 2012): 1664-1676.e1.
PMID
22698485
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
11
Publish Date
2012
Start Page
1664
End Page
1676.e1
DOI
10.1016/j.bbmt.2012.06.005

Mini test dose of intravenous busulfan (busulfex(®)) in allogeneic non-myeloablative stem cell transplantation, followed by liquid chromatography tandem-mass spectrometry.

Authors
Spasojevic, I; da Costa, LRS; Horwitz, ME; Long, GD; Sullivan, KM; Chute, JP; Gasparetto, C; Morris, A; Chao, NJ; Rizzieri, DA
MLA Citation
Spasojevic, I, da Costa, LRS, Horwitz, ME, Long, GD, Sullivan, KM, Chute, JP, Gasparetto, C, Morris, A, Chao, NJ, and Rizzieri, DA. "Mini test dose of intravenous busulfan (busulfex(®)) in allogeneic non-myeloablative stem cell transplantation, followed by liquid chromatography tandem-mass spectrometry." Cancer Invest 30.9 (November 2012): 679-682.
PMID
23020519
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
30
Issue
9
Publish Date
2012
Start Page
679
End Page
682
DOI
10.3109/07357907.2012.726386

Transplantation for autoimmune diseases in north and South America: a report of the Center for International Blood and Marrow Transplant Research.

Hematopoietic cell transplantation (HCT) is an emerging therapy for patients with severe autoimmune diseases (AID). We report data on 368 patients with AID who underwent HCT in 64 North and South American transplantation centers reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2009. Most of the HCTs involved autologous grafts (n = 339); allogeneic HCT (n = 29) was done mostly in children. The most common indications for HCT were multiple sclerosis, systemic sclerosis, and systemic lupus erythematosus. The median age at transplantation was 38 years for autologous HCT and 25 years for allogeneic HCT. The corresponding times from diagnosis to HCT were 35 months and 24 months. Three-year overall survival after autologous HCT was 86% (95% confidence interval [CI], 81%-91%). Median follow-up of survivors was 31 months (range, 1-144 months). The most common causes of death were AID progression, infections, and organ failure. On multivariate analysis, the risk of death was higher in patients at centers that performed fewer than 5 autologous HCTs (relative risk, 3.5; 95% CI, 1.1-11.1; P = .03) and those that performed 5 to 15 autologous HCTs for AID during the study period (relative risk, 4.2; 95% CI, 1.5-11.7; P = .006) compared with patients at centers that performed more than 15 autologous HCTs for AID during the study period. AID is an emerging indication for HCT in the region. Collaboration of hematologists and other disease specialists with an outcomes database is important to promote optimal patient selection, analysis of the impact of prognostic variables and long-term outcomes, and development of clinical trials.

Authors
Pasquini, MC; Voltarelli, J; Atkins, HL; Hamerschlak, N; Zhong, X; Ahn, KW; Sullivan, KM; Carrum, G; Andrey, J; Bredeson, CN; Cairo, M; Gale, RP; Hahn, T; Storek, J; Horowitz, MM; McSweeney, PA; Griffith, LM; Muraro, PA; Pavletic, SZ; Nash, RA
MLA Citation
Pasquini, MC, Voltarelli, J, Atkins, HL, Hamerschlak, N, Zhong, X, Ahn, KW, Sullivan, KM, Carrum, G, Andrey, J, Bredeson, CN, Cairo, M, Gale, RP, Hahn, T, Storek, J, Horowitz, MM, McSweeney, PA, Griffith, LM, Muraro, PA, Pavletic, SZ, and Nash, RA. "Transplantation for autoimmune diseases in north and South America: a report of the Center for International Blood and Marrow Transplant Research." Biol Blood Marrow Transplant 18.10 (October 2012): 1471-1478.
PMID
22705497
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
10
Publish Date
2012
Start Page
1471
End Page
1478
DOI
10.1016/j.bbmt.2012.06.003

Preemptive dosing of plerixafor given to poor stem cell mobilizers on day 5 of G-CSF administration.

Plerixafor, given on day 4 of G-CSF treatment is more effective than G-CSF alone in mobilizing hematopoietic progenitor cells. We tested a strategy of preemptive plerixafor use following assessment of the peak mobilization response to 5 days of G-CSF. Patients were eligible for plerixafor if, on day 5 of G-CSF, there were <7 circulating CD34+ cells/μL or if <1.3 × 10(6) CD34+ cells/kg were collected on the first day of apheresis. Plerixafor (0.24 mg/kg s.c.) was given on day 5 of G-CSF followed by apheresis on day 6. This was repeated for up to two additional doses of plerixafor. The primary end point of the study was the percentage of patients who collected at least 2 × 10(6) CD34+ cells/kg. Twenty candidates for auto-SCT enrolled on the trial. The circulating CD34+ cell level increased a median of 3.1 fold (range 1-8 fold) after the first dose of plerixafor and a median of 1.2 fold (range 0.3-6.5 fold) after the second dose of plerixafor. In all, 15 out of 20 (75%) patients achieved the primary end point. In conclusion, the decision to administer plerixafor can be delayed until after the peak mobilization response to G-CSF has been fully assessed.

Authors
Horwitz, ME; Chute, JP; Gasparetto, C; Long, GD; McDonald, C; Morris, A; Rizzieri, DA; Sullivan, KM; Chao, NJ
MLA Citation
Horwitz, ME, Chute, JP, Gasparetto, C, Long, GD, McDonald, C, Morris, A, Rizzieri, DA, Sullivan, KM, and Chao, NJ. "Preemptive dosing of plerixafor given to poor stem cell mobilizers on day 5 of G-CSF administration." Bone Marrow Transplant 47.8 (August 2012): 1051-1055.
PMID
22080963
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
47
Issue
8
Publish Date
2012
Start Page
1051
End Page
1055
DOI
10.1038/bmt.2011.217

Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors.

The impact of activating KIR (aKIR) and inhibitory KIR (iKIR) on OS, relapse-related mortality (RRM) and acute GVHD (aGVHD) was prospectively studied in 84 adults with high-risk hematologic malignancies receiving reduced intensity conditioning (RIC) T-cell depleted hematopoietic SCT (HSCT) from haploidentical related donors. In this clinical model, freedom from RRM is dependent on GVL effect. Patients were divided into myeloid (n=49) and lymphoid (n=35) malignancy groups. KIR-ligand and ligand-ligand models were studied in both GVH and rejection directions and statistically correlated with outcome measures. In the myeloid group, OS was higher (P=0.009) and RRM was lower (P=0.036) in patients missing HLA-C group2 ligand to donor iKIR. OS was higher if patients had >1 missing ligand (P=0.018). In lymphoid malignancy, missing ligand to donor KIR had no impact on OS or RRM. However, OS was better with donor aKIR 2DS2 (P=0.028). There was a trend towards shorter OS in recipient with KIR 2DS1, 2DS5 and 3DS1, although sample sizes were too small to provide inferential statistics. Findings in lymphoid malignancy patients should be further studied. These results suggest that the absence of appropriate HLA ligands in the recipient to donor iKIR may induce GVL without aGVHD in myeloid malignancy patients undergoing TCD-RIC transplants.

Authors
Chen, D-F; Prasad, VK; Broadwater, G; Reinsmoen, NL; DeOliveira, A; Clark, A; Sullivan, KM; Chute, JP; Horwitz, ME; Gasparetto, C; Long, GD; Yang, Y; Chao, NJ; Rizzieri, DA
MLA Citation
Chen, D-F, Prasad, VK, Broadwater, G, Reinsmoen, NL, DeOliveira, A, Clark, A, Sullivan, KM, Chute, JP, Horwitz, ME, Gasparetto, C, Long, GD, Yang, Y, Chao, NJ, and Rizzieri, DA. "Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors." Bone Marrow Transplant 47.6 (June 2012): 817-823.
PMID
22139069
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
47
Issue
6
Publish Date
2012
Start Page
817
End Page
823
DOI
10.1038/bmt.2011.181

Outcomes of a 1-day nonmyeloablative salvage regimen for patients with primary graft failure after allogeneic hematopoietic cell transplantation.

Primary graft failure after allogeneic hematopoietic cell transplantation is a life-threatening complication. A shortened conditioning regimen may reduce the risk of infection and increase the chance of survival. Here, we report the outcome of 11 patients with hematologic diseases (median age, 44; range, 25-67 years, seven males) who received a 1-day reduced-intensity preparative regimen given as a re-transplantation for primary graft failure. The salvage regimen consisted of fludarabine, cyclophosphamide, alemtuzumab and TBI, all administered 1 day before re-transplantation. All patients received T-cell replete PBSCs from the same or a different haploidentical donor (n=10) or from the same matched sibling donor (n=1). Neutrophil counts promptly increased to >500/μL for 10 of the 11 patients at a median of 13 days. Of these, none developed grade III/IV acute GVHD. At present, 8 of the 11 patients are alive with a median follow-up of 11.2 months from re-transplantation and 5 of the 8 are in remission. In conclusion, this series suggests that our 1-day preparative regimen is feasible, leads to successful engraftment in a high proportion of patients, and is appropriate for patients requiring immediate re-transplantation after primary graft failure following reduced-intensity transplantation.

Authors
Kanda, J; Horwitz, ME; Long, GD; Gasparetto, C; Sullivan, KM; Chute, JP; Morris, A; Hennig, T; Li, Z; Chao, NJ; Rizzieri, DA
MLA Citation
Kanda, J, Horwitz, ME, Long, GD, Gasparetto, C, Sullivan, KM, Chute, JP, Morris, A, Hennig, T, Li, Z, Chao, NJ, and Rizzieri, DA. "Outcomes of a 1-day nonmyeloablative salvage regimen for patients with primary graft failure after allogeneic hematopoietic cell transplantation." Bone Marrow Transplant 47.5 (May 2012): 700-705.
PMID
21804612
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
47
Issue
5
Publish Date
2012
Start Page
700
End Page
705
DOI
10.1038/bmt.2011.158

USE OF CYCLOSPORINE IS ASSOCIATED WITH THE INCREASE IN PRE-ENGRAFTMENT SYNDROME AFTER MYELOABLATIVE DUAL CORD BLOOD TRANSPLANTATION

Authors
Kanda, J; Kaynar, L; Kanda, Y; Prasad, VK; Parikh, SH; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; Winkel, S; McPherson, J; Kurtzberg, J; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Kaynar, L, Kanda, Y, Prasad, VK, Parikh, SH, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, Winkel, S, McPherson, J, Kurtzberg, J, Chao, NJ, and Horwitz, ME. "USE OF CYCLOSPORINE IS ASSOCIATED WITH THE INCREASE IN PRE-ENGRAFTMENT SYNDROME AFTER MYELOABLATIVE DUAL CORD BLOOD TRANSPLANTATION." February 2012.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
2
Publish Date
2012
Start Page
S332
End Page
S332

Haemopoietic stem-cell transplantation for systemic sclerosis

Authors
Sullivan, KM; Wigley, FM; Denton, CP; van Laar, JM; Furst, DE
MLA Citation
Sullivan, KM, Wigley, FM, Denton, CP, van Laar, JM, and Furst, DE. "Haemopoietic stem-cell transplantation for systemic sclerosis." LANCET 379.9812 (January 21, 2012): 219-219.
PMID
22265628
Source
wos-lite
Published In
The Lancet
Volume
379
Issue
9812
Publish Date
2012
Start Page
219
End Page
219

Cell-based therapies

© Springer Science+Business Media, LLC 2012. All rights reserved. Cell therapy describes the process of introducing new cells into a tissue in order to treat a disease. Cell therapies often focus on the treatment of hereditary diseases, with or without the addition of gene therapy. There are many potential forms of cell therapy: the transplantation of stem cells that are autologous (from the patient) or allogeneic (from another donor), the transplantation of mature, functional cells, the application of modified human cells that are used to produce a needed substance, the xenotransplantation of non-human cells that are used to produce a needed substance (e.g., treating diabetic patients by introducing insulin-producing pig cells directly into their muscle) and the transplantation of trans-differentiated cells derived from the patient's own differentiated cells (e.g., the use of insulin producing beta cells trans-differentiated from isolated hepatocytes as a treatment for diabetes). Increasingly, mesenchymal stem cells are being proposed as agents for cell-based therapies, due to their plasticity, established isolation procedures, and capacity for ex vivo expansion. For safety reasons, cell therapy of systemic sclerosis (SSc) has most commonly employed autologous hematopoietic stem cell transplantation (HSCT) to replace a previously ablated or markedly reduced lymphohematopoietic/immune system with the aim of "resetting" autoimmunity. Some cases of allogeneic HSCT and mesenchymal stem cell (MSC) transplantation have also been performed, and the results and ongoing programs of these cellular therapies will be reviewed in this chapter.

Authors
Tyndall, AG; Sullivan, KM
MLA Citation
Tyndall, AG, and Sullivan, KM. "Cell-based therapies." Scleroderma: From Pathogenesis to Comprehensive Management. January 1, 2012. 591-602.
Source
scopus
Publish Date
2012
Start Page
591
End Page
602
DOI
10.1007/978-1-4419-5774-0_49

Haemopoietic stem-cell transplantation for systemic sclerosis

Authors
Sullivan, KM; Wigley, FM; Denton, CP; Laar, JMV; Furst, DE
MLA Citation
Sullivan, KM, Wigley, FM, Denton, CP, Laar, JMV, and Furst, DE. "Haemopoietic stem-cell transplantation for systemic sclerosis." The Lancet 379.9812 (2012): 219--.
Source
scival
Published In
The Lancet
Volume
379
Issue
9812
Publish Date
2012
Start Page
219-
DOI
10.1016/S0140-6736(12)60100-7

Impact of High Dose Cyclophosphamide on the Outcome of Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma

Authors
Bacon, WA; Long, GD; Rizzieri, DA; Horwitz, ME; Chute, JP; Sullivan, KM; Yopp, A; Johns, A; Chao, NJ; Gasparetto, C
MLA Citation
Bacon, WA, Long, GD, Rizzieri, DA, Horwitz, ME, Chute, JP, Sullivan, KM, Yopp, A, Johns, A, Chao, NJ, and Gasparetto, C. "Impact of High Dose Cyclophosphamide on the Outcome of Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1765
End Page
1765

The Impact of Lymphocyte Subset Recovery At 3 Months on Progression-Free Survival After Myeloablative Allogeneic Stem Cell Transplantation

Authors
Kanda, J; Rizzieri, DA; Long, GD; Gasparetto, C; Chute, JP; Sullivan, KM; Morris, A; McPherson, J; Livingston, JA; Broadwater, G; Niedzwiecki, D; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Rizzieri, DA, Long, GD, Gasparetto, C, Chute, JP, Sullivan, KM, Morris, A, McPherson, J, Livingston, JA, Broadwater, G, Niedzwiecki, D, Chao, NJ, and Horwitz, ME. "The Impact of Lymphocyte Subset Recovery At 3 Months on Progression-Free Survival After Myeloablative Allogeneic Stem Cell Transplantation." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1736
End Page
1736

High Dose BCNU/Melphalan Preparative Regimen Doubles Event Free Survival of Myeloma Patients Undergoing Autologous Transplantation

Authors
Gasparetto, C; Bacon, WA; Doan, P; Rizzieri, DA; Horwitz, ME; Chute, JP; Sullivan, KM; Yopp, A; Li, Z; Chao, NJ; Long, GD
MLA Citation
Gasparetto, C, Bacon, WA, Doan, P, Rizzieri, DA, Horwitz, ME, Chute, JP, Sullivan, KM, Yopp, A, Li, Z, Chao, NJ, and Long, GD. "High Dose BCNU/Melphalan Preparative Regimen Doubles Event Free Survival of Myeloma Patients Undergoing Autologous Transplantation." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
879
End Page
879

Adult dual umbilical cord blood transplantation using myeloablative total body irradiation (1350 cGy) and fludarabine conditioning.

High treatment-related mortality (TRM) and high graft failure rate are serious concerns in HLA-mismatched umbilical cord blood (UCB) transplantation with myeloablative conditioning. We conducted a prospective trial of dual UCB transplantation using modified myeloablation consisting of total-body irradiation (TBI; 1350 cGy) and fludarabine (Flu) (160 mg/m(2)). Twenty-seven patients (median age, 33 years; range: 20-58 years) with hematologic malignancies were enrolled. The median combined cryopreserved total nucleated cell (TNC) dose was 4.3 × 10(7)/kg (range: 3.2-7.7 × 10(7)/kg). The cumulative incidences of neutrophil (≥500/μL) and platelet (≥50,000/μL) engraftment were 80% (95% confidence interval [CI], 58%-91%) and 68% (95% CI, 46%-83%), respectively. Among engrafted patients, a single cord blood unit was predominant by 100 days posttransplantation. A higher cryopreserved and infused TNC dose and infused CD3(+) cell dose were significant factors associated with the predominant UCB unit (P = .032, .020, and .042, respectively). TRM and relapse rates at 2 years were 28% (95% CI, 12%-47%) and 20% (95% CI, 7%-37%), respectively. Cumulative incidences of grades II-IV and grades III-IV acute graft-versus-host disease (aGVHD) were 37% (95% CI, 20%-55%) and 11% (95% CI, 3%-26%), respectively, and that of chronic GVHD was 31% (95% CI, 15%-49%). With a median follow-up of 23 months, overall survival and disease-free survival rates at 2 years were 58% (95% CI, 34%-75%) and 52% (95% CI, 29%-70%), respectively. This study supports the use of TBI 1350 cGy/Flu as an alternative to conventional myeloablative conditioning for dual UCB transplantation.

Authors
Kanda, J; Rizzieri, DA; Gasparetto, C; Long, GD; Chute, JP; Sullivan, KM; Morris, A; Smith, CA; Hogge, DE; Nitta, J; Song, K; Niedzwiecki, D; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Rizzieri, DA, Gasparetto, C, Long, GD, Chute, JP, Sullivan, KM, Morris, A, Smith, CA, Hogge, DE, Nitta, J, Song, K, Niedzwiecki, D, Chao, NJ, and Horwitz, ME. "Adult dual umbilical cord blood transplantation using myeloablative total body irradiation (1350 cGy) and fludarabine conditioning." Biol Blood Marrow Transplant 17.6 (June 2011): 867-874.
PMID
20868761
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
6
Publish Date
2011
Start Page
867
End Page
874
DOI
10.1016/j.bbmt.2010.09.009

Renal shielding and dosimetry for patients with severe systemic sclerosis receiving immunoablation with total body irradiation in the scleroderma: cyclophosphamide or transplantation trial.

PURPOSE: To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled in a hematopoietic stem cell transplant protocol. METHODS AND MATERIALS: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy fractions twice a day before CD34(+) selected autologous hematopoietic stem cell transplantation. Lung and kidney doses are limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated, and guidelines were developed for acceptable lumbar area TBI dosing. Information about kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry was performed at several locations to determine the radiation doses delivered. RESULTS: Eleven patients were treated at our center with an anteroposterior (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4 to 5 cm. The average lumbar spine dose was 179.6 ± 18.1 cGy, with an average dkB of 5.0 ± 1.0 cm. Kidney block shield design was accomplished using a combination of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 ± 5.1 cGy. CONCLUSIONS: The dose to the kidneys can be attenuated while maintaining a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved, and the study continues to enroll patients.

Authors
Craciunescu, OI; Steffey, BA; Kelsey, CR; Larrier, NA; Paarz-Largay, CJ; Prosnitz, RG; Chao, N; Chute, J; Gasparetto, C; Horwitz, M; Long, G; Rizzieri, D; Sullivan, KM
MLA Citation
Craciunescu, OI, Steffey, BA, Kelsey, CR, Larrier, NA, Paarz-Largay, CJ, Prosnitz, RG, Chao, N, Chute, J, Gasparetto, C, Horwitz, M, Long, G, Rizzieri, D, and Sullivan, KM. "Renal shielding and dosimetry for patients with severe systemic sclerosis receiving immunoablation with total body irradiation in the scleroderma: cyclophosphamide or transplantation trial." Int J Radiat Oncol Biol Phys 79.4 (March 15, 2011): 1248-1255.
PMID
20800376
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
79
Issue
4
Publish Date
2011
Start Page
1248
End Page
1255
DOI
10.1016/j.ijrobp.2010.05.036

OUTCOMES OF A 1-DAY NONMYELOABLATIVE PREPARATIVE REGIMEN FOR PRIMARY GRAFT FAILURE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION

Authors
Kanda, J; Horwitz, ME; Long, GD; Gasparetto, C; Sullivan, KM; Chute, JP; Morris, A; Hennig, T; Chao, NJ; Rizzieri, DA
MLA Citation
Kanda, J, Horwitz, ME, Long, GD, Gasparetto, C, Sullivan, KM, Chute, JP, Morris, A, Hennig, T, Chao, NJ, and Rizzieri, DA. "OUTCOMES OF A 1-DAY NONMYELOABLATIVE PREPARATIVE REGIMEN FOR PRIMARY GRAFT FAILURE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S308
End Page
S308
DOI
10.1016/j.bbmt.2010.12.460

ORGAN FUNCTION AND QUALITY OF LIFE CORRELATES AT RANDOMIZATION ON THE SCOT (SCLERODERMA: CYCLOPHOSPHAMIDE OR TRANSPLANTATION) TRIAL

Authors
Sullivan, KM; Froshaug, DB; Furst, DE; Nash, RA; Mayes, MD; Crofford, LJ; McSweeney, PA; Goldmuntz, EA; Keyes-Elstein, L; Khanna, D
MLA Citation
Sullivan, KM, Froshaug, DB, Furst, DE, Nash, RA, Mayes, MD, Crofford, LJ, McSweeney, PA, Goldmuntz, EA, Keyes-Elstein, L, and Khanna, D. "ORGAN FUNCTION AND QUALITY OF LIFE CORRELATES AT RANDOMIZATION ON THE SCOT (SCLERODERMA: CYCLOPHOSPHAMIDE OR TRANSPLANTATION) TRIAL." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S195
End Page
S195
DOI
10.1016/j.bbmt.2010.12.134

Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors.

INTRODUCTION: High relapse rates and infections remain primary causes of failure in nonmyeloablative transplantation. Interleukin-2 (IL-2) may stimulate the immune system and improve outcomes. The primary objective of this pilot study was to evaluate the feasibility of administering IL-2 following a T-cell-depleted nonmyeloablative hematopoietic stem cell transplant. METHODS: Patients received T-cell-depleted nonmyeloablative transplant from a matched or mismatched related donor. Those with allogeneic engraftment,

Authors
Rizzieri, DA; Crout, C; Storms, R; Golob, J; Long, GD; Gasparetto, C; Sullivan, KM; Horwitz, M; Chute, J; Lagoo, AS; Morris, A; Beaven, A; Yang, Y; Peterson, B; Li, Z; Chao, NJ
MLA Citation
Rizzieri, DA, Crout, C, Storms, R, Golob, J, Long, GD, Gasparetto, C, Sullivan, KM, Horwitz, M, Chute, J, Lagoo, AS, Morris, A, Beaven, A, Yang, Y, Peterson, B, Li, Z, and Chao, NJ. "Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors." Cancer Invest 29.1 (January 2011): 56-61.
PMID
21166499
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
29
Issue
1
Publish Date
2011
Start Page
56
End Page
61
DOI
10.3109/07357907.2010.535055

Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma

Positron emission tomography (PET) in conjunction with computed tomography is a frequently used modality for staging patients with lymphoma. Utility of PET-computed tomography before or early following auto-SCT has not been as rigorously evaluated. We retrospectively analyzed patients who received auto-SCT for treatment of relapsed or refractory non-Hodgkins lymphoma or Hodgkins disease between the years of 1996 and 2007. Patients who had either a PET scan following salvage chemotherapy within 14 weeks of transplantation (pre-PET), and/or a PET scan 6-14 weeks following transplantation (post-PET) were included. A total of 90 patients were identified for analysis. The median follow-up time is 3.3 years, with a range of 0.13-12.0 years. The median PFS was 4.6 years, and median OS was 5.1 years. At the time of this analysis, 34 patients (37%) experienced disease relapse, and 25 (27%) of the patients died from disease progression. In multivariate Cox proportional hazards analysis, post-PET did not predict for outcome, pre-PET positivity predicted for decrease in PFS. In conclusion, post-PET scan did not predict for PFS or OS in multivariate analysis. Positive pre-PET scan did predict for PFS as seen in previous studies, and may help identify patients who would benefit from innovative post transplant therapies. © 2011 Macmillan Publishers Limited All rights reserved.

Authors
Palmer, J; Goggins, T; Broadwater, G; Chao, N; Horwitz, M; Beaven, A; Sullivan, K; Coleman, RE; Rizzieri, D
MLA Citation
Palmer, J, Goggins, T, Broadwater, G, Chao, N, Horwitz, M, Beaven, A, Sullivan, K, Coleman, RE, and Rizzieri, D. "Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma." Bone Marrow Transplantation 46.6 (2011): 847-851.
PMID
20856212
Source
scival
Published In
Bone Marrow Transplantation
Volume
46
Issue
6
Publish Date
2011
Start Page
847
End Page
851
DOI
10.1038/bmt.2010.203

Acute Kidney Injury in Patients with Systemic Sclerosis Participating in Hematopoietic Cell Transplantation Trials in the United States

Recipients of hematopoietic cell transplantation may be at risk for developing acute kidney injury (AKI), and this risk may be increased in patients who undergo transplantation for severe systemic sclerosis (SSc) due to underlying scleroderma renal disease. AKI after transplantation can increase treatment-related mortality. To better define these risks, we analyzed 91 patients with SSc who were enrolled in 3 clinical trials in the United States of autologous or allogeneic hematopoietic cell transplantation (HCT). Eleven (12%) of the 91 patients with SSc in these studies (8 undergoing autologous HCT, 1 undergoing allogeneic HCT, 1 pretransplantation, 1 given i.v. cyclophosphamide on a transplantation trial) experienced AKI, of whom 8 required dialysis and/or therapeutic plasma exchange. AKI injury in the 9 HCT recipients developed a median of 35 days (range, 0-90 days) after transplantation. Ten of 11 patients with AKI received angiotensin-converting enzyme inhibitor (ACE-I) therapy. The etiology of AKI was attributed to scleroderma renal crisis in 6 patients (including 2 with normotensive renal crisis), to AKI of uncertain etiology in 2 patients, and to AKI superimposed on scleroderma kidney disease in 3 patients. Eight of the 11 patients died, one each because of progression of SSc, multiorgan failure, gastrointestinal and pulmonary bleeding, pericardial tamponade and pulmonary complications, diffuse alveolar hemorrhage, pulmonary embolism, graft-versus-host disease, and malignancy. Limiting nephrotoxins, cautious use of corticosteroids, renal shielding during total body irradiation, strict control of blood pressure, and aggressive use of ACE-Is may be of importance in preventing renal complications after HCT for SSc. © 2011 American Society for Blood and Marrow Transplantation.

Authors
Hosing, C; Nash, R; McSweeney, P; Mineishi, S; Seibold, J; Griffith, LM; Shulman, H; Goldmuntz, E; Mayes, M; Parikh, CR; Crofford, L; Keyes-Elstein, L; Furst, D; Steen, V; Sullivan, KM
MLA Citation
Hosing, C, Nash, R, McSweeney, P, Mineishi, S, Seibold, J, Griffith, LM, Shulman, H, Goldmuntz, E, Mayes, M, Parikh, CR, Crofford, L, Keyes-Elstein, L, Furst, D, Steen, V, and Sullivan, KM. "Acute Kidney Injury in Patients with Systemic Sclerosis Participating in Hematopoietic Cell Transplantation Trials in the United States." Biology of Blood and Marrow Transplantation 17.5 (2011): 674-681.
PMID
20708086
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
5
Publish Date
2011
Start Page
674
End Page
681
DOI
10.1016/j.bbmt.2010.08.003

Adult Dual Umbilical Cord Blood Transplantation Using Myeloablative Total Body Irradiation (1350cGy) and Fludarabine Conditioning

Authors
Kanda, J; Rizzieri, DA; Gasparetto, C; Long, GD; Chute, JP; Sullivan, KM; Morris, A; Smith, CA; Hogge, DE; Nitta, J; Song, K; Niedzwiecki, D; Chao, NJ; Horwitz, ME
MLA Citation
Kanda, J, Rizzieri, DA, Gasparetto, C, Long, GD, Chute, JP, Sullivan, KM, Morris, A, Smith, CA, Hogge, DE, Nitta, J, Song, K, Niedzwiecki, D, Chao, NJ, and Horwitz, ME. "Adult Dual Umbilical Cord Blood Transplantation Using Myeloablative Total Body Irradiation (1350cGy) and Fludarabine Conditioning." November 19, 2010.
PMID
28729147
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1448
End Page
1448

Prospective, Biological Randomized Study of T-Cell Depleted Nonmyeloablative Allogeneic Transplantation From HLA-Matched Related, Unrelated or Haploidentical Donors for Patients with Hematologic Malignancies.

Authors
Kanda, J; Long, GD; Gasparetto, C; Horwitz, ME; Sullivan, KM; Chute, JP; Morris, A; Li, Z; Chao, NJ; Rizzieri, DA
MLA Citation
Kanda, J, Long, GD, Gasparetto, C, Horwitz, ME, Sullivan, KM, Chute, JP, Morris, A, Li, Z, Chao, NJ, and Rizzieri, DA. "Prospective, Biological Randomized Study of T-Cell Depleted Nonmyeloablative Allogeneic Transplantation From HLA-Matched Related, Unrelated or Haploidentical Donors for Patients with Hematologic Malignancies." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
1456
End Page
1457

Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation.

Infusing natural killer (NK) cells following transplantation may allow less infections and relapse with little risk of acute graft-versus-host disease (aGVHD). We delivered 51 total NK cell-enriched donor lymphocyte infusions (DLIs) to 30 patients following a 3-6/6 HLA matched T cell-depleted nonmyeloablative allogeneic transplant. The primary endpoint of this study was feasibility and safety. Eight weeks following transplantation, donor NK cell-enriched DLIs were processed using a CD56(+) selecting column with up to 3 fresh infusions allowed. Toxicity, relapse, and survival were monitored. T cell phenotype, NK cell functional recovery, and KIR typing were assessed for association with outcomes. Fourteen matched and 16 mismatched transplanted patients received a total of 51 NK cell-enriched DLIs. Selection resulted in 96% (standard deviation [SD] 8%) purity and 83% (SD 21%) yield in the matched setting and 97% (SD 3%) purity and 77% (SD 24%) yield in the mismatched setting. The median number of CD3(-) CD56(+) NK cells infused was 10.6 (SD 7.91) x 10(6) cells/kg and 9.21 (SD 5.6) x 10(6) cells/kg, respectively. The median number of contaminating CD3(+)CD56(-) T cells infused was .53 (1.1) x 10(6) and .27 (.78) x 10(6) in the matched and mismatched setting, respectively. Only 1 patient each in the matched (n = 14) or mismatched (n = 16) setting experienced severe aGVHD with little other toxicity attributable to the infusions. Long-term responders with multiple NK cell-enriched infusions and improved T cell phenotypic recovery had improved duration of responses (p = .0045) and overall survival (OS) (P = .0058). A 1-step, high-yield process is feasible, and results in high doses of NK cells infused with little toxicity. NK cell-enriched DLIs result in improved immune recovery and outcomes for some. Future studies must assess whether the improved outcomes are the direct result of the high doses and improved NK cell function or other aspects of immune recovery.

Authors
Rizzieri, DA; Storms, R; Chen, D-F; Long, G; Yang, Y; Nikcevich, DA; Gasparetto, C; Horwitz, M; Chute, J; Sullivan, K; Hennig, T; Misra, D; Apple, C; Baker, M; Morris, A; Green, PG; Hasselblad, V; Chao, NJ
MLA Citation
Rizzieri, DA, Storms, R, Chen, D-F, Long, G, Yang, Y, Nikcevich, DA, Gasparetto, C, Horwitz, M, Chute, J, Sullivan, K, Hennig, T, Misra, D, Apple, C, Baker, M, Morris, A, Green, PG, Hasselblad, V, and Chao, NJ. "Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation." Biol Blood Marrow Transplant 16.8 (August 2010): 1107-1114.
PMID
20188202
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
16
Issue
8
Publish Date
2010
Start Page
1107
End Page
1114
DOI
10.1016/j.bbmt.2010.02.018

"Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma.

The purpose of this study was to evaluate the efficacy and safety of short-course bortezomib, melphalan, prednisone (VMP) in previously untreated multiple myeloma as frontline therapy for transplant-ineligible patients and induction prior to autologous stem cell transplantation (ASCT). Patients received up to 6 28-day cycles of bortezomib 1.3 mg/m(2), days 1, 4, 8, and 11, plus melphalan 6 mg/m(2) and prednisone 60 mg/m(2), days 1-7. After 2-6 cycles, eligible and consenting patients could proceed to ASCT. Responses were assessed by International Uniform Response Criteria. The primary endpoint was complete response (CR) rate with VMP. Forty-five patients were enrolled. Among 44 evaluable patients, response rate was 95%, including 18% >or=CR (9% stringent CR), 27% very good partial responses (VGPR), and 50% partial responses (PR). Twenty patients proceeded to ASCT. Stem cell collection was successful in all; median yield was 5.6 x 10(6) CD34(+) cells/kg. Posttransplant response rates were 30% >or=CR (10% stringent CR), 65% VGPR, and 5% PR. After median follow-up of 14.0/14.6 months, median time to progression and progression-free survival were both 19.8/27.9 months in non-ASCT/ASCT patients. Seven patients have died; 1-year survival rates were 82%/95% in non-ASCT/ASCT patients. The most common grade 3/4 toxicities were thrombocytopenia (20%), neutropenia (28%), and infection (9%). Peripheral neuropathy grade 2-4 was the most common nonhematopoietic side effect occurring 17 patients (38%), although it was typically reversible, and only 5 patients (11%) discontinued therapy as a result of it. Short-course VMP is highly effective and generally well tolerated, both as initial treatment in non-ASCT patients and induction prior to ASCT. VMP did not negatively affect stem cell collection. Longer follow-up and prospective phase III trials are required to validate these initial observations.

Authors
Gasparetto, C; Gockerman, JP; Diehl, LF; de Castro, CM; Moore, JO; Long, GD; Horwitz, ME; Keogh, G; Chute, JP; Sullivan, KM; Neuwirth, R; Davis, PH; Sutton, LM; Anderson, RD; Chao, NJ; Rizzieri, D
MLA Citation
Gasparetto, C, Gockerman, JP, Diehl, LF, de Castro, CM, Moore, JO, Long, GD, Horwitz, ME, Keogh, G, Chute, JP, Sullivan, KM, Neuwirth, R, Davis, PH, Sutton, LM, Anderson, RD, Chao, NJ, and Rizzieri, D. ""Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma." Biol Blood Marrow Transplant 16.1 (January 2010): 70-77.
PMID
19733251
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
16
Issue
1
Publish Date
2010
Start Page
70
End Page
77
DOI
10.1016/j.bbmt.2009.08.017

Hematopoietic cell transplantation for autoimmune disease: updates from Europe and the United States.

Considerable advances have been made in our understanding of the immunobiology of autoimmune disease and its treatment with hematopoietic cell transplantation (HCT). In autoimmune disorders, the reconstituted immune system following lymphoablation and autologous HCT yields qualitative changes in immune defects and modifications in adaptive immune responses. Seminal experiments in animals demonstrated that allogeneic or autologous HCT could prevent progression or reverse organ damage from inherited (genetic) or acquired (antigen induced) autoimmune diseases. Convincing animal and clinical data now show that after HCT, the immune system is normalized and "reset". Following autologous transplantation, this resetting occurs via repertoire replacement. It is currently being studied whether and to what extent suppression of inflammation after HCT is due to reregulation of function or due to the eradication of disease associated T and/or B cell populations. There are now a number of published clinical reports with sufficient follow-up for determinations of safety and efficacy of HCT for autoimmune diseases. On behalf of colleagues in the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT), we review the experience with more than 1000 transplants for autoimmune disease in Europe along with the three major multinational randomized trials in for systemic sclerosis (SSc, the ASTIS study), multiple sclerosis (MS, the ASTIMS study), and Crohn's disease (CD, the ASTIC study). Completed phase II studies in the USA of transplantation for severe SSc, SLE and MS yield promising results. For individuals with SSc, there is dramatic improvement/resolution of dermal fibrosis and stabilization/improvement of pulmonary dysfunction reported up to 8 years after lymphoablative conditioning and autologous HCT. Currently, randomized phase III studies are recruiting subjects in the USA with SSc, MS and CD. In addition, 9 other phase I and II trials in the USA are recruiting patients with autoimmune diseases for nonmyeloablative transplants from allogeneic stem cell donors. Research opportunities abound, but recruitment challenges restrict study entry due to organ impairment from advanced autoimmune disease or insurance denial of coverage for HCT. However, within several NIH sponsored trials there are ongoing immunologic, genomic and mechanistic studies to further understand the molecular mechanisms of autoimmunity, immune regulation and response to treatment. These clinical trials will provide basic scientists with insight into immunoregulatory pathways and clinicians with a context to weigh the progress and evidence in this evolving treatment for autoimmune diseases.

Authors
Sullivan, KM; Muraro, P; Tyndall, A
MLA Citation
Sullivan, KM, Muraro, P, and Tyndall, A. "Hematopoietic cell transplantation for autoimmune disease: updates from Europe and the United States." Biol Blood Marrow Transplant 16.1 Suppl (January 2010): S48-S56. (Review)
PMID
19895895
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
16
Issue
1 Suppl
Publish Date
2010
Start Page
S48
End Page
S56
DOI
10.1016/j.bbmt.2009.10.034

Long Term Survival Following High-dose Sequential Therapy with Autologous Hematopoietic Cell Rescue for Multiple Myeloma

High-dose therapy (HDT) with autologous hematopoietic cell rescue (AHCR) improves survival in patients with multiple myeloma, but is not curative due to a continuous risk of relapse. One approach to try to reduce relapse is to optimize the pretransplant therapy and preparative regimen. We investigated the outcome of sequential HDT with AHCR. Patients were initially treated with standard dose chemotherapy (primarily VAD) to maximum response. They then received cyclophosphamide 4 gm/m2 followed by G-CSF and peripheral blood hematopoietic cell collection by apheresis upon count recovery. They were then treated with etoposide 2 gm/m2 followed by G-CSF and apheresis upon count recovery. The transplant preparative regimen consisted of carmustine 500 mg/m2 on day -4 and melphalan 200 mg/m2 on day -2 followed by AHCR on day 0. Seventy-seven patients were enrolled between 1997 and 2001. Patients were eligible for enrollment if they had a confirmed diagnosis of multiple myeloma at the transplant center, had received multi-agent based chemotherapy for cytoreduction, and had no serious comorbidities. The patient population included 56% men with a median age at transplant of 54 years (range 39-68 years). Thirty-eight patients had IgG myeloma, 14 patients had IgA myeloma, 8 patients had light chain only disease, 4 patients had nonsecretory disease and subtype is unknown in six patients. The median progression-free survival was 3.9 years [CI 2.7-6.0 years] with a median overall survival of 9.5 years (CI 4.7-11 years). The median follow up of the 36 surviving patients is 8.43 years with a range of 4.71 to 11.09 years. One patient was lost to follow up. The Kaplan-Meir estimated progression-free survival at 10 years is 35% with overall survival of 45%. One patient developed secondary acute myeloid leukemia and one patient developed secondary myelodysplastic syndrome. High dose sequential therapy results in long term survival in a significant proportion of patients with multiple myeloma.

Authors
Doan, PL; Chute, JP; Gasparetto, C; Horwitz, M; Rizzieri, D; Smith, C; Sullivan, K; Edwards, J; Jacobson, R; Corbett, K; Chao, N; Long, G
MLA Citation
Doan, PL, Chute, JP, Gasparetto, C, Horwitz, M, Rizzieri, D, Smith, C, Sullivan, K, Edwards, J, Jacobson, R, Corbett, K, Chao, N, and Long, G. "Long Term Survival Following High-dose Sequential Therapy with Autologous Hematopoietic Cell Rescue for Multiple Myeloma." American Society of Blood and Marrow Transplantation. 2010.
Source
manual
Volume
16
Issue
2
Publish Date
2010
Start Page
S201
End Page
S201

Stem-cell transplantation for sickle cell disease [2]

Authors
Walters, MC; Sullivan, KM
MLA Citation
Walters, MC, and Sullivan, KM. "Stem-cell transplantation for sickle cell disease [2]." New England Journal of Medicine 362.10 (2010): 955-956.
PMID
20225347
Source
scival
Published In
The New England journal of medicine
Volume
362
Issue
10
Publish Date
2010
Start Page
955
End Page
956
DOI
10.1056/NEJMc1000134

Pulmonary, Gonadal, and Central Nervous System Status after Bone Marrow Transplantation for Sickle Cell Disease

We conducted a prospective, multicenter investigation of human-leukocyte antigen (HLA) identical sibling bone marrow transplantation (BMT) in children with severe sickle cell disease (SCD) between 1991 and 2000. To determine if children were protected from complications of SCD after successful BMT, we extended our initial study of BMT for SCD to conduct assessments of the central nervous system (CNS) and of pulmonary function 2 or more years after transplantation. In addition, the impact on gonadal function was studied. After BMT, patients with stroke who had stable engraftment of donor cells experienced no subsequent stroke events after BMT, and brain magnetic resonance imaging (MRI) exams demonstrated stable or improved appearance. However, 2 patients with graft rejection had a second stroke after BMT. After transplantation, most patients also had unchanged or improved pulmonary function. Among the 11 patients who had restrictive lung changes at baseline, 5 were improved and 6 had persistent restrictive disease after BMT. Of the 2 patients who had obstructive changes at baseline, 1 improved and 1 had worsened obstructive disease after BMT. There was, however, significant gonadal toxicity after BMT, particularly among female recipients. In summary, individuals who had stable donor engraftment did not experience sickle-related complications after BMT, and were protected from progressive CNS and pulmonary disease. © 2010 American Society for Blood and Marrow Transplantation.

Authors
Walters, MC; Hardy, K; Edwards, S; Adamkiewicz, T; Barkovich, J; Bernaudin, F; Buchanan, GR; Bunin, N; Dickerhoff, R; Giller, R; Haut, PR; Horan, J; Hsu, LL; Kamani, N; Levine, JE; Margolis, D; Ohene-Frempong, K; Patience, M; Redding-Lallinger, R; Roberts, IAG; Rogers, ZR; Sanders, JE; Scott, JP; Sullivan, KM
MLA Citation
Walters, MC, Hardy, K, Edwards, S, Adamkiewicz, T, Barkovich, J, Bernaudin, F, Buchanan, GR, Bunin, N, Dickerhoff, R, Giller, R, Haut, PR, Horan, J, Hsu, LL, Kamani, N, Levine, JE, Margolis, D, Ohene-Frempong, K, Patience, M, Redding-Lallinger, R, Roberts, IAG, Rogers, ZR, Sanders, JE, Scott, JP, and Sullivan, KM. "Pulmonary, Gonadal, and Central Nervous System Status after Bone Marrow Transplantation for Sickle Cell Disease." Biology of Blood and Marrow Transplantation 16.2 (2010): 263-272.
PMID
19822218
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
16
Issue
2
Publish Date
2010
Start Page
263
End Page
272
DOI
10.1016/j.bbmt.2009.10.005

Pharmacologic Prevention of Acute Graft-Versus-Host Disease

Authors
Chao, NJ; Sullivan, KM
MLA Citation
Chao, NJ, and Sullivan, KM. "Pharmacologic Prevention of Acute Graft-Versus-Host Disease." (March 5, 2009): 1257-1274. (Chapter)
Source
scopus
Publish Date
2009
Start Page
1257
End Page
1274
DOI
10.1002/9781444303537.ch84

Response and toxicity of donor lymphocyte infusions following T-cell depleted non-myeloablative allogeneic hematopoietic SCT from 3-6/6 HLA matched donors.

We report the outcome of early donor lymphocyte infusions (DLIs) after T-cell depleted non-myeloablative transplantation using stem cells from HLA-matched or mismatched donors. Sixty-nine patients with high-risk hematologic malignancies received DLI following fludarabine, CY and alemtuzumab with infusion of stem cells from a matched sibling (52) or partially matched family member donor (17). Patients received the first infusion at a median of 50 days after transplant, and doses ranged from 1 x 10(4) CD3+ cells/kg to 3.27 x 10(8) CD3+ cells/kg, depending on clinical status and the physician's discretion. A median cell dose of 1 x 10(5) CD3+ cells/kg in the mismatched setting and 1 x 10(6) CD3+ cells/kg in the matched sibling setting appears safe with only 1 of 7 (14%) and 4 of 31 patients (13%), respectively, experiencing severe acute GVHD at these doses. Importantly, 38% of patients with persistent disease before DLI attained a remission after infusion. Nine of the 69 patients remain alive and disease-free 32-71 months after the first DLI. In conclusion, low doses of DLI can be safely provided soon after T-cell depleted non-myeloablative therapy and provide a chance of remission. However, long-term survival still remains poor, primarily because of relapse in these patients.

Authors
Rizzieri, DA; Dev, P; Long, GD; Gasparetto, C; Sullivan, KM; Horwitz, M; Chute, J; Chao, NJ
MLA Citation
Rizzieri, DA, Dev, P, Long, GD, Gasparetto, C, Sullivan, KM, Horwitz, M, Chute, J, and Chao, NJ. "Response and toxicity of donor lymphocyte infusions following T-cell depleted non-myeloablative allogeneic hematopoietic SCT from 3-6/6 HLA matched donors." Bone Marrow Transplant 43.4 (February 2009): 327-333.
PMID
18850014
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
43
Issue
4
Publish Date
2009
Start Page
327
End Page
333
DOI
10.1038/bmt.2008.321

Carbon Monoxide Diffusion Capacity: How Low Can You Go for Hematopoietic Cell Transplantation Eligibility?

Current guidelines suggest that patients with a pretransplantation diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 60% are not ideal candidates for hematopoietic cell transplantation (HCT); however, recent studies suggest this criterion may exclude patients who will benefit from the procedure. We conducted a study of all adult patients who underwent autologous or allogeneic HCT between 1990 and 2005, and had a DLCO < 60%, of predicted normal, to examine whether there is a lower limit for the DLCO threshold in the context of respiratory failure and nonrelapse mortality risk (NRM), and whether a comprehensive risk scoring system, such as the Pretransplant Assessment of Mortality (PAM) risk score, can more effectively risk stratify these patients with a very low pretransplantation DLCO. We found that among patients with a DLCO ≤ 60% the risk of respiratory failure or NRM was not significantly different; however, the PAM score effectively risk-stratified these patients for NRM risk. There was a stepwise relationship between PAM score category and NRM risk; the highest PAM score category was associated with a 4.38-fold increase in risk (P < .001). These findings suggest that the pretransplantation DLCO should not be considered the sole eligibility criteria for allogeneic HCT. © 2009 American Society for Blood and Marrow Transplantation.

Authors
Chien, JW; Sullivan, KM
MLA Citation
Chien, JW, and Sullivan, KM. "Carbon Monoxide Diffusion Capacity: How Low Can You Go for Hematopoietic Cell Transplantation Eligibility?." Biology of Blood and Marrow Transplantation 15.4 (2009): 447-453.
PMID
19285632
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
4
Publish Date
2009
Start Page
447
End Page
453
DOI
10.1016/j.bbmt.2008.12.509

Therapy with mycophenolate mofetil for refractory acute and chronic GVHD

We evaluated the pharmacokinetics and efficacy of oral mycophenolate mofetil (MMF) for treatment of refractory GVHD. In a prospective study of acute GVHD, 9 of 19 patients (47%) had a response and 10 (53%) had no improvement. Survival at 6 and 12 months after the start of MMF was 37 and 16%, respectively. In a retrospective study of acute GVHD, 14 of 29 patients (48%) had a response and 15 (52%) had no improvement. Survival at 6 and 12 months was 55 and 52%, respectively. In a prospective study of chronic GVHD, the cumulative incidence of disease resolution and withdrawal of all systemic immunosuppressive treatment was 9, 17 and 26% at 12, 24 and 36 months, respectively, after starting MMF. Thirteen patients (59%) required additional systemic immunosuppressive treatment for chronic GVHD. Nine of the 42 patients (21%) in the prospective studies discontinued MMF treatment because of toxicity. The area under the curve plasma concentrations of mycophenolic acid seemed to be suboptimal among patients with acute GVHD but not among those with chronic GVHD. MMF can be used effectively for treatment of GVHD. © 2009 Macmillan Publishers Limited All rights reserved.

Authors
Furlong, T; Martin, P; Flowers, MED; Carnevale-Schianca, F; Yatscoff, R; Chauncey, T; Appelbaum, FR; Deeg, HJ; Doney, K; Witherspoon, R; Storer, B; Sullivan, KM; Storb, R; Nash, RA
MLA Citation
Furlong, T, Martin, P, Flowers, MED, Carnevale-Schianca, F, Yatscoff, R, Chauncey, T, Appelbaum, FR, Deeg, HJ, Doney, K, Witherspoon, R, Storer, B, Sullivan, KM, Storb, R, and Nash, RA. "Therapy with mycophenolate mofetil for refractory acute and chronic GVHD." Bone Marrow Transplantation 44.11 (2009): 739-748.
PMID
19377515
Source
scival
Published In
Bone Marrow Transplantation
Volume
44
Issue
11
Publish Date
2009
Start Page
739
End Page
748
DOI
10.1038/bmt.2009.76

Immunodeficiencies

Primary immunodeficiencies (PIDs) are uncommon, chronic and severe disorders of the immune system in which patients cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections. The treatment of choice for PID patients with predominant antibody deficiency is intravenous immunoglobulin (Ig) replacement therapy. Despite major advances over the last 20 years in the molecular characterization of PIDs, many patients remain undiagnosed or are diagnosed too late, with severe consequences. Various strategies to ensure timely diagnosis of PIDs are in place, and novel approaches are being developed. In recent years, several patient registries have been established. Such registries shed light on the pathology and natural history of these varied disorders. Analyses of the registry data may also reveal which patients are likely to respond well to higher Ig infusion rates and may help to determine the optimal dosing of Ig products. Faster infusion rates may lead to improved convenience for patients and thus increase patient compliance, and may reduce nursing time and the need for hospital resources. Data from two recent studies suggest that Gamunex® and Privigen® are well tolerated at high infusion rates. Nevertheless, careful selection of patients for high infusion rates, based on co-morbid conditions and tolerance of the current infusion rate, is advisable. Based on the available data, intravenous Ig offers broad protection against encapsulated organisms. As vaccine trends change, careful monitoring of specific antibody levels in the general population, such as those against pneumococcal and meningococcal bacteria, should be implemented. © 2009 British Society for Immunology.

Authors
Ballow, M; Notarangelo, L; Grimbacher, B; Cunningham-Rundles, C; Stein, M; Helbert, M; Gathmann, B; Kindle, G; Knight, AK; Ochs, HD; Sullivan, K; Franco, JL
MLA Citation
Ballow, M, Notarangelo, L, Grimbacher, B, Cunningham-Rundles, C, Stein, M, Helbert, M, Gathmann, B, Kindle, G, Knight, AK, Ochs, HD, Sullivan, K, and Franco, JL. "Immunodeficiencies." Clinical and Experimental Immunology 158.SUPPL. 1 (2009): 14-22.
PMID
19883420
Source
scival
Published In
Clinical & Experimental Immunology
Volume
158
Issue
SUPPL. 1
Publish Date
2009
Start Page
14
End Page
22
DOI
10.1111/j.1365-2249.2009.04023.x

Improvements in digital vasculature observed using micro magnetic resonance angiography after high-dose immunosuppression for severe systemic sclerosis

Authors
Wang, J; Nash, RA; Chu, B; Yarnykh, VL; Schwartz, SM; Sullivan, KM; Yuan, C
MLA Citation
Wang, J, Nash, RA, Chu, B, Yarnykh, VL, Schwartz, SM, Sullivan, KM, and Yuan, C. "Improvements in digital vasculature observed using micro magnetic resonance angiography after high-dose immunosuppression for severe systemic sclerosis." Bone Marrow Transplantation 44.6 (2009): 387-389.
PMID
19252528
Source
scival
Published In
Bone Marrow Transplantation
Volume
44
Issue
6
Publish Date
2009
Start Page
387
End Page
389
DOI
10.1038/bmt.2009.35

Early Pre/Post Fluoro-Deoxyglucose Positive Emission Tomography (PET) Does Not Predict Outcome of Patients Undergoing Hematopoietic Stem Cell Transplantation in Hodgkins Disease and Non-Hodgkins Lymphoma

Authors
Palmer, J; Goggins, T; Broadwater, G; Chao, NJ; Chute, J; Coleman, RE; Sullivan, KM; Long, G; Gasparetto, C; Beaven, A; Rizzieri, D
MLA Citation
Palmer, J, Goggins, T, Broadwater, G, Chao, NJ, Chute, J, Coleman, RE, Sullivan, KM, Long, G, Gasparetto, C, Beaven, A, and Rizzieri, D. "Early Pre/Post Fluoro-Deoxyglucose Positive Emission Tomography (PET) Does Not Predict Outcome of Patients Undergoing Hematopoietic Stem Cell Transplantation in Hodgkins Disease and Non-Hodgkins Lymphoma." BLOOD 112.11 (November 16, 2008): 760-760.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
760
End Page
760

Bortezomib Plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Non-Transplant Candidates in Patients with Previously Untreated Multiple Myeloma

Authors
Gasparet, C; Gockerman, JP; Diehl, LF; III, DCC; Moore, J; Long, GD; Horwitz, M; Chute, J; Sullivan, KM; Netuwirth, R; Davis, PH; Sutton, LM; Anderson, RD; Chao, N; Rizzieri, DA
MLA Citation
Gasparet, C, Gockerman, JP, Diehl, LF, III, DCC, Moore, J, Long, GD, Horwitz, M, Chute, J, Sullivan, KM, Netuwirth, R, Davis, PH, Sutton, LM, Anderson, RD, Chao, N, and Rizzieri, DA. "Bortezomib Plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Non-Transplant Candidates in Patients with Previously Untreated Multiple Myeloma." BLOOD 112.11 (November 16, 2008): 1142-1142.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
1142
End Page
1142

Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients.

The efficacy of once-daily intravenous busulfan with fludarabine as a preparative regimen for partially matched umbilical cord blood transplantation has not been formally studied. We randomized 10 adult patients with myeloid malignancies to receive either concurrent or sequential administration of intravenous busulfan 130 mg/m(2) once daily x 4 days and fludarabine 40 mg/m(2) daily x 4 days, followed by dual umbilical cord blood transplantation. The median combined cryopreserved total nucleated cell dose was 3.6 x 10(7)/kg recipient body weight (range: 2.8-4.5 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was provided by tacrolimus and mycophenolate mofetil (MMF). Donor-derived neutrophil recovery was observed in only 2 of 10 patients, resulting in premature closure of the study as per graft failure stopping rules. We conclude that the myeloablative conditioning regimen of once-daily intravenous busulfan with fludarabine provides insufficient immunosuppression to allow for engraftment of partially matched, dual umbilical cord blood grafts.

Authors
Horwitz, ME; Morris, A; Gasparetto, C; Sullivan, K; Long, G; Chute, J; Rizzieri, D; McPherson, J; Chao, N
MLA Citation
Horwitz, ME, Morris, A, Gasparetto, C, Sullivan, K, Long, G, Chute, J, Rizzieri, D, McPherson, J, and Chao, N. "Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients." Biol Blood Marrow Transplant 14.5 (May 2008): 591-594.
PMID
18410902
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
5
Publish Date
2008
Start Page
591
End Page
594
DOI
10.1016/j.bbmt.2008.02.016

CHRONIC HEPATITIS C, CIRRHOSIS, AND END STAGE LIVER DISEASE AMONG 30-YEAR SURVIVORS OF BONE MARROW TRANSPLANT

Authors
Pergam, SA; Strasser, SI; Flowers, ME; Sullivan, KM; McDonald, GB
MLA Citation
Pergam, SA, Strasser, SI, Flowers, ME, Sullivan, KM, and McDonald, GB. "CHRONIC HEPATITIS C, CIRRHOSIS, AND END STAGE LIVER DISEASE AMONG 30-YEAR SURVIVORS OF BONE MARROW TRANSPLANT." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
31
End Page
31
DOI
10.1016/j.bbmt.2007.12.086

Outcomes of a second non-myeloablative allogeneic stem cell transplantation following graft rejection.

Following initial graft rejection, a second attempt at allogeneic immunotherapy is often contemplated, but data on the success is limited. We therefore report on 11 patients with hematologic malignancies, renal cell cancer or marrow failure who underwent a second reduced-intensity regimen for primary or secondary graft failure. Nine of the 11 patients initially engrafted with the second attempt including two of four who used the same donor. One of the patients engrafted after the third attempt using a different donor and conditioning regimen. There were two treatment-related deaths. Four patients died from progressive disease 1-9 months after the second transplant. Two patients are still in recovery phase less than 1 year from the second transplant. Long-term remission is possible and three patients are alive in complete remission.

Authors
Byrne, BJ; Horwitz, M; Long, GD; Gasparetto, C; Sullivan, KM; Chute, J; Chao, NJ; Rizzieri, DA
MLA Citation
Byrne, BJ, Horwitz, M, Long, GD, Gasparetto, C, Sullivan, KM, Chute, J, Chao, NJ, and Rizzieri, DA. "Outcomes of a second non-myeloablative allogeneic stem cell transplantation following graft rejection." Bone Marrow Transplant 41.1 (January 2008): 39-43.
PMID
17982503
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
41
Issue
1
Publish Date
2008
Start Page
39
End Page
43
DOI
10.1038/sj.bmt.1705882

Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics.

End-organ damage is common in patients with sickle cell disease (SCD) thereby limiting the use of allogeneic stem cell transplantation (SCT). We report the outcome of 2 adult SCD patients, 1 with end-stage renal disease (ESRD), who underwent fludarabine-based nonmyeloablative SCT from HLA-identical matched siblings. To prevent fludarabine toxicity, the patient with ESRD underwent aggressive dialysis following adjusted fludarabine dosing. Pharmacokinetics of the fludarabine metabolite F-Ara-A was studied on the patient with ESRD and 2 additional patients with normal renal function. Both patients with SCD achieved full donor erythroid chimerism, have normal blood counts, and are on no immunosuppressive medications. With a 20% dose reduction followed by daily dialysis, we achieved fludarabine drug exposure that is nearly identical to that achieved in patients with normal renal function. We conclude that fludarabine-based nonmyeloablative allogeneic SCT for adult patients with SCD is feasible, even in the setting of ESRD.

Authors
Horwitz, ME; Spasojevic, I; Morris, A; Telen, M; Essell, J; Gasparetto, C; Sullivan, K; Long, G; Chute, J; Chao, N; Rizzieri, D
MLA Citation
Horwitz, ME, Spasojevic, I, Morris, A, Telen, M, Essell, J, Gasparetto, C, Sullivan, K, Long, G, Chute, J, Chao, N, and Rizzieri, D. "Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics." Biol Blood Marrow Transplant 13.12 (December 2007): 1422-1426.
PMID
18022571
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
12
Publish Date
2007
Start Page
1422
End Page
1426
DOI
10.1016/j.bbmt.2007.08.050

TU-EE-A2-05: Challenges in Limiting Kidney Dose When Delivering Total Body Irradiation (TBI) for Patients with Severe Systemic Sclerosis (SSc)

Authors
Craciunescu, O; Steffey, B; Yoo, S; Larrier, N; Paarz-Largay, C; Sullivan, K; Prosnitz, R
MLA Citation
Craciunescu, O, Steffey, B, Yoo, S, Larrier, N, Paarz-Largay, C, Sullivan, K, and Prosnitz, R. "TU-EE-A2-05: Challenges in Limiting Kidney Dose When Delivering Total Body Irradiation (TBI) for Patients with Severe Systemic Sclerosis (SSc)." June 2007.
Source
crossref
Published In
Medical physics
Volume
34
Issue
6Part19
Publish Date
2007
Start Page
2568
End Page
2568
DOI
10.1118/1.2761426

Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution.

PURPOSE: Allogeneic transplantation is typically limited to younger patients having a matched donor. To allow a donor to be found for nearly all patients, we have used a nonmyeloablative conditioning regimen in conjunction with stem cells from a related donor with one fully mismatched HLA haplotype. PATIENTS AND METHODS: Fludarabine, cyclophosphamide, and alemtuzumab were used as the preparatory regimen. Additional graft-versus-host disease (GVHD) prophylaxis included mycophenolate with or without cyclosporine. Patients with persistence of disease had a donor lymphocyte boost planned. Toxicities, engraftment, response, survival, and immune recovery are reported. RESULTS: Forty-nine patients with hematologic malignancies or marrow failure and no other available donors were enrolled. Ninety-four percent of patients had successful engraftment, and 8% had secondary graft failure. The treatment-related mortality rate was 10.2%, and 8% of patients had severe GVHD. Encouraging evidence of quantitative lymphocyte recovery through expansion of transplanted T cells was noted by 3 to 6 months. Seventy-five percent of patients attained a complete remission, and 1-year survival rate was 31% (95% CI, 18% to 44%). A standard-risk group of 19 patients with aplasia or in remission at transplantation demonstrated a 63% 1-year survival rate (95% CI, 38% to 80%) and 2.9-year median overall survival time (95% CI, 6.2 to 48 months). CONCLUSION: Nonmyeloablative therapy using haploidentical family member donors is feasible because the main obstacles of GVHD and graft rejection are manageable, allowing readily available stem-cell donors to be found for nearly all patients. Further qualitative and quantitative improvement in immune recovery is needed to address the high rate of relapse and risk of severe infections.

Authors
Rizzieri, DA; Koh, LP; Long, GD; Gasparetto, C; Sullivan, KM; Horwitz, M; Chute, J; Smith, C; Gong, JZ; Lagoo, A; Niedzwiecki, D; Dowell, JM; Waters-Pick, B; Liu, C; Marshall, D; Vredenburgh, JJ; Gockerman, J; Decastro, C; Moore, J; Chao, NJ
MLA Citation
Rizzieri, DA, Koh, LP, Long, GD, Gasparetto, C, Sullivan, KM, Horwitz, M, Chute, J, Smith, C, Gong, JZ, Lagoo, A, Niedzwiecki, D, Dowell, JM, Waters-Pick, B, Liu, C, Marshall, D, Vredenburgh, JJ, Gockerman, J, Decastro, C, Moore, J, and Chao, NJ. "Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution." J Clin Oncol 25.6 (February 20, 2007): 690-697.
PMID
17228020
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
6
Publish Date
2007
Start Page
690
End Page
697
DOI
10.1200/JCO.2006.07.0953

High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: Long-term follow-up of the US multicenter pilot study

More effective therapeutic strategies are required for patients with poor-prognosis systemic sclerosis (SSc). A phase 2 single-arm study of high-dose immunosuppressive therapy (HDIT) and autologous CD34-selected hematopoietic cell transplantation (HCT) was conducted in 34 patients with diffuse cutaneous SSc. HDIT included total body irradiation (800 cGy) with lung shielding, cyclophosphamide (120 mg/kg), and equine antithymocyte globulin (90 mg/kg). Neutrophil and platelet counts were recovered by 9 (range, 7 to 13) and 11 (range, 7 to 25) days after HCT, respectively. Seventeen of 27 (63%) evaluable patients who survived at least 1 year after HDIT had sustained responses at a median follow-up of 4 (range, 1 to 8) years. There was a major improvement in skin (modified Rodnan skin score, -22.08;P < .001) and overall function (modified Health Assessment Questionnaire Disability Index, -1.03;P < .001) at final evaluation. Importantly, for the first time, biopsies confirmeda statistically significant decrease of dermal fibrosis compared with baseline (P < .001). Lung, heart, and kidney function, in general, remained clinically stable. There were 12 deaths during the study (transplantation-related, 8; SSc-related, 4). The estimated progression-free survival was 64% at 5 years. Sustained responses including a decrease in dermal fibrosis were observed exceeding those previously reported with other therapies. HDIT and autologous HCT for SSc should be evaluated in a randomized clinical trial. © 2007 by The American Society of Hematology.

Authors
Nash, RA; McSweeney, PA; Crofford, LJ; Abidi, M; Chen, C-S; Godwin, JD; Gooley, TA; Holmberg, L; Henstorf, G; LeMaistre, CF; Mayes, MD; McDonagh, KT; McLaughlin, B; Molitor, JA; Nelson, JL; Shulman, H; Storb, R; Viganego, F; Wener, MH; Seibold, JR; Sullivan, KM; Furst, DE
MLA Citation
Nash, RA, McSweeney, PA, Crofford, LJ, Abidi, M, Chen, C-S, Godwin, JD, Gooley, TA, Holmberg, L, Henstorf, G, LeMaistre, CF, Mayes, MD, McDonagh, KT, McLaughlin, B, Molitor, JA, Nelson, JL, Shulman, H, Storb, R, Viganego, F, Wener, MH, Seibold, JR, Sullivan, KM, and Furst, DE. "High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: Long-term follow-up of the US multicenter pilot study." Blood 110.4 (2007): 1388-1396.
PMID
17452515
Source
scival
Published In
Blood
Volume
110
Issue
4
Publish Date
2007
Start Page
1388
End Page
1396
DOI
10.1182/blood-2007-02-072389

Matched-related donor transplantation for sickle cell disease: Report from the Center for International Blood and Transplant Research

We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide- containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy. © 2007 The Authors.

Authors
Panepinto, JA; Walters, MC; Carreras, J; Marsh, J; Bredeson, CN; Gale, RP; Hale, GA; Horan, J; Hows, JM; Klein, JP; Pasquini, R; Roberts, I; Sullivan, K; Eapen, M; Ferster, A
MLA Citation
Panepinto, JA, Walters, MC, Carreras, J, Marsh, J, Bredeson, CN, Gale, RP, Hale, GA, Horan, J, Hows, JM, Klein, JP, Pasquini, R, Roberts, I, Sullivan, K, Eapen, M, and Ferster, A. "Matched-related donor transplantation for sickle cell disease: Report from the Center for International Blood and Transplant Research." British Journal of Haematology 137.5 (2007): 479-485.
PMID
17459050
Source
scival
Published In
British Journal of Haematology
Volume
137
Issue
5
Publish Date
2007
Start Page
479
End Page
485
DOI
10.1111/j.1365-2141.2007.06592.x

Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: Results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia

Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt. © 2007 The Authors.

Authors
Eggleston, B; Patience, M; Edwards, S; Adamkiewicz, T; Buchanan, GR; Davies, SC; Dickerhoff, R; Donfield, S; Feig, SA; Giller, RH; Haight, A; Horan, J; Hsu, LL; Kamani, N; Lane, P; Levine, JE; Margolis, D; Moore, TB; Ohene-Frempong, K; Redding-Lallinger, R; Roberts, IAG; Rogers, ZR; Sanders, JE; Scott, JP; Sleight, B; Thompson, AA; Sullivan, KM; Walters, MC
MLA Citation
Eggleston, B, Patience, M, Edwards, S, Adamkiewicz, T, Buchanan, GR, Davies, SC, Dickerhoff, R, Donfield, S, Feig, SA, Giller, RH, Haight, A, Horan, J, Hsu, LL, Kamani, N, Lane, P, Levine, JE, Margolis, D, Moore, TB, Ohene-Frempong, K, Redding-Lallinger, R, Roberts, IAG, Rogers, ZR, Sanders, JE, Scott, JP, Sleight, B, Thompson, AA, Sullivan, KM, and Walters, MC. "Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: Results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia." British Journal of Haematology 136.4 (2007): 673-676.
PMID
17223910
Source
scival
Published In
British Journal of Haematology
Volume
136
Issue
4
Publish Date
2007
Start Page
673
End Page
676
DOI
10.1111/j.1365-2141.2006.06486.x

Cyclophosphamide in scleroderma lung disease

Authors
Sullivan, KM; McSweeney, PA; Nash, RA
MLA Citation
Sullivan, KM, McSweeney, PA, and Nash, RA. "Cyclophosphamide in scleroderma lung disease." NEW ENGLAND JOURNAL OF MEDICINE 355.11 (September 14, 2006): 1173-1174.
PMID
16977701
Source
wos-lite
Published In
The New England journal of medicine
Volume
355
Issue
11
Publish Date
2006
Start Page
1173
End Page
1174

5-year follow-up of high-dose immunosuppressive therapy (HDIT) for systemic sclerosis (SSc).

Authors
Nash, RA; McSweeney, PA; Crofford, LJ; McDonagh, KT; Sullivan, KM; Maureen, M; Nelson, JL; Gooley, T; Holmberg, L; Shulman, H; Wener, M; McLaughlin, B; Henstorf, G; Molitor, J; Seibold, JR; Furst, DE
MLA Citation
Nash, RA, McSweeney, PA, Crofford, LJ, McDonagh, KT, Sullivan, KM, Maureen, M, Nelson, JL, Gooley, T, Holmberg, L, Shulman, H, Wener, M, McLaughlin, B, Henstorf, G, Molitor, J, Seibold, JR, and Furst, DE. "5-year follow-up of high-dose immunosuppressive therapy (HDIT) for systemic sclerosis (SSc)." September 2006.
Source
wos-lite
Published In
Arthritis and Rheumatism
Volume
54
Issue
9
Publish Date
2006
Start Page
S315
End Page
S315

Chronic graft-versus-host disease.

Chronic graft versus host disease (GVHD) remains today one of the most vexing late complications of allogeneic stem cell transplantation. Occurring a minimum of 100 days following stem cell transplantation, approximately 50% of patients will experience some degree of chronic GVHD. Host-reactive lymphocytes of donor origin are the cells responsible for the "alloimmune" attack. The increased use of hematopoietic stem cells collected from the peripheral blood instead of bone marrow and the increasing age of stem cell transplant recipients has led to a higher incidence of chronic GVHD. Chronic GVHD most commonly affects the skin, liver, eyes or the mouth, however multiple other sites may also be affected. Chronic GVHD and the medications used to treat it result in a profoundly immunocompromised state. Death due to severe chronic GVHD is usually a consequence of infectious complications. Standard treatment for severe chronic GVHD is a combination of cyclosporine and prednisone. An alternating day regimen of these two agents prolongs survival and reduces drug-related adverse events. Topical therapy to affected areas is preferred for patients with mild disease. The 10-year survival of patients with mild chronic GVHD is approximately 80%, but is less than 5% for patients affected by severe chronic GVHD.

Authors
Horwitz, ME; Sullivan, KM
MLA Citation
Horwitz, ME, and Sullivan, KM. "Chronic graft-versus-host disease." Blood Rev 20.1 (January 2006): 15-27. (Review)
PMID
16426941
Source
pubmed
Published In
Blood Reviews
Volume
20
Issue
1
Publish Date
2006
Start Page
15
End Page
27
DOI
10.1016/j.blre.2005.01.007

Normal interleukin-7 (IL7) levels and normal IL7 response to CD4 T lymphopenia in patients with multiple sclerosis and systemic sclerosis

Authors
Storek, J; Nash, RA; McSweeney, PA; Furst, DE; Sullivan, KM
MLA Citation
Storek, J, Nash, RA, McSweeney, PA, Furst, DE, and Sullivan, KM. "Normal interleukin-7 (IL7) levels and normal IL7 response to CD4 T lymphopenia in patients with multiple sclerosis and systemic sclerosis." Clinical Immunology 121.1 (2006): 118-119.
PMID
16844418
Source
scival
Published In
Clinical Immunology
Volume
121
Issue
1
Publish Date
2006
Start Page
118
End Page
119
DOI
10.1016/j.clim.2006.05.016

Allogeneic marrow transplantation in patients with severe systemic sclerosis: Resolution of dermal fibrosis

Objective. To evaluate the safety and efficacy of allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning in patients with severe systemic sclerosis (SSc). Methods. Eligibility criteria for the study included SSc patients with features indicative of a poor prognosis. The myeloablative conditioning regimen included busulfan, cyclophosphamide, and antithymocyte globulin. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate. Bone marrow was transplanted from HLA-identical siblings. Results. Two patients with diffuse cutaneous SSc and lung involvement who were refractory to conventional immunosuppressive treatment were enrolled in the study. In patient 1, there were no complications related to the conditioning regimen, and GVHD did not develop after transplantation. At 5 years after HCT, there was nearly complete resolution of the scleroderma and marked improvement in physical functioning. Internal organ function improved (lung) or remained stable. On examination of serial skin biopsy samples, there was resolution of the dermal fibrosis. Patient 2 experienced skin toxicity from the conditioning regimen and hypertensive crisis that was likely related to high-dose corticosteroids given for treatment of GVHD. Although this patient experienced an improvement in scleroderma and overall functioning, a fatal opportunistic infection developed 17 months after HCT. Conclusion. Allogeneic HCT may result in sustained remission of SSc. GVHD and opportunistic infections are the major risks associated with allogeneic HCT for SSc, as for allogeneic HCT in general. © 2006, American College of Rheumatology.

Authors
Nash, RA; McSweeney, PA; Nelson, JL; Wener, M; Georges, GE; Langston, AA; Shulman, H; Sullivan, KM; Lee, J; Henstorf, G; Storb, R; Furst, DE
MLA Citation
Nash, RA, McSweeney, PA, Nelson, JL, Wener, M, Georges, GE, Langston, AA, Shulman, H, Sullivan, KM, Lee, J, Henstorf, G, Storb, R, and Furst, DE. "Allogeneic marrow transplantation in patients with severe systemic sclerosis: Resolution of dermal fibrosis." Arthritis and Rheumatism 54.6 (2006): 1982-1986.
PMID
16732546
Source
scival
Published In
Arthritis and Rheumatism
Volume
54
Issue
6
Publish Date
2006
Start Page
1982
End Page
1986
DOI
10.1002/art.21908

To the editor [3]

Authors
Sullivan, KM; McSweeney, PA; Nash, RA
MLA Citation
Sullivan, KM, McSweeney, PA, and Nash, RA. "To the editor [3]." New England Journal of Medicine 355.11 (2006): 1173-1174.
Source
scival
Published In
The New England journal of medicine
Volume
355
Issue
11
Publish Date
2006
Start Page
1173
End Page
1174
DOI
10.1056/NEJMc061920

Partially HLA matched, non-myeloablative allogeneic transplantation

Authors
Rizzieri, DA; Koh, LP; Long, GD; Gasparetto, C; Sullivan, KM; Horwitz, M; Chute, J; Gong, JZ; Lagoo, AS; Niedzwiecki, D; Lu, CX; Marshall, D; Dowell, JM; Chao, NJ
MLA Citation
Rizzieri, DA, Koh, LP, Long, GD, Gasparetto, C, Sullivan, KM, Horwitz, M, Chute, J, Gong, JZ, Lagoo, AS, Niedzwiecki, D, Lu, CX, Marshall, D, Dowell, JM, and Chao, NJ. "Partially HLA matched, non-myeloablative allogeneic transplantation." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
812A
End Page
812A

Outcome and immune reconstitution following T cell depleted nonmyeloablative allogeneic transplantation using matched donors

Authors
Rizzieri, DA; Koh, LP; Long, GD; Gasparetto, C; Gong, JZ; Lagoo, AS; Niedzwiecki, D; Sullivan, KM; Chute, J; Horwitz, M; Ashley, M; Chao, NJ
MLA Citation
Rizzieri, DA, Koh, LP, Long, GD, Gasparetto, C, Gong, JZ, Lagoo, AS, Niedzwiecki, D, Sullivan, KM, Chute, J, Horwitz, M, Ashley, M, and Chao, NJ. "Outcome and immune reconstitution following T cell depleted nonmyeloablative allogeneic transplantation using matched donors." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
576A
End Page
576A

Feasibility of allogeneic hematopoietic stem cell transplantation for autoimmune disease: Position statement from a National Institute of Allergy and Infectious Diseases and National Cancer Institute-Sponsored International Workshop, Bethesda, MD, March 12 and 13, 2005

Authors
Griffith, LM; Pavletic, SZ; Tyndall, A; Bredeson, CN; Bowen, JD; Childs, RW; Gratwohl, A; Laar, JMV; Mayes, MD; Martin, R; McSweeney, PA; Muraro, PA; Openshaw, H; Saccardi, R; Sandmaier, BM; Forman, SJ; Nash, RA; Antin, JH; Bishop, MR; Bredeson, CN; Forman, SJ; Giralt, S; Gratwohl, A; Gress, R; Hosing, C; Petersdorf, EW; Shizuru, JA; Sullivan, K; Tisdale, JF; Bowen, JD; Chen, J; Lassmann, H; Narayanan, S; Bocelli-Tyndall, C; Clements, PJ; Furst, DE; Illei, GG; McNamara, JD; Mittleman, BB et al.
MLA Citation
Griffith, LM, Pavletic, SZ, Tyndall, A, Bredeson, CN, Bowen, JD, Childs, RW, Gratwohl, A, Laar, JMV, Mayes, MD, Martin, R, McSweeney, PA, Muraro, PA, Openshaw, H, Saccardi, R, Sandmaier, BM, Forman, SJ, Nash, RA, Antin, JH, Bishop, MR, Bredeson, CN, Forman, SJ, Giralt, S, Gratwohl, A, Gress, R, Hosing, C, Petersdorf, EW, Shizuru, JA, Sullivan, K, Tisdale, JF, Bowen, JD, Chen, J, Lassmann, H, Narayanan, S, Bocelli-Tyndall, C, Clements, PJ, Furst, DE, Illei, GG, McNamara, JD, and Mittleman, BB et al. "Feasibility of allogeneic hematopoietic stem cell transplantation for autoimmune disease: Position statement from a National Institute of Allergy and Infectious Diseases and National Cancer Institute-Sponsored International Workshop, Bethesda, MD, March 12 and 13, 2005." Biology of Blood and Marrow Transplantation 11.11 (2005): 862-870.
PMID
16275589
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
11
Issue
11
Publish Date
2005
Start Page
862
End Page
870
DOI
10.1016/j.bbmt.2005.07.009

Hematopoietic cell transplantation for sickle cell disease: Updated results of the multicenter trial.

Authors
Walters, MC; Patience, M; Edwards, S; Robertson, S; McMurray, M; Donfield, S; Sullivan, KM
MLA Citation
Walters, MC, Patience, M, Edwards, S, Robertson, S, McMurray, M, Donfield, S, and Sullivan, KM. "Hematopoietic cell transplantation for sickle cell disease: Updated results of the multicenter trial." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
33A
End Page
33A

High-Dose Immunosuppressive Therapy (HDIT) for SSc: Results of 3 year follow-up demonstrate continued improvement in function and skin with stability in the lungs

Authors
Furst, DE; McSweeney, PA; Crofford, LJ; McDonagh, KT; Sullivan, KM; Mayes, MD; Nelson, JL; Gooley, TA; Holmberg, LA; Chen, CS; Wener, MH; Lee, J; Henstorf, G; Abidi, M; Nash, RA
MLA Citation
Furst, DE, McSweeney, PA, Crofford, LJ, McDonagh, KT, Sullivan, KM, Mayes, MD, Nelson, JL, Gooley, TA, Holmberg, LA, Chen, CS, Wener, MH, Lee, J, Henstorf, G, Abidi, M, and Nash, RA. "High-Dose Immunosuppressive Therapy (HDIT) for SSc: Results of 3 year follow-up demonstrate continued improvement in function and skin with stability in the lungs." September 2004.
Source
wos-lite
Published In
Arthritis and Rheumatism
Volume
50
Issue
9
Publish Date
2004
Start Page
S693
End Page
S693

Adult recipients of umbilical cord blood transplants after nonmyeloablative preparative regimens.

We report the outcome of 13 patients with advanced malignancies who underwent nonmyeloablative conditioning therapy followed by infusion of partially matched unrelated cord blood cells. The median age of these patients was 49 years, and their median weight was 65.7 kg. The median nucleated cell dose infused was 2.07 x 10(7)/kg. Eight of the 13 patients demonstrated donor chimerism between 4 weeks and 6 months, and subsequent conversion to full donor chimerism was achieved in 5 patients. Three patients were alive and free of disease at 158 to 1054 days, with a median survival of 288 days after transplantation. The 100-day event-free survival is 69%, and overall survival is 77%. At 1 year, the event-free and overall survival was 43%. Treatment-related mortality observed within the first 100 days after transplantation was low: 1 previously extensively pretreated patient died of multiorgan failure. This result provides a basis for further exploring this potentially curative approach to selected patients who lack matched related or unrelated hematopoietic stem cell donors.

Authors
Chao, NJ; Koh, L-P; Long, GD; Gasparetto, C; Horwitz, M; Morris, A; Lassiter, M; Sullivan, KM; Rizzieri, DA
MLA Citation
Chao, NJ, Koh, L-P, Long, GD, Gasparetto, C, Horwitz, M, Morris, A, Lassiter, M, Sullivan, KM, and Rizzieri, DA. "Adult recipients of umbilical cord blood transplants after nonmyeloablative preparative regimens." Biol Blood Marrow Transplant 10.8 (August 2004): 569-575.
PMID
15282535
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
10
Issue
8
Publish Date
2004
Start Page
569
End Page
575
DOI
10.1016/j.bbmt.2004.05.001

Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan.

: To determine and directly compare the clinical course of white and Asian patients with paroxysmal nocturnal hemoglobinuria (PNH), data were collected for epidemiologic analysis on 176 patients from Duke University and 209 patients from Japan. White patients were younger with significantly more classical symptoms of PNH including thrombosis, hemoglobinuria, and infection, while Asian patients were older with more marrow aplasia. The mean fraction of CD59-negative polymorphonuclear cells (PMN) at initial analysis was higher among Duke patients than Japanese patients. In both cohorts, however, a larger PNH clone was associated with classical PNH symptoms, while a smaller PNH clone was associated with marrow aplasia. Thrombosis was significantly more prevalent in white patients than Asian patients, and was associated with a significantly higher proportion of CD59-negative PMN. For individual patients, CD59-negative populations varied considerably over time, but a decreasing PNH clone portended hematopoietic failure. Survival analysis revealed a similar death rate in each group, although causes of death were different and significantly more Duke patients died from thrombosis. Japanese patients had a longer mean survival time (32.1 yr vs. 19.4 yr), although Kaplan-Meier survival curves were not significantly different. Poor survival in both groups was associated with age over 50 years, severe leukopenia/neutropenia at diagnosis, and severe infection as a complication; additionally, thrombosis at diagnosis or follow-up for Duke patients and renal failure for Japanese patients were poor prognostic factors. These data identify important differences between white and Asian patients with PNH. Identification of prognostic factors will help the design of prospective clinical trials for PNH.

Authors
Nishimura, J-I; Kanakura, Y; Ware, RE; Shichishima, T; Nakakuma, H; Ninomiya, H; Decastro, CM; Hall, S; Kanamaru, A; Sullivan, KM; Mizoguchi, H; Omine, M; Kinoshita, T; Rosse, WF
MLA Citation
Nishimura, J-I, Kanakura, Y, Ware, RE, Shichishima, T, Nakakuma, H, Ninomiya, H, Decastro, CM, Hall, S, Kanamaru, A, Sullivan, KM, Mizoguchi, H, Omine, M, Kinoshita, T, and Rosse, WF. "Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan." Medicine (Baltimore) 83.3 (May 2004): 193-207.
PMID
15118546
Source
pubmed
Published In
Medicine
Volume
83
Issue
3
Publish Date
2004
Start Page
193
End Page
207

Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases)

To ascertain the consequences of severe leukopenia and the tempo of recovery, we studied the immunity of 56 adult patients treated for multiple sclerosis or systemic sclerosis with autologous CD34 cell transplantation using extremely lymphoablative conditioning. NK cell, monocyte, and neutrophil counts recovered to normal by 1 month; dendritic cell and B cell counts by 6 months; and T cell counts by 2 years posttransplant, although CD4 T cell counts remained borderline low. Initial peripheral expansion was robust for CD8 T cells but only moderate for CD4 T cells. Subsequent thymopoiesis was slow, especially in older patients. Importantly, levels of antibodies, including autoantibodies, did not drop substantially. Infections were frequent during the first 6 months, when all immune cells were deficient, and surprisingly rare (0.21 per patient year) at 7-24 months posttransplant, when only T cells (particularly CD4 T cells) were deficient. In conclusion, peripheral expansion of CD8 but not CD4 T cells is highly efficient. Prolonged CD4 lymphopenia is associated with relatively few infections, possibly due to antibodies produced by persisting pretransplant plasma cells. © 2004 Elsevier Inc. All rights reserved.

Authors
Storek, J; Zhao, Z; Lin, E; Berger, T; McSweeney, PA; Nash, RA; Akatsuka, Y; Metcalf, MD; Lu, H; Kalina, T; Reindl, M; Storb, R; Hansen, JA; Sullivan, KM; Kraft, GH; Furst, DE; Maloney, DG
MLA Citation
Storek, J, Zhao, Z, Lin, E, Berger, T, McSweeney, PA, Nash, RA, Akatsuka, Y, Metcalf, MD, Lu, H, Kalina, T, Reindl, M, Storb, R, Hansen, JA, Sullivan, KM, Kraft, GH, Furst, DE, and Maloney, DG. "Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases)." Clinical Immunology 113.3 (2004): 285-298.
PMID
15507394
Source
scival
Published In
Clinical Immunology
Volume
113
Issue
3
Publish Date
2004
Start Page
285
End Page
298
DOI
10.1016/j.clim.2004.07.006

High dose immunotherapy with stem cell rescue in severe systemic sclerosis: An idea that is moving forward

Authors
Furst, DE; Nash, R; Sullivan, KM; Saccardi, R; McSweeney, P
MLA Citation
Furst, DE, Nash, R, Sullivan, KM, Saccardi, R, and McSweeney, P. "High dose immunotherapy with stem cell rescue in severe systemic sclerosis: An idea that is moving forward." Journal of Rheumatology 31.12 (2004): 2331-2335.
PMID
15570631
Source
scival
Published In
Journal of Rheumatology
Volume
31
Issue
12
Publish Date
2004
Start Page
2331
End Page
2335

Medical expert systems

Authors
Wang, PP; Sullivan, KM
MLA Citation
Wang, PP, and Sullivan, KM. "Medical expert systems." Information Sciences 162.2 (2004): 63-64.
Source
scival
Published In
Information Sciences
Volume
162
Issue
2
Publish Date
2004
Start Page
63
End Page
64
DOI
10.1016/j.ins.2004.03.001

Bronchiolitis obliterans organizing pneumonia (BOOP) after bone marrow transplantation (BMT) for sickle cell disease (SCD): Association with acute chest syndrome (ACS).

Authors
Woodard, JP; Cunningham, JM; Sullivan, KM; Kamani, NR; Walters, MC
MLA Citation
Woodard, JP, Cunningham, JM, Sullivan, KM, Kamani, NR, and Walters, MC. "Bronchiolitis obliterans organizing pneumonia (BOOP) after bone marrow transplantation (BMT) for sickle cell disease (SCD): Association with acute chest syndrome (ACS)." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
460B
End Page
461B

Polymyositis as a manifestation of chronic graft-versus-host disease.

OBJECTIVE: Chronic graft-versus-host disease (GVHD) after haematopoietic stem cell transplantation (HSCT) has similarities to some idiopathic autoimmune diseases, including polymyositis. To investigate the relationship between chronic GVHD and idiopathic myositis we conducted a detailed analysis of all cases of myositis occurring in a large series of HSCT patients. METHODS: We conducted a retrospective chart review of all cases of myositis that developed in 7161 patients who underwent HSCT at the Fred Hutchinson Cancer Research Center between 1969 and 1999. RESULTS: Among 1859 individuals who developed chronic GVHD, 12 developed myositis. No patients developed myositis without chronic GVHD. Myositis was first identified between 7 and 55 months after transplantation. In histopathology, electromyography, laboratory values and response to immunosuppressive therapy, the cases resembled idiopathic polymyositis. Autoantibodies were found in eight cases. CONCLUSIONS: Myositis in the chronic GVHD population occurred with an incidence higher than expected by chance, suggesting that muscle may be a target tissue for chronic GVHD. Recent studies have implicated allogeneic cells persisting after maternal-fetal cell transfer in selected autoimmune diseases, including myositis. This report lends support to the possibility that both idiopathic myositis and chronic GVHD-related myositis could involve allo-autoimmune responses.

Authors
Stevens, AM; Sullivan, KM; Nelson, JL
MLA Citation
Stevens, AM, Sullivan, KM, and Nelson, JL. "Polymyositis as a manifestation of chronic graft-versus-host disease." Rheumatology (Oxford) 42.1 (January 2003): 34-39. (Review)
PMID
12509610
Source
pubmed
Published In
Rheumatology
Volume
42
Issue
1
Publish Date
2003
Start Page
34
End Page
39

Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination

Rates and severity of pneumococcal infections in children with sickle cell disease were examined before licensure of pneumococcal-conjugated vaccine (PVC). Rates of peak invasive infection rates in 1-year-old children with hemoglobin SS and mortality in those 0 to 10 years of age were 36.5 to 63.4 and 1.4 to 2.8 per 1000 person-years, respectively (>10 and 100 times as frequent as in the general population). Overall, 71% of serotyped isolates (n = 80) were PVC serotypes and 71% of nonvaccine serotype strains were penicillin-sensitive. Clinical presentation in children with hemoglobin SS (n = 71; more with hypotension) and hemoglobin SC (n = 18; more with acute chest syndrome, otitis media) differed. Penicillin nonsusceptibility (38% of isolates) varied between geographic study sites. Penicillin prophylaxis appeared less effective against intermediate and resistant strains. Of all infected children, meningitis developed in 20% and 15% died (hemoglobin SS, n = 15 and 11; hemoglobin SC, n = 1 each). Factors associated with death included age >4 years (58%), serotype 19F, and not being followed by a hematologist (42% each). The pneumococcal-polysaccharide vaccine was 80.4% effective within 3 years after vaccination (95% CI, 39.7, 93.6). Children with sickle cell disease of all ages may benefit from PVC boosted with polysaccharide vaccination.

Authors
Adamkiewicz, TV; Sarnaik, S; Buchanan, GR; Iyer, RV; Miller, ST; Pegelow, CH; Rogers, ZR; Vichinsky, E; Elliott, J; Facklam, RR; O'Brien, KL; Schwartz, B; Beneden, CAV; Cannon, MJ; Eckman, JR; Keyserling, H; Sullivan, K; Wong, W-Y; Wang, WC
MLA Citation
Adamkiewicz, TV, Sarnaik, S, Buchanan, GR, Iyer, RV, Miller, ST, Pegelow, CH, Rogers, ZR, Vichinsky, E, Elliott, J, Facklam, RR, O'Brien, KL, Schwartz, B, Beneden, CAV, Cannon, MJ, Eckman, JR, Keyserling, H, Sullivan, K, Wong, W-Y, and Wang, WC. "Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination." Journal of Pediatrics 143.4 (2003): 438-444.
PMID
14571216
Source
scival
Published In
Journal of Pediatrics
Volume
143
Issue
4
Publish Date
2003
Start Page
438
End Page
444
DOI
10.1067/S0022-3476(03)00331-7

High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis

There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS). Median baseline expanded disability status scale (EDSS) was 7.0 (range, 5.0-8.0). HDIT consisted of total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG) and was followed by transplantation of autologous, granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells. Regimen-related toxicities were mild. Because of bladder dysfunction, there were 8 infectious events of the lower urinary tract. One patient died from Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disorder (PTLD) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen. An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms. There were 2 significant adverse neurologic events that occurred, including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever. With a median follow-up of 24 (range, 3-36) months, the Kaplan-Meier estimate of progression (≥ 1.0 point EDSS) at 3 years was 27%. Of 12 patients who had oligocional bands in the cerebro-spinal fluid at baseline, 9 had persistence after HDIT. After HDIT, 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain. The estimate of survival at 3 years was 91%. Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks. This was a heterogeneous high-risk group, and a phase 3 study is planned to fully assess efficacy. © 2003 by The American Society of Hematology.

Authors
Nash, RA; Bowen, JD; McSweeney, PA; Pavletic, SZ; Maravilla, KR; Park, M-S; Storek, J; Sullivan, KM; Al-Omaishi, J; Corboy, JR; DiPersio, J; Georges, GE; Gooley, TA; Holmberg, LA; LeMaistre, CF; Ryan, K; Openshaw, H; Sunderhaus, J; Storb, R; Zunt, J; Kraft, GH
MLA Citation
Nash, RA, Bowen, JD, McSweeney, PA, Pavletic, SZ, Maravilla, KR, Park, M-S, Storek, J, Sullivan, KM, Al-Omaishi, J, Corboy, JR, DiPersio, J, Georges, GE, Gooley, TA, Holmberg, LA, LeMaistre, CF, Ryan, K, Openshaw, H, Sunderhaus, J, Storb, R, Zunt, J, and Kraft, GH. "High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis." Blood 102.7 (2003): 2364-2372.
PMID
12763935
Source
scival
Published In
Blood
Volume
102
Issue
7
Publish Date
2003
Start Page
2364
End Page
2372
DOI
10.1182/blood-2002-12-3908

Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases

High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk of transplant-related complications secondary to the immunosuppressed state, including Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD), but this is an unusual complication after autologous HSCT. Fifty-six patients (median age, 42 years; range, 23-61 years) with either multiple sclerosis (n = 26) or systemic sclerosis (n = 30) have been treated. The median follow-up has been 24 months (range, 2-60 months). Two patients (multiple sclerosis, n = 1; systemic sclerosis, n = 1) had significant reactivations of herpesvirus infections early after HSCT and then developed aggressive EBV-PTLD and died on days +53 and +64. Multiorgan clonal B-cell infiltrates that were EBV positive by molecular studies or immunohistology were identified at both autopsies. Both patients had positive screening skin tests for equine ATG (Atgam) and had been converted to rabbit ATG (Thymoglobulin) from the first dose. Of the other 54 patients, 2 of whom had partial courses of rabbit ATG because of a reaction to the intravenous infusion of equine ATG, only 1 patient had a significant clinical reactivation of a herpesvirus infection (herpes simplex virus 2) early after HSCT, and none developed EBV-PTLD. The T-cell count in the peripheral blood on day 28 was 0/μL in all 4 patients who received rabbit ATG; this was significantly less than in patients who received equine ATG (median, 174/μL; P =.001; Mann-Whitney ranked sum test). Although the numbers are limited, the time course and similarity of the 2 cases of EBV-PTLD and the effect on day 28 T-cell counts support a relationship between the development of EBV-PTLD and the administration of rabbit ATG. The differences between equine and rabbit ATG are not yet clearly defined, and they should not be considered interchangeable in this regimen without further study. © 2003 American Society for Blood and Marrow Transplantation.

Authors
Nash, RA; Dansey, R; Storek, J; Georges, GE; Bowen, JD; Holmberg, LA; Kraft, GH; Mayes, MD; McDonagh, KT; Chen, C-S; DiPersio, J; LeMaistre, CF; Pavletic, S; Sullivan, KM; Sunderhaus, J; Furst, DE; McSweeney, PA
MLA Citation
Nash, RA, Dansey, R, Storek, J, Georges, GE, Bowen, JD, Holmberg, LA, Kraft, GH, Mayes, MD, McDonagh, KT, Chen, C-S, DiPersio, J, LeMaistre, CF, Pavletic, S, Sullivan, KM, Sunderhaus, J, Furst, DE, and McSweeney, PA. "Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases." Biology of Blood and Marrow Transplantation 9.9 (2003): 583-591.
PMID
14506660
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
9
Issue
9
Publish Date
2003
Start Page
583
End Page
591
DOI
10.1016/S1083-8791(03)00228-3

Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and β-thalassemia

We describe previously transfused patients with sickle cell disease (n = 6) and thalassemia (n = 1) who received nonmyeloablative hematopoietic stem cell transplantation (HCT) to induce stable (full or partial) donor engraftment. Patients were 3 to 20 years (median, 9 years) old. All 7 received pretransplantation fludarabine and 200 cGy of total body irradiation; 2 patients also received horse antithymocyte globulin. Patients received bone marrow (n = 6) or peripheral blood stem cells (n = 1) from HLA-identical siblings, followed by a combination of mycophenolate mofetil and cyclosporine or tacrolimus for postgrafting immunosuppression. After nonmyeloablative HCT, absolute neutrophil counts were <0.5 × 109/L and <0.2 × 109/L for a median of 5 days (range, 0-13 days) and 0 days (range 0-13 days), respectively. A median of 0 (range, 0-9) platelet transfusions were administered. No grade IV nonhematologic toxicities were observed. One patient experienced grade II acute graft-versus-host disease. Two months after transplantation, 6 of 7 patients had evidence of donor chimerism (range, 25%-85%). Independent of red blood cell transfusions, these 6 patients initially had increased total hemoglobin and hemoglobin A concentrations and a reduction of reticulocytosis and transfusion requirements. There were no complications attributable to sickle cell disease during the interval of transient mixed chimerism. However, after posttransplantation immunosuppression was tapered, there was loss of the donor graft, and all patients experienced autologous hematopoietic recovery and disease recurrence. One patient did not engraft. The duration of transient mixed chimerism ranged from 97 to 441 days after transplantation in patients 4 and 6, respectively, and persisted until immunosuppressive drugs were discontinued after transplantation. In summary, the nonmyeloablative HCT regimens described here produced minimal toxicity and resulted in transient donor engraftment in 6 of 7 patients with hemoglobinopathies. Although complications from the underlying hemoglobinopathies did not occur during the period of mixed chimerism, these results suggest that stable (full or partial) donor engraftment after nonmyeloablative HCT is more difficult to achieve among immunocompetent pediatric patients with hemoglobinopathies than among adults with hematologic malignancies, perhaps in part because recipients may have been sensitized to minor histocompatibility antigens of their donor by preceding blood transfusions. © 2003 American Society for Blood and Marrow Transplantation.

Authors
Iannone, R; Casella, JF; Fuchs, EJ; Chen, AR; Jones, RJ; Woolfrey, A; Amylon, M; Sullivan, KM; Storb, RF; Walters, MC
MLA Citation
Iannone, R, Casella, JF, Fuchs, EJ, Chen, AR, Jones, RJ, Woolfrey, A, Amylon, M, Sullivan, KM, Storb, RF, and Walters, MC. "Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and β-thalassemia." Biology of Blood and Marrow Transplantation 9.8 (2003): 519-528.
PMID
12931121
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
9
Issue
8
Publish Date
2003
Start Page
519
End Page
528
DOI
10.1016/S1083-8791(03)00192-7

Case based reasoning for medical decision-support in a safety critical environment

Case-based reasoning systems applied to safety-critical environments justify specific measures to ensure that the assistance provided is not dangerous to human life. This article presents a case-based reasoning system developed for medical decision-support in a safety-critical environment, the CARE-PARTNER system. Based on the evaluation of the reliability of the system, it stresses the importance to differentiate between reliability and safety, and how case-based reasoning can ensure safety. A knowledge-based approach has enabled to model what types of information are safety-critical, and to adapt the decision-support system results, by introspective reasoning, based on the knowledge type, the user, and the task.

Authors
Bichindaritz, I; Moinpour, C; Kansu, E; Donaldson, G; Bush, N; Sullivan, KM
MLA Citation
Bichindaritz, I, Moinpour, C, Kansu, E, Donaldson, G, Bush, N, and Sullivan, KM. "Case based reasoning for medical decision-support in a safety critical environment." Lecture Notes in Artificial Intelligence (Subseries of Lecture Notes in Computer Science) 2780 (2003): 314-323.
Source
scival
Published In
Lecture notes in computer science
Volume
2780
Publish Date
2003
Start Page
314
End Page
323

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation

The incidence, etiology, outcome, and risk factors for developing pneumonia late after hematopoietic stem cell transplantation (SCT) were investigated in 1359 patients transplanted in Seattle. A total of 341 patients (25% of the cohort) developed at least one pneumonic episode. No microbial or tissue diagnosis (ie clinical pneumonia) was established in 197 patients (58% of first pneumonia cases). Among the remaining 144 patients, established etiologies included 33 viral (10%), 31 bacterial (9%), 25 idiopathic pneumonia syndrome (IPS, 7%), 20 multiple organisms (6%), 19 fungal (6%), and 16 Pneumocystis carinii pneumonia (PCP) (5%). The overall cumulative incidence of first pneumonia at 4 years after discharge home was 31%. The cumulative incidences of pneumonia according to donor type at 1 and 4 years after discharge home were 13 and 18% (autologous/syngeneic), 22 and 34% (HLA-matched related), and 26 and 39% (mismatched related/unrelated), respectively. Multivariate analysis of factors associated with development of late pneumonia after allografting were increasing patient age (RR 0.5 for <20 years, 1.2 for >40 years, P=0.009), donor HLA-mismatch (RR 1.6 for unrelated/mismatched related, P=0.01), and chronic graft-versus-host disease (GVHD; RR 1.5, P=0.007). Our data suggest that extension of PCP prophylaxis may be beneficial in high-risk autograft recipients. Further study of long-term anti-infective prophylaxis based on patient risk factors after SCT appear warranted.

Authors
Chen, C-S; Boeckh, M; Seidel, K; Clark, JG; Kansu, E; Madtes, DK; Wagner, JL; Witherspoon, RP; Anasetti, C; Appelbaum, FR; Bensinger, WI; Deeg, HJ; Martin, PJ; Sanders, JE; Storb, R; Storek, J; Wade, J; Siadak, M; Flowers, MED; Sullivan, KM
MLA Citation
Chen, C-S, Boeckh, M, Seidel, K, Clark, JG, Kansu, E, Madtes, DK, Wagner, JL, Witherspoon, RP, Anasetti, C, Appelbaum, FR, Bensinger, WI, Deeg, HJ, Martin, PJ, Sanders, JE, Storb, R, Storek, J, Wade, J, Siadak, M, Flowers, MED, and Sullivan, KM. "Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation." Bone Marrow Transplantation 32.5 (2003): 515-522.
PMID
12942099
Source
scival
Published In
Bone Marrow Transplantation
Volume
32
Issue
5
Publish Date
2003
Start Page
515
End Page
522
DOI
10.1038/sj.bmt.1704162

Chronic graft-versus-host disease after allogeneic stem cell transplantation

Chronic Graft-versus-Host disease (chronic GVHD) is a clinicopathological syndrome which is the major determinant of long-term outcome and quality of life after allogeneic bone marrow or peripheral stem cell transplantation. Chronic GVHD may develop within 3 to 18 months after allografting and occurs in approximately 33% of HLA-identical sibling recipients and 50-70% of recipients of unrelated or mismatched-related marrow grafts. Individuals with the limited chronic GVHD have a favorable course and patients with extensive chronic GVHD have an unfavorable natural history. Chronic GVHD is a pleiotropic disease with clinical and pathological signs and symptoms similar to several naturally occurring autoimmune disorders. Organ involvement in extensive chronic GVHD affects the skin, mouth, eyes, sinuses, gastrointestinal tract, lungs, muscles, tendons, serous surfaces and nerves. Owing to the prolonged time to immunological recovery sinopulmonary infections may be common in patients with chronic GVHD. In standard-risk chronic GVHD patients early treatment with prednisone and cyclosporine has better results in high-risk patients. New treatment approaches include the use of FK506, thalidomide, mycophenolate mofetil, rapamycin and extracorporeal photopheresis. Supportive care includes correction of hypogammaglobulinemia and administration of antibiotics to reduce the risk of infection.

Authors
Kansu, E; Koç, Y; Sullivan, KM
MLA Citation
Kansu, E, Koç, Y, and Sullivan, KM. "Chronic graft-versus-host disease after allogeneic stem cell transplantation." Turkish Journal of Cancer 33.1 (2003): 9-22.
Source
scival
Published In
Turkish Journal of Cancer
Volume
33
Issue
1
Publish Date
2003
Start Page
9
End Page
22

Treatment of severe multiple sclerosis (MS) with high-dose immunosuppressive therapy (HDIT) and autologous stem cell transplantation (SCT): 2 year follow-up.

Authors
Nash, RA; Bowen, JD; McSweeney, PA; Sullivan, KM; Pavletic, ZS; Maravilla, KR; Al-Omaishi, J; Corboy, JR; Derrington, D; DiPersio, J; Georges, GE; Gooley, T; Holmberg, LA; LeMaistre, CF; Openshaw, H; Ryan, K; Sunderhaus, J; Storek, J; Zunt, J; Storb, R; Kraft, GH
MLA Citation
Nash, RA, Bowen, JD, McSweeney, PA, Sullivan, KM, Pavletic, ZS, Maravilla, KR, Al-Omaishi, J, Corboy, JR, Derrington, D, DiPersio, J, Georges, GE, Gooley, T, Holmberg, LA, LeMaistre, CF, Openshaw, H, Ryan, K, Sunderhaus, J, Storek, J, Zunt, J, Storb, R, and Kraft, GH. "Treatment of severe multiple sclerosis (MS) with high-dose immunosuppressive therapy (HDIT) and autologous stem cell transplantation (SCT): 2 year follow-up." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
864A
End Page
864A

Treatment of severe systemic sclerosis with allogenic marrow transplantation.

Authors
Nash, RA; McSweeney, PA; Storb, R; Sullivan, KM; Langston, A; Sunderhaus, JL; Wener, M; Furst, D
MLA Citation
Nash, RA, McSweeney, PA, Storb, R, Sullivan, KM, Langston, A, Sunderhaus, JL, Wener, M, and Furst, D. "Treatment of severe systemic sclerosis with allogenic marrow transplantation." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
460B
End Page
461B

Updated results of bone marrow transplantation (BMT) for sickle cell disease (SCD): Impact on CNS disease.

Authors
Walters, MC; Patience, M; Leisenring, W; Steen, RG; Zamani, C; Vichinsky, E; Storb, R; Sullivan, KM
MLA Citation
Walters, MC, Patience, M, Leisenring, W, Steen, RG, Zamani, C, Vichinsky, E, Storb, R, and Sullivan, KM. "Updated results of bone marrow transplantation (BMT) for sickle cell disease (SCD): Impact on CNS disease." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
45A
End Page
46A

Failure of a minimally toxic non-myeloablative regimen to establish stable donor engraftment after transplantation for sickle cell anemia and beta-thalassemia.

Authors
Iannone, R; Casella, JF; Fuchs, EJ; Chen, AR; Woolfrey, A; Amylon, M; Sullivan, KM; Storb, RF; Walters, MC
MLA Citation
Iannone, R, Casella, JF, Fuchs, EJ, Chen, AR, Woolfrey, A, Amylon, M, Sullivan, KM, Storb, RF, and Walters, MC. "Failure of a minimally toxic non-myeloablative regimen to establish stable donor engraftment after transplantation for sickle cell anemia and beta-thalassemia." November 16, 2002.
Source
wos-lite
Published In
Blood
Volume
100
Issue
11
Publish Date
2002
Start Page
46A
End Page
46A

High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes.

Systemic sclerosis (SSc) is a multisystem disease of presumed autoimmune pathogenesis for which no proven effective treatment exists. High-dose immunosuppressive therapy (HDIT) has been proposed as an investigational treatment for severe autoimmune diseases. Nineteen patients with poor-prognosis SSc underwent HDIT. The median age was 40 years (range, 23-61 years), the median modified Rodnan skin score (a measure of dermal sclerosis) was 31, and the median DLCO was 57%. Conditioning therapy involved 800 cGy total body irradiation (TBI) (+/- lung shielding to approximately 200 cGy), 120 mg/kg cyclophosphamide, and 90 mg/kg equine antithymocyte globulin. CD34-selected granulocyte-colony-stimulating factor-mobilized autologous blood stem cells provided hematopoietic rescue. With median follow-up at 14.7 months, the Kaplan-Meier estimated 2-year survival rate was 79%. Three patients died of treatment complications and one of disease progression. Two of the first 8 patients had fatal regimen-related pulmonary injury, a complication not found among 11 subsequent patients who received lung shielding for TBI. Overall, internal organ functions were stable to slightly worse after HDIT, and 4 patients had progressive or nonresponsive disease. As measured by modified Rodnan skin scores and modified health assessment questionnaire disability index (mHAQ-DI) scores, significant disease responses occurred in 12 of 12 patients evaluated at 1 year after HDIT. In conclusion, though important treatment-related toxicities occurred after HDIT for SSc, modifications of initial approaches appear to reduce treatment risks. Responses in skin and mHAQ-DI scores exceed those reported with other therapies, suggesting that HDIT is a promising new therapy for SSc that should be evaluated in prospective randomized studies.

Authors
McSweeney, PA; Nash, RA; Sullivan, KM; Storek, J; Crofford, LJ; Dansey, R; Mayes, MD; McDonagh, KT; Nelson, JL; Gooley, TA; Holmberg, LA; Chen, CS; Wener, MH; Ryan, K; Sunderhaus, J; Russell, K; Rambharose, J; Storb, R; Furst, DE
MLA Citation
McSweeney, PA, Nash, RA, Sullivan, KM, Storek, J, Crofford, LJ, Dansey, R, Mayes, MD, McDonagh, KT, Nelson, JL, Gooley, TA, Holmberg, LA, Chen, CS, Wener, MH, Ryan, K, Sunderhaus, J, Russell, K, Rambharose, J, Storb, R, and Furst, DE. "High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes." Blood 100.5 (September 1, 2002): 1602-1610.
PMID
12176878
Source
pubmed
Published In
Blood
Volume
100
Issue
5
Publish Date
2002
Start Page
1602
End Page
1610

Bone marrow transplantation for non-malignant disease.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Bone marrow transplantation for non-malignant disease." Int J Hematol 76 Suppl 1 (August 2002): 169-170. (Review)
PMID
12430848
Source
pubmed
Published In
International Journal of Hematology
Volume
76 Suppl 1
Publish Date
2002
Start Page
169
End Page
170

Morbidity and mortality of chronic GVHD after hematopoietic stem cell transplantation from HLA-identical siblings for patients with aplastic or refractory anemias.

We analyzed effects of successive changes in prevention and treatment of chronic GVHD in 405 patients with aplastic anemia and refractory anemia given HLA-matched hematopoietic stem cell transplantation (HSCT) from 1970-1997. For analysis, patients were divided into group I, transplantations from 1970-1976; group II, 1977-1983; group III, 1984-1990; and group IV, 1991-1997. The overall incidence of chronic GVHD was 28%. Incidences of chronic GVHD for groups I through IV were 20%, 46%, 41%, and 22%, respectively, reflecting added buffy coat infusions in groups II and III. Five-year survival rates of patients with chronic GVHD for groups I through IV were 58%, 74%, 82%, and 76%, respectively (NS). Among group I patients, 50% were alive off immunosuppression, none were alive on immunosuppression, and 50% died. These figures were 76%, 0%, and 24% in group II; 80%, 10%, and 10% in group III; and 64%, 21%, and 14% in group IV patients. More serious infections and skin contractures were seen in group I than in groups II, III, and IV (P = .0001, .02, .01 and P =.0003, .001, .05, respectively). Lung complications, aseptic necroses, depression, and Karnofsky scores were comparable among groups. Gastrointestinal complications seemed less frequent among groups II through IV. Diabetes mellitus was more frequent in group IV than in groups I through III (P = .008). Secondary malignancies occurred in 33%, 6%, 3%, and 0% of patients in the 4 groups, respectively. In conclusion, over 28 years, chronic GVHD has remained challenging, with only slight improvements in quality of life. Decisive improvements in therapy and survival will have to await both a better understanding of the immunological events underlying chronic GVHD and better infection prevention and control.

Authors
Goerner, M; Gooley, T; Flowers, MED; Sullivan, KM; Kiem, H-P; Sanders, JE; Martin, PJ; Storb, R
MLA Citation
Goerner, M, Gooley, T, Flowers, MED, Sullivan, KM, Kiem, H-P, Sanders, JE, Martin, PJ, and Storb, R. "Morbidity and mortality of chronic GVHD after hematopoietic stem cell transplantation from HLA-identical siblings for patients with aplastic or refractory anemias." Biol Blood Marrow Transplant 8.1 (2002): 47-56.
PMID
11858190
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
8
Issue
1
Publish Date
2002
Start Page
47
End Page
56

Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies.

In the early 1990s, 4 randomized studies compared conditioning regimens before transplantation for leukemia with either cyclophosphamide (CY) and total-body irradiation (TBI), or busulfan (Bu) and CY. This study analyzed the long-term outcomes for 316 patients with chronic myeloid leukemia (CML) and 172 patients with acute myeloid leukemia (AML) who participated in these 4 trials, now with a mean follow-up of more than 7 years. Among patients with CML, no statistically significant difference in survival or disease-free survival emerged from testing the 2 regimens. The projected 10-year survival estimates were 65% and 63% with Bu-CY versus CY-TBI, respectively. Among patients with AML, the projected 10-year survival estimates were 51% and 63% (95% CI, 52%-74%) with Bu-CY versus CY-TBI, respectively. At last follow-up, most surviving patients had unimpaired health and had returned to work, regardless of the conditioning regimen. Late complications were analyzed after adjustment for patient age and for acute and chronic graft-versus-host disease (GVHD). CML patients who received CY-TBI had an increased risk of cataract formation, and patients treated with Bu-CY had an increased risk of irreversible alopecia. Chronic GVHD was the primary risk factor for late pulmonary disease and avascular osteonecrosis. Thus, Bu-CY and CY-TBI provided similar probabilities of cure for patients with CML. In patients with AML, a nonsignificant 10% lower survival rate was observed after Bu-CY. Late complications occurred equally after both conditioning regimens (except for increased risk of cataract after CY-TBI and of alopecia with Bu-CY).

Authors
Socié, G; Clift, RA; Blaise, D; Devergie, A; Ringden, O; Martin, PJ; Remberger, M; Deeg, HJ; Ruutu, T; Michallet, M; Sullivan, KM; Chevret, S
MLA Citation
Socié, G, Clift, RA, Blaise, D, Devergie, A, Ringden, O, Martin, PJ, Remberger, M, Deeg, HJ, Ruutu, T, Michallet, M, Sullivan, KM, and Chevret, S. "Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies." Blood 98.13 (December 15, 2001): 3569-3574.
PMID
11739158
Source
pubmed
Published In
Blood
Volume
98
Issue
13
Publish Date
2001
Start Page
3569
End Page
3574

Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation.

The duration of immunodeficiency following marrow transplantation is not known. Questionnaires were used to study the infection rates in 72 patients surviving 20 to 30 years after marrow grafting. Furthermore, in 33 of the 72 patients and in 16 donors (siblings who originally donated the marrow) leukocyte subsets were assessed by flow cytometry. T-cell receptor excision circles (TRECs), markers of T cells generated de novo, were quantitated by real-time polymerase chain reaction. Immunoglobulin G(2) (IgG(2)) and antigen-specific IgG levels were determined by enzyme-linked immunosorbent assay. Infections diagnosed more than [corrected] 15 years after transplantation occurred rarely. The average rate was 0.07 infections per patient-year (one infection every 14 years), excluding respiratory tract infections, gastroenteritis, lip sores, and hepatitis C. The counts of circulating monocytes, natural killer cells, B cells, CD4 T cells, and CD8 T cells in the patients were not lower than in the donors. The counts of TREC(+) CD4 T cells in transplant recipients younger than age 18 years (at the time of transplantation) were not different from the counts in their donors. In contrast, the counts of TREC(+) CD4 T cells were lower in transplant recipients age 18 years or older, even in those with no history of clinical extensive chronic graft-versus-host disease, compared with their donors. The levels of total IgG(2) and specific IgG against Haemophilus influenzae and Streptococcus pneumoniae were similar in patients and donors. Overall, the immunity of patients surviving 20 to 30 years after transplantation is normal or near normal. Patients who received transplants in adulthood have a clinically insignificant deficiency of de novo-generated CD4 T cells, suggesting that in these patients the posttransplantation thymic insufficiency may not be fully reversible.

Authors
Storek, J; Joseph, A; Espino, G; Dawson, MA; Douek, DC; Sullivan, KM; Flowers, ME; Martin, P; Mathioudakis, G; Nash, RA; Storb, R; Appelbaum, FR; Maloney, DG
MLA Citation
Storek, J, Joseph, A, Espino, G, Dawson, MA, Douek, DC, Sullivan, KM, Flowers, ME, Martin, P, Mathioudakis, G, Nash, RA, Storb, R, Appelbaum, FR, and Maloney, DG. "Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation." Blood 98.13 (December 15, 2001): 3505-3512.
PMID
11739150
Source
pubmed
Published In
Blood
Volume
98
Issue
13
Publish Date
2001
Start Page
3505
End Page
3512

Flow cytometric analysis in two large cohorts of patients with PNH.

Authors
Nishimura, J; Kanakura, Y; Ware, RE; Shichishima, T; Nakakuma, H; Ninomiya, H; DeCastro, CM; Hall, S; Kanamaru, A; Sullivan, KM; Mizoguchi, H; Omine, M; Kinoshita, T; Rosse, WF
MLA Citation
Nishimura, J, Kanakura, Y, Ware, RE, Shichishima, T, Nakakuma, H, Ninomiya, H, DeCastro, CM, Hall, S, Kanamaru, A, Sullivan, KM, Mizoguchi, H, Omine, M, Kinoshita, T, and Rosse, WF. "Flow cytometric analysis in two large cohorts of patients with PNH." BLOOD 98.11 (November 16, 2001): 221A-221A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
221A
End Page
221A

The clinical course of PNH in the USA and in Japan.

Authors
Nishimura, J; Kanakura, Y; Ware, RE; Shichishima, T; Nakakuma, H; Ninomiya, H; DeCastro, CM; Hall, S; Kanamaru, A; Sullivan, KM; Mizoguchi, H; Omine, M; Kinoshita, T; Rosse, WF
MLA Citation
Nishimura, J, Kanakura, Y, Ware, RE, Shichishima, T, Nakakuma, H, Ninomiya, H, DeCastro, CM, Hall, S, Kanamaru, A, Sullivan, KM, Mizoguchi, H, Omine, M, Kinoshita, T, and Rosse, WF. "The clinical course of PNH in the USA and in Japan." BLOOD 98.11 (November 16, 2001): 220A-220A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
220A
End Page
220A

Enrichment of donor erythroid cells after non-myeloablative bone marrow transplantation (BMT) for sickle cell anemia (SCA).

Authors
Walters, MC; Woolfrey, A; Torok-Storb, B; Zaucha, JM; Little, MT; Trachtenberg, E; Sullivan, KM; Storb, R
MLA Citation
Walters, MC, Woolfrey, A, Torok-Storb, B, Zaucha, JM, Little, MT, Trachtenberg, E, Sullivan, KM, and Storb, R. "Enrichment of donor erythroid cells after non-myeloablative bone marrow transplantation (BMT) for sickle cell anemia (SCA)." BLOOD 98.11 (November 16, 2001): 490A-490A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
490A
End Page
490A

High-dose immunosuppressive therapy (HDIT) for severe systemic sclerosis (SSc).

Authors
McSweeney, PA; Nash, RA; Sullivan, KM; Crofford, LJ; McDonagh, KT; Dansey, R; Mayes, M; Holmberg, LA; Chen, CS; Rambharose, J; Storek, J; Gooley, TA; LeMaistre, CF; Ryan, K; Sunderhaus, J; Furst, DE
MLA Citation
McSweeney, PA, Nash, RA, Sullivan, KM, Crofford, LJ, McDonagh, KT, Dansey, R, Mayes, M, Holmberg, LA, Chen, CS, Rambharose, J, Storek, J, Gooley, TA, LeMaistre, CF, Ryan, K, Sunderhaus, J, and Furst, DE. "High-dose immunosuppressive therapy (HDIT) for severe systemic sclerosis (SSc)." BLOOD 98.11 (November 16, 2001): 395B-395B.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
395B
End Page
395B

Treatment of severe multiple sclerosis (MS) with high-dose immunosuppressive therapy (HDIT) and autologous stem cell transplantation (SCT).

Authors
Nash, RA; Bowen, JD; McSweeney, PA; Sullivan, KM; Pavletic, ZS; Maravilla, KR; Al-Omaishi, J; Corboy, JR; Derrington, D; DiPersio, J; Georges, GE; Holmberg, LA; LeMaistre, CF; Openshaw, H; Ryan, K; Sunderhaus, J; Storek, J; Zunt, J; Kraft, GH
MLA Citation
Nash, RA, Bowen, JD, McSweeney, PA, Sullivan, KM, Pavletic, ZS, Maravilla, KR, Al-Omaishi, J, Corboy, JR, Derrington, D, DiPersio, J, Georges, GE, Holmberg, LA, LeMaistre, CF, Openshaw, H, Ryan, K, Sunderhaus, J, Storek, J, Zunt, J, and Kraft, GH. "Treatment of severe multiple sclerosis (MS) with high-dose immunosuppressive therapy (HDIT) and autologous stem cell transplantation (SCT)." BLOOD 98.11 (November 16, 2001): 687A-687A.
Source
wos-lite
Published In
Blood
Volume
98
Issue
11
Publish Date
2001
Start Page
687A
End Page
687A

Bone density loss after allogeneic hematopoietic stem cell transplantation: a prospective study.

The incidence and course of bone density abnormalities following hematopoietic stem cell transplantation are poorly understood and complicated by the impact of multiple factors. Hip, spine, and wrist bone mineral densities (BMDs) were measured in 104 adults (54 women, 54 men; mean age, 40 years [range, 18-64 years]) at 3 and 12 months after allogeneic transplantation. Clinical and laboratory variables were evaluated using univariate and multivariate analyses to determine risk factors for osteoporosis, fracture, and avascular necrosis. At 3 months posttransplantation, combined (male and female) hip, spine, and wrist z scores were -0.35, -0.42, and +0.04 standard deviations, respectively. At 12 months both men and women experienced significant loss of hip BMD (4.2%, P < .0001); changes in the spine and wrist were minimal. The cumulative dose and number of days of glucocorticoid therapy and the number of days of cyclosporine or tacrolimus therapy showed significant associations with loss of BMD; age, total body irradiation, diagnosis, and donor type did not. Nontraumatic fractures occurred in 10.6% of patients and avascular necrosis in 9.6% within 3 years posttransplantation. The decrease in height between pretransplantation and 12 months posttransplantation was significant (P = .0001). Results indicate that loss of BMD after allogeneic stem cell transplantation is common and accelerated by the length of immunosuppressive therapy and cumulative dose of glucocorticoid. An increased incidence of fracture and avascular necrosis may adversely impact long-term quality of life. Prevention of bone demineralization appears warranted after stem cell transplantation.

Authors
Stern, JM; Sullivan, KM; Ott, SM; Seidel, K; Fink, JC; Longton, G; Sherrard, DJ
MLA Citation
Stern, JM, Sullivan, KM, Ott, SM, Seidel, K, Fink, JC, Longton, G, and Sherrard, DJ. "Bone density loss after allogeneic hematopoietic stem cell transplantation: a prospective study." Biol Blood Marrow Transplant 7.5 (2001): 257-264.
PMID
11400947
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
7
Issue
5
Publish Date
2001
Start Page
257
End Page
264
DOI
10.1053/bbmt.2001.v7.pm11400947

Secondary failure of platelet recovery after hematopoietic stem cell transplantation.

After primary recovery of platelet counts after transplantation, there can be a late persistent decline called secondary failure of platelet recovery (SFPR), which may occur although the counts of other cell lineages remain within the normal range. SFPR was defined as a decline of platelet counts below 20,000/microL for 7 consecutive days or requiring transfusion support after achieving sustained platelet counts > or = 50,000/microL without transfusions for 7 consecutive days after hematopoietic stem cell transplantation (HSCT). The study population consisted of 2871 consecutive patients receiving transplants from January 1990 to March 1997. After primary recovery of platelet counts, SFPR not due to relapse of the underlying disease was observed in 285 of 1401 (20%) patients undergoing allogeneic transplantation and 36 (8%) of 444 patients undergoing autologous transplantation, with a median time of onset after transplantation at day 63 (range, day 21-156) and day 44 (range, day 24-89), respectively. Concomitant neutropenia was seen in 57 (20%) of 285 patients undergoing allogeneic HSCT and 7 (19%) of 36 patients undergoing autologous HSCT with SFPR. By multivariable analysis, the following were factors significantly associated with SFPR after allogeneic HSCT: a transplant from an unrelated donor; a graft-versus-host disease (GVHD) prophylaxis other than methotrexate and cyclosporine; development of grade 2 through 4 acute GVHD; impaired renal or liver function; conditioning with the combination of busulfan, cyclophosphamide, and total body irradiation; stem cell dose; and infections. Cytomegalovirus infection after engraftment and source of stem cells were the only significant risk factors after autologous HSCT. The hazard rate of death was significantly higher in patients who experienced SFPR (hazard ratio = 2.6 for allogeneic HSCT; hazard ratio = 2.2 for autologous HSCT). SFPR was associated with serious complications and poor outcome after transplantation. The identification of the characteristics and risk factors for SFPR could improve patient counseling and management and lead to the design of effective treatment strategies.

Authors
Bruno, B; Gooley, T; Sullivan, KM; Davis, C; Bensinger, WI; Storb, R; Nash, RA
MLA Citation
Bruno, B, Gooley, T, Sullivan, KM, Davis, C, Bensinger, WI, Storb, R, and Nash, RA. "Secondary failure of platelet recovery after hematopoietic stem cell transplantation." Biol Blood Marrow Transplant 7.3 (2001): 154-162.
PMID
11302549
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
7
Issue
3
Publish Date
2001
Start Page
154
End Page
162
DOI
10.1053/bbmt.2001.v7.pm11302549

Preventing opportunistic infections after hematopoietic stem cell transplantation: the Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation Practice Guidelines and beyond.

This review presents evidence-based guidelines for the prevention of infection after blood and marrow transplantation. Recommendations apply to all myeloablative transplants regardless of recipient (adult or child), type (allogeneic or autologous) or source (peripheral blood, marrow or cord blood) of transplant. In Section I, Dr. Dykewicz describes the methods used to rate the strength and quality of published evidence supporting these recommendations and details the two dozen scholarly societies and federal agencies involved in the genesis and review of the guidelines. In Section II, Dr. Longworth presents recommendations for hospital infection control. Hand hygiene, room ventilation, health care worker and visitor policies are detailed along with guidelines for control of specific nosocomial and community-acquired pathogens. In Section III, Dr. Boeckh details effective practices to prevent viral diseases. Leukocyte-depleted blood is recommended for cytomegalovirus (CMV) seronegative allografts, while ganciclovir given as prophylaxis or preemptive therapy based on pp65 antigenemia or DNA assays is advised for individuals at risk for CMV. Guidelines for preventing varicella-zoster virus (VZV), herpes simplex virus (HSV) and community respiratory virus infections are also presented. In Section IV, Drs. Baden and Rubin review means to prevent invasive fungal infections. Hospital design and policy can reduce exposure to air contaminated with fungal spores and fluconazole prophylaxis at 400 mg/day reduces invasive yeast infection. In Section V, Dr. Sepkowitz details effective clinical practices to reduce or prevent bacterial or protozoal disease after transplantation. In Section VI, Dr. Sullivan reviews vaccine-preventable infections and guidelines for active and passive immunizations for stem cell transplant recipients, family members and health care workers.

Authors
Sullivan, KM; Dykewicz, CA; Longworth, DL; Boeckh, M; Baden, LR; Rubin, RH; Sepkowitz, KA; Centers for Disease Control and Prevention, ; Infectious Diseases Society of America, ; American Society for Blood and Marrow Transplantation Practice Guidelines and beyond,
MLA Citation
Sullivan, KM, Dykewicz, CA, Longworth, DL, Boeckh, M, Baden, LR, Rubin, RH, Sepkowitz, KA, Centers for Disease Control and Prevention, , Infectious Diseases Society of America, , and American Society for Blood and Marrow Transplantation Practice Guidelines and beyond, . "Preventing opportunistic infections after hematopoietic stem cell transplantation: the Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation Practice Guidelines and beyond." Hematology Am Soc Hematol Educ Program (2001): 392-421. (Review)
PMID
11722995
Source
pubmed
Published In
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
Publish Date
2001
Start Page
392
End Page
421

Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia.

A multicenter investigation of allogeneic bone marrow transplantation for children with sickle cell disease was conducted that included 27 European and North American transplant centers. Fifty-nine patients who ranged in age from 3.3 to 15.9 years (median, 10.1 years) received HLA-identical sibling marrow allografts between September 1991 and April 2000. Fifty-five patients survive, and 50 survive free from sickle cell disease, with a median follow-up of 42.2 months (range, 11.8 to 115 months) after transplantation. Of the 50 patients with successful allografts, 13 developed stable mixed donor-host hematopoietic chimerism. The level of donor chimerism, measured > or =6 months after transplantation in peripheral blood, varied between 90% and 99% in 8 patients. Five additional patients had a lower proportion of donor cells (range, 11% to 74%). Among these 5 patients, hemoglobin levels varied between 11.2 and 14.2 g/dL (median, 11.3 g/dL; mean, 12.0 g/dL). In patients who had donors with a normal hemoglobin genotype (Hb), the Hb S fractions were 0%, 0%, and 7%, corresponding to donor chimerism levels of 67%, 74%, and 11%, respectively. Among patients who had donors with sickle trait, the Hb S fractions were 36% and 37%, corresponding to donor chimerism levels of 25% and 60%, respectively. Thus, allograft recipients with stable mixed chimerism had Rb S levels similar to donor levels, and only 1 patient required a red blood cell transfusion beyond 90 days posttransplantation. None of the patients have experienced painful events or other clinical complications related to sickle cell disease after transplantation. These observations strongly suggest that patients with sickle cell disease who develop persistent mixed hematopoietic chimerism after transplantation experience a significant ameliorative effect.

Authors
Walters, MC; Patience, M; Leisenring, W; Rogers, ZR; Aquino, VM; Buchanan, GR; Roberts, IA; Yeager, AM; Hsu, L; Adamkiewicz, T; Kurtzberg, J; Vichinsky, E; Storer, B; Storb, R; Sullivan, KM; Multicenter Investigation of Bone Marrow Transplantation for Sickle Cell Disease,
MLA Citation
Walters, MC, Patience, M, Leisenring, W, Rogers, ZR, Aquino, VM, Buchanan, GR, Roberts, IA, Yeager, AM, Hsu, L, Adamkiewicz, T, Kurtzberg, J, Vichinsky, E, Storer, B, Storb, R, Sullivan, KM, and Multicenter Investigation of Bone Marrow Transplantation for Sickle Cell Disease, . "Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia." Biol Blood Marrow Transplant 7.12 (2001): 665-673.
PMID
11787529
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
7
Issue
12
Publish Date
2001
Start Page
665
End Page
673

Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease

Background. In a pilot trial we evaluated the toxicity and efficacy of sirolimus (rapamycin) as secondline therapy for the treatment of acute graft-versushost disease (GVHD) in 21 patients (1-46 years of age) after allogeneic hematopoietic stem cell transplantation (HSCT). Methods. All patients were treated with methylprednisolone at 2 mg/kg/day, but failed to respond satisfactorily. Sirolimus was started 19-78 (median 37) days after HSCT when 10 patients had grade III and 11 had grade IV GVHD. The first four patients received a loading dose (15 mg/m2) of oral sirolimus on day 1 followed by 5 mg/m2/day for 13 days. The next 17 patients received either 5 (n=7) or 4 (n=10) mg/m2/day for 14 days without a loading dose. Eleven patients completed the 14-day sirolimus course. Five patients were treated for 9-13 days, two for 6 days, and three for 1-3 days. Results. Sirolimus was discontinued early in 10 patients because of lack of improvement in GVHD (n=5), myelosuppression (n=2), seizure (n=2), and attending physician preference (n=1). The most common and significant adverse events were thrombocytopenia (n=7) and neutropenia (n=4). Other side effects included increased blood triglycerides (n = 8) and cholesterol (n=3). Five patients had evidence of a hemolytic uremic syndrome concurrently with or after sirolimus treatment. Eighteen of the 21 patients received 6 or more doses of sirolimus and 12 responded, 5 with complete and 7 with partial responses. Six of the 12 responders (28% of all patients enrolled) and 1 nonresponder are currently alive at 400-907 days after HSCT, 3 with chronic GVHD. Fourteen of the 21 patients (66%) died 40-263 days after transplant. Conclusion. These data suggest that sirolimus has activity in the treatment of steroid-refractory acute GVHD. However, there was considerable toxicity and further dose optimization studies seem warranted.

Authors
Benito, AI; Furlong, T; Martin, PJ; Anasetti, C; Appelbaum, FR; Doney, K; Nash, RA; Papayannopoulou, T; Storb, R; Sullivan, KM; Witherspoon, R; Deeg, HJ
MLA Citation
Benito, AI, Furlong, T, Martin, PJ, Anasetti, C, Appelbaum, FR, Doney, K, Nash, RA, Papayannopoulou, T, Storb, R, Sullivan, KM, Witherspoon, R, and Deeg, HJ. "Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease." Transplantation 72.12 (2001): 1924-1929.
PMID
11773890
Source
scival
Published In
Transplantation
Volume
72
Issue
12
Publish Date
2001
Start Page
1924
End Page
1929

Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: Procedure related mortality and impact on skin disease

Background - Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. Methods - Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being <70% of the predicted value in 18/36 (50%). Pulmonary hypertension was described in 7/37 (19%) patients and renal disease in 5/37 (14%). The Scl-70 antibody was positive in 18/32 (56%) and the anticentromere antibody in 10% of evaluable patients. Peripheral blood stem cell mobilisation was performed with cyclophosphamide or granulocyte colony stimulating factor, alone or in combination. Thirty eight patients had ex vivo CD34 stem cell selection, with additional T cell depletion in seven. Seven conditioning regimens were used, but six of these used haemoimmunoablative doses of cyclophosphamide +/- anti-thymocyte globulin +/- total body irradiation. The median duration of follow up was 12 months (3-55). Results - An improvement in skin score of >25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. Conclusion - Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

Authors
Binks, M; Passweg, JR; Furst, D; McSweeney, P; Sullivan, K; Besenthal, C; Finke, J; Peter, HH; Laar, JV; Breedveld, FC; Fibbe, WE; Farge, D; Gluckman, E; Locatelli, F; Martini, A; Hoogen, FVD; Putte, LVD; Schattenberg, AVN; Arnold, R; Bacon, PA; Emery, P; Espigado, I; Hertenstein, B; Hiepe, F; Kashyap, A; Kötter, I; Marmont, A; Martinez, A; Pascual, MJ; Gratwohl, A; Prentice, HG; Black, C; Tyndall, A
MLA Citation
Binks, M, Passweg, JR, Furst, D, McSweeney, P, Sullivan, K, Besenthal, C, Finke, J, Peter, HH, Laar, JV, Breedveld, FC, Fibbe, WE, Farge, D, Gluckman, E, Locatelli, F, Martini, A, Hoogen, FVD, Putte, LVD, Schattenberg, AVN, Arnold, R, Bacon, PA, Emery, P, Espigado, I, Hertenstein, B, Hiepe, F, Kashyap, A, Kötter, I, Marmont, A, Martinez, A, Pascual, MJ, Gratwohl, A, Prentice, HG, Black, C, and Tyndall, A. "Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: Procedure related mortality and impact on skin disease." Annals of the Rheumatic Diseases 60.6 (2001): 577-584.
PMID
11350846
Source
scival
Published In
Annals of the rheumatic diseases
Volume
60
Issue
6
Publish Date
2001
Start Page
577
End Page
584
DOI
10.1136/ard.60.6.577

High-dose immunosuppressive therapy (HDIT) and autologous stem cell transplant for severe systemic sclerosis (SSc).

Authors
McSweeney, PA; Furst, DE; Nash, RA; Holmberg, L; McDonagh, K; Crofford, L; Dansey, R; Mayes, M; Storek, J; Viganego, F; Agee, G; Ryan, K; Sullivan, KM
MLA Citation
McSweeney, PA, Furst, DE, Nash, RA, Holmberg, L, McDonagh, K, Crofford, L, Dansey, R, Mayes, M, Storek, J, Viganego, F, Agee, G, Ryan, K, and Sullivan, KM. "High-dose immunosuppressive therapy (HDIT) and autologous stem cell transplant for severe systemic sclerosis (SSc)." BLOOD 96.11 (November 16, 2000): 844A-844A.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
844A
End Page
844A

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) after high-dose immunosuppressive therapy (HDIT) and autologous CD34-selected stem cell transplantation (SCT) for severe autoimmune diseases.

Authors
Nash, RA; Dansey, R; Storek, J; Sullivan, KM; Pavletic, S; McDonagh, KT; Kraft, GH; Mayes, MD; Forman, SJ; Holmberg, LA; McSweeney, PA
MLA Citation
Nash, RA, Dansey, R, Storek, J, Sullivan, KM, Pavletic, S, McDonagh, KT, Kraft, GH, Mayes, MD, Forman, SJ, Holmberg, LA, and McSweeney, PA. "Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) after high-dose immunosuppressive therapy (HDIT) and autologous CD34-selected stem cell transplantation (SCT) for severe autoimmune diseases." BLOOD 96.11 (November 16, 2000): 406A-406A.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
406A
End Page
406A

Treatment of severe multiple sclerosis (MS) with high-dose immunosuppressive therapy (HDIT) and autologous stem cell transplantation (SCT).

Authors
Nash, RA; Kraft, GH; Bowen, JD; McSweeney, PA; Pavletic, S; Al-Omaishi, J; Corboy, JR; Holmberg, LA; Openshaw, H; Prather, K; Ryan, K; Storek, J; Zunt, JR; Sullivan, KM
MLA Citation
Nash, RA, Kraft, GH, Bowen, JD, McSweeney, PA, Pavletic, S, Al-Omaishi, J, Corboy, JR, Holmberg, LA, Openshaw, H, Prather, K, Ryan, K, Storek, J, Zunt, JR, and Sullivan, KM. "Treatment of severe multiple sclerosis (MS) with high-dose immunosuppressive therapy (HDIT) and autologous stem cell transplantation (SCT)." BLOOD 96.11 (November 16, 2000): 842A-843A.
Source
wos-lite
Published In
Blood
Volume
96
Issue
11
Publish Date
2000
Start Page
842A
End Page
843A

Impact of a randomized, controlled trial of liberal vs conservative hospital discharge criteria on energy, protein, and fluid intake in patients who received marrow transplants.

OBJECT: To determine if adult patients who received marrow transplants had faster resumption of oral energy and nutrient intake and shorter duration of intravenous (i.v.) fluid requirement if discharged from the hospital earlier than is customary. DESIGN: Randomized, controlled trial of patients remaining hospitalized because of inadequate oral intake. Consenting patients were assigned randomly to remain hospitalized (hospital group) or be discharged to an ambulatory setting (ambulatory group). SUBJECTS: Seventy-eight patients of the Fred Hutchinson Cancer Research Center who were consuming less than 33% of estimated energy requirement and requiring up to 3,000 mL of fluids per day intravenously. INTERVENTION: Participants received nutrition counseling by a registered dietitian to promote resumption of oral intake. Daily oral intake records were analyzed to determine energy and nutrient content. MAIN OUTCOME MEASURES: Days after study enrollment to consume 33% of energy and protein requirements and total number of days of i.v. fluid support were analyzed by group until discharge from the center, approximately 100 days after transplantation. STATISTICAL ANALYSES: Demographic data were defined by group means. Differences between treatment procedures were determined by Cox regression analysis. No variables were confounding. RESULTS: The hospital group took fewer days than the ambulatory group to resume oral energy intake (4.5 vs 8.0, P = .004) and to discontinue i.v. fluids (30.5 vs 48.5, P = .019). There was no difference between groups in days of parenteral nutrition support (P = .817) or days to resume oral protein intake (P = .470). APPLICATIONS/CONCLUSIONS: Oral and gastrointestinal complications delay resumption of oral energy and protein intakes after transplantation. Earlier hospital discharge can achieve cost savings but may delay resumption of oral energy intake. Because of continued high-risk nutrition status and potential for rapid change in medical status, nutrition assessment and counseling are necessary in both the hospital and ambulatory setting to promote resumption of oral intake and discontinuation of i.v. fluids.

Authors
Stern, JM; Bruemmer, B; Moinpour, CM; Sullivan, KM; Lenssen, P; Aker, SN
MLA Citation
Stern, JM, Bruemmer, B, Moinpour, CM, Sullivan, KM, Lenssen, P, and Aker, SN. "Impact of a randomized, controlled trial of liberal vs conservative hospital discharge criteria on energy, protein, and fluid intake in patients who received marrow transplants." J Am Diet Assoc 100.9 (September 2000): 1015-1022.
PMID
11019348
Source
pubmed
Published In
Journal of the American Dietetic Association
Volume
100
Issue
9
Publish Date
2000
Start Page
1015
End Page
1022

Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease.

Fifty children who had symptomatic sickle cell disease received matched sibling marrow allografts between September 1991 and March 1999, with Kaplan-Meier probabilities of survival and event-free survival of 94% and 84%, respectively. Twenty-six patients (16 male, 10 female) had at least 2 years of follow-up after transplantation and were evaluated for late effects of transplantation and for its impact on sickle cell-related central nervous system (CNS) and pulmonary disease. Patients ranged between 3.3 and 14.0 (median, 9. 4) years of age and had a median follow-up of 57.9 (range 38-95) months after transplantation. Among 22 of 26 patients who had stable donor engraftment, complications related to sickle cell disease resolved, and none experienced further episodes of pain, stroke, or acute chest syndrome. All 10 engrafted patients with a prior history of stroke had stable or improved cerebral magnetic resonance imaging results. Pulmonary function tests were stable in 22 of the 26 patients, worse in two, and not studied in two. Seven of eight patients transplanted for recurrent acute chest syndrome had stable pulmonary function. Linear growth measured by median height standard deviation score improved from -0.7 before transplantation to -0.2 after transplantation. An adverse effect of busulfan conditioning on ovarian function was demonstrated in five of seven evaluable females who are currently at least 13 years of age. None of the four males tested had elevated serum gonadotropin levels. These data confirm that allogenic bone marrow transplantation establishes normal erythropoiesis and is associated with improved growth and stable CNS imaging and pulmonary function in most patients. (Blood. 2000;95:1918-1924)

Authors
Walters, MC; Storb, R; Patience, M; Leisenring, W; Taylor, T; Sanders, JE; Buchanan, GE; Rogers, ZR; Dinndorf, P; Davies, SC; Roberts, IA; Dickerhoff, R; Yeager, AM; Hsu, L; Kurtzberg, J; Ohene-Frempong, K; Bunin, N; Bernaudin, F; Wong, WY; Scott, JP; Margolis, D; Vichinsky, E; Wall, DA; Wayne, AS; Pegelow, C; Redding-Lallinger, R; Wiley, J; Klemperer, M; Mentzer, WC; Smith, FO; Sullivan, KM
MLA Citation
Walters, MC, Storb, R, Patience, M, Leisenring, W, Taylor, T, Sanders, JE, Buchanan, GE, Rogers, ZR, Dinndorf, P, Davies, SC, Roberts, IA, Dickerhoff, R, Yeager, AM, Hsu, L, Kurtzberg, J, Ohene-Frempong, K, Bunin, N, Bernaudin, F, Wong, WY, Scott, JP, Margolis, D, Vichinsky, E, Wall, DA, Wayne, AS, Pegelow, C, Redding-Lallinger, R, Wiley, J, Klemperer, M, Mentzer, WC, Smith, FO, and Sullivan, KM. "Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease." Blood 95.6 (March 15, 2000): 1918-1924.
PMID
10706855
Source
pubmed
Published In
Blood
Volume
95
Issue
6
Publish Date
2000
Start Page
1918
End Page
1924

New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia.

PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. PATIENTS AND METHODS: We studied a cohort of 3, 182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression. RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P <.001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7. 5), T-cell-depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). CONCLUSION: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.

Authors
Socié, G; Curtis, RE; Deeg, HJ; Sobocinski, KA; Filipovich, AH; Travis, LB; Sullivan, KM; Rowlings, PA; Kingma, DW; Banks, PM; Travis, WD; Witherspoon, RP; Sanders, J; Jaffe, ES; Horowitz, MM
MLA Citation
Socié, G, Curtis, RE, Deeg, HJ, Sobocinski, KA, Filipovich, AH, Travis, LB, Sullivan, KM, Rowlings, PA, Kingma, DW, Banks, PM, Travis, WD, Witherspoon, RP, Sanders, J, Jaffe, ES, and Horowitz, MM. "New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia." J Clin Oncol 18.2 (January 2000): 348-357.
PMID
10637249
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
18
Issue
2
Publish Date
2000
Start Page
348
End Page
357
DOI
10.1200/JCO.2000.18.2.348

Conditional and unconditional estimation of multidimensional quality of life after hematopoietic stem cell transplantation: a longitudinal follow-up of 415 patients.

Emerging literature suggests that quality of life (QOL) after bone marrow transplantation is relatively good but is accompanied in some patients by a variety of residual difficulties. The studies supporting this finding, however, have been somewhat limited in scale, scope, design, and analysis. We comprehensively measured changes in multidimensional QOL in a 4-year longitudinal follow-up of 415 adult patients who received hematopoietic stem cell transplants at Fred Hutchinson Cancer Research Center. Questionnaire packets containing 271 items were mailed annually posttransplantation to patients' homes. Standard methods of analysis yielded conditional estimates depending on compliance and survival, whereas new, likelihood-based methods generated unconditional estimates applicable to the full intent-to-treat population. Typical QOL levels generally remained high over the entire study period. Most QOL functioning significantly improved over 4 years, with the remainder showing no important decrement. Although isolated problem areas, such as sexual dissatisfaction, did emerge, the level of dysfunction for most physical and psychological scales remained below 30% of scale maxima. Broadly similar results were obtained for conditional estimation, which may contain an optimistic bias, and for unconditional estimation, which largely avoids the bias. Because concurrence was obtained between the 2 types of estimation, we conclude that most patients really do experience good levels of QOL in the 4 years after transplantation. Although some problems can be anticipated, typical patients can look forward to a QOL after transplantation that is broadly comparable to that of the normal population.

Authors
Bush, NE; Donaldson, GW; Haberman, MH; Dacanay, R; Sullivan, KM
MLA Citation
Bush, NE, Donaldson, GW, Haberman, MH, Dacanay, R, and Sullivan, KM. "Conditional and unconditional estimation of multidimensional quality of life after hematopoietic stem cell transplantation: a longitudinal follow-up of 415 patients." Biol Blood Marrow Transplant 6.5A (2000): 576-591.
PMID
11071263
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
6
Issue
5A
Publish Date
2000
Start Page
576
End Page
591

Bone Marrow Transplantation for Non-Malignant Disease.

This article reviews the experience in hematopoietic stem cell transplantation (HSCT) for non-malignant disease. HSCT has long been applied as treatment of life-threatening congenital immunodeficiency and metabolic diseases. In Section I, Dr. Parkman reviews that experience for severe combined immunodeficiency, Wiscott-Aldrich syndrome, hyper IGM syndrome, Chédiak-Higashi disease and hereditary lymphohistiocytosis. The value of HSCT in genetic metabolic diseases such as osteopetrosis, osteogenesis imperfecta and the storage diseases are reviewed. In Section II, Dr. Walters reviews the experience over the last decade with allogeneic stem cell transplantation in patients with thalassemia major and sickle cell disease. In Section III, Dr. Sullivan reviews the more recent investigations using stem cell transplantation in patients with advanced autoimmune diseases such as systemic sclerosis, systemic lupus erythematosus, multiple sclerosis and juvenile rheumatoid arthritis. The pathogenesis and outcome with conventional care of these patients, the selection criteria and current results for HSCT, and the future directions in clinical research and patient care using this modality are addressed.

Authors
Sullivan, KM; Parkman, R; Walters, MC
MLA Citation
Sullivan, KM, Parkman, R, and Walters, MC. "Bone Marrow Transplantation for Non-Malignant Disease." Hematology Am Soc Hematol Educ Program (2000): 319-338.
PMID
11701549
Source
pubmed
Published In
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
Publish Date
2000
Start Page
319
End Page
338

Impact of bone marrow transplantation for symptomatic sickle cell disease: An interim report

Fifty children who had symptomatic sickle cell disease received matched sibling marrow allografts between September 1991 and March 1999, with Kaplan- Meier probabilities of survival and event-free survival of 94% and 84%, respectively. Twenty-six patients (16 male, 10 female) had at least 2 years of follow-up after transplantation and were evaluated for late effects of transplantation and for its impact on sickle cell-related central nervous system (CNS) and pulmonary disease. Patients ranged between 3.3 and 14.0 (median, 9.4) years of age and had a median follow-up of 57.9 (range 38-95) months after transplantation. Among 22 of 26 patients who had stable donor engraftment, complications related to sickle cell disease resolved, and none experienced further episodes of pain, stroke, or acute chest syndrome. All 10 engrafted patients with a prior history of stroke had stable or improved cerebral magnetic resonance imaging results. Pulmonary function tests were stable in 22 of the 26 patients, worse in two, and not studied in two. Seven of eight patients transplanted for recurrent acute chest syndrome had stable pulmonary function. Linear growth measured by median height standard deviation score improved from -0.7 before transplantation to -0.2 after transplantation. An adverse effect of busulfan conditioning on ovarian function was demonstrated in five of seven evaluable females who are currently at least 13 years of age. None of the four males tested had elevated serum gonadotropin levels. These data confirm that allogenic bone marrow transplantation establishes normal erythropoiesis and is associated with improved growth and stable CNS imaging and pulmonary function in most patients. (C) 2000 by The American Society of Hematology.

Authors
Walters, MC; Storb, R; Patience, M; Leisenring, W; Taylor, T; Sanders, JE; Buchanan, GE; Rogers, ZR; Dinndorf, P; Davies, SC; Roberts, IAG; Dickerhoff, R; Yeager, AM; Lewis, H; Kurtzberg, J; Ohene-Frempong, K; Bunin, N; Bernaudin, F; Wong, W-Y; Scott, JP; Margolis, D; Vichinsky, E; Wall, DA; Wayne, AS; Pegelow, C; Redding-Lallinger, R; Wiley, J; Klemperer, M; Mentzer, WC; Smith, FO; Sullivan, KM
MLA Citation
Walters, MC, Storb, R, Patience, M, Leisenring, W, Taylor, T, Sanders, JE, Buchanan, GE, Rogers, ZR, Dinndorf, P, Davies, SC, Roberts, IAG, Dickerhoff, R, Yeager, AM, Lewis, H, Kurtzberg, J, Ohene-Frempong, K, Bunin, N, Bernaudin, F, Wong, W-Y, Scott, JP, Margolis, D, Vichinsky, E, Wall, DA, Wayne, AS, Pegelow, C, Redding-Lallinger, R, Wiley, J, Klemperer, M, Mentzer, WC, Smith, FO, and Sullivan, KM. "Impact of bone marrow transplantation for symptomatic sickle cell disease: An interim report." Blood 95.6 (2000): 1918-1924.
Source
scival
Published In
Blood
Volume
95
Issue
6
Publish Date
2000
Start Page
1918
End Page
1924

Managing Personnel through Staff Scheduling Algorithms

This article presents a literature review of the current state of staff scheduling, in particular nurse scheduling. In current health care service, the critical problem in nurse scheduling in a hospital is how to determine day-to-day shift assignments of each nurse for a period of time in a way that satisfies the given requirements of a hospital. As a basis, the formal analysis of the problem is performed and a general scheduling procedure was established. Based on the method, a word processing template or software system which produces a scheduling program for a given institution was developed. Another objective of scheduling is optimization. Optimization of personnel scheduling consists of the selection of those work patterns that meet total work requirements at the lowest cost. Various approaches to alleviate the scheduling quagmire while attaining optimization are presented in this paper. Analysis of each of these approaches along with their effectiveness is presented. We anticipate that one of these approaches researched will provide the backbone to develop a system suitable for use at Duke University's medical oncology department.

Authors
Naidu, KD; Sullivan, KM; Wang, PP; Yang, Y
MLA Citation
Naidu, KD, Sullivan, KM, Wang, PP, and Yang, Y. "Managing Personnel through Staff Scheduling Algorithms." Proceedings of the Joint Conference on Information Sciences 5.2 (2000): 829-835.
Source
scival
Published In
Proceedings of the Joint Conference on Information Sciences
Volume
5
Issue
2
Publish Date
2000
Start Page
829
End Page
835

Research on Medical Informatics and Telemedicine

This paper addresses concisely the approach taken to research the area of Medical Informatics for the Oncology Department at Duke University Medical Center. The basic ideas behind medical informatics and telemedicine will be presented and how both are related to each other. Also how these research efforts will be approached from the researchers at Duke University.

Authors
Wang, PP; Sullivan, KM; Naidu, KD; Yang, Y
MLA Citation
Wang, PP, Sullivan, KM, Naidu, KD, and Yang, Y. "Research on Medical Informatics and Telemedicine." Proceedings of the Joint Conference on Information Sciences 5.2 (2000): 827-828.
Source
scival
Published In
Proceedings of the Joint Conference on Information Sciences
Volume
5
Issue
2
Publish Date
2000
Start Page
827
End Page
828

Conditional and Unconditional Estimation of Multidimensional Quality of Life after Hematopoietic Stem Cell Transplantation: A Longitudinal Follow-up of 415 Patients

Emerging literature suggests that quality of life (QOL) after bone marrow transplantation is relatively good but is accompanied in some patients by a variety of residual difficulties. The studies supporting this finding, however, have been somewhat limited in scale, scope, design, and analysis. We comprehensively measured changes in multi-dimensional QOL in a 4-year longitudinal follow-up of 415 adult patients who received hematopoietic stem cell transplants at Fred Hutchinson Cancer Research Center. Questionnaire packets containing 271 items were mailed annually posttransplantation to patients' homes. Standard methods of analysis yielded conditional estimates depending on compliance and survival, whereas new, likelihood-based methods generated unconditional estimates applicable to the full intent-to-treat population. Typical QOL levels generally remained high over the entire study period. Most QOL functioning significantly improved over 4 years, with the remainder showing no important decrement. Although isolated problem areas, such as sexual dissatisfaction, did emerge, the level of dysfunction for most physical and psychological scales remained below 30% of scale maxima. Broadly similar results were obtained for conditional estimation, which may contain an optimistic bias, and for unconditional estimation, which largely avoids the bias. Because concurrence was obtained between the 2 types of estimation, we conclude that most patients really do experience good levels of QOL in the 4 years after transplantation. Although some problems can be anticipated, typical patients can look forward to a QOL after transplantation that is broadly comparable to that of the normal population.

Authors
Bush, NE; Donaldson, GW; Haberman, MH; Dacanay, R; Sullivan, KM
MLA Citation
Bush, NE, Donaldson, GW, Haberman, MH, Dacanay, R, and Sullivan, KM. "Conditional and Unconditional Estimation of Multidimensional Quality of Life after Hematopoietic Stem Cell Transplantation: A Longitudinal Follow-up of 415 Patients." Biology of Blood and Marrow Transplantation 6.5 A (2000): 576-591.
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
6
Issue
5 A
Publish Date
2000
Start Page
576
End Page
591

Applications of Computer Simulation in Medical Scheduling

In current health care service, it's important to minimize staff idle time and maintain a high utilization rate of the medical facilities. More and more hospitals, however, recognize waiting is a universal and serious problem for patients. The critical problem in medical scheduling is how to keep the balance of all these factors. Computer simulation is a powerful tool for medical management and scheduling. This paper presents a literature review of the current state of computer simulation in medical scheduling. Various approaches to simulate the operations in medical area, as well as analysis of these approaches along with their effectiveness are presented in this paper. We anticipate such a survey would help us to develop a computer simulation system for use at Duke University's medical oncology department.

Authors
Yang, Y; Sullivan, KM; Wang, PP; Naidu, KD
MLA Citation
Yang, Y, Sullivan, KM, Wang, PP, and Naidu, KD. "Applications of Computer Simulation in Medical Scheduling." Proceedings of the Joint Conference on Information Sciences 5.2 (2000): 836-841.
Source
scival
Published In
Proceedings of the Joint Conference on Information Sciences
Volume
5
Issue
2
Publish Date
2000
Start Page
836
End Page
841

Late effects of hematopoietic stem cell transplantation

Authors
Kansu, E; Sullivan, KM
MLA Citation
Kansu, E, and Sullivan, KM. "Late effects of hematopoietic stem cell transplantation." Hematology 5.3 (2000): 209-222.
Source
scival
Published In
Hematology
Volume
5
Issue
3
Publish Date
2000
Start Page
209
End Page
222

Clinical outcome after conversion to FK 506 (tacrolimus) therapy for acute graft-versus-host disease resistant to cyclosporine or for cyclosporine-associated toxicities

This retrospective study describes the outcome in 53 patients who had immunosuppressive treatment changed from cyclosporine (CSP) to tacrolimus for resistant acute GVHD (n = 23), hemolytic uremic syndrome (HUS) (n = 13) or CSP-associated neurotoxicity (n = 17). Tacrolimus was administered at doses of 0.03 mg/kg/day intravenously or 0.12 mg/kg/day orally in divided doses, as tolerated. Median time of conversion to tacrolimus after transplant was day 47. Nineteen patients had treatment changed to tacrolimus for resistant acute GVHD grades III or IV, with the median day of conversion being day 49 after transplant. Two of 20 evaluable patients had a complete resolution of GVHD after changing treatment to tacrolimus, with 18 showing no improvement. Eleven evaluable patients had therapy changed to tacrolimus for CSP-associated neurotoxicity at a median of 36 days after transplant. Eight patients had resolution of neurotoxicity and three had partial improvement. Eleven evaluable patients had therapy changed to tacrolimus for HUS at a median of 46 days after transplant. One patient had complete resolution of HUS and 10 showed no response. Side-effects related to tacrolimus included renal toxicity (34%), neurotoxicity (15%) and HUS (9%). Nine (17%) patients remain alive, including six patients who had therapy changed to tacrolimus for CSP-associated neurotoxicity. While often successful for dealing with neurotoxicity, only a rare patient improved after therapy was changed from CSP to tacrolimus for HUS or resistant acute GVHD.

Authors
Furlong, T; Storb, R; Anasetti, C; Appelbaum, FR; Deeg, HJ; Doney, K; Martin, P; Sullivan, K; Witherspoon, R; Nash, RA
MLA Citation
Furlong, T, Storb, R, Anasetti, C, Appelbaum, FR, Deeg, HJ, Doney, K, Martin, P, Sullivan, K, Witherspoon, R, and Nash, RA. "Clinical outcome after conversion to FK 506 (tacrolimus) therapy for acute graft-versus-host disease resistant to cyclosporine or for cyclosporine-associated toxicities." Bone Marrow Transplantation 26.9 (2000): 985-991.
PMID
11100278
Source
scival
Published In
Bone Marrow Transplantation
Volume
26
Issue
9
Publish Date
2000
Start Page
985
End Page
991

Changing from Cyclosporine to Tacrolimus as Salvage Therapy for Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (GVHD) is the principal cause of transplantation-related morbidity and nonrelapse mortality late after allogeneic hematopoietic stem cell transplantation. The safety and potential efficacy of tacrolimus for the salvage treatment of chronic GVHD was evaluated in a single-arm, open-label phase 2 study. A total of 39 evaluable patients with chronic GVHD who failed previous immunosuppressive therapy with cyclosporine and prednisone were treated with tacrolimus starting at a median of 20 months (range, 3-68 months) after transplantation. At 3 years after the start of treatment, 5 patients (13%) had discontinued tacrolimus and were in complete remission, and 3 were considered clinically stable but not able to discontinue tacrolimus. A total of 31 patients (79%) experienced treatment failure; 22 (56%) who failed therapy had a change in immunosuppressive regimen because of progression (n = 18) or toxicity (n = 4). Nine patients (23%) died during continued treatment with tacrolimus. Two patients were lost to follow-up, at 11 and 19 months. The median duration of treatment with tacrolimus was 9 months (range, 1-29 months). Infections (144 episodes) were the most frequent adverse event. Nephrotoxicity occurred in 16 patients (41%); tacrolimus was discontinued in only 2 patients because of progressive deterioration in renal function. The Kaplan-Meier estimate of survival was 64% (95% confidence interval, 49%-79%) at 3 years posttransplantation. Seven patients had discontinued all immunosuppression at last contact, leading to an estimated 29% probability of stopping all immunosuppression by 3 years posttransplantation. Four patients died after relapse of malignancy. The response rate is consistent with previous reports of salvage treatment for chronic GVHD, indicating that a small group of patients failing cyclosporine may respond or stabilize with tacrolimus.

Authors
Carnevale-Schianca, F; Martin, P; Sullivan, K; Flowers, M; Gooley, T; Anasetti, C; Deeg, J; Furlong, T; McSweeney, P; Storb, R; Nash, RA
MLA Citation
Carnevale-Schianca, F, Martin, P, Sullivan, K, Flowers, M, Gooley, T, Anasetti, C, Deeg, J, Furlong, T, McSweeney, P, Storb, R, and Nash, RA. "Changing from Cyclosporine to Tacrolimus as Salvage Therapy for Chronic Graft-Versus-Host Disease." Biology of Blood and Marrow Transplantation 6.6 (2000): 613-620.
PMID
11128811
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
6
Issue
6
Publish Date
2000
Start Page
613
End Page
620

Stable mixed chimerism after bone marrow transplantation (BMT) for Sickle Cell Disease (SCD).

Authors
Walters, MC; Storb, R; Patience, M; Rogers, ZR; Buchanan, GR; Roberts, I; Ogden, A; Wiley, JM; Kurtzberg, J; Vichinsky, E; Sullivan, KM
MLA Citation
Walters, MC, Storb, R, Patience, M, Rogers, ZR, Buchanan, GR, Roberts, I, Ogden, A, Wiley, JM, Kurtzberg, J, Vichinsky, E, and Sullivan, KM. "Stable mixed chimerism after bone marrow transplantation (BMT) for Sickle Cell Disease (SCD)." BLOOD 94.10 (November 15, 1999): 645A-645A.
Source
wos-lite
Published In
Blood
Volume
94
Issue
10
Publish Date
1999
Start Page
645A
End Page
645A

Evaluation of thalidomide for the treatment of chronic graft-versus-host disease in "high risk" patients.

Authors
Koc, S; Leisenring, W; Flowers, ME; Sullivan, KM; Martin, PJ
MLA Citation
Koc, S, Leisenring, W, Flowers, ME, Sullivan, KM, and Martin, PJ. "Evaluation of thalidomide for the treatment of chronic graft-versus-host disease in "high risk" patients." BLOOD 94.10 (November 15, 1999): 158A-158A.
Source
wos-lite
Published In
Blood
Volume
94
Issue
10
Publish Date
1999
Start Page
158A
End Page
158A

Cirrhosis of the liver in long-term marrow transplant survivors.

Patients who survive hematopoietic cell transplantation (HCT) have multiple risk factors for chronic liver disease, including hepatitis virus infection, iron overload, and chronic graft-versus-host disease (GVHD). We studied 3,721 patients who had survived 1 or more years after HCT at a single center and identified patients with histologic or clinical evidence of cirrhosis. Risk factors for the development of cirrhosis were evaluated and compared with a group of matched control subjects. Cirrhosis was identified in 31 of 3,721 patients surviving 1 or more years after HCT, 23 of 1,850 patients surviving 5 or more years, and in 19 of 860 patients surviving 10 or more years. Cumulative incidence after 10 years was estimated to be 0.6% and after 20 years was 3.8%. The median time from HCT to the diagnosis of cirrhosis was 10.1 years (range, 1.2 to 24.9 years). Twenty-three patients presented with complications of portal hypertension, and 1 presented with hepatocellular carcinoma. Thirteen patients have died from complications of liver disease, and 2 died of other causes. Three patients have undergone orthotopic liver transplantation. Hepatitis C virus infection was present in 25 of 31 (81%) of patients with cirrhosis and in 14 of 31 (45%) of controls (P =.01). Cirrhosis was attibutable to hepatitis C infection in 15 of 16 patients presenting more than 10 years after HCT. There was no difference in the prevalence of acute or chronic GVHD, duration of posttransplant immunosuppression, or posttransplant marrow iron stores between cases and controls. Cirrhosis is an important late complication of hematopoietic cell transplantation and in most cases is due to chronic hepatitis C. Long-term survivors should be evaluated for the presence of abnormal liver function and hepatitis virus infection.

Authors
Strasser, SI; Sullivan, KM; Myerson, D; Spurgeon, CL; Storer, B; Schoch, HG; Murakami, CS; McDonald, GB
MLA Citation
Strasser, SI, Sullivan, KM, Myerson, D, Spurgeon, CL, Storer, B, Schoch, HG, Murakami, CS, and McDonald, GB. "Cirrhosis of the liver in long-term marrow transplant survivors." Blood 93.10 (May 15, 1999): 3259-3266.
PMID
10233877
Source
pubmed
Published In
Blood
Volume
93
Issue
10
Publish Date
1999
Start Page
3259
End Page
3266

Reduced dose intravenous immunoglobulin does not decrease transplant-related complications in adults given related donor marrow allografts.

Graft-vs.-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Intravenous immunoglobulin (IVIg) given at a dose of 500 mg/kg/wk has been shown to decrease the risk of acute GVHD, interstitial pneumonia, and infection in adults early after allogeneic transplantation. The current study is a controlled trial to determine whether a lower total dose of IVIg given with pretransplant loading reduces the incidence of transplant-related complications. In a randomized trial of 241 patients > or =20 years of age who were given related donor marrow allografts, 121 individuals receiving Ig prophylaxis (500 mg/kg/d loading from day -6 to -1 and then 100 mg/kg every 3 days from day 3 to 90) were compared with 120 control patients who did not receive IVIg. Randomization was stratified by human leucocyte antigen-matching, remission status of malignancy, GVHD prophylaxis, and cytomegalovirus (CMV) serology. The study was powered to detect a reduction in acute GVHD by 18% and a decrease in transplant-related mortality by 17%. Pretransplant IVIg loading and posttransplant maintenance achieved median serum IgG levels >1350 mg/dL, which were approximately twofold greater than the untreated controls (p<0.01). White blood cell and platelet recoveries were similar for the two groups, although control patients required fewer units of platelets per day (2.5 vs. 3.3, p = 0.008). No significant differences in the incidence of CMV infection, interstitial pneumonia, or bacteremia were observed. The incidence of acute GVHD did not differ between the two groups; however, acute GVHD was less frequent among IVIg recipients achieving maximum serum IgG levels >3000 mg/dL (60 vs. 79%). Neither transplant-related mortality nor disease-free survival was significantly altered by Ig prophylaxis. However, the cumulative incidence of relapse of malignancy was higher in IVIg recipients than in controls (31 vs. 18%, p = 0.03). Multivariable regression analysis demonstrated a 1.89 increased relative risk of relapse for individuals given IVIg (p = 0.021). We conclude that pretransplant loading and a shorter course and lower total dose of IVIg prophylaxis did not appear to decrease the risk of acute GVHD or mortality among adults receiving related donor marrow transplants. Note, IVIg administration may be associated with an increased risk of recurrent malignancy, a finding that warrants further investigation.

Authors
Feinstein, LC; Seidel, K; Jocum, J; Bowden, RA; Anasetti, C; Deeg, HJ; Flowers, ME; Kansu, E; Martin, PJ; Nash, RA; Storek, J; Etzioni, R; Applebaum, FR; Hansen, JA; Storb, R; Sullivan, KM
MLA Citation
Feinstein, LC, Seidel, K, Jocum, J, Bowden, RA, Anasetti, C, Deeg, HJ, Flowers, ME, Kansu, E, Martin, PJ, Nash, RA, Storek, J, Etzioni, R, Applebaum, FR, Hansen, JA, Storb, R, and Sullivan, KM. "Reduced dose intravenous immunoglobulin does not decrease transplant-related complications in adults given related donor marrow allografts." Biol Blood Marrow Transplant 5.6 (1999): 369-378.
PMID
10595814
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
5
Issue
6
Publish Date
1999
Start Page
369
End Page
378

Physician participation in research surveys. A randomized study of inducements to return mailed research questionnaires

The authors randomly selected 400 physicians from a population of 1,545 practicing physicians providing follow-up care to patients who received bone marrow or blood stem cell transplants at the Fred Hutchinson Cancer Research Center to determine interest in receiving Internet-based transplant information. In a two-factor completely randomized factorial design, the 400 physicians were assigned to receive mailed surveys with either no compensation or a $5 check and either no follow-up call or a follow-up call 3 weeks after mailing. Overall, 51.5% of the physicians returned the mailed surveys. Comparison of logit models showed that inclusion of a $5 check in the mailer significantly (p =. 016) increased the probability of returning the surveys (57.5% vs. 45.5%). In contrast, the telephone follow-up had no overall effect. The authors concluded a modest financial reward can significantly improve physician response rates to research surveys but a telephone follow-up may be inefficient and even ineffective.

Authors
Donaldson, GW; Moinpour, CM; Bush, NE; Chapko, M; Jocom, J; Siadak, M; Nielsen-Stoeck, M; Bradshaw, JM; Bichindaritz, I; Sullivan, KM
MLA Citation
Donaldson, GW, Moinpour, CM, Bush, NE, Chapko, M, Jocom, J, Siadak, M, Nielsen-Stoeck, M, Bradshaw, JM, Bichindaritz, I, and Sullivan, KM. "Physician participation in research surveys. A randomized study of inducements to return mailed research questionnaires." Evaluation and the Health Professions 22.4 (1999): 427-441.
PMID
10623399
Source
scival
Published In
Evaluation & the Health Professions
Volume
22
Issue
4
Publish Date
1999
Start Page
427
End Page
441
DOI
10.1177/01632789922034392

Risk of lymphoproliferative disorders after bone marrow transplantation: A multi-institutional study

We evaluated 18,014 patients who underwent allogeneic bone marrow transplantation (BMT) at 236 centers worldwide to examine the incidence of and risk factors for posttransplant lymphoproliferative disorders (PTLD). PTLD developed in 78 recipients, with 64 cases occurring less than 1 year after transplantation. The cumulative incidence of PTLD was 1.0% ± 0.3% at 10 years. Incidence was highest 1 to 5 months posttransplant (120 cases/10,000 patients/yr) followed by a steep decline to less than 5/10,000/yr among ≥ 1-year survivors. In multivariate analyses, risk of early-onset PTLD (<1 year) was strongly associated (P < .0001) with unrelated or human leukocyte antigen (HLA) mismatched related donor (relative risk [RR] = 4.1), T-cell depletion of donor marrow (RR = 12.7), and use of antithymocyte globulin (RR = 6.4) or anti-CD3 monoclonal antibody (RR = 43.2) for prophylaxis or treatment of acute graft-versus-host disease (GVHD). There was a weaker association with the occurrence of acute GVHD grades II to IV (RR = 1.9, P = .02) and with conditioning regimens that included radiation (RR = 2.9, P = .02). Methods of T-cell depletion that selectively targeted T cells or T plus natural killer (NK) cells were associated with markedly higher risks of PTLD than methods that removed both T and B cells, such as the CAMPATH-1 monoclonal antibody or elutriation (P = .009). The only risk factor identified for late-onset PTLD was extensive chronic GVHD (RR = 4.0, P = .01). Rates of PTLD among patients with 2 or ≥3 major risk factors were 8.0% ± 2.9% and 22% ± 17.9%, respectively. We conclude that factors associated with altered immunity and T-cell regulatory mechanisms are predictors of both early- and late-onset PTLD.

Authors
Curtis, RE; Travis, LB; Rowlings, PA; Socié, G; Kingma, DW; Banks, PM; Jaffe, ES; Sale, GE; Horowitz, MM; Witherspoon, RP; Shriner, DA; Weisdorf, DJ; Kolb, H-J; Sullivan, KM; Sobocinski, KA; Gale, RP; Hoover, RN; Jr, JFF; Deeg, HJ
MLA Citation
Curtis, RE, Travis, LB, Rowlings, PA, Socié, G, Kingma, DW, Banks, PM, Jaffe, ES, Sale, GE, Horowitz, MM, Witherspoon, RP, Shriner, DA, Weisdorf, DJ, Kolb, H-J, Sullivan, KM, Sobocinski, KA, Gale, RP, Hoover, RN, Jr, JFF, and Deeg, HJ. "Risk of lymphoproliferative disorders after bone marrow transplantation: A multi-institutional study." Blood 94.7 (1999): 2208-2216.
PMID
10498590
Source
scival
Published In
Blood
Volume
94
Issue
7
Publish Date
1999
Start Page
2208
End Page
2216

Hepatitis C virus infection and bone marrow transplantation: A cohort study with 10-year follow-up

Before the introduction of routine blood donor screening in 1991, marrow transplant recipients were at significant transfusion-associated risk for infection with hepatitis C virus (HCV). We followed a cohort of 355 patients undergoing transplant in Seattle during 1987 to 1988 to determine (1) the impact of pretransplant HCV infection on the occurrence and severity of venocclusive disease (VOD); (2) the impact of HCV infection on liver dysfunction, other than VOD, occurring between 21 and 60 days after transplantation; and (3) the natural history of post-transplant HCV liver disease with a 10-year follow-up. HCV-RNA status was determined on serum stored before transplant and at day 100 post-transplant. Sixty-two (17%) patients were HCV-RNA positive before transplant, and 113 (32%) were HCV-RNA positive by day 100 post-transplant (or before death). Severe VOD developed in 22 of 46 (48%) evaluable patients with pretransplant HCV infection and in 150 of 229 (14%) evaluable patients without HCV (P < .0001). In multivariable analysis of risk factors for developing VOD, pretransplant HCV infection associated with elevated serum aspartate transaminase (AST) levels predicted the development of severe VOD (relative risk, 9.6; P = .0001). The presence of HCV with normal AST levels before transplant was not a risk factor for severe VOD. Between 21 and 60 days after transplant, HCV-RNA positive- patients had higher AST levels (median 101 U/L), but similar alkaline phosphatase and total bilirubin levels compared with HCV-negative patients, suggesting that cholestatic liver disease (particularly graft-versus-host disease [GVHD]) was not related to HCV infection. An acute flare of hepatitis (AST > 10 times the upper limit of normal) developed at a mean of 136 ± 58 days in 31% of HCV-positive patients; no patients developed fulminant hepatitis. Between 5 and 10 years after transplant, 57% of HCV-positive and 6% of HCV-negative patients had mild to moderate elevations of AST (P < .0001), but HCV infection was not associated with excess mortality between 3 and 10 years after bone marrow transplantation. In summary, HCV infection with elevated AST levels is a significant risk factor for severe VOD after marrow transplant. However, the decision to proceed to transplantation in HCV-positive patients must balance the absolute risk of death from VOD against the risks of the underlying disease. In long-term survivors, HCV infection is not associated with excess mortality over 10 years of follow- up.

Authors
Strasser, SI; Myerson, D; Spurgeon, CL; Sullivan, KM; Storer, B; Schoch, HG; Kim, S; Flowers, MED; McDonald, GB
MLA Citation
Strasser, SI, Myerson, D, Spurgeon, CL, Sullivan, KM, Storer, B, Schoch, HG, Kim, S, Flowers, MED, and McDonald, GB. "Hepatitis C virus infection and bone marrow transplantation: A cohort study with 10-year follow-up." Hepatology 29.6 (1999): 1893-1899.
PMID
10347135
Source
scival
Published In
Hepatology
Volume
29
Issue
6
Publish Date
1999
Start Page
1893
End Page
1899
DOI
10.1002/hep.510290609

Pathophysiology and treatment of graft-versus-host disease

Acute graft-versus-host disease denotes a distinctive syndrome characterized by a triad of dermatitis (rash), hepatitis (jaundice), and gastroenteritis (abdominal pain, diarrhea) developing in the first 100 days after allogeneic hematopoietic cell transplantation. Chronic graft-versus- host disease designates a more diverse syndrome, usually presenting with multiorgan involvement and commonly developing 100 days after hematopoietic cell transplantation. This article discusses the pathophysiology, incidence and predictive factors, clinical manifestations, diagnosis and grading, prevention, and treatment for both types of the disease.

Authors
Flowers, MED; Kansu, E; Sullivan, KM
MLA Citation
Flowers, MED, Kansu, E, and Sullivan, KM. "Pathophysiology and treatment of graft-versus-host disease." Hematology/Oncology Clinics of North America 13.5 (1999): 1091-1112.
PMID
10553263
Source
scival
Published In
Hematology/Oncology Clinics of North America
Volume
13
Issue
5
Publish Date
1999
Start Page
1091
End Page
1112
DOI
10.1016/S0889-8588(05)70111-8

Autologous haematopoietic stem cell transplants for autoimmune disease - Feasibility and transplant-related mortality

This ongoing multicentre prospective phase I/II trial enrolled 74 consecutive patients from 22 centres worldwide with severe autoimmune disease, 35 with rheumatological disorders, 31 with neurological, five with haematological and three with vasculitides. They were treated with autologous peripheral blood or bone marrow transplants according to predetermined criteria. Two patients died after mobilisation before transplant. Seventy-two patients were given 73 transplants, seven bone marrow; and 66 mobilised peripheral blood stem cell transplants. The graft was manipulated to remove T and/or B cells in 43 cases. All 73 transplants engrafted. Five patients died of transplant-related complications: two from bleeding, three from infections, Two patients died of progressive disease. The transplant-related mortality at 1 year of 9% (1-17%; 95% CI) is comparable to the transplant-related mortality of 6% (3-9%; 95% CI) in patients transplanted during the same period in Europe for non-Hodgkin's lymphoma in sensitive relapse (P = 0.39). Sixty patients are evaluable for response, 40 patients (65%) showed some improvement in their disease. Haematopoietic stem cell transplants are feasible for patients with severe refractory autoimmune disease. Transplant-related mortality is comparable to results in patients with non-Hodgkin's lymphoma in responsive relapse. Two-thirds of the patients show at least some response. These preliminary data are promising. Although associated with considerable risk, randomised trials comparing autologous stem cell transplants to conventional therapy are warranted.

Authors
Tyndall, A; Fassas, A; Passweg, J; Elvira, CRD; Attal, M; Brooks, P; Black, C; Durez, P; Finke, J; Forman, S; Fouillard, L; Furst, D; Holmes, JA; Joske, D; Jouet, JP; Kötter, I; Locatelli, F; Prentice, HG; Marmont, AM; McSweeney, P; Musso, M; Peter, HH; Snowden, JA; Sullivan, K; Tichelli, A; Vavriec, J; Wulffraat, NM; Schmitz, N; Gratwohl, A
MLA Citation
Tyndall, A, Fassas, A, Passweg, J, Elvira, CRD, Attal, M, Brooks, P, Black, C, Durez, P, Finke, J, Forman, S, Fouillard, L, Furst, D, Holmes, JA, Joske, D, Jouet, JP, Kötter, I, Locatelli, F, Prentice, HG, Marmont, AM, McSweeney, P, Musso, M, Peter, HH, Snowden, JA, Sullivan, K, Tichelli, A, Vavriec, J, Wulffraat, NM, Schmitz, N, and Gratwohl, A. "Autologous haematopoietic stem cell transplants for autoimmune disease - Feasibility and transplant-related mortality." Bone Marrow Transplantation 24.7 (1999): 729-734.
PMID
10516675
Source
scival
Published In
Bone Marrow Transplantation
Volume
24
Issue
7
Publish Date
1999
Start Page
729
End Page
734

Secure JAVA applets and applications: Guidelines and lessons learnt from the JAVA security model

Authors
Bichindaritz, I; Siadak, MF; Jocom, J; Moinpour, C; Donaldson, G; Bush, N; Chapko, M; Sullivan, KM
MLA Citation
Bichindaritz, I, Siadak, MF, Jocom, J, Moinpour, C, Donaldson, G, Bush, N, Chapko, M, and Sullivan, KM. "Secure JAVA applets and applications: Guidelines and lessons learnt from the JAVA security model." JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION (1999): 1028-1028.
Source
wos-lite
Published In
Journal of American Medical Informatics Association
Publish Date
1999
Start Page
1028
End Page
1028

Long-term follow-Up of a randomized trial of two irradiation regimens for patients receiving allogeneic marrow transplants during first remission of acute myeloid leukemia.

Authors
Clift, RA; Buckner, CD; Appelbaum, FR; Sullivan, KM; Storb, R; Thomas, ED
MLA Citation
Clift, RA, Buckner, CD, Appelbaum, FR, Sullivan, KM, Storb, R, and Thomas, ED. "Long-term follow-Up of a randomized trial of two irradiation regimens for patients receiving allogeneic marrow transplants during first remission of acute myeloid leukemia." Blood 92.4 (August 15, 1998): 1455-1456. (Letter)
PMID
9694737
Source
pubmed
Published In
Blood
Volume
92
Issue
4
Publish Date
1998
Start Page
1455
End Page
1456

Association between pretransplant interferon-alpha and outcome after unrelated donor marrow transplantation for chronic myelogenous leukemia in chronic phase.

Treatment options for patients diagnosed with chronic myelogenous leukemia (CML) in chronic phase (CP) who lack a suitable related donor for marrow transplantation include hydroxyurea, interferon-alpha (IFN-alpha), or transplantation from an unrelated donor (URD). Most studies support the view that treatment with IFN-alpha results in prolonged survival compared with hydroxyurea therapy. Some patients are offered URD transplantation as a second-line treatment; however, the impact of pretransplant IFN-alpha on the outcome of URD transplantation is uncertain. To address this question, we evaluated the effect of pretransplant IFN-alpha therapy in 184 patients undergoing URD transplantation for CML in CP at a single center. Of the 184 patients, 114 did not receive IFN-alpha, whereas 22, 23, and 25 patients received IFN-alpha for, respectively, 1 to 5, 6 to 12, and more than 12 months before transplant. Pretransplant IFN-alpha therapy administered for > or = 6 months was associated with an increased risk of severe (grades III-IV) acute graft-versus-host disease (GVHD; relative risk [RR], 3.0; 95% confidence interval [CI], 1.4 to 6.2; P = .004) and mortality (RR, 2. 1; 95% CI, 1.3 to 3.5; P = .003) relative to less than 6 months or no IFN-alpha therapy. Increased mortality occurred between 100 and 365 days after transplant (P = .005), was limited to patients with severe acute GVHD, and was due to chronic GVHD refractory to immunosuppressive therapy. Other variables associated with mortality included HLA-DRB1 or DQB1 (but not HLA-A or B) mismatched donors, age greater than 50 years, weight > or = 110% of ideal body weight, and the absence of cytomegalovirus (CMV) or fungal prophylaxis. For patients treated with IFN-alpha for less than 6 months before transplant, who were < or = 50 years of age, received a HLA-A, B, DRB1, and DQB1 matched URD transplant, and received CMV and fungal prophylaxis after transplant (n = 48), survival was 87% +/- 5% at 5 years. These data provide a rationale for immediate transplantation in preference to extended treatment with IFN-alpha when the patient is < or = 50 years of age and has an HLA-compatible unrelated volunteer donor.

Authors
Morton, AJ; Gooley, T; Hansen, JA; Appelbaum, FR; Bruemmer, B; Bjerke, JW; Clift, R; Martin, PJ; Petersdorf, EW; Sanders, JE; Storb, R; Sullivan, KM; Woolfrey, A; Anasetti, C
MLA Citation
Morton, AJ, Gooley, T, Hansen, JA, Appelbaum, FR, Bruemmer, B, Bjerke, JW, Clift, R, Martin, PJ, Petersdorf, EW, Sanders, JE, Storb, R, Sullivan, KM, Woolfrey, A, and Anasetti, C. "Association between pretransplant interferon-alpha and outcome after unrelated donor marrow transplantation for chronic myelogenous leukemia in chronic phase." Blood 92.2 (July 15, 1998): 394-401.
PMID
9657736
Source
pubmed
Published In
Blood
Volume
92
Issue
2
Publish Date
1998
Start Page
394
End Page
401

Current and future preparative regimens for bone marrow transplantation in thalassemia.

Preparative regimens for marrow allografts in thalassemia have two objectives. One is eradication of diseased marrow and the other suppression of host-versus-graft (HVG) reactions so that the allograft survives. A common regimen to accomplish these goals has combined high-dose busulfan with cyclophosphamide. Postgrafting immunosuppression with cyclosporine/methotrexate has been used for GVHD prevention. Some patients may die from regimen-related toxicity. Overall event-free survival is 75%. Occasional patients have become mixed donor/host hematopoietic chimeras and, yet, disease symptoms have abated. This has raised the possibility of developing safer and less toxic transplant programs that result in stable mixed hematopoietic chimerism. We have devised such a program in dogs consisting of a nonlethal dose of total body irradiation (200 cGy) before and a novel combination of mycophenolate mofetil and cyclosporine after transplant. Mixed donor/host chimerism (> or = 50% donor cells in all lineages) has persisted for > 80 weeks, even though immunosuppression was discontinued after five weeks.

Authors
Storb, R; Yu, C; Deeg, HJ; Georges, G; Kiem, HP; Mcsweeney, PA; Nash, RA; Sandmaier, BM; Sullivan, KM; Wagner, JL; Walters, MC
MLA Citation
Storb, R, Yu, C, Deeg, HJ, Georges, G, Kiem, HP, Mcsweeney, PA, Nash, RA, Sandmaier, BM, Sullivan, KM, Wagner, JL, and Walters, MC. "Current and future preparative regimens for bone marrow transplantation in thalassemia." Ann N Y Acad Sci 850 (June 30, 1998): 276-287.
PMID
9668549
Source
pubmed
Published In
Annals of the New York Academy of Sciences
Volume
850
Publish Date
1998
Start Page
276
End Page
287

Unrelated and HLA-nonidentical related donor marrow transplantation for thalassemia and leukemia. A combined report from the Seattle Marrow Transplant Team and the International Bone Marrow Transplant Registry.

Allogeneic marrow transplantation is curative therapy for thalassemia, but fewer than 30% of patients have an HLA-identical sibling marrow donor. Selection of alternative donors of hematopoietic stem cells (unrelated individuals or HLA-nonidentical family members) has been aided by establishment of world-wide donor registries now exceeding 3.6 million volunteers and by DNA-based HLA typing to more closely match potential donors. Coupled with improved methods to control graft-versus-host disease and prevent fungal and cytomegalovirus infection, remarkable progress has been made in alternative donor transplantation. For patients 50 years of age or younger, with recently diagnosed chronic myelogenous leukemia (CML) in chronic phase, 1- and 5-year survivals after HLA-A, B, DRB1 identical unrelated marrow transplantation in Seattle are 82% and 74%, respectively. These results are essentially identical to outcome in similar patients given HLA-matched sibling allografts. However, the world-wide number of alternative donor transplants for thalassemia remains limited to date: 4 unrelated and 60 HLA-nonidentical related transplants have been reported to the IBMTR since 1969 with actuarial overall survival of 75%. Using the paradigm of CML, it is likely that access to curative therapy of thalassemia will improve with optimal HLA typing and donor selection early in the course of disease.

Authors
Sullivan, KM; Anasetti, C; Horowitz, M; Rowlings, PA; Petersdorf, EW; Martin, PJ; Clift, RA; Walters, MC; Gooley, T; Sierra, J; Anderson, JE; Bjerke, J; Siadak, M; Flowers, ME; Nash, RA; Sanders, JE; Appelbaum, FR; Storb, R; Hansen, JA
MLA Citation
Sullivan, KM, Anasetti, C, Horowitz, M, Rowlings, PA, Petersdorf, EW, Martin, PJ, Clift, RA, Walters, MC, Gooley, T, Sierra, J, Anderson, JE, Bjerke, J, Siadak, M, Flowers, ME, Nash, RA, Sanders, JE, Appelbaum, FR, Storb, R, and Hansen, JA. "Unrelated and HLA-nonidentical related donor marrow transplantation for thalassemia and leukemia. A combined report from the Seattle Marrow Transplant Team and the International Bone Marrow Transplant Registry." Ann N Y Acad Sci 850 (June 30, 1998): 312-324.
PMID
9668553
Source
pubmed
Published In
Annals of the New York Academy of Sciences
Volume
850
Publish Date
1998
Start Page
312
End Page
324

Body weight and outcome of hematopoietic stem cell transplantation.

Authors
Deeg, HJ; Seidel, K; Sullivan, KM
MLA Citation
Deeg, HJ, Seidel, K, and Sullivan, KM. "Body weight and outcome of hematopoietic stem cell transplantation." Am J Med 104.6 (June 1998): 607-608. (Letter)
PMID
9674727
Source
pubmed
Published In
The American Journal of Medicine
Volume
104
Issue
6
Publish Date
1998
Start Page
607
End Page
608

Long-term outcome after marrow transplantation for severe aplastic anemia.

We reviewed the records and reevaluated 212 patients with aplastic anemia transplanted at the Fred Hutchinson Cancer Research Center (FHCRC) between 1970 and 1993 who survived >/=2 years and who have been followed for up to 26 years. Parameters analyzed included hematopoietic function, chronic graft-versus-host disease (GVHD), skin disease, cataracts, lung disease, skeletal problems, posttransplant malignancy, depression, pregnancy/fatherhood, and the return to work or school, as well as patient self-assessment of physical and psychosocial health, social interactions, memory and concentration, and overall severity of symptoms. Survival probabilities at 20 years were 89% for patients without (n = 125) and 69% for patients with chronic GVHD (n = 86) (the status was uncertain in 1 surviving patient). All patients had normal hematopoietic parameters. Skin problems occurred in 14%, cataracts in 12%, lung disease in 24%, and bone and joint problems in 18% of patients. Eleven patients (12%) developed a solid tumor malignancy and 19% of patients experienced depression. Chronic GVHD was the dominant risk factor for late complications. Seventeen patients died at 2.5 to 20.4 years posttransplant; 13 of these had chronic GVHD and related complications. At 2 years, 83% of patients had returned to school or work; the proportion increased to 90% by 20 years. At least half of the patients preserved or regained the ability to become pregnant or father children. Patients rated their quality of life as excellent and symptoms as minimal or mild. In conclusion, marrow transplantation in patients with aplastic anemia established long-term normal hematopoiesis. No new hematologic disorders occurred. The major cause of morbidity and mortality was chronic GVHD. However, the majority of patients who survived beyond 2 years returned to a fully functional life.

Authors
Deeg, HJ; Leisenring, W; Storb, R; Nims, J; Flowers, ME; Witherspoon, RP; Sanders, J; Sullivan, KM
MLA Citation
Deeg, HJ, Leisenring, W, Storb, R, Nims, J, Flowers, ME, Witherspoon, RP, Sanders, J, and Sullivan, KM. "Long-term outcome after marrow transplantation for severe aplastic anemia." Blood 91.10 (May 15, 1998): 3637-3645.
PMID
9572999
Source
pubmed
Published In
Blood
Volume
91
Issue
10
Publish Date
1998
Start Page
3637
End Page
3645

Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia.

BACKGROUND: Chronic myeloid leukemia can be cured by marrow transplantation from an HLA-identical sibling donor. The use of transplants from unrelated donors is an option for the 70 percent of patients without an HLA-identical sibling, but the morbidity and mortality associated with such transplants have been cause for concern. We analyzed the safety and efficacy of transplants from unrelated donors for the treatment of chronic myeloid leukemia and identified variables that predict a favorable outcome. METHODS: Between May 1985 and December 1994, 196 patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase received marrow transplants from unrelated donors. RESULTS: The median follow-up was 5 years (range, 1.2 to 10.1). Graft failure occurred in 5 percent of patients who could be evaluated. Acute graft-versus-host disease of grade III or IV severity was observed in 35 percent of patients who received HLA-matched transplants, and the estimated cumulative incidence of relapse at five years was 10 percent. The Kaplan-Meier estimate of survival at five years was 57 percent. Survival was adversely affected by an interval from diagnosis to transplantation of one year or more, an HLA-DRB1 mismatch, a high body-weight index, and an age of more than 50 years. Survival was improved by the prophylactic use of fluconazole and ganciclovir. The Kaplan-Meier estimate of survival at five years was 74 percent (95 percent confidence interval, 62 to 86 percent) for patients who were 50 years of age or younger who received a transplant from an HLA-matched donor within one year after diagnosis. CONCLUSIONS: Transplantation of marrow from an HLA-matched, unrelated donor is safe and effective therapy for selected patients with chronic myeloid leukemia.

Authors
Hansen, JA; Gooley, TA; Martin, PJ; Appelbaum, F; Chauncey, TR; Clift, RA; Petersdorf, EW; Radich, J; Sanders, JE; Storb, RF; Sullivan, KM; Anasetti, C
MLA Citation
Hansen, JA, Gooley, TA, Martin, PJ, Appelbaum, F, Chauncey, TR, Clift, RA, Petersdorf, EW, Radich, J, Sanders, JE, Storb, RF, Sullivan, KM, and Anasetti, C. "Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia." N Engl J Med 338.14 (April 2, 1998): 962-968.
PMID
9521984
Source
pubmed
Published In
The New England journal of medicine
Volume
338
Issue
14
Publish Date
1998
Start Page
962
End Page
968
DOI
10.1056/NEJM199804023381405

Course of Crohn's disease after allogeneic marrow transplantation.

BACKGROUND & AIMS: Remission of several autoimmune diseases has been described after allogeneic marrow transplantation. The aim of this study was to determine if the natural history of Crohn's disease was altered by hematopoietic cell transplants from healthy allogeneic donors. METHODS: Between 1982 and 1992, 6 patients with Crohn's disease and leukemia underwent allogeneic marrow transplantation and were followed up clinically. RESULTS: Five patients had active Crohn's disease before transplantation, and 3 had clinical evidence of sclerosing cholangitis. Four marrow donors were HLA-identical siblings, 1 related donor was mismatched at the DR locus, and 1 unrelated donor was HLA-matched. One patient died of septicemia 97 days after transplantation; 5 patients were observed for 4.5, 5.8, 8.4, 9.9, and 15.3 years after transplantation. Four of 5 patients evaluated had no signs or symptoms of Crohn's disease after transplantation. One patient with mixed donor-host hematopoietic chimerism had a relapse of Crohn's disease 1.5 years after transplantation. CONCLUSIONS: Four of 5 patients followed up for 4.5 to 15.3 years after allogeneic hematopoietic cell transplantation remained free of Crohn's disease. These observations suggest that host immune dysregulation plays a role in the perpetuation of Crohn's disease that can be corrected by allogeneic hematopoietic cell transplantation.

Authors
Lopez-Cubero, SO; Sullivan, KM; McDonald, GB
MLA Citation
Lopez-Cubero, SO, Sullivan, KM, and McDonald, GB. "Course of Crohn's disease after allogeneic marrow transplantation." Gastroenterology 114.3 (March 1998): 433-440.
PMID
9496932
Source
pubmed
Published In
Gastroenterology
Volume
114
Issue
3
Publish Date
1998
Start Page
433
End Page
440

Case-based reasoning in care-partner: Gathering evidence for evidence-based medical practice

© Springer-Verlag Berlin Heidelberg 1998. This paper presents the CARE-PARTNER system. Functionally, it offers via the WWW knowledge-support assistance to clinicians responsible for the long-term follow-up of stem-cell post-transplant patient care. CAREPARTNER aims at implementing the concept of evidence-based medical practice, which recommends the practice of medicine based on proven and validated knowledge. From an artificial intelligence viewpoint, it proposes a multimodal reasoning framework for the cooperation of case-based reasoning, rule-based reasoning and information retrieval to solve problems. The role of case-based reasoning is presented in this paper as the collection of evidence for evidence-based medical practice. Case-based reasoning permits to refine and complete the knowledge of the system. It enhances the system by conferring an ability to learn from experience, and thus improve results over time.

Authors
Bichindaritz, I; Kansu, E; Sullivan, KM
MLA Citation
Bichindaritz, I, Kansu, E, and Sullivan, KM. "Case-based reasoning in care-partner: Gathering evidence for evidence-based medical practice." January 1, 1998.
Source
scopus
Published In
Lecture notes in computer science
Volume
1488
Publish Date
1998
Start Page
334
End Page
345
DOI
10.1007/BFb0056345

Avascular necrosis following bone marrow transplantation: a case-control study.

The role of specific immunosuppressive agents in the development of avascular necrosis (AVN) following hematopoietic stem cell and solid organ transplantation remains unclear. To further explore this question, we conducted a case-control study of patients who underwent bone marrow transplantation (BMT) at the Fred Hutchinson Cancer Research Center. 96 of 1939 long-term survivors transplanted between May 1976 and October 1993 were identified as having AVN. Eight patients were excluded because AVN developed before transplant and one was excluded due to restrictions on reviewing follow-up records. The remaining 87 patients developed AVN a mean of 26.3 +/- 2 months posttransplant and were matched for age, gender, and date of transplant to other BMT recipients. Records were reviewed for corticosteroid and cyclosporine use, pretransplant conditioning with total body irradiation (TBI), and other information including disease for which the transplant was indicated, type of transplant, the occurrence of acute and chronic graft-vs.-host disease, and steroid use prior to transplant. Adjusted odds ratios (ORs) were obtained from conditional logistic regression for 87 matched pairs. Posttransplant steroid use was a risk factor for the occurrence of AVN (adjusted OR, 14.4; 95% CI, 2.8-73.2), with the greatest risk associated with those receiving steroids at the time of diagnosis of AVN (adjusted OR, 31.9; 95% CI, 4.4-248.9). There was no further increasing risk associated with increasing duration of steroid use. Conditioning with TBI was also associated with the occurrence of AVN (adjusted OR, 3.2; 95% CI, 1.1-9.7); however, cyclosporine was not a risk factor for AVN (adjusted OR, 0.5; 95% CI, 0.1-1.9). Our results support the hypothesis that AVN following BMT has a strong association with the administration of corticosteroids. TBI may be an additional risk factor, and cyclosporine does not appear to contribute to an increased incidence of AVN.

Authors
Fink, JC; Leisenring, WM; Sullivan, KM; Sherrard, DJ; Weiss, NS
MLA Citation
Fink, JC, Leisenring, WM, Sullivan, KM, Sherrard, DJ, and Weiss, NS. "Avascular necrosis following bone marrow transplantation: a case-control study." Bone 22.1 (January 1998): 67-71.
PMID
9437515
Source
pubmed
Published In
BONE
Volume
22
Issue
1
Publish Date
1998
Start Page
67
End Page
71

CARE-PARTNER: a computerized knowledge-support system for stem-cell post-transplant long-term follow-up on the World-Wide-Web.

Evidence-based practice in medicine promotes the performance of medicine based upon proven and validated practice. The CARE-PARTNER system presented here is a computerized knowledge-support system for stem-cell post-transplant long-term follow-up (LTFU) care on the WWW, which means that it monitors the quality of the knowledge both of its own knowledge-base and of its users. Its aim is to support the evidence-based practice of the LTFU clinicians and of the home-town physicians who actually care for the transplanted patients. Currently, three fundamental characteristics of CARE-PARTNER are accountable for its knowledge-support function: the quality of its knowledge-base, its availability on the WWW, and its learning from experience capability. As a matter of fact, the integration of a case-based reasoner in the reasoning framework enables the system to introspectively study its results, and to learn from its successes and failures, thus confronting the quality of the guidelines and pathways it reuses to the reality and complexity of the clinical cases.

Authors
Bichindaritz, I; Siadak, MF; Jocom, J; Moinpour, C; Kansu, E; Donaldson, G; Bush, N; Chapko, M; Bradshaw, JM; Sullivan, KM
MLA Citation
Bichindaritz, I, Siadak, MF, Jocom, J, Moinpour, C, Kansu, E, Donaldson, G, Bush, N, Chapko, M, Bradshaw, JM, and Sullivan, KM. "CARE-PARTNER: a computerized knowledge-support system for stem-cell post-transplant long-term follow-up on the World-Wide-Web." Proc AMIA Symp (1998): 386-390.
PMID
9929247
Source
pubmed
Published In
Proceedings / AMIA . Annual Symposium. AMIA Symposium
Publish Date
1998
Start Page
386
End Page
390

The development of chronic graft-versus-host disease: An analysis of screening studies and the impact of corticosteroid use at 100 days after transplantation

The value of routine chronic graft-versus-host disease (GVHD) screening studies performed between 70 and 120 days after allogeneic marrow transplantation was retrospectively evaluated among 241 patients. All patients received methotrexate and cyclosporine for GVHD prophylaxis and survived without relapse more than 4 months after transplant. Ninety-one patients (38%) developed clinical extensive chronic GVHD requiring systemic therapy. Data on patients who developed clinical extensive chronic GVHD were compared with those on patients without chronic GVHD to determine which of the following screening tests predicted the subsequent development of clinical extensive chronic GVHD: skin biopsy, oral exam, lip biopsy, Schirmer's test, serum alkaline phosphatase, aspartate transaminase, immunoglobulin level and platelet count. In a univariable analysis, a positive oral examination and a low platelet count were predictive of chronic extensive GVHD development. In a multivariable analysis which adjusted for the contribution of other chronic GVHD risk factors, such as age and a history of acute GVHD none of the screening tests were predictive of chronic GVHD development. The risk factors in this multivariable analysis which had the strongest association with the development of chronic GVHD was a history of acute GVHD and use of corticosteroids at day 100 (RR = 3.9, P = 0.001). The use of corticosteroids for acute GVHD at day 100 had a predictive effect on chronic GVHD development independent of the grade of acute GVHD (RR = 2.1, P = 0.004). Based on these study results, the use of chronic GVHD screening tests may not be of value in predicting who will develop this complication. Patients on corticosteroids at day 100 should be considered for clinical trials to determine the efficacy of new immunosuppressive agents in preventing chronic GVHD.

Authors
Wagner, JL; Flowers, MED; Longton, G; Storb, R; Schubert, M; Sullivan, KM
MLA Citation
Wagner, JL, Flowers, MED, Longton, G, Storb, R, Schubert, M, and Sullivan, KM. "The development of chronic graft-versus-host disease: An analysis of screening studies and the impact of corticosteroid use at 100 days after transplantation." Bone Marrow Transplantation 22.2 (1998): 139-146.
PMID
9707021
Source
scival
Published In
Bone Marrow Transplantation
Volume
22
Issue
2
Publish Date
1998
Start Page
139
End Page
146

Body weight and outcome of hematopoietic stem cell transplantation (multiple letters)

Authors
Deeg, HJ; Seidel, K; Sullivan, KM; Fleming, DR; Goldsmith, GH; Rayens, MK; Garrison, J
MLA Citation
Deeg, HJ, Seidel, K, Sullivan, KM, Fleming, DR, Goldsmith, GH, Rayens, MK, and Garrison, J. "Body weight and outcome of hematopoietic stem cell transplantation (multiple letters)." American Journal of Medicine 104.6 (1998): 607-608.
Source
scival
Published In
The American Journal of Medicine
Volume
104
Issue
6
Publish Date
1998
Start Page
607
End Page
608
DOI
10.1016/S0002-9343(98)00217-4

Intravenous immunoglobulin and the risk of hepatic veno-occlusive disease after bone marrow transplantation

Recent reports using historical controls or registry cohorts suggest, respectively, either an increase in the mortality or a decrease in the incidence of hepatic veno-occlusive disease (VOD) with the administration of intravenous immunoglobulin (IVIg) after bone marrow transplantation. These divergent results prompted us to conduct a retrospective analysis of two randomized clinical trials conducted at our center to determine the effect of IVIg infusions on the development and severity of VOD. Patients were randomized to receive (n=318) or not to receive (n=315) IVIg prophylaxis after human leukocyte antigen-identical sibling (n=414), mismatched or unrelated (n=178), or autologous or syngeneic (n=41) marrow transplantation. To determine the relationship of IVIg to the development and severity of VOD, a single observer reviewed data displays created for each patient for grading VOD without knowledge of patient IVIg use. In this analysis, VOD was defined as hyperbilirubinemia ≥2.0 mg/dL before day 20 and abrupt weight gain ≥2% before day 14 posttransplant in the absence of other causes of liver disease. Hepatic VOD developed in 235 (37%) of the 633 randomized patients. No evidence for VOD was found in 230 (36%) patients. The remaining 168 (27%) patients were classified as having liver disease of uncertain etiology. Hepatic VOD was judged to be severe in 63 (10%) and mild or moderate in 172 (27%) patients. The number of patients developing any VOD or severe VOD was similar between those randomized to IVIg prophylaxis and untreated controls (115 vs. 120 and 32 vs. 31, respectively). Logistic regression models identified several covariates as significant (p < 0.01) factors associated with the development of severe VOD. Increased risk occurred with elevated pretransplant serum aspartate aminotransferase (odds ratio [OR] = 2.64) and earlier year of transplant (OR = 3.73); decreased risk occurred with autologous or twin donors (OR = 0.09) and acute myeloid leukemia (OR = 0.39). The development of any VOD was associated with an elevated pretransplant alkaline phosphatase (OR = 4.1), pretransplant use of vancomycin (OR = 1.6) or amphotericin (OR = 3.0), posttransplant use of cyclosporine (OR = 2.5), older patient age (OR = 1.03), and obesity (OR = 0.78). We concluded from the controlled trials of 633 patients that the administration of IVIg did not influence the development or severity of VOD after bone marrow transplantation.

Authors
Sullivan, KM; Kansu, E; Storer, B; Jocom, J; Emerson, G; Reagan, T; Emerson, V; Siadak, MF; Davis, C; Appelbaum, FR; Buckner, CD; Hansen, JA; Shulman, HM; Storb, R; McDonald, GB
MLA Citation
Sullivan, KM, Kansu, E, Storer, B, Jocom, J, Emerson, G, Reagan, T, Emerson, V, Siadak, MF, Davis, C, Appelbaum, FR, Buckner, CD, Hansen, JA, Shulman, HM, Storb, R, and McDonald, GB. "Intravenous immunoglobulin and the risk of hepatic veno-occlusive disease after bone marrow transplantation." Biology of Blood and Marrow Transplantation 4.1 (1998): 20-26.
PMID
9701388
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
4
Issue
1
Publish Date
1998
Start Page
20
End Page
26

Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is likely caused by donor T lymphocytes. Because unmodified blood stem cell grafts contain one log more T lymphocytes than unmodified marrow grafts, we evaluated the incidence of chronic GVHD in previously reported 37 blood stem cell recipients and 37 computer-matched historical control marrow recipients (Bensinger et al, Blood 88:2794, 1996). All patients have been followed until death, relapse, or occurrence of chronic GVHD or for a minimum of 2 years. In a univariable proportional hazards regression model, the relative risk of developing clinical chronic GVHD (includes clinical limited and clinical extensive disease) by 2 years posttransplant among the peripheral blood stem cell recipients compared with the marrow recipients was 2.22 (95% confidence interval, 1.04 to 4.74; P = .039). For clinical extensive chronic GVHD, the relative risk was 2.37 (95% confidence interval, 1.07 to 5. 29; P = .035). In multivariable analyses, considering also the covariables of patient age, patient cytomegalovirus serostatus, and donor cytomegalovirus serostatus, the relative risks of clinical chronic GVHD and clinical extensive chronic GVHD were also greater than 2 (P < .05). We conclude that the transplantation of unmanipulated filgrastim-mobilized blood stem cells may result in a relatively high incidence of chronic GVHD.

Authors
Storek, J; Gooley, T; Siadak, M; Bensinger, WI; Maloney, DG; Chauncey, TR; Flowers, M; Sullivan, KM; Witherspoon, RP; Rowley, SD; Hansen, JA; Storb, R; Appelbaum, FR
MLA Citation
Storek, J, Gooley, T, Siadak, M, Bensinger, WI, Maloney, DG, Chauncey, TR, Flowers, M, Sullivan, KM, Witherspoon, RP, Rowley, SD, Hansen, JA, Storb, R, and Appelbaum, FR. "Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease." Blood 90.12 (December 15, 1997): 4705-4709.
PMID
9389685
Source
pubmed
Published In
Blood
Volume
90
Issue
12
Publish Date
1997
Start Page
4705
End Page
4709

Safeguarding the administration of high-dose chemotherapy: a national practice survey by the American Society for Blood and Marrow Transplantation.

Overdoses of high-dose chemotherapy before hematopoietic cell transplantation are serious adverse events, but their frequency and etiology are unknown. The American Society for Blood and Marrow Transplantation (ASBMT) conducted an anonymous national survey to identify errors in safety practices during the administration of high-dose chemotherapy. The questionnaire was returned from 115 (68%) of 170 hematopoietic transplant centers in the United States. Ninety-four of the programs were university or affiliated centers, 19 were community hospitals, and 41 were founded since 1990. A total of 7650 transplants were reported for 1994: 22% of the programs performed 1-20 transplants, 60% performed 21-100 transplants, and 18% performed more than 100 transplants. Fifteen of the 115 responding centers reported a total of 18 patients inadvertently given overdoses of cisplatin (n=3), carboplatin (n=2), busulfan (n=2), cytosine arabinoside (n=2), cyclophosphamide (n=2), interleukin-2 (n=2), or other agents (n=5) between 1989 and 1994. Cumulative drug doses given as a daily dose (six cases) and nursing infusion errors (six cases) were the most common errors. The estimated chemotherapy overdose error rate was 0.06%, or 6 cases/10,000 transplants, with 95% confidence limits of 0.03-0.11%. The overdose rate among more experienced centers in operation before 1990 was lower than that among newer centers (p < 0.01). Large centers (> 100 transplants performed in 1994) experienced errors at rates lower than those in medium-sized centers (21-100 transplants, p = 0.03). Although the number of events was small in this self-reporting survey, overdoses were noted in 13% of the responding centers, especially among more recently established units. Safety practices need to emphasize multidisciplinary checkpoints at the physician, pharmacist, nursing, and institutional levels. Based on these survey results, ASBMT recommendations for further safeguards for high-dose chemotherapy administration are proposed.

Authors
Chen, CS; Seidel, K; Armitage, JO; Fay, JW; Appelbaum, FR; Horowitz, MM; Shpall, EJ; Weiden, PL; Antman, KS; Champlin, RE; Kersey, JH; Sullivan, KM
MLA Citation
Chen, CS, Seidel, K, Armitage, JO, Fay, JW, Appelbaum, FR, Horowitz, MM, Shpall, EJ, Weiden, PL, Antman, KS, Champlin, RE, Kersey, JH, and Sullivan, KM. "Safeguarding the administration of high-dose chemotherapy: a national practice survey by the American Society for Blood and Marrow Transplantation." Biol Blood Marrow Transplant 3.6 (December 1997): 331-340.
PMID
9502301
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
3
Issue
6
Publish Date
1997
Start Page
331
End Page
340

Collaborative multicenter investigation of marrow transplantation for sickle cell disease: current results and future directions.

We present updated results of a multicenter collaborative investigation of bone marrow transplantation for sickle cell disease. Between September 1991 and April 1997, thirty-four children less than 16 years of age with severe sickle cell disease received marrow allografts from HLA-identical siblings. Indications for transplantation included a history of stroke (n = 17), recurrent acute chest syndrome or sickle pulmonary disease (n = 10), and recurrent vaso-occlusive crises (n = 7). Twenty-one patients received regular red blood cell (RBC) transfusions to prevent complications of sickle cell disease. Patients were prepared for transplantation with busulfan, cyclophosphamide, and antithymocyte globulin or CAMPATH (Cambridge Pathology) antibody. Thirty-two of the 34 patients survived, with a median follow-up of 26.5 months (range, 0.2-66.9 months); and 28 patients demonstrated stable engraftment of donor hematopoietic cells. Graft rejection or recurrence of sickle cell disease occurred in four patients, and two patients died of intracranial hemorrhage or graft-vs.-host disease. In the group of 34 children with symptoms of advanced sickle cell disease, current Kaplan-Meier estimates of survival and event-free survival are 93% and 79%, respectively.

Authors
Walters, MC; Patience, M; Leisenring, W; Rogers, ZR; Dinndorf, P; Davies, SC; Roberts, IA; Yeager, A; Kurtzberg, J; Bunin, N; Scott, JP; Wall, DA; Wayne, AS; Wiley, J; Darbyshire, PJ; Mentzer, WC; Smith, FO; Sullivan, KM
MLA Citation
Walters, MC, Patience, M, Leisenring, W, Rogers, ZR, Dinndorf, P, Davies, SC, Roberts, IA, Yeager, A, Kurtzberg, J, Bunin, N, Scott, JP, Wall, DA, Wayne, AS, Wiley, J, Darbyshire, PJ, Mentzer, WC, Smith, FO, and Sullivan, KM. "Collaborative multicenter investigation of marrow transplantation for sickle cell disease: current results and future directions." Biol Blood Marrow Transplant 3.6 (December 1997): 310-315.
PMID
9502298
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
3
Issue
6
Publish Date
1997
Start Page
310
End Page
315

Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine?

One hundred three patients with leukemia, aplastic anemia, or myelodysplastic syndrome were treated by marrow transplantation from genotypically HLA-identical siblings (n = 92) or HLA haploidentical family members differing for one HLA antigen on the nonshared haplotype (n = 11). To prevent graft-vs.-host disease (GVHD), they were administered postgrafting immunosuppression with a short course of intermittent methotrexate with daily cyclosporine for no more than 11 days. Customarily, we have given cyclosporine for 180 days after transplant. In the current study, we asked whether cyclosporine could be stopped earlier without affecting the risk of chronic GVHD. By day 60, patients who never had acute GVHD, or whose acute GVHD had resolved, were randomized to have cyclosporine stopped (n = 52) or continued for the usual 180 days (n = 51). Results were analyzed with a median follow-up of 9.3 years after transplant, and showed that patients in whom cyclosporine was discontinued on day 60 had a significantly more rapid onset (p = 0.001), but not a significantly higher overall incidence of chronic GVHD than those in whom the drug was stopped on day 180 (43 vs. 54%; p = 0.26). Transplant-related mortality was comparable among patients without preceding acute GVHD, regardless of when cyclosporine was discontinued (11% for both study arms). However, transplant-related mortality appeared to increase among patients with preceding acute GVHD in whom cyclosporine was stopped by day 60 (38 vs. 17%). Results suggest that cyclosporine can safely be discontinued early in patients who never had evidence of acute GVHD, while those with preceding acute GVHD would benefit from a longer course of the drug. Because of the relatively small sample sizes, these results would best be treated as promising preliminary findings that should be confirmed in larger randomized studies.

Authors
Storb, R; Leisenring, W; Anasetti, C; Appelbaum, FR; Deeg, HJ; Doney, K; Martin, P; Sullivan, KM; Witherspoon, R; Pettinger, M; Bensinger, W; Buckner, CD; Clift, R; Flowers, ME; Hansen, JA; Pepe, M; Chauncey, T; Sanders, J; Thomas, ED
MLA Citation
Storb, R, Leisenring, W, Anasetti, C, Appelbaum, FR, Deeg, HJ, Doney, K, Martin, P, Sullivan, KM, Witherspoon, R, Pettinger, M, Bensinger, W, Buckner, CD, Clift, R, Flowers, ME, Hansen, JA, Pepe, M, Chauncey, T, Sanders, J, and Thomas, ED. "Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine?." Biol Blood Marrow Transplant 3.4 (October 1997): 194-201.
PMID
9360781
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
3
Issue
4
Publish Date
1997
Start Page
194
End Page
201

Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

Transplantation of marrow from unrelated donors was investigated in patients with Philadelphia chromosome-positive (Ph1+) acute lymphoblastic leukemia (ALL) who lacked a suitable family donor. Eighteen patients underwent transplantation at our center between 1988 and 1995. The median patient age was 25 years (range, 1.7 to 51 years). Seven patients were in first complete remission, 1 in second remission, 3 in first relapse, and the remaining 7 had more advanced or chemotherapy refractory leukemia at transplant. All patients were conditioned with cyclophosphamide and total body irradiation followed by marrow transplants from closely HLA-matched, unrelated volunteers. Posttransplant graft-versus-host disease (GVHD) prophylaxis included methotrexate with either cyclosporine or FK506. Graft failure was not observed. Severe (grades III-IV) GVHD appeared in 6 of 17 evaluable patients and chronic extensive GVHD in 7 of 13 patients at risk. Five patients had recurrent ALL after transplantation and another 4 died from causes other than leukemia. Six patients transplanted in first remission, 2 in first relapse, and 1 in second remission remain alive and leukemia-free at a median follow-up of 17 months (range, 9 to 73 months). The probability of leukemia-free survival at 2 years is 49% +/- 12%. These data indicate that unrelated donor marrow transplantation is an effective treatment option for patients with early stage Ph1+ ALL without a family match and suggest that in such patients an unrelated donor search should be initiated as soon as possible after diagnosis.

Authors
Sierra, J; Radich, J; Hansen, JA; Martin, PJ; Petersdorf, EW; Bjerke, J; Bryant, E; Nash, RA; Sanders, JE; Storb, R; Sullivan, KM; Appelbaum, FR; Anasetti, C
MLA Citation
Sierra, J, Radich, J, Hansen, JA, Martin, PJ, Petersdorf, EW, Bjerke, J, Bryant, E, Nash, RA, Sanders, JE, Storb, R, Sullivan, KM, Appelbaum, FR, and Anasetti, C. "Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia." Blood 90.4 (August 15, 1997): 1410-1414.
PMID
9269758
Source
pubmed
Published In
Blood
Volume
90
Issue
4
Publish Date
1997
Start Page
1410
End Page
1414

Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose.

Transplantation of hematopoietic stem cells from an HLA-compatible unrelated volunteer is an option for patients with acute leukemia lacking a family match. However, criteria for patient and donor selection and the most effective transplant procedures, including the number of hematopoietic cells, remain to be defined. We tested factors influencing outcome of 174 patients with primary acute leukemia receiving non-T-cell depleted marrow from unrelated donors. Median patient age was 20 years (range, 0.5 to 54 years). A multivariable analysis found that leukemia in remission at the time of transplantation was associated with improved leukemia-free survival (relative risk [RR] of treatment failure: 0.5, confidence interval [CI]: 0.3 to 0.7), and presence of blasts in the peripheral blood, as opposed to marrow involvement only or isolated extramedullary relapse, was associated with impaired outcome (RR of treatment failure: 2.5, CI: 1.7 to 5.0). The use of donors with a limited HLA-mismatch was associated with decreased leukemic relapse (RR: 0.5, CI: 0.3 to 0.9) but no improvement in leukemia-free survival compared with HLA-matched unrelated donors. Transplantation of a marrow cell dose above the median value of 3.65 x 10(8)/kg was associated with faster neutrophil (RR: 1.5, CI: 1.1 to 2.0) and platelet (RR: 4.5, CI: 2.7 to 7.5) engraftment, and decreased incidence of severe acute graft-versus-host disease (RR: 0.6, CI: 0.4 to 0.9). In patients transplanted in remission, the use of a marrow cell dose above the median translated into less nonleukemic death (RR: 0.2, CI: 0.1 to 0.4) and better leukemia-free survival (RR of treatment failure: 0.3, CI: 0.2 to 0.6). Transplant in remission with a high dose of marrow cells was associated with the best outcome in both children and adults.

Authors
Sierra, J; Storer, B; Hansen, JA; Bjerke, JW; Martin, PJ; Petersdorf, EW; Appelbaum, FR; Bryant, E; Chauncey, TR; Sale, G; Sanders, JE; Storb, R; Sullivan, KM; Anasetti, C
MLA Citation
Sierra, J, Storer, B, Hansen, JA, Bjerke, JW, Martin, PJ, Petersdorf, EW, Appelbaum, FR, Bryant, E, Chauncey, TR, Sale, G, Sanders, JE, Storb, R, Sullivan, KM, and Anasetti, C. "Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose." Blood 89.11 (June 1, 1997): 4226-4235.
PMID
9166868
Source
pubmed
Published In
Blood
Volume
89
Issue
11
Publish Date
1997
Start Page
4226
End Page
4235

Long-term follow-up of allogeneic marrow transplants in patients with aplastic anemia conditioned by cyclophosphamide combined with antithymocyte globulin.

Authors
Storb, R; Leisenring, W; Anasetti, C; Appelbaum, FR; Buckner, CD; Bensinger, WI; Chauncey, T; Clift, RA; Deeg, HJ; Doney, KC; Flowers, ME; Hansen, JA; Martin, PJ; Sanders, JE; Sullivan, KM; Witherspoon, RP
MLA Citation
Storb, R, Leisenring, W, Anasetti, C, Appelbaum, FR, Buckner, CD, Bensinger, WI, Chauncey, T, Clift, RA, Deeg, HJ, Doney, KC, Flowers, ME, Hansen, JA, Martin, PJ, Sanders, JE, Sullivan, KM, and Witherspoon, RP. "Long-term follow-up of allogeneic marrow transplants in patients with aplastic anemia conditioned by cyclophosphamide combined with antithymocyte globulin." Blood 89.10 (May 15, 1997): 3890-3891. (Letter)
PMID
9160700
Source
pubmed
Published In
Blood
Volume
89
Issue
10
Publish Date
1997
Start Page
3890
End Page
3891

Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial.

Patients with a lymphohematopoietic malignancy considered to be at high risk for posttransplant relapse were enrolled in a study to compare the use of cyclosporine (CSP) as a single agent with a combination of methylprednisolone (MP) and CSP for graft-versus-host disease (GVHD) prophylaxis after marrow transplantation from an HLA-identical sibling donor. Sixty patients were randomized to receive CSP only and 62 were randomized to receive CSP plus MP. Daily CSP was started on day -1 (5 mg/kg/d intravenously) and administered at gradually reduced doses until day 180. MP was started on day 7 at 0.5 mg/kg/d, increased to 1.0 mg/kg/d on day 15, started on a taper schedule on day 29, and discontinued on day 72. All 104 evaluable patients (surviving > or =28 days) had sustained engraftment. The incidence rates of grades II-IV acute GVHD were 73% and 60% for patients receiving CSP and CSP plus MP, respectively (P = .01). No difference was seen for grades III-IV GVHD. However, chronic GVHD occurred somewhat more frequently in patients receiving CSP plus MP (44%) than in patients receiving only CSP (21%; P = .02). The incidence of de novo chronic GVHD was marginally higher in patients receiving CSP plus MP (P = .08). No significant differences in the risk of infections were observed. There was a suggestion that the risk of relapse was lower in patients receiving CSP plus MP (P = .10) and, although the overall survival in the two groups was not different (P = .44), there was a slight advantage in favor of CSP plus MP-treated patients for relapse-free survival (P = .07). These results suggest that prophylactic MP, when combined with CSP, has only limited efficacy in acute GVHD prevention and may increase the probability of chronic GVHD.

Authors
Deeg, HJ; Lin, D; Leisenring, W; Boeckh, M; Anasetti, C; Appelbaum, FR; Chauncey, TR; Doney, K; Flowers, M; Martin, P; Nash, R; Schoch, G; Sullivan, KM; Witherspoon, RP; Storb, R
MLA Citation
Deeg, HJ, Lin, D, Leisenring, W, Boeckh, M, Anasetti, C, Appelbaum, FR, Chauncey, TR, Doney, K, Flowers, M, Martin, P, Nash, R, Schoch, G, Sullivan, KM, Witherspoon, RP, and Storb, R. "Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial." Blood 89.10 (May 15, 1997): 3880-3887.
PMID
9160697
Source
pubmed
Published In
Blood
Volume
89
Issue
10
Publish Date
1997
Start Page
3880
End Page
3887

Longterm followup and quality of life after hematopoietic stem cell transplantation.

The success of marrow or blood stem cell transplantation may depend upon events arising months to years later. Transplant regimen related toxicity may include cataract formation due to corticosteroids or total body irradiation (TBI) and endocrine or gonadal dysfunction requiring hormonal replacement. By 15 to 20 years post-transplant, the cumulative incidence of secondary malignancies (including skin cancers) ranges from 4% (no TBI) to 14% (prior irradiation) in patients with previous aplastic anemia. Chronic graft versus-host-disease (GVHD) develops in 33% of HLA-identical sibling transplants and requires 1 to 2 years of immunosuppressive therapy. In allograft recipients free of GVHD, there are very few late infections or complications. These findings are confirmed by multidimensional studies of the quality of life of adult patients surviving 6 to 18 years after marrow transplantation and demonstrate that 80% of patients rate their quality of life as good to excellent and 5%, as poor. Considerations of late effects of transplant and maintenance of quality of life are key considerations when weighing the risks and benefits of stem cell grafts for the treatment of severe autoimmune diseases. Careful followup and reporting of these initial patient cohorts will be vital in determining the longterm success of stem cell transplantation.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Longterm followup and quality of life after hematopoietic stem cell transplantation." J Rheumatol Suppl 48 (May 1997): 46-52. (Review)
PMID
9150118
Source
pubmed
Published In
The Journal of rheumatology. Supplement
Volume
48
Publish Date
1997
Start Page
46
End Page
52

The evolving role of blood and marrow transplantation for the treatment of autoimmune diseases.

With over 4 decades of seminal contributions to the development and application of BMT, Dr. Thomas stresses the importance of collaboration between rheumatologists and transplant clinicians in developing this evolving area of treatment. While the debate concerning the value of TBI in the conditioning regimen and the use of autologous or allogeneic stem cells will continue, he states there is simply no other way to answer these questions than to begin well designed clinical studies. As pointed out by Dr. Hahn, unexpected post-transplant complications may arise in patients with SSc and SLE and possibly require modifications to the transplant procedure similar to the experience in patients with other specific diseases. Other difficulties may be encountered, including restricted funding of the transplant procedure by insurance carriers. The emergence of managed care contracts and payer limitations in the United States described by Dr. Appelbaum could hinder the development of innovative, curative therapies. As initial clinical data are being collected, it is vital to actively support patient referral and participation in clinical studies that will ultimately establish the indications, risks, costs, and benefits of hematopoietic stem cell transplantation for autoimmune disease.

Authors
Sullivan, KM; Furst, DE
MLA Citation
Sullivan, KM, and Furst, DE. "The evolving role of blood and marrow transplantation for the treatment of autoimmune diseases." J Rheumatol Suppl 48 (May 1997): 1-4. (Review)
PMID
9150110
Source
pubmed
Published In
The Journal of rheumatology. Supplement
Volume
48
Publish Date
1997
Start Page
1
End Page
4

Pre-existing autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation.

We reviewed the experience with allogeneic bone marrow transplantation (BMT) at Fred Hutchinson Cancer Research Center and affiliated Seattle hospitals for patients with preexisting autoimmune diseases. The review was limited to patients who received transplants between 1969 and 1989 from a related donor and who had at least 3 years of relapse-free survival. Of 901 evaluable patients, 11 were identified with a preexisting autoimmune disease and 2 with diseases that were possibly autoimmune in nature. Pretransplant diseases identified in this review included rheumatoid arthritis (n = 1), discoid or systemic lupus (n = 2), insulin dependent Type 1 diabetes (n = 3), hyperthyroidism (n = 4), dermatitis herpetiformis (n = 1), vasculitis (n = 1), and Crohn's disease (n = 1). All 13 patients survive with a median followup of 14 (range, 7-20) years after transplantation from an HLA identical sibling (n = 10), parent (n = 1) or identical twin (n = 2). Pre and post-transplant histories are presented. Variables to be considered in the assessment of any beneficial effect of BMT are discussed, including consideration of different patterns of activity that describe the natural history of various autoimmune diseases. Although autoimmune disease did not recur after allogeneic BMT in these 13 patients, disease and post-transplant variables may confound the interpretation of results from retrospective analysis.

Authors
Nelson, JL; Torrez, R; Louie, FM; Choe, OS; Storb, R; Sullivan, KM
MLA Citation
Nelson, JL, Torrez, R, Louie, FM, Choe, OS, Storb, R, and Sullivan, KM. "Pre-existing autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation." J Rheumatol Suppl 48 (May 1997): 23-29.
PMID
9150114
Source
pubmed
Published In
The Journal of rheumatology. Supplement
Volume
48
Publish Date
1997
Start Page
23
End Page
29

Development of a protocol for allogeneic marrow transplantation for severe systemic sclerosis: paradigm for autoimmune disease.

Some types of severe autoimmune disease are associated with significant morbidity and a high mortality rate. Many of these cases occur in young adults who, even if they survive, become severely debilitated. Systemic sclerosis (SSc) is a paradigm for other severe autoimmune diseases in which patients with poor prognostic features can be identified early in the course of the disease. Allogeneic marrow transplantation may be effective for the control of autoimmune diseases like SSc because the preparative regimen will significantly suppress the host immune system and the antihost effects of the donor immune system in the engrafted marrow will help maintain the suppression of the host immune system. Considering the morbidity and poor prognosis associated with severe SSc and the favorable outcome now associated with allogeneic marrow transplantation from HLA identical siblings for other nonmalignant diseases, Phase I and II studies are warranted. These will evaluate the safety of allogeneic marrow transplantation and explore its role in the management and control of a severe autoimmune disease. We review issues important in the development of an allogeneic marrow transplant protocol for severe SSc, including patient selection, plan of treatment, prevention of graft versus host disease, supportive care, and evaluation after transplant.

Authors
Nash, RA; McSweeney, PA; Storb, R; Nelson, JL; Gauthier, J; Furst, DE; Sullivan, KM
MLA Citation
Nash, RA, McSweeney, PA, Storb, R, Nelson, JL, Gauthier, J, Furst, DE, and Sullivan, KM. "Development of a protocol for allogeneic marrow transplantation for severe systemic sclerosis: paradigm for autoimmune disease." J Rheumatol Suppl 48 (May 1997): 72-78. (Review)
PMID
9150123
Source
pubmed
Published In
The Journal of rheumatology. Supplement
Volume
48
Publish Date
1997
Start Page
72
End Page
78

A double-blind randomized trial comparing outpatient parenteral nutrition with intravenous hydration: effect on resumption of oral intake after marrow transplantation.

BACKGROUND: Outpatient parenteral nutrition (PN) is often given to marrow transplant recipients after high-dose chemoradiotherapy until the resumption of adequate oral intake; however, it may adversely prolong resumption or oral calorie intake by contributing to early satiety. METHODS: A double-blind, randomized study compared standard PN (final concentration 25% dextrose, 5% amino acids) with a hydration solution (5% dextrose) during the first 28 days of outpatient treatment. Patients were eligible for the study if they were > or = 2 years of age, < 65 days posttransplant, had < 70% oral caloric intake at hospital discharge, and required < or = 10 U insulin/L PN. Solutions were provided until the patient's oral intake met > or = 85% caloric requirements for 3 consecutive days. RESULTS: Two hundred fifty-eight marrow transplant recipients (128, PN and 130, hydration solution) were studied. Age, donor type, and diagnoses were similar in the two groups. Time to resumption of > or = 85% oral caloric intake was 6 days sooner in the hydration group than in the PN group (median 10 vs 16 days, respectively; p = .049). When adjusting for sex, age, donor type, total body irradiation, previous oral intake, acute graft-versus-host disease, and prednisone therapy, the hydration group resumed oral intake sooner than the PN group (relative risk = 1.51; 95% confidence interval [CI] 1.04 to 2.19; p = .029). The percentage of weight change from pretransplant values, adjusted for the above covariates and the number of weeks of treatment, indicated that the hydration solution group lost weight (4.63%) compared with the PN group (1.27%) after 4 weeks of therapy (p = .004). Rates of hospital readmissions, relapse of malignancy, and survival did not differ between the two treatment groups. CONCLUSIONS: We conclude that outpatient PN delays resumption of oral intake and that its replacement with hydration solution does not result in adverse patient outcome.

Authors
Charuhas, PM; Fosberg, KL; Bruemmer, B; Aker, SN; Leisenring, W; Seidel, K; Sullivan, KM
MLA Citation
Charuhas, PM, Fosberg, KL, Bruemmer, B, Aker, SN, Leisenring, W, Seidel, K, and Sullivan, KM. "A double-blind randomized trial comparing outpatient parenteral nutrition with intravenous hydration: effect on resumption of oral intake after marrow transplantation." JPEN J Parenter Enteral Nutr 21.3 (May 1997): 157-161.
PMID
9168368
Source
pubmed
Published In
Journal of Parenteral and Enteral Nutrition
Volume
21
Issue
3
Publish Date
1997
Start Page
157
End Page
161
DOI
10.1177/0148607197021003157

Autologous stem cell transplantation for autoimmune diseases: issues in protocol development.

For patients with autoimmune disease resistant to conventional therapy, aggressive strategies employing high dose chemoradiotherapy and autologous stem cell transplant appear to be warranted. Support for this approach comes from animal studies employing marrow transplantation, which have shown promising results. Likewise, longterm control of autoimmune disease has been demonstrated in some survivors of allogeneic transplants for malignancy who incidentally had preexisting autoimmune disease. Initial strategies for autografting will use intensive transplant regimens incorporating cyclophosphamide with or without total body irradiation. Peripheral blood stem cell grafts purified by CD34 selection will be depleted of lymphocytes, and lead to rapid hematologic reconstitution after treatment. Close monitoring for disease responses, adverse effects of intensive immunosuppression, and longterm sequelae of high dose therapies will be required. Initial studies are best performed as close collaborations between rheumatologists and transplant specialists in appropriate research centers.

Authors
McSweeney, PA; Nash, RA; Storb, R; Furst, DE; Gauthier, J; Sullivan, KM
MLA Citation
McSweeney, PA, Nash, RA, Storb, R, Furst, DE, Gauthier, J, and Sullivan, KM. "Autologous stem cell transplantation for autoimmune diseases: issues in protocol development." J Rheumatol Suppl 48 (May 1997): 79-84.
PMID
9150124
Source
pubmed
Published In
The Journal of rheumatology. Supplement
Volume
48
Publish Date
1997
Start Page
79
End Page
84

Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts

Survivors of allogeneic marrow transplants are immunodeficient for at least 1 year after grafting. Multiple defects of immunity have been found; however, it is not known which defect primarily accounts for the high infectious morbidity of these patients. Twenty-nine allograft recipients who were in complete remission of the original disease were examined for fhe following parameters of immunity at 1 year after transplant: infection score (gauging the number and severity of infections within the 6 months prior to the annual exam), serum total IgM, IgG, and IgA, anti-Haemophilus influenzae IgG, anti-Streptococcus pneumoniae IgG, skin test reactivity, and the blood counts of B cells, CD4 + T cells, CD8 + T cells, and their subsets. THe only parameter inversely correlated with the infection score was CD4 + T cell count (P = 0.005 in univariable analysis, P = 0.06 in multivariable analysis). We conclude that infectious morbidity of long-term transplant survivors is related to the reconstitution of CD4 + T cells.

Authors
Storek, J; Gooley, T; Witherspoon, RP; Sullivan, KM; Storb, R
MLA Citation
Storek, J, Gooley, T, Witherspoon, RP, Sullivan, KM, and Storb, R. "Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts." American Journal of Hematology 54.2 (February 26, 1997): 131-138.
Source
scopus
Published In
American Journal of Hematology
Volume
54
Issue
2
Publish Date
1997
Start Page
131
End Page
138
DOI
10.1002/(SICI)1096-8652(199702)54:2<131::AID-AJH6>3.0.CO;2-Y

Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts.

Survivors of allogeneic marrow transplants are immunodeficient for at least 1 year after grafting. Multiple defects of immunity have been found; however, it is not known which defect primarily accounts for the high infectious morbidity of these patients. Twenty-nine allograft recipients who were in complete remission of the original disease were examined for the following parameters of immunity at 1 year after transplant: infection score (gauging the number and severity of infections within the 6 months prior to the annual exam), serum total IgM, IgG, and IgA, anti-Haemophilus influenzae IgG, anti-Streptococcus pneumoniae IgG, skin test reactivity, and the blood counts of B cells, CD4+ T cells, CD8+ T cells, and their subsets. THe only parameter inversely correlated with the infection score was CD4+ T cell count (P = 0.005 in univariable analysis, P = 0.06 in multivariable analysis). We conclude that infectious morbidity of long-term transplant survivors is related to the reconstitution of CD4+ T cells.

Authors
Storek, J; Gooley, T; Witherspoon, RP; Sullivan, KM; Storb, R
MLA Citation
Storek, J, Gooley, T, Witherspoon, RP, Sullivan, KM, and Storb, R. "Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts." Am J Hematol 54.2 (February 1997): 131-138.
PMID
9034287
Source
pubmed
Published In
American Journal of Hematology
Volume
54
Issue
2
Publish Date
1997
Start Page
131
End Page
138

Marrow transplantation for chronic myeloid leukemia: The influence of plasma busulfan levels on the outcome of transplantation

The influence of busulfan (BU) plasma concentration on outcome of transplantation from HLA identical family members for the treatment of chronic myelogenous leukemia (CML) was examined in 45 patients transplanted in chronic phase (CP) (n = 39) or accelerated phase (AP) (n = 6). All patients received the same regimen of BU, 16 mg/kg orally and cyclophosphamide (CY), 120 mg/kg intravenously. Plasma concentrations of BU at steady state (C(ss)BU) during the dosing interval were measured for each patient. The mean C(ss)BU was 917 ng/mL (range, 642 to 1,749; median, 917; standard deviation, 213). Of patients with C(ss)BU below the median, seven (five of 18 in CP and two of four in AP) developed persistent cytogenetic relapse and three of these patients died. There were no relapses in patients with C(ss)BU above the median. The difference in the cumulative incidence of relapse between the two groups was statistically significant (P = .0003). C(ss)BU was the only statistically significant determinant of relapse in univariable or multivariable analysis. The 3-year survival estimates were 0.82 and 0.64 for patients with C(ss)BU above and below the median (P = .33). There was no statistically significant association of C(ss)BU with survival or nonrelapse mortality, although the power to detect a difference in survival between 0.82 and 0.64 was only 0.24, similarly C(ss)BU above the median was not associated with an increased risk of severe regimen-related toxicity. We conclude that low BU plasma levels are associated with an increased risk of relapse.

Authors
Slattery, JT; Clift, RA; Buckner, CD; Radich, J; Storer, B; Bensinger, WI; Soll, E; Anasetti, C; Bowden, R; Bryant, E; Chauncey, T; Deeg, HJ; Doney, KC; Flowers, M; Gooley, T; Hansen, JA; Martin, PJ; McDonald, GB; Nash, R; Petersdorf, EW; Sanders, JE; Schoch, G; Stewart, P; Storb, R; Sullivan, KM; Thomas, ED; Witherspoon, RP; Appelbaum, FR
MLA Citation
Slattery, JT, Clift, RA, Buckner, CD, Radich, J, Storer, B, Bensinger, WI, Soll, E, Anasetti, C, Bowden, R, Bryant, E, Chauncey, T, Deeg, HJ, Doney, KC, Flowers, M, Gooley, T, Hansen, JA, Martin, PJ, McDonald, GB, Nash, R, Petersdorf, EW, Sanders, JE, Schoch, G, Stewart, P, Storb, R, Sullivan, KM, Thomas, ED, Witherspoon, RP, and Appelbaum, FR. "Marrow transplantation for chronic myeloid leukemia: The influence of plasma busulfan levels on the outcome of transplantation." Blood 89.8 (1997): 3055-3060.
PMID
9108427
Source
scival
Published In
Blood
Volume
89
Issue
8
Publish Date
1997
Start Page
3055
End Page
3060

Collaborative study of marrow transplantation for sickle cell disease: Aspects specific for transplantation of hemoglobin disorders

Authors
Sullivan, KM; Walters, MC; Patience, M; Leisenring, W; Buchanan, GR; Castro, O; Davies, SC; Dickerhoff, R; Eckman, JR; Graham, ML; Ohene-Frempong, K; Powars, D; Rogers, ZR; Scott, JP; Styles, L; Vichinsky, E; Wall, DA; Wayne, AS; Wiley, J; Wingard, J; Bunin, N; Camitta, B; Darbyshire, PJ; Dinndorf, P; Klingebiel, T; McMahon, L; Mentzer, WC; Olivieri, N; Orringer, E; Parkman, R; Roberts, IAG; Sanders, JE; Smith, FO; Storb, R
MLA Citation
Sullivan, KM, Walters, MC, Patience, M, Leisenring, W, Buchanan, GR, Castro, O, Davies, SC, Dickerhoff, R, Eckman, JR, Graham, ML, Ohene-Frempong, K, Powars, D, Rogers, ZR, Scott, JP, Styles, L, Vichinsky, E, Wall, DA, Wayne, AS, Wiley, J, Wingard, J, Bunin, N, Camitta, B, Darbyshire, PJ, Dinndorf, P, Klingebiel, T, McMahon, L, Mentzer, WC, Olivieri, N, Orringer, E, Parkman, R, Roberts, IAG, Sanders, JE, Smith, FO, and Storb, R. "Collaborative study of marrow transplantation for sickle cell disease: Aspects specific for transplantation of hemoglobin disorders." Bone Marrow Transplantation 19.SUPPL. 2 (1997): 102-105.
Source
scival
Published In
Bone Marrow Transplantation
Volume
19
Issue
SUPPL. 2
Publish Date
1997
Start Page
102
End Page
105

Distributed Reuse of Knowledge in a Computerized Decision Support System for Bone-Marrow Post-Transplant Care over the World-Wide Web

Authors
Bichindaritz, I; Bradshaw, JM; Sullivan, KM
MLA Citation
Bichindaritz, I, Bradshaw, JM, and Sullivan, KM. "Distributed Reuse of Knowledge in a Computerized Decision Support System for Bone-Marrow Post-Transplant Care over the World-Wide Web." Journal of the American Medical Informatics Association 4.SUPPL. (1997): 844--.
Source
scival
Published In
Journal of the American Medical Informatics Association
Volume
4
Issue
SUPPL.
Publish Date
1997
Start Page
844-

Quasielastic light scattering study of the living human lens as a function of age

Purpose. To determine contributions of molecular scattering elements to the increase with age in the light scattered from the human ocular lens in vivo. Methods. We used quasielastic light scattering to measure autocorrelation functions of the intensity of light scattered in vivo from three locations (anterior, nuclear and posterior) along the optic axis in ocular lenses of 225 subjects, ranging from 17 to 63 years of age. We deduced probability distributions of key parameters (I(s), I(f), I(i), I(T)), which describe contributions of slowly diffusing (I(s)), rapidly diffusing (I(f)) and relatively immobile (I(i)) scattering elements to the total light intensity (I(T)) scattered into the collection optics. We deduced characteristic times τ(s), and τ(f) that describe the Brownian motion of scattering elements. Results. Probability distributions for each age decile show clearly defined shifts in key parameters with age. I(T) at the nucleus increases by a factor of three from age 20 to 60 years. This increase is produced principally by an approximate fivefold increase in I(s). I(T) and I(s) and can be detected with an accuracy of ~ ± 10%. We estimate threshold values for I(T), which mark the boundary beyond which clinical cataract becomes manifest. This boundary represents 6 to 8 times the light scattering efficiency expected from the newborn lens. Conclusions. This methodology permits a sensitive, quantitative, clinically useful representation of the pre-cataractous molecular changes associated with aging in the living human lens.

Authors
Thurston, GM; Hayden, DL; Burrows, P; Clark, JI; Taret, VG; Kandel, J; Courogen, M; Peetermans, JA; Bowen, MS; Miller, D; Sullivan, KM; Storb, R; Stern, H; Benedek, GB
MLA Citation
Thurston, GM, Hayden, DL, Burrows, P, Clark, JI, Taret, VG, Kandel, J, Courogen, M, Peetermans, JA, Bowen, MS, Miller, D, Sullivan, KM, Storb, R, Stern, H, and Benedek, GB. "Quasielastic light scattering study of the living human lens as a function of age." Current Eye Research 16.3 (1997): 197-207.
PMID
9088735
Source
scival
Published In
Current Eye Research (Informa)
Volume
16
Issue
3
Publish Date
1997
Start Page
197
End Page
207
DOI
10.1076/ceyr.16.3.197.15410

Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) response to FDA (Docket No. 97N-0068)

We believe the proposed model is appropriate to our current state of knowledge and recognize that FDA regulations will evolve as the field evolves. We thank you for the opportunity to work with FDA as its regulatory strategy is developed in the near future.

Authors
Shpall, EJ; Champlin, RE; Eaves, AC; Gee, AP; Collins, N; LeMaistre, CF; O'Reilly, R; Rowley, SD; Sullivan, K; Vaughan, WP; Warkentin, PL
MLA Citation
Shpall, EJ, Champlin, RE, Eaves, AC, Gee, AP, Collins, N, LeMaistre, CF, O'Reilly, R, Rowley, SD, Sullivan, K, Vaughan, WP, and Warkentin, PL. "Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) response to FDA (Docket No. 97N-0068)." Journal of Hematotherapy 6.4 (1997): 287-289.
PMID
9377066
Source
scival
Published In
Stem Cells and Development
Volume
6
Issue
4
Publish Date
1997
Start Page
287
End Page
289

FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors.

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus-host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno-occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan-Meier estimates of disease-free survival at 2 years for good-risk, poor-risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.

Authors
Nash, RA; Piñeiro, LA; Storb, R; Deeg, HJ; Fitzsimmons, WE; Furlong, T; Hansen, JA; Gooley, T; Maher, RM; Martin, P; McSweeney, PA; Sullivan, KM; Anasetti, C; Fay, JW
MLA Citation
Nash, RA, Piñeiro, LA, Storb, R, Deeg, HJ, Fitzsimmons, WE, Furlong, T, Hansen, JA, Gooley, T, Maher, RM, Martin, P, McSweeney, PA, Sullivan, KM, Anasetti, C, and Fay, JW. "FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors." Blood 88.9 (November 1, 1996): 3634-3641.
PMID
8896434
Source
pubmed
Published In
Blood
Volume
88
Issue
9
Publish Date
1996
Start Page
3634
End Page
3641

Bone marrow transplantation for sickle cell disease.

BACKGROUND: We investigated the risks and benefits of allogeneic bone marrow transplantation in children with complications of sickle cell disease. METHODS: Twenty-two children less than 16 years of age who had symptomatic sickle cell disease received marrow allografts from HLA-identical siblings between September 1991 and April 1995. The indications for transplantation included a history of stroke (n = 12), recurrent acute chest syndrome (n = 5), and recurrent painful crises (n = 5). Patients were prepared for transplantation with busulfan, cyclophosphamide, and antithymocyte globulin. RESULTS: Twenty of the 22 patients survived, with a median follow-up of 23.9 months (range, 10.1 to 51.0), and 16 patients had stable engraftment of donor hematopoietic cells. In three patients the graft was rejected and sickle cell disease recurred; in a fourth patient graft rejection was accompanied by marrow aplasia. In 1 of the 16 patients with engraftment, there was stable mixed chimerism. Two patients died of central nervous system hemorrhage or graft-versus-host disease. Kaplan-Meier estimates of survival and event-free survival at four years were 91 percent and 73 percent, respectively. Among patients with a history of acute chest syndrome, lung function stabilized; among patients with prior central nervous system vasculopathy who had engraftment, stabilization of cerebrovascular disease was documented by magnetic resonance imaging. CONCLUSIONS: Allogeneic stem-cell transplantation can be curative in young patients with symptomatic sickle cell disease.

Authors
Walters, MC; Patience, M; Leisenring, W; Eckman, JR; Scott, JP; Mentzer, WC; Davies, SC; Ohene-Frempong, K; Bernaudin, F; Matthews, DC; Storb, R; Sullivan, KM
MLA Citation
Walters, MC, Patience, M, Leisenring, W, Eckman, JR, Scott, JP, Mentzer, WC, Davies, SC, Ohene-Frempong, K, Bernaudin, F, Matthews, DC, Storb, R, and Sullivan, KM. "Bone marrow transplantation for sickle cell disease." N Engl J Med 335.6 (August 8, 1996): 369-376.
PMID
8663884
Source
pubmed
Published In
The New England journal of medicine
Volume
335
Issue
6
Publish Date
1996
Start Page
369
End Page
376
DOI
10.1056/NEJM199608083350601

Evaluation of a CD5-specific immunotoxin for treatment of acute graft-versus-host disease after allogeneic marrow transplantation.

Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, but less than half of patients have durable overall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate symptoms of GVHD. In a randomized, double-blind trial, we compared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation. The study drug (XomaZyme. CD5-Plus or an identical appearing placebo) was administered at a dose of 0.1 mg/kg body weight on each of 14 consecutive days. All patients were treated concomitantly with a standard regimen of methylprednisolone. At the time of entry on study, 94% of patients had a rash, 56% had hyperbilirubinemia, 61% had diarrhea, and 84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment, symptom severity was less in the CD5 group than in the placebo group. At 4 weeks, 40% of patients assigned to the CD5 group had complete response compared with 25% of those assigned to the control group (P = .019). At 6 weeks, 44% of patients assigned to the CD5 group had complete response as compared with 38% in the placebo group (P = .36). Clinical extensive chronic GVHD developed in 65% of patients in the CD5 group compared with 72% in the control group (P = .35). Survival at 1 year after treatment was 49% in the CD5 group and 45% in the control group (P = .68). Side effects required close monitoring and appropriate adjustment of treatment. The combined administration of a CD5-specific immunotoxin and glucocorticoids controls GVHD manifestations more effectively than treatment with glucocorticoids alone during the first 5 weeks after starting treatment. Use of this immunotoxin does not result in any long-term clinical benefit for patients with acute GVHD.

Authors
Martin, PJ; Nelson, BJ; Appelbaum, FR; Anasetti, C; Deeg, HJ; Hansen, JA; McDonald, GB; Nash, RA; Sullivan, KM; Witherspoon, RP; Scannon, PJ; Friedmann, N; Storb, R
MLA Citation
Martin, PJ, Nelson, BJ, Appelbaum, FR, Anasetti, C, Deeg, HJ, Hansen, JA, McDonald, GB, Nash, RA, Sullivan, KM, Witherspoon, RP, Scannon, PJ, Friedmann, N, and Storb, R. "Evaluation of a CD5-specific immunotoxin for treatment of acute graft-versus-host disease after allogeneic marrow transplantation." Blood 88.3 (August 1, 1996): 824-830.
PMID
8704237
Source
pubmed
Published In
Blood
Volume
88
Issue
3
Publish Date
1996
Start Page
824
End Page
830

Graft-versus-host reactions: anti-leukemia effects of donor T cells.

Authors
Flowers, ME; Sullivan, KM; Deeg, HJ
MLA Citation
Flowers, ME, Sullivan, KM, and Deeg, HJ. "Graft-versus-host reactions: anti-leukemia effects of donor T cells." Transplant Proc 28.3 (June 1996): 1184-1185.
PMID
8658620
Source
pubmed
Published In
Transplantation Proceedings
Volume
28
Issue
3
Publish Date
1996
Start Page
1184
End Page
1185

Immunomodulation in allogeneic marrow transplantation: use of intravenous immune globulin to suppress acute graft-versus-host disease.

Intravenous immune globulin (IVIG) has been used with success to prevent and treat infection in patients with immunodeficiencies of humoral immune function. More recently, IVIG has been shown to modulate immune responses and to treat successfully several autoimmune disease. Initial trials in bone marrow transplant recipients were aimed at the prevention of cytomegalovirus (CMV) disease. Although most studies showed such a benefit, CMV prophylaxis is now commonly provided by use of CMV-negative blood products or ganciclovir prophylaxis in, respectively, CMV-seronegative and CMV-seropositive patients. Acute and chronic graft-versus-host disease (GVHD) and associated infections remain critical barriers to the wider application of allogeneic blood or marrow transplantation, especially among patients given HLA-disparate grafts. To date, four controlled clinical trials have shown a significant reduction in acute GVHD in patients given IVIG (500-1000 mg/kg) weekly until 90-120 days post-transplant. In addition, bacterial infection in the early transplant period appears reduced. Meta-analysis of controlled trials reporting acute GVHD endpoints in 379 patients found a relative risk of acute GVHD of 0.68 (95% CI, 0.45-1.02) in IVIG recipients compared to untreated controls. Overall mortality reported in 809 patients in these trials showed an odds ratio of mortality of 0.74 (0.55-0.99) in IVIG recipients compared to controls (values < 1.0 suggest that IVIG was effective in preventing the event). More recently it has been shown that in the absence of hypogammaglobulinaemia, IVIG (500 mg/kg) given monthly from day 90 to 360 did not reduce the incidence of chronic GVHD or late complications. Future research is aimed at characterizing the mechanism of action of suppression of acute GVHD with weekly IVIG prophylaxis and the role of IVIG prophylaxis in patients receiving unrelated marrow grafts.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Immunomodulation in allogeneic marrow transplantation: use of intravenous immune globulin to suppress acute graft-versus-host disease." Clin Exp Immunol 104 Suppl 1 (May 1996): 43-48. (Review)
PMID
8625543
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
104 Suppl 1
Publish Date
1996
Start Page
43
End Page
48

Barriers to bone marrow transplantation for sickle cell anemia.

While allogeneic marrow transplantation is curative therapy for patients with sickle cell anemia, only a small fraction of patients in the United States receive this treatment. We surveyed participants in our multicenter study of marrow transplantation for sickle cell anemia to determine reasons for not proceeding to transplantation. Among the 4848 patients less than 16 years of age with sickle cell anemia that were followed in 22 collaborating centers, 315 (6.5%) patients were reported to meet protocol entry criteria for transplantation, although there was wide variation among the institutions (0.9-36%). Among the 315 patients eligible for transplantation, 128 (41%) had human leukocyte antigen (HLA) typing performed, and of these 44 (14% of those meeting entry criteria) had an HLA-identical sibling. Common reasons for not proceeding with HLA typing in the remaining 187 patients included lack of a candidate sibling donor (76 patients, 24% of those meeting criteria) and lack of financial or psychosocial support (33, 10.5%). Parental refusal (30, 9.5%), physician refusal (13, 4%), history of medical noncompliance (2, < 1%), and other reasons (33, 10.5%) were less frequently cited. To date, 25 patients have been transplanted. Of the remaining 19 patients with HLA-matched donors, seven did not proceed to transplantation because of parental refusal, while the others anticipate a future transplantation (6), have experienced symptomatic improvement (4), or have relocated abroad (2). We conclude that the major barrier to marrow transplantation for sickle cell anemia is lack of an HLA-identical donor. But since only 6.5% of all children with sickle cell disease were considered eligible for transplantation, it is possible that other significant obstacles remain to be identified. For patients reported to meet eligibility criteria, parental refusal and limited financial or psychosocial support were infrequent barriers to transplantation.

Authors
Walters, MC; Patience, M; Leisenring, W; Eckman, JR; Buchanan, GR; Rogers, ZR; Olivieri, NE; Vichinsky, E; Davies, SC; Mentzer, WC; Powars, D; Scott, JP; Bernaudin, F; Ohene-Frempong, K; Darbyshire, PJ; Wayne, A; Roberts, IA; Dinndorf, P; Brandalise, S; Sanders, JE; Matthews, DC; Appelbaum, FR; Storb, R; Sullivan, KM
MLA Citation
Walters, MC, Patience, M, Leisenring, W, Eckman, JR, Buchanan, GR, Rogers, ZR, Olivieri, NE, Vichinsky, E, Davies, SC, Mentzer, WC, Powars, D, Scott, JP, Bernaudin, F, Ohene-Frempong, K, Darbyshire, PJ, Wayne, A, Roberts, IA, Dinndorf, P, Brandalise, S, Sanders, JE, Matthews, DC, Appelbaum, FR, Storb, R, and Sullivan, KM. "Barriers to bone marrow transplantation for sickle cell anemia." Biol Blood Marrow Transplant 2.2 (May 1996): 100-104.
PMID
9118298
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
2
Issue
2
Publish Date
1996
Start Page
100
End Page
104

Marrow transplantation for hepatitis-associated aplastic anemia: a follow-up of long-term survivors.

Between 1971 and 1989 we have treated 19 patients with hepatitis-associated aplastic anemia by marrow transplantation from their HLA-identical siblings following conditioning with 200 mg/kg cyclophosphamide (Cy) administered over a period of 4 days. One patient failed to engraft by day 34 and was given a second transplantation. He died from infection 15 days after the second transplantation. Eighteen patients had sustained engraftment. Six patients developed acute graft-vs.-host disease (GVHD) and two of these patients died 2.8 and 3.3 months after transplantation. Fifteen patients are surviving 4 to 24 (median 13) years after transplantation, while one patient died in a car accident 17 years after successful transplantation. Six of the surviving patients developed chronic GVHD. Two of the patients with chronic GVHD had preceding acute GVHD and four did not. Five of the six patients with chronic GVHD received donor buffy coat cells in addition to the marrow inoculum to prevent graft rejection. Twelve of the 15 surviving patients have Karnofsky performance scores of 100%. One patient, living more than 4 years after transplantation, has a Karnofsky score of 40% because of persistent cognitive deficits following non-A, non-B hepatitis with hepatic coma. Two patients developed hepatitis C infection 12 and 18 years after transplantation, respectively. Except for mild fatigue and mildly elevated liver function tests, these patients are doing well with Karnofsky performance scores between 95 and 100%. One patient developed severe coronary artery disease 10 years after transplantation, decreasing his Karnofsky performance score to 80%. Serum samples before and after transplantation from 13 patients were tested for hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA by polymerase chain reaction (PCR). Only one patient tested positive for HCV RNA before transplantation. Seven of 15 sera were hepatitis C RNA-positive posttransplantation, but only one of these patients has developed active hepatitis C. All 13 patients were were negative for hepatitis B surface antigen and HBV DNA. Only one patient had IgM antibodies against hepatitis A virus (HAV) before transplantation, which suggested HAV infection. Hepatitis-associated aplastic anemia apparently was caused in most patients by a non-A, non-B, non-C agent. HLA-identical marrow transplantation for hepatitis-associated aplastic anemia with Cy as conditioning regimen is well-tolerated and has a long-term event-free survival in excess of 80%, not different from results of marrow transplantations for aplastic anemia of other etiologies.

Authors
Kiem, HP; McDonald, GB; Myerson, D; Spurgeon, CL; Deeg, HJ; Sanders, JE; Doney, K; Appelbaum, FR; Sullivan, KM; Witherspoon, RP; Storb, R
MLA Citation
Kiem, HP, McDonald, GB, Myerson, D, Spurgeon, CL, Deeg, HJ, Sanders, JE, Doney, K, Appelbaum, FR, Sullivan, KM, Witherspoon, RP, and Storb, R. "Marrow transplantation for hepatitis-associated aplastic anemia: a follow-up of long-term survivors." Biol Blood Marrow Transplant 2.2 (May 1996): 93-99.
PMID
9118304
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
2
Issue
2
Publish Date
1996
Start Page
93
End Page
99

Unrelated donor marrow transplantation for myelodysplasia (MDS) and MDS-related acute myeloid leukaemia.

Allogeneic marrow transplantation using related marrow donors for myelodysplasia (MDS) and acute myeloid leukaemia (AML) arising from MDS results in 35-56% actuarial disease-free survival. Because the use of unrelated donors has not been well-characterized, we report on the outcome of 52 patients with MDS or MDS-related AML consecutively treated between 1987 and 1993 with unrelated donor marrow transplantation. The median age was 33 (range 1-53) years. 33 patients received chemotherapy and total body irradiation and the remainder busulfan and cyclophosphamide. The donors were phenotypically identical at the HLA-A, B and Dw/DRB1 loci in 34 cases and mismatched for one HLA locus in 17 cases and two loci in one case. Marrow was non-T-cell depleted and methotrexate with cyclosporine or FK506 was used for postgrafting immunosuppression. The 2-year disease-free survival, relapse, and non-relapse mortality rates were 38%, 28% and 48%, respectively. One patient who relapsed survives disease-free after withdrawal of immunosuppressive therapy. 16/19 survivors have a performance status of 90-100%. Patients with MDS in transformation or with AML had a significantly higher risk of relapse than patients with less advanced disease (P = 0.0014). Increased non-relapse mortality was significantly associated with higher age, longer disease duration before transplant, lower neutrophil count on admission and, unexpectedly, being seronegative for cytomegalovirus. We conclude that the outcome with transplantation using unrelated donors is similar to reported results using related donors and that a meaningful proportion of eligible patients with an otherwise incurable disease may be cured with this treatment. However, mortality from the transplant procedure is high and future studies should focus on reducing toxicity.

Authors
Anderson, JE; Anasetti, C; Appelbaum, FR; Schoch, G; Gooley, TA; Hansen, JA; Buckner, CD; Sanders, JE; Sullivan, KM; Storb, R
MLA Citation
Anderson, JE, Anasetti, C, Appelbaum, FR, Schoch, G, Gooley, TA, Hansen, JA, Buckner, CD, Sanders, JE, Sullivan, KM, and Storb, R. "Unrelated donor marrow transplantation for myelodysplasia (MDS) and MDS-related acute myeloid leukaemia." Br J Haematol 93.1 (April 1996): 59-67.
PMID
8611476
Source
pubmed
Published In
British Journal of Haematology
Volume
93
Issue
1
Publish Date
1996
Start Page
59
End Page
67

Allogeneic marrow transplantation for aplastic anaemia associated with dyskeratosis congenita.

Eight patients with aplastic anaemia associated with dyskeratosis congenita received allogeneic marrow grafts from either HLA-identical siblings (six patients) or HLA-matched unrelated donors (two patients). Patients who received marrow from HLA-identical siblings were conditioned with cyclophosphamide (140-200 mg/kg), with or without antithymocyte globulin. Patients who received unrelated donor marrow were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (1200 cGy). The six patients who survived for >2 weeks following transplant all had haematological evidence of engraftment, and all three patients who survived for at least a year following transplant recovered normal haematological function. Three patients died with respiratory failure and pulmonary fibrosis at 70 d. 8 years and 20 years posttransplant; three patients died during the neutropenic period of invasive fungal infections; one patient died on day 44 of refractory acute graft-versus-host disease; and one patient remains alive 463 d following transplant. The surviving patient recently underwent surgical resection of a Dukes' stage C rectal carcinoma diagnosed 14 months posttransplant. The aplastic anaemia associated with dyskeratosis congenita can be successfully treated by allogeneic bone marrow transplantation; however, this approach does not reverse the other systemic manifestations of the syndrome. The pathogenesis of the intestinal lung disease observed in dyskeratosis congenita patients following marrow transplantation is not understood.

Authors
Langston, AA; Sanders, JE; Deeg, HJ; Crawford, SW; Anasetti, C; Sullivan, KM; Flowers, ME; Storb, R
MLA Citation
Langston, AA, Sanders, JE, Deeg, HJ, Crawford, SW, Anasetti, C, Sullivan, KM, Flowers, ME, and Storb, R. "Allogeneic marrow transplantation for aplastic anaemia associated with dyskeratosis congenita." Br J Haematol 92.3 (March 1996): 758-765.
PMID
8616050
Source
pubmed
Published In
British Journal of Haematology
Volume
92
Issue
3
Publish Date
1996
Start Page
758
End Page
765

Bone density loss during treatment of chronic GVHD.

Nine adult patients 31-47 (median 39) years of age treated with prednisone and cyclosporin A (CsA) for chronic graft-versus-host disease (GVHD) were evaluated for biochemical factors associated with skeletal turnover at initiation of immunosuppressive therapy (3 months after marrow transplant) and 9 months later (follow-up). Absorptiometry studies of the wrist and lumbar spine were also performed. Serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D) were decreased at enrollment, particularly in the six males. Values for all nine patients remained low at follow-up. Levels of serum 25-hydroxycholecalciferol (25(OH)D), parathyroid hormone, and ionized calcium were normal at enrollment and follow-up. Mean urine hydroxyproline and calcium levels were elevated at enrollment, suggesting increased bone resorption; the mean values decreased to the high normal range at follow-up. Urine magnesium excretion was elevated in eight of nine patients at baseline and remained elevated at follow-up in three of eight evaluable patients. Single and dual photon absorptiometry of the wrist and spine, respectively, and dual energy X-ray absorptiometry of the spine, were utilized to evaluate bone mineral density over time. The precision of these tests was, respectively, +/- 3.5%, +/- 3.1% and +/- 1.0%. Results showed a significant ( > 2.5 times the precision) decrease over 9 months in bone mineral density in three of five evaluable males and all three females. The findings indicate increased collagen and bone turnover, increased urinary magnesium and calcium excretion and a significant risk of osteoporosis in patients receiving treatment for chronic GVHD. Preventive measures, including gonadal hormone replacement in females, should be initiated early after transplantation. Further studies are needed to identify patients at highest risk of bone loss and to monitor the effects of preventive therapy.

Authors
Stern, JM; Chesnut, CH; Bruemmer, B; Sullivan, KM; Lenssen, PS; Aker, SN; Sanders, J
MLA Citation
Stern, JM, Chesnut, CH, Bruemmer, B, Sullivan, KM, Lenssen, PS, Aker, SN, and Sanders, J. "Bone density loss during treatment of chronic GVHD." Bone Marrow Transplant 17.3 (March 1996): 395-400.
PMID
8704693
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
17
Issue
3
Publish Date
1996
Start Page
395
End Page
400

A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery.

To determine whether intravenous immunoglobulin (IVIg) given monthly from day 90 to day 360 posttransplantation decreased the incidence of late infection, chronic graft-vs.-host disease (GVHD), and obliterative bronchiolitis after marrow transplantation, patients were assigned randomly to receive either IVIg (500 mg/kg/month) or no IVIg prophylaxis. Participants were registered before transplantation, and 250 patients (123 IVIg and 127 control) were evaluable for events after day 100. The two groups were balanced for age, marrow source, cytomegalovirus (CMV) seropositivity, pretransplantation conditioning, and prophylaxis for infection and GVHD. Between days 100 and 365 posttransplantation, the incidence of bacteremia or septicemia per 100 patient-days of risk was 0.10 in the IVIg group and 0.12 in the controls (p = not significant). During the same period, the incidence of localized infection was marginally higher in control patients than in IVIg recipients (0.44 vs. 0.24, respectively; relative risk [RR] 1.46, p < 0.07). Administration of IVIg prophylaxis had no effect on survival, the incidence of obliterative bronchiolitis, severity of airflow obstruction, or the incidence or mortality of chronic GVHD. After discontinuing IVIg prophylaxis at day 360, subsequent recovery of endogeneous humoral immunity was impaired (serum IgG1 and IgA levels were significantly lower than controls at day 730), and total infections were less common in the second year in control patients than in former IVIg recipients (0.12 vs 0.19, respectively; RR 0.61, p = 0.03). We conclude that in the absence of hypogammaglobulinemia, monthly administration of IVIg given from day 90 to 360 does not reduce late complications and may impair long-term humoral immune recovery after marrow transplantation.

Authors
Sullivan, KM; Storek, J; Kopecky, KJ; Jocom, J; Longton, G; Flowers, M; Siadak, M; Nims, J; Witherspoon, RP; Anasetti, C; Appelbaum, FR; Bowden, RA; Buckner, CD; Crawford, SW; Deeg, HJ; Hansen, JA; McDonald, GB; Sanders, JE; Storb, R
MLA Citation
Sullivan, KM, Storek, J, Kopecky, KJ, Jocom, J, Longton, G, Flowers, M, Siadak, M, Nims, J, Witherspoon, RP, Anasetti, C, Appelbaum, FR, Bowden, RA, Buckner, CD, Crawford, SW, Deeg, HJ, Hansen, JA, McDonald, GB, Sanders, JE, and Storb, R. "A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery." Biol Blood Marrow Transplant 2.1 (February 1996): 44-53.
PMID
9078354
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
2
Issue
1
Publish Date
1996
Start Page
44
End Page
53

Bone marrow transplantation for severe aplastic anemia from genotypically HLA-nonidentical relatives. An update of the Seattle experience.

This report updates the results of marrow transplantation at the Fred Hutchinson Cancer Research Center for patients with severe aplastic anemia whose donors were HLA-nonidentical relatives. Between 1970 and 1993, 40 patients received transplants for severe aplastic anemia from related donors other than HLA genotypically matched siblings. Nine patients (group 1) were conditioned with cyclophosphamide (Cy) at 50 mg/kg for 4 doses and received marrow from phenotypically HLA-matched relatives. With the exception of one accidental death, all patients are alive and disease free 3-18 years after transplantation. Thirty-one patients received marrow from HLA-mismatched relatives who differed by one or more loci. Fifteen of these patients (group 2) received Cy at 50 mg/kg for 4 doses without total body irradiation (TBI) and none survived. Because of failure to sustain engraftment in 9 of 14 evaluable patients in group 2, the regimen for HLA-mismatched patients was changed in 1984 to include Cy at 60 mg/kg for 2 doses and TBI was added at 1200 cGy to increase immunosuppression (group 3). Sixteen patients in group 3 received marrow grafts after failure to respond to immunosuppressive therapy. Eight of the 16 patients in group 3 remain alive without disease between 1.5 and 11.3 years after transplantation. In conclusion, transplants from phenotypically HLA-identical related donors can be carried after Cy alone and results are comparable to those observed with genotypically HLA-identical siblings. Transplants from related donors mismatched for one or more HLA loci require a more intensive conditioning regimen, for example, one containing TBI, to achieve sustained engraftment.

Authors
Wagner, JL; Deeg, HJ; Seidel, K; Anasetti, C; Doney, K; Sanders, J; Sullivan, KM; Storb, R
MLA Citation
Wagner, JL, Deeg, HJ, Seidel, K, Anasetti, C, Doney, K, Sanders, J, Sullivan, KM, and Storb, R. "Bone marrow transplantation for severe aplastic anemia from genotypically HLA-nonidentical relatives. An update of the Seattle experience." Transplantation 61.1 (January 15, 1996): 54-61.
PMID
8560574
Source
pubmed
Published In
Transplantation
Volume
61
Issue
1
Publish Date
1996
Start Page
54
End Page
61

Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients.

Risk factors for the development of a new (secondary) malignancy after marrow transplantation are still incompletely defined. In the present study, we analyzed results in 700 patients with severe aplastic anemia treated with allogeneic marrow transplantation at the Fred Hutchinson Cancer Research Center in Seattle, WA, or at the Hôpital St Louis in Paris, France. Twenty-three patients developed a malignancy 1.4 to 221 months (median, 91 months) after transplantation for a Kaplan-Meier estimate of 14% (95% confidence interval, 4% to 24%) at 20 years. Five cases were lymphoid malignancies (two acute lymphoblastic leukemias and three lymphoproliferative disorders) occurring 1.4 to 14.6 months (median, 3 months) posttransplant, and 18 were solid tumors (17 squamous cell and one mucoepidermoid carcinoma) presenting 30 to 221 months (median, 99 months) posttransplant. Thus, the hazard for lymphoid malignancies declined rapidly posttransplant, while the hazard for solid tumors increased progressively with time posttransplant. Risk factors for solid tumors identified in univariable analysis included the underlying diagnosis of Fanconi anemia (P = .0002), azathioprine therapy for chronic graft-versus-host disease (GVHD) (P < .0001), irradiation (total body or thoracoabdominal) as part of the conditioning regimen (P = .0002), chronic GVHD (P = .0099), acute GVHD (P = .0135), and male sex (P = .0499). In multivariable, stepwise proportional hazards models, azathioprine therapy (P < .0001) and the diagnosis of Fanconi anemia (P < .0001) were significant factors for all patients. Irradiation was a significant factor (P = .004) only if the time-dependent variable azathioprine was not included in the analysis. If only non-Fanconi patients were considered, azathioprine (P = .0043), age (P = .025), and irradiation (P = .042) were significant factors. Results in patients with Fanconi anemia and malignancies other than solid tumors were not subjected to an analysis because of the small number of events. It is of note, however, that no case of myeloproliferative disorder was observed. In summary, the highest risk of developing a solid tumor was associated with the diagnosis of Fanconi anemia. Better prevention of GVHD or omission of azathioprine as GVHD therapy (or both) may reduce the risk of late tumor development. Similarly, nonirradiation conditioning regimens may reduce the tumor risk, at least in patients without Fanconi anemia. Interactions between potential risk factors are complex, and further observation and additional analyses will be of interest.

Authors
Deeg, HJ; Socié, G; Schoch, G; Henry-Amar, M; Witherspoon, RP; Devergie, A; Sullivan, KM; Gluckman, E; Storb, R
MLA Citation
Deeg, HJ, Socié, G, Schoch, G, Henry-Amar, M, Witherspoon, RP, Devergie, A, Sullivan, KM, Gluckman, E, and Storb, R. "Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients." Blood 87.1 (January 1, 1996): 386-392.
PMID
8547667
Source
pubmed
Published In
Blood
Volume
87
Issue
1
Publish Date
1996
Start Page
386
End Page
392

Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors.

From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3-year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.

Authors
Anderson, JE; Appelbaum, FR; Schoch, G; Gooley, T; Anasetti, C; Bensinger, WI; Bryant, E; Buckner, CD; Chauncey, TR; Clift, RA; Doney, K; Flowers, M; Hansen, JA; Martin, PJ; Matthews, DC; Sanders, JE; Shulman, H; Sullivan, KM; Witherspoon, RP; Storb, R
MLA Citation
Anderson, JE, Appelbaum, FR, Schoch, G, Gooley, T, Anasetti, C, Bensinger, WI, Bryant, E, Buckner, CD, Chauncey, TR, Clift, RA, Doney, K, Flowers, M, Hansen, JA, Martin, PJ, Matthews, DC, Sanders, JE, Shulman, H, Sullivan, KM, Witherspoon, RP, and Storb, R. "Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors." Blood 87.1 (January 1, 1996): 51-58.
PMID
8547676
Source
pubmed
Published In
Blood
Volume
87
Issue
1
Publish Date
1996
Start Page
51
End Page
58

Secondary immunodeficiencies and stem cell transplantation: issues of administration and safety of intravenous immunoglobulin.

This article reviews the administration, efficacy, and safety of prophylactic intravenous immunoglobulin in patients with secondary immunodeficiency and those undergoing allogeneic bone marrow transplantation. Associated infections in these immunosuppressed patients are examined as they relate to transfusion-associated transmission, graft-versus-host disease, and other factors. In addition, the safety issues (including infection with cytomegalovirus and hepatitis C virus) involved in hematopoietic stem cell transplant patients given intravenous immunoglobulin are detailed by long-term follow-up of controlled clinical trials.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Secondary immunodeficiencies and stem cell transplantation: issues of administration and safety of intravenous immunoglobulin." Clin Ther 18 Suppl B (1996): 126-136.
PMID
8930450
Source
pubmed
Published In
Clinical Therapeutics
Volume
18 Suppl B
Publish Date
1996
Start Page
126
End Page
136

Allogeneic Marrow Transplantation for Myelodysplastic Syndrome with Advanced Disease Morphology: A Phase II Study of Busulfan, Cyclophosphamide, and Total-Body Irradiation and Analysis of Prognostic Factors

Purpose: To determine if an intensive preparative regimen of busulfan (BU), cyclophosphamide (CY), and total-body irradiation (TBI) could improve outcome after marrow transplantation for advanced morphology myelodysplasia (refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEB-T], and chronic myelomonocytic leukemia [CMML]) compared with that obtained with conventional CY/TBI and to analyze prognostic factors for transplantation for myelodysplasia. Patients and Methods: A phase II study was conducted of 31 patients (median age, 41 years) treated with BU (7 mg/kg), CY (50 mg/kg), TBI (12 Gy), and human leukocyte antigen (HLA)-matched (n = 23) or -mismatched (n = 2) related or unrelated donor (n = 6) marrow transplantation. Results were compared with 44 historical control patients treated with CY (120 mg/kg) and TBI. Results: The 3-year actuarial disease-free survival (DFS) rate was similar for the BU/CY/TBI group and the CY/TBI group (23% v 30%, P = .6), but there were trends toward lower relapse rates (28% v 54%, P = .27) and higher nonrelapse mortality rates (68% v 36%, P = .12) among the current patients compared with historical controls. Multivariate analysis showed that a normal karyotype pretransplant and the use of methotrexate as part of posttransplant immunosuppression were associated with improved survival and reduced nonrelapse mortality. Univariate analysis showed significant differences in relapse rates based on marrow source (57% for HLA genotypically matched marrow v 18% for all others, P = .04) and on disease morphology (66% for RAEB-T v 38% for RAEB and CMML, P = .05). Conclusion: Patients with advanced morphology myelodysplasia tolerated the intensified BU/CY/TBI preparative regimen and reduced posttransplant immunosuppression poorly. Novel transplant procedures are needed to reduce relapse rates without increasing nonrelapse mortality rates. In addition, transplantation before progression to RAEB-T, if possible, may reduce the risk of relapse. © 1996 by American Society of Clinical Oncology.

Authors
Anderson, JE; Appelbaum, FR; Schoch, G; Gooley, T; Anasetti, C; Bensinger, WI; Bryant, E; Buckner, CD; Chauncey, T; Clift, RA; Deeg, HJ; Doney, K; Flowers, M; Hansen, JA; Martin, PJ; Matthews, DC; Nash, RA; Sanders, JE; Shulman, H; Sullivan, KM; Witherspoon, RP; Storb, R
MLA Citation
Anderson, JE, Appelbaum, FR, Schoch, G, Gooley, T, Anasetti, C, Bensinger, WI, Bryant, E, Buckner, CD, Chauncey, T, Clift, RA, Deeg, HJ, Doney, K, Flowers, M, Hansen, JA, Martin, PJ, Matthews, DC, Nash, RA, Sanders, JE, Shulman, H, Sullivan, KM, Witherspoon, RP, and Storb, R. "Allogeneic Marrow Transplantation for Myelodysplastic Syndrome with Advanced Disease Morphology: A Phase II Study of Busulfan, Cyclophosphamide, and Total-Body Irradiation and Analysis of Prognostic Factors." Journal of Clinical Oncology 14.1 (1996): 220-226.
PMID
8558201
Source
scival
Published In
Journal of Clinical Oncology
Volume
14
Issue
1
Publish Date
1996
Start Page
220
End Page
226

Marrow transplantation for Fanconi anaemia: Conditioning with reduced doses of cyclophosphamide without radiation

Nine patients with Fanconi anaemia (FA) were conditioned for HLA-identical sibling bone marrow transplant (BMT) with reduced dose of cyclophosphamide (Cy) without radiation or antithymocyte globulin (ATG). The total dose of Cy was 140 mg/kg (n=2) or 120 mg/kg (n=7). The median patient age was 8 years (range 4-19). Graft-versus-host disease (GVHD) prophylaxis was with methotrexate and cyclosporine (n = 8) or cyclosporine alone (n = 1). All patients had sustained engraftment and two developed grade ≥ II acute GVHD. Cy toxicity included grade ≥2 mucositis seen in all evaluable patients and haemorrhagic cystitis in two patients. The Kaplan-Meier survival estimate is 89% with a median follow-up of 285 d (range 56-528). For the purpose of comparison, this report also reviews and updates long-term follow-up data on 32 previously reported FA patients conditioned with 140-200 mg Cy/kg without radiation. The lowest dose of Cy (without radiation or ATG) after which HLA-identical sibling marrow transplant can be successfully performed in FA patients has yet to be determined, but it appears that uniform and sustained engraftment can be achieved with a Cy dose of as low as 120 mg/kg.

Authors
Flowers, MED; Zanis, J; Pasquini, R; Deeg, HJ; Ribeiro, R; Longton, G; Medeiros, CR; Doney, K; Sanders, J; Bryant, E; Hansen, J; Sullivan, KM; Appelbaum, F; Thomas, ED; Storb, R
MLA Citation
Flowers, MED, Zanis, J, Pasquini, R, Deeg, HJ, Ribeiro, R, Longton, G, Medeiros, CR, Doney, K, Sanders, J, Bryant, E, Hansen, J, Sullivan, KM, Appelbaum, F, Thomas, ED, and Storb, R. "Marrow transplantation for Fanconi anaemia: Conditioning with reduced doses of cyclophosphamide without radiation." British Journal of Haematology 92.3 (1996): 699-706.
PMID
8616040
Source
scival
Published In
British Journal of Haematology
Volume
92
Issue
3
Publish Date
1996
Start Page
699
End Page
706

IVIG in bone marrow transplantation

The principal causes of allogeneic transplant-related mortality are graft- versus-host disease (GVHD), interstitial pneumonia, and cytomegalovirus (CMV) infection. In bone marrow-transplant recipients, intravenous immunoglobulin (IVIG) has shown the ability to reduce the incidence of symptomatic CMV infection and interstitial pneumonia. Reductions in acute GVHD, bacteremia, septicemia, and local infection have been observed in IVIG recipients in the first 100 days post-transplant. Reduction in transplant-related mortality has also been observed, especially among adult patients receiving allogeneic marrow grafts.

Authors
Sullivan, K
MLA Citation
Sullivan, K. "IVIG in bone marrow transplantation." P and T 21.4 SUPPL. (1996): 17S-20S.
Source
scival
Published In
P and T
Volume
21
Issue
4 SUPPL.
Publish Date
1996
Start Page
17S
End Page
20S

Bone marrow transplantation for sickle cell disease [4]

Authors
Rehman, KL; Sullivan, KM; Walters, MC; Ohene-Frempong, K
MLA Citation
Rehman, KL, Sullivan, KM, Walters, MC, and Ohene-Frempong, K. "Bone marrow transplantation for sickle cell disease [4]." New England Journal of Medicine 335.24 (1996): 1845-1846.
PMID
8965897
Source
scival
Published In
The New England journal of medicine
Volume
335
Issue
24
Publish Date
1996
Start Page
1845
End Page
1846
DOI
10.1056/NEJM199612123352415

Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation

Patients successfully treated with a marrow transplant often have concerns about fertility and pregnancy. This study was performed to determine pregnancy outcome among patients who had received high-dose chemotherapy alone or with total-body irradiation (TBI) and marrow transplantation for aplastic anemia or hematologic malignancy. Records of 1,326 postpubertal and 196 prepubertal patients currently more than 12 years of age after marrow transplant in Seattle from August 1971 to January 1992 were reviewed to determine the patients with normal gonadal function and pregnancies. Among 708 postpubertal women, 110 recovered normal ovarian function and 32 became pregnant. In addition, nine formerly prepubertal girls with normal gonadal function became pregnant. Among 618 postpubertal men, 157 recovered testicular function and partners of 33 became pregnant. An additional two formerly prepubertal men had partners who became pregnant. Forty-one female patients and partners of 35 male patients had 146 pregnancies after transplant. All 76 patients responded to a questionnaire requesting pregnancy history, outcome, infant birth weight, and congenital anomalies information for all clinically recognized pregnancies. There were 115 live births among 146 (79%) pregnancies. Spontaneous abortion terminated four of 56 (7%) pregnancies for 28 female cyclophosphamide (CY) recipients and six of 16 (37%) pregnancies for 13 TBI recipients (P = .02). Partners of 28 male CY recipients had four of 62 (6.4%) pregnancies terminate with spontaneous abortion, but there were no spontaneous abortions among eight pregnancies of five TBI recipients' partners. Preterm delivery occurred for eight of 44 (18%) and five of eight (63%) live births for 24 CY and eight TBI female recipients (P = .01). This 25% incidence among all female patient pregnancies is higher than the expected incidence of 8% to 10% (P = .0001). The 13 preterm deliveries resulted in 10 low birth weight ([LBW] 1.8 to 2.24 kg) and three very low birth weight ([VLBW] ≤ 1.36 kg) infants, for an overall incidence of 25%, which is higher than the expected incidence of 6.5% for the general population (P = .0001). Twelve of the 13 premature infants survive. Congenital anomalies were seen among two of 52 (3.8%) live-born infants of female and six of 63 (9.5%) live-born infants of male patients, which is not different from the 13% of single congenital anomalies reported for the general population. These data demonstrate that clinically recognized pregnancies among women who have received a marrow transplant incorporating TBI are likely to be accompanied by an increased risk of spontaneous abortion. Pregnancies among all women who received a marrow transplant are likely to be accompanied by preterm labor and delivery of LBW or VLBW babies who do not seem to be at an increased risk of congenital anomalies. However, determination of possible adverse effects of parental exposure to high-dose alkylating agents with or without TBI on children born posttransplant requires longer, additional follow-up. © 1996 by The American Society of Hematology.

Authors
Sanders, JE; Hawley, J; Levy, W; Gooley, T; Buckner, CD; Deeg, HJ; Doney, K; Storb, R; Sullivan, K; Witherspoon, R; Appelbaum, FR
MLA Citation
Sanders, JE, Hawley, J, Levy, W, Gooley, T, Buckner, CD, Deeg, HJ, Doney, K, Storb, R, Sullivan, K, Witherspoon, R, and Appelbaum, FR. "Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation." Blood 87.7 (1996): 3045-3052.
PMID
8639928
Source
scival
Published In
Blood
Volume
87
Issue
7
Publish Date
1996
Start Page
3045
End Page
3052

A retrospective analysis of the long-term effect of splenectomy on late infections, graft-versus-host disease, relapse, and survival after allogeneic marrow transplantation for chronic myelogenous leukemia.

The present study was performed as a retrospective analysis of the role of pretransplant splenectomy to determine the incidence of late bacterial infections, acute and chronic graft-versus-host disease (GVHD), relapse, and survival among 358 patients receiving HLA-identical marrow grafts for chronic myelogenous leukemia. Sixty-eight (19%) of the 358 patients had undergone splenectomy before transplantation. There was a trend towards more grade II-IV acute GVHD among splenectomized patients, but this was not significant in the multivariate analysis. The incidence of chronic GVHD was similar for splenectomized and nonsplenectomized patients. Late infectious complications did not significantly differ between splenectomized and control patients (rates per patient year were 0.16 and 0.14, respectively). The overall risk of leukemic relapse was significantly increased for splenectomized patients (56% v 32% for controls, P = .001) and control patients with splenomegaly (P < .0001). Splenectomy and splenomegaly remained significant and independent hazards for relapse in the multivariate analysis (hazard ratio [HR], 1.82, P = .029; and HR, 1.49, P = .002; respectively). Relapse was also increased in patients with advanced disease (HR, 2.95; P = .0001), in patients with T-cell-depleted marrow (HR, 4.51; P = .0001), and in the female donor and male recipient combination (HR, 1.74; P = .044). Patients with splenectomy had an increased overall mortality (HR, 1.18), but this was not statistically significant in the multivariate analysis. In summary, our study showed no significant influence of splenectomy on late posttransplant infections, acute or chronic GVHD, or overall survival. There was no evidence that splenectomy decreased recurrence of chronic myelogenous leukemia.

Authors
Kalhs, P; Schwarzinger, I; Anderson, G; Mori, M; Clift, RA; Storb, R; Buckner, CD; Appelbaum, FR; Hansen, JA; Sullivan, KM
MLA Citation
Kalhs, P, Schwarzinger, I, Anderson, G, Mori, M, Clift, RA, Storb, R, Buckner, CD, Appelbaum, FR, Hansen, JA, and Sullivan, KM. "A retrospective analysis of the long-term effect of splenectomy on late infections, graft-versus-host disease, relapse, and survival after allogeneic marrow transplantation for chronic myelogenous leukemia." Blood 86.5 (September 1, 1995): 2028-2032.
PMID
7655031
Source
pubmed
Published In
Blood
Volume
86
Issue
5
Publish Date
1995
Start Page
2028
End Page
2032

A toxicity study of trimetrexate used in combination with cyclosporine as acute graft-versus-host disease prophylaxis in HLA-mismatched, related donor bone marrow transplants.

This study evaluated the acute toxicity of trimetrexate (TMTX) used in combination with cyclosporine (CsA) for prevention of acute graft-versus-host disease (GVHD) in patients undergoing allogeneic marrow transplantation from HLA-mismatched, related donors. TMTX has a mechanism of action similar to that of methotrexate (MTX); however, unlike MTX, TMTX is not primarily dependent on renal excretion. Patients were conditioned for transplant with cyclophosphamide, anti-thymocyte globulin, and total body irradiation. TMTX, 10 mg/m2 i.v., was administered on days 1, 3, 6, 11, 18, 25, 32, and 39 after transplant. CsA, 1.5 mg/kg i.v., was administered every 12 hr beginning on day-1. Eleven patients with hematologic malignancies or aplastic anemia (median age = 34 yr) received TMTX. Toxicity assessed included nausea, vomiting, fever, rash, time to myeloid and platelet engraftment, mucositis, and hepatic and renal dysfunction. Toxicity of TMTX was not different from that observed with MTX in a similar patient population. One patient died on day 16 before engraftment. The other 10 patients all engrafted and all developed acute GVHD at a median time of 11 days after transplant. The major manifestation of acute GVHD was in the skin, and all but one patient responded to primary therapy with corticosteroids. Seven patients have survived a median of 447 days after transplant. No significant toxicity from TMTX was observed. Further trials are warranted to define the role of TMTX in marrow transplantation.

Authors
Doney, KC; Storb, R; Beach, K; Anasetti, C; Deeg, HJ; Hansen, JA; Martin, PJ; Nash, RA; Schubert, MM; Sullivan, KM
MLA Citation
Doney, KC, Storb, R, Beach, K, Anasetti, C, Deeg, HJ, Hansen, JA, Martin, PJ, Nash, RA, Schubert, MM, and Sullivan, KM. "A toxicity study of trimetrexate used in combination with cyclosporine as acute graft-versus-host disease prophylaxis in HLA-mismatched, related donor bone marrow transplants." Transplantation 60.1 (July 15, 1995): 55-58.
PMID
7624943
Source
pubmed
Published In
Transplantation
Volume
60
Issue
1
Publish Date
1995
Start Page
55
End Page
58

Cataracts after bone marrow transplantation: long-term follow-up of adults treated with fractionated total body irradiation.

PURPOSE: To determine the risk of, and risk factors for, developing cataracts after bone marrow transplantation. METHODS AND MATERIALS: Four hundred and ninety-two adults who underwent bone marrow transplantation in Seattle were followed for 2 to 18 (median, 6) years. Before transplantation, patients received a preparative regimen of chemotherapy plus total body irradiation (TBI) (n = 407) or chemotherapy alone, without TBI (n = 85). TBI was administered in a single dose of 10 Gy (n = 74) or in fractionated doses totaling 12-15.75 Gy (n = 333). The risk of cataracts was determined for groups of patients with respect to the type of preparative regimen received and other pretransplant and posttransplant variables. RESULTS: One hundred and fifty-nine patients (32%) developed cataracts between 0.5 to 11 (median, 2.3) years after transplantation. The probability of cataracts at 11 years after transplantation was 85%, 50%, 34%, and 19% for patients receiving 10 Gy of single-dose TBI, > 12 Gy fractionated TBI, 12 Gy fractionated TBI, and no TBI, respectively (p < 0.0001). Among those developing cataracts, the severity was greater in patients after single-dose TBI (59% probability of surgical extraction) than after > 12 Gy fractionated TBI, 12 Gy fractionated TBI, or no TBI (33%, 22% and 23%, respectively). Patients given corticosteroids after transplant had a higher probability of cataracts (45%) than those without steroids (38%) (p < 0.0001). In a proportional hazards regression model, the variables that were correlated with an increased probability of cataracts were single-dose TBI (relative risk (RR) = 2.46) and steroid therapy (RR = 2.34), while a decreased probability of cataracts was correlated with a nonTBI preparative regimen (RR = 0.41). The yearly hazard of developing cataracts in recipients of single-dose TBI was highest during the third year after transplantation, while in recipients of fractionated TBI, the hazard was distributed among years one through seven. The probability of cataracts in all groups reached a plateau at 7 years after transplantation, after which the development of cataracts was extremely unlikely. CONCLUSION: TBI is the major risk factor for developing cataracts after BMT. Single-dose TBI results in the highest risk of cataracts. However, the risk of cataracts in recipients of fractionated-TBI is significantly higher than in patients who receive no TBI. In addition to TBI, steroid therapy is an independent risk factor for cataracts after BMT.

Authors
Benyunes, MC; Sullivan, KM; Deeg, HJ; Mori, M; Meyer, W; Fisher, L; Bensinger, R; Jack, MK; Hicks, J; Witherspoon, R
MLA Citation
Benyunes, MC, Sullivan, KM, Deeg, HJ, Mori, M, Meyer, W, Fisher, L, Bensinger, R, Jack, MK, Hicks, J, and Witherspoon, R. "Cataracts after bone marrow transplantation: long-term follow-up of adults treated with fractionated total body irradiation." Int J Radiat Oncol Biol Phys 32.3 (June 15, 1995): 661-670.
PMID
7790252
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
32
Issue
3
Publish Date
1995
Start Page
661
End Page
670

Neurologic complications after allogeneic marrow transplantation for sickle cell anemia.

Seven of 21 patients with sickle cell anemia developed neurologic complications 5 to 243 days (median, 33 days) after allogeneic marrow transplantation. Among these 7 patients, indications for transplantation included either a past history of stroke (4 patients) or recurrent severe vaso-occlusive events (3 patients). All received marrow from an HLA-identical sibling after preparation with busulfan and cyclophosphamide, and in 4 patients with antithymocyte globulin. Five of 6 patients developing seizures received anticonvulsant and supportive treatment with resolution of neurologic abnormalities. Three patients experienced intracranial bleeding, which was fatal in two. Of the 14 patients free of neurologic complications, 4 patients had experienced stroke before transplantation. However, among all patients with prior stroke, the incidence of intracranial hemorrhage was 38% (3/8), whereas none of the 13 patients without prior stroke developed posttransplant intracranial bleeding (P = .026). We conclude that patients with sickle cell anemia are at increased risk for neurologic complications after marrow ablative therapy and that patients with prior stroke are at increased risk for intracranial hemorrhage. Transplantation of patients before the onset of overt stroke may reduce this risk.

Authors
Walters, MC; Sullivan, KM; Bernaudin, F; Souillet, G; Vannier, JP; Johnson, FL; Lenarsky, C; Powars, D; Bunin, N; Ohene-Frempong, K
MLA Citation
Walters, MC, Sullivan, KM, Bernaudin, F, Souillet, G, Vannier, JP, Johnson, FL, Lenarsky, C, Powars, D, Bunin, N, and Ohene-Frempong, K. "Neurologic complications after allogeneic marrow transplantation for sickle cell anemia." Blood 85.4 (February 15, 1995): 879-884.
PMID
7849310
Source
pubmed
Published In
Blood
Volume
85
Issue
4
Publish Date
1995
Start Page
879
End Page
884

Quality of life of 125 adults surviving 6-18 years after bone marrow transplantation.

BACKGROUND: Recent studies examining the medical and psychosocial sequelae of bone marrow transplantation have reported most survivors do relatively well while a smaller group continues to experience less than optimal quality of life (QOL). Many of these studies are limited by small sample sizes, limited scope, and focus on a narrow (1-4 year) window of survival. METHODS: The descriptive survey examined the QOL, late medical complications, psychological distress, demands of long-term recovery, and health perceptions of 125 adults surviving 6-18 (mean 10) years after marrow transplantation. Seven wide-ranging tests covering 271 items were completed on average in 90 min. Two tests were developed by the authors specifically for assessing QOL in this population. RESULTS: 74% of long-term survivors of bone marrow transplantation reported their current QOL was the same or better than before transplantation, 80% rated their current health status and QOL as good to excellent, and 88% said the benefits of transplantation outweighed the side effects. Ten years or more post-transplantation, long-term survivors continued to experience a moderate incidence of lingering complications and demands, including emotional and sexual dysfunction, fatigue, eye problems, sleep disturbance, general pain and cognitive dysfunction. However, the severity or degree of distress attributed to those complications was, for most survivors, consistently low. Nearly all were back to work or school. Only 5% rated both their QOL and health status as poor. Long-term survivors demonstrated good mood and low psychological distress compared to cancer and population norms, and had the same perceptions as the general population of their current health and expectation of future health. Demands attributed to long-term survival appeared to impose little hardship. The most frequently cited demand of recovery was the perceived lack of social support as time went on. CONCLUSIONS: Almost all long-term survivors were leading full and meaningful lives. Persistent complications were, on the whole, dismissed as relatively trivial and the overwhelming majority viewed themselves as cured and well.

Authors
Bush, NE; Haberman, M; Donaldson, G; Sullivan, KM
MLA Citation
Bush, NE, Haberman, M, Donaldson, G, and Sullivan, KM. "Quality of life of 125 adults surviving 6-18 years after bone marrow transplantation." Soc Sci Med 40.4 (February 1995): 479-490.
PMID
7725122
Source
pubmed
Published In
Social Science & Medicine
Volume
40
Issue
4
Publish Date
1995
Start Page
479
End Page
490

High-dose cyclophosphamide, carmustine, and etoposide followed by allogeneic bone marrow transplantation in patients with lymphoid malignancies who had received prior dose-limiting radiation therapy

Purpose: To evaluate a high-dose chemotherapy regimen without total-body irradiation (TBI) followed by allogeneic (allo) bone marrow transplantation (BMT) in patients with lymphoid malignancies who had received prior dose- limiting radiotherapy. Patients and Methods: Fifty-six patients with non- Hodgkin's lymphoma (NHL, n = 26), Hodgkin's disease (HD, n = 17), or acute lymphoblastic leukemia (ALL, n = 13) with a history of previous radiation therapy were treated with cyclophosphamide (7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2; CBV) followed by allo BMT. Results: Nine of 56 patients are alive and disease-free a median of 1,091 (range, 512 to 1,784) days posttransplant. The probabilities of transplant-related mortality, relapse, and event-free survival at 2 years for the entire group of 56 patients were .62, .59, and .17, respectively. Patients who received 600 mg/m2 of carmustine had a higher incidence of grade 3 or 4 regimen-related toxicities (RRTs) (14 of 22) than did patients who received 300 mg/m2 (12 of 33; P < .04), whereas there was no difference in relapse (.34 and .53, respectively, P = .73). Fourteen of 16 patients who received allo BMT for advanced disease (n = 12) or less-advanced disease (n = 4) but who were also eligible far auto BMT relapsed (n = 4) or died of transplant-related complications (n = 10). Conclusion: Allo BMT following a high-dose CBV regimen resulted in long-term disease-free survival in 17% of patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. A high incidence of transplant-related complications, especially fatal idiopathic pneumonia syndrome (IPS) and a high relapse rate limited success. Morbidity and mortality associated with carmustine 600 mg/m2 were high and were not associated with a decrease in relapse. The number of patients in this study eligible for either alia or auto BMT was limited and precluded meaningful analysis of relative effectiveness.

Authors
Demirer, T; Weaver, CH; Buckner, CD; Petersen, FB; Bensinger, WI; Sanders, J; Clift, RA; Lilleby, K; Anasetti, C; Martin, P; Storb, R; Chauncey, T; Doney, K; Sullivan, K; Appelbaum, FR
MLA Citation
Demirer, T, Weaver, CH, Buckner, CD, Petersen, FB, Bensinger, WI, Sanders, J, Clift, RA, Lilleby, K, Anasetti, C, Martin, P, Storb, R, Chauncey, T, Doney, K, Sullivan, K, and Appelbaum, FR. "High-dose cyclophosphamide, carmustine, and etoposide followed by allogeneic bone marrow transplantation in patients with lymphoid malignancies who had received prior dose-limiting radiation therapy." Journal of Clinical Oncology 13.3 (1995): 596-602.
PMID
7884421
Source
scival
Published In
Journal of Clinical Oncology
Volume
13
Issue
3
Publish Date
1995
Start Page
596
End Page
602

Unrelated donor marrow transplantation in children

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acute or chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA- matched and 57% of HLA-mismatched recipients were discharged home disease- free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%. These data show that marrow transplantation from fully or partially HLA-matched unrelated donors can be effective therapy for children with hematologic disorders and that pretransplantation disease status and posttransplantation GVHD remain important factors affecting patient outcome.

Authors
Balduzzi, A; Gooley, T; Anasetti, C; Sanders, JE; Martin, PJ; Petersdorf, EW; Appelbaum, FR; Buckner, CD; Matthews, D; Storb, R; Sullivan, KM; Hansen, JA
MLA Citation
Balduzzi, A, Gooley, T, Anasetti, C, Sanders, JE, Martin, PJ, Petersdorf, EW, Appelbaum, FR, Buckner, CD, Matthews, D, Storb, R, Sullivan, KM, and Hansen, JA. "Unrelated donor marrow transplantation in children." Blood 86.8 (1995): 3247-3256.
PMID
7579422
Source
scival
Published In
Blood
Volume
86
Issue
8
Publish Date
1995
Start Page
3247
End Page
3256

Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: Results and implications in 346 patients

We studied 346 patients after bone marrow transplantation (BMT) for chronic myeloid leukemia (CML) for the presence of the bcr-abl transcript detected by the polymerase chain reaction (PCR) to understand the frequency and implication of a positive test. A total of 634 samples of BM and/or peripheral blood were obtained for PCR analysis between 3 and 192 months after BMT. A positive PCR test at 3 months post-BMT was not statistically significantly associated with an increased risk of relapse compared with PCR- negative patients. However, a positive PCR assay at 6 months and beyond was highly associated with subsequent relapse. The Kaplan-Meier estimate of relapse for patients testing PCR-positive at 6 to 12 months was 42% versus 3% for PCR-negative patients (P < .0001). The Kaplan-Meier estimate of survival at 4 years for the PCR-positive patients was 74% compared with 83% for the PCR-negative group (P = .002). Multivariable analysis indicated that a PCR- positive result at 6 to 12 months post-BMT, the type of BMT donor (allogeneic matched donor v mismatched or unrelated), and the presence of acute GVHD were independent risk factors for subsequent relapse. The relative risk (RR) for relapse for patients PCR-positive at 6 to 12 months post-BMT was 26.1 (95% confidence interval, 8.9 to 76.1, P < .0001). The outcome of long-term patients (>36 months post-BMT) who tested PCR-positive was much better, as 15 of 59 (25%) tested positive for bcr-abl, but only one patient relapsed. There was a 91% concordance between PCR tests of simultaneously obtained BM and peripheral blood. These analyses show that the PCR assay of the bcr-abl fusion transcript 6 to 12 months post-BMT is an independent predictor of subsequent relapse which provides an opportunity for early therapeutic intervention.

Authors
Radich, JP; Gehly, G; Gooley, T; Bryant, E; Clift, RA; Collins, S; Edmands, S; Kirk, J; Lee, A; Kessler, P; Schoch, G; Buckner, CD; Sullivan, KM; Appelbaum, FR; Thomas, ED
MLA Citation
Radich, JP, Gehly, G, Gooley, T, Bryant, E, Clift, RA, Collins, S, Edmands, S, Kirk, J, Lee, A, Kessler, P, Schoch, G, Buckner, CD, Sullivan, KM, Appelbaum, FR, and Thomas, ED. "Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: Results and implications in 346 patients." Blood 85.9 (1995): 2632-2638.
PMID
7727789
Source
scival
Published In
Blood
Volume
85
Issue
9
Publish Date
1995
Start Page
2632
End Page
2638

Immunosuppressive agents for prevention of graft-versus-host disease

Authors
Storb, R; Anasetti, C; Appelbaum, FR; Deeg, HJ; Doney, K; Martin, P; Nash, R; Sullivan, K; Witherpoon, R
MLA Citation
Storb, R, Anasetti, C, Appelbaum, FR, Deeg, HJ, Doney, K, Martin, P, Nash, R, Sullivan, K, and Witherpoon, R. "Immunosuppressive agents for prevention of graft-versus-host disease." Bone Marrow Transplantation 15.SUPPL. 1 (1995): S98-S103.
Source
scival
Published In
Bone Marrow Transplantation
Volume
15
Issue
SUPPL. 1
Publish Date
1995
Start Page
S98
End Page
S103

Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: A single-center study

The pharmacokinetics, safety, and efficacy in marrow transplantation of FK506-based immunosuppression for graft-versus-host disease (GVHD) prophylaxis was evaluated in an open label pilot study of 18 patients. Patients more than 12 years of age (median, 35 years; range, 15 to 50 years) with advanced hematologic malignancies receiving HLA-matched sibling marrow grafts were randomized to receive FK506 alone, FK506 and methotrexate (MTX), or FK506 and methylprednisolone. Of 17 evaluable patients, all had evidence of sustained marrow engraftment. The median time to an absolute neutrophil count of greater than 500/μL was 15 days for patients receiving FK506 alone or FK506 plus methylprednisolone and 23 days for FK506 plus short MTX. Pharmacokinetic studies did not show any significant difference in clearance of FK506 when administered alone or in combination with methylprednisolone or MTX. The mean bioavailability after oral administration in these same three groups was 0.49 ± 0.1, 0.27 ± 0.12, and 0.16 ± 0.08, respectively (P = .003). The decrease in bioavailability may have resulted from an exacerbation of radiation-induced gastroenteritis by MTX. The most significant adverse effect associated with the administration of FK506 was nephrotoxicity, which occurred in 14 of 18 patients (78%). The mean glomerular filtration rate, determined by clearance of (99MTc)DTPA, decreased to 56% (±18%) of the pretransplant baseline level by week 8(P = .002). Eight of 18 patients (44%) developed grades II-IV acute GVHD, predominantly of the skin and gastrointestinal tract. The actuarial probability of transplant-related mortality during the first 100 days was 24%. The actuarial probability of 1-year disease-free survival was 39%. In conclusion, although bioavailability of FK506 may be affected in patients receiving MTX, this study suggests that FK506 may have a role in the management of patients after allogeneic marrow transplantation. © 1995 by The American Society of Hematology.

Authors
Nash, RA; Etzioni, R; Storb, R; Furlong, T; Gooley, T; Anasetti, C; Appelbaum, FR; Doney, K; Martin, P; Slattery, J; Sullivan, K; Jagt, RVD; Witherspoon, R; Jusko, WJ; Zager, RA; Deeg, HJ
MLA Citation
Nash, RA, Etzioni, R, Storb, R, Furlong, T, Gooley, T, Anasetti, C, Appelbaum, FR, Doney, K, Martin, P, Slattery, J, Sullivan, K, Jagt, RVD, Witherspoon, R, Jusko, WJ, Zager, RA, and Deeg, HJ. "Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: A single-center study." Blood 85.12 (1995): 3746-3753.
PMID
7540071
Source
scival
Published In
Blood
Volume
85
Issue
12
Publish Date
1995
Start Page
3746
End Page
3753

Complications of allogeneic bone marrow transplantation.

Recent research has increased our understanding of the pathogenesis and prevention of the immediate and delayed complications of allogeneic bone marrow transplantation. Cytokines appear to play a major role in the pathogenesis of acute graft-versus-host disease and new therapies are being developed to modulate these effects. Risk factors for fatal venoocclusive disease of the liver such as elevated serum transaminase levels and fever prior to transplantation can be used in mathematical models to predict the outcome of venoocclusive disease. Use of total-body irradiation in pretransplantation conditioning regimens increases the risk of secondary cancers and is being used less commonly in patients with nonmalignant hematologic conditions. For patients with malignant diseases, fractionation of total-body irradiation have been shown to delay the onset and reduce the severity of radiation-induced cataracts. These and other late effects such as the development of chronic graft-versus-host disease and associated infections are major determinants of the quality of life following allogeneic marrow transplantation. Increased understanding of these complications assists the hematologist in long-term follow-up care of the marrow graft recipient.

Authors
Robinson, N; Sullivan, KM
MLA Citation
Robinson, N, and Sullivan, KM. "Complications of allogeneic bone marrow transplantation." Curr Opin Hematol 1.6 (November 1994): 406-411. (Review)
PMID
9371314
Source
pubmed
Published In
Current Opinion in Hematology
Volume
1
Issue
6
Publish Date
1994
Start Page
406
End Page
411

The management of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is a major cause of late morbidity and mortality following allogeneic marrow transplantation. The pathogenesis and clinical features of chronic GVHD resemble those of several autoimmune diseases including progressive systemic sclerosis, systemic lupus erythematous, lichen planus, Sjögren's syndrome, rheumatoid arthritis, and primary biliary cirrhosis. Chronic GVHD retards the tempo of immune reconstitution following allogeneic transplantation and is a major risk factor for late infections. Although in vivo immunosuppression and in vitro depletion of T-cells can reduce the incidence of acute GVHD, improved long-term survival free of chronic GVHD has not been observed. Early treatment of multiorgan extensive chronic GVHD with an alternating-day regimen of cyclosporine and prednisone has led to improved disability-free survival. Functional performance of the long-term survivors receiving combination immunosuppressive therapy remained near normal and the incidence of disabling scleroderma has decreased from over 50% to 6%. However, infections remain a frequent cause of morbidity especially in high-risk patients with advanced age, HLA-nonidentical marrow grafts, progressive onset of chronic GVHD and continued thrombocytopenia.

Authors
Siadak, M; Sullivan, KM
MLA Citation
Siadak, M, and Sullivan, KM. "The management of chronic graft-versus-host disease." Blood Rev 8.3 (September 1994): 154-160. (Review)
PMID
7529605
Source
pubmed
Published In
Blood Reviews
Volume
8
Issue
3
Publish Date
1994
Start Page
154
End Page
160

Reduction in transplant-related complications in patients given intravenous immuno globulin after allogeneic marrow transplantation.

Bone marrow transplantation renders patients immunocompetent due to the need for supralethal doses of chemoradiotherapy prior to infusion of the donor stem cells. Multiple immunological deficiencies are seen and patients are at high risk of developing a variety of infections. This period of immunological incompetence usually lasts from 6 to 12 months. In some subsets of patients [those with chronic graft-versus-host disease (GVHD); recipients of unrelated transplants; increasing patient age] persistent T and B cell abnormalities may be seen for years, despite normal serum immunoglobulin levels. This review summarizes a number of trials of intravenous immune globulin (IVIG) therapy to prevent infection following bone marrow transplantation. IVIG has shown benefit in reducing septicaemia, interstitial pneumonia, fatal cytomegalovirus (CMV) disease, acute GVHD and transplant-related mortality in adult recipients of related marrow transplants. Further investigation into dose, schedule and duration of IVIG prophylaxis needs to be conducted.

Authors
Siadak, MF; Kopecky, K; Sullivan, KM
MLA Citation
Siadak, MF, Kopecky, K, and Sullivan, KM. "Reduction in transplant-related complications in patients given intravenous immuno globulin after allogeneic marrow transplantation." Clin Exp Immunol 97 Suppl 1 (July 1994): 53-57. (Review)
PMID
8033436
Source
pubmed
Published In
Clinical & Experimental Immunology
Volume
97 Suppl 1
Publish Date
1994
Start Page
53
End Page
57

Cyclophosphamide plus ATG conditioning is insufficient for sustained hematopoietic reconstitution in patients with severe aplastic anemia transplanted with marrow from HLA-A, B, DRB matched unrelated donors.

Authors
Deeg, HJ; Anasetti, C; Petersdorf, E; Storb, R; Doney, K; Hansen, JA; Sanders, J; Sullivan, KM; Appelbaum, FR
MLA Citation
Deeg, HJ, Anasetti, C, Petersdorf, E, Storb, R, Doney, K, Hansen, JA, Sanders, J, Sullivan, KM, and Appelbaum, FR. "Cyclophosphamide plus ATG conditioning is insufficient for sustained hematopoietic reconstitution in patients with severe aplastic anemia transplanted with marrow from HLA-A, B, DRB matched unrelated donors." Blood 83.11 (June 1, 1994): 3417-3418. (Letter)
PMID
8193380
Source
pubmed
Published In
Blood
Volume
83
Issue
11
Publish Date
1994
Start Page
3417
End Page
3418

Spontaneous factor VIII inhibitor occurring in association with chronic graft-versus-host disease.

The development of spontaneously acquired Factor VIII inhibitors is rare and may lead to serious hemorrhagic sequelae. We report here the case of a patient who acquired a Factor VIII inhibitor two years after an allogeneic bone marrow transplant for CML. This occurred in association with a flare of chronic graft versus host disease (GVDH). He responded to corticosteroid therapy. A review of autoimmune phenomena associated with chronic GVDH and the treatment of Factor VIII inhibitors is discussed.

Authors
Seidler, CW; Mills, LE; Flowers, ME; Sullivan, KM
MLA Citation
Seidler, CW, Mills, LE, Flowers, ME, and Sullivan, KM. "Spontaneous factor VIII inhibitor occurring in association with chronic graft-versus-host disease." Am J Hematol 45.3 (March 1994): 240-243. (Review)
PMID
8296796
Source
pubmed
Published In
American Journal of Hematology
Volume
45
Issue
3
Publish Date
1994
Start Page
240
End Page
243

Bone marrow transplantation for sickle cell disease. The United States experience.

PURPOSE: As of June 1992, five patients with sickle cell disease had been treated by matched sibling bone marrow transplantation in the United States. PATIENTS AND METHODS: Three patients underwent transplantations for complications related to sickle cell disease, two with previous cerebrovascular accidents (CVAs) and one who had had multiple severe vasoocclusive crises. Two patients had other indications for allogeneic bone marrow transplantation: one had acute myeloid leukemia and the other had Morquio's disease. The patients' ages ranged from 3 to 10 years, and four were girls. Ages of the donors ranged from 4 to 13 years; four of the donors were boys and three carried the sickle cell trait. For four patients, the preparative regimen consisted of busulfan and cyclophosphamide given either alone or combined with antithymocyte globulin (ATG). The patient with leukemia was prepared with cyclophosphamide and total body irradiation (TBI). The regimens for prophylaxis of graft-versus-host disease (GVHD) included various combinations of cyclosporine A, methotrexate, and prednisone. RESULTS: The patient with Morquio's disease failed to engraft but underwent a successful retransplantation from the same donor. All patients eventually demonstrated donor engraftment and the donor's hemoglobin electrophoretic pattern posttransplant. Two patients had moderately severe GVHD of the skin and gastrointestinal tract, which resolved with prednisone therapy. One of these patients developed transient chronic GVHD involving the skin. Other acute complications included mild venoocclusive disease of the liver, central line infection with bacteremias, uterine hemorrhage in one patient, and pseudomonas sepsis in another. CONCLUSIONS: Both patients who underwent transplantation after CVAs have experienced subsequent neurological events. However, with a median follow-up of 16 months (range 8 months to 9.3 years), all patients are surviving in good to excellent clinical condition and appear to have benefitted from treatment by bone marrow transplantation.

Authors
Johnson, FL; Mentzer, WC; Kalinyak, KA; Sullivan, KM; Abboud, MR
MLA Citation
Johnson, FL, Mentzer, WC, Kalinyak, KA, Sullivan, KM, and Abboud, MR. "Bone marrow transplantation for sickle cell disease. The United States experience." Am J Pediatr Hematol Oncol 16.1 (February 1994): 22-26.
PMID
8311168
Source
pubmed
Published In
American Journal of Pediatric Hematology/Oncology
Volume
16
Issue
1
Publish Date
1994
Start Page
22
End Page
26

Bone marrow transplantation for thalassemia. The USA experience.

PURPOSE: We have reviewed the results of bone marrow transplantation in 30 patients with thalassemia major who were treated in the United States. PATIENTS AND METHODS: Ten patients who underwent transplantation in Seattle and 20 patients from five other U.S. centers were identified through a survey of the International Bone Marrow Transplant Registry. These transplants were performed between November 1981 and April 1992 in patients with diverse ethnic backgrounds and ranged in age from 6 months to 14 years (median 4.0 years). Twenty-seven of the 30 patients received marrow from a human leukocyte antigen (HLA)-identical sibling or other family member, one patient received HLA-matched marrow from an unrelated donor, and two patients were given haploidentical but HLA-mismatched marrow from a related donor. Cytoreductive (preparative) therapy varied among institutions and pretransplant risk categories. In general, patients were given busulfan (12-24 mg/kg) or dimethylmyleran (5 mg/kg) in combination with cyclophosphamide (120-240 mg/kg). A subset of patients were given total body irradiation (TBI) at a dose of 720 cGy followed by cyclophosphamide (120 mg/kg). RESULTS: Sixteen of 27 patients (59%) who received marrow from an HLA-identical family member are event-free survivors, with a duration of follow-up ranging from 2 months to > 10 years after transplantation. Six of these 27 patients (22%) had recurrence of thalassemia and five (19%) died. The estimated actuarial rate of thalassemia recurrence was 24% and the rate of event-free survival was 57%. Only one of the three patients who received marrow from HLA-nonidentical or unrelated donors survives event-free. Liver biopsies were not routinely performed before transplant. Thus, classification of patients into Lucarelli risk groups was not possible. A modified risk classification was devised by using liver size and iron status assessed by the regularity of chelation and the serum ferritin level. With use of this classification, there was no significant difference in event-free survival between transplant risk groups. CONCLUSIONS: The findings observed in this small series of patients confirms that thalassemia can be cured with bone marrow transplantation. Although most patients are event-free survivors, a significant number experienced recurrence of their disease. A cooperative multicenter trial of U.S. transplant centers may be necessary to evaluate the use of marrow transplantation for thalassemia and to determine optimal treatment.

Authors
Walters, MC; Sullivan, KM; O'Reilly, RJ; Boulad, F; Brockstein, J; Blume, K; Amylon, M; Johnson, FL; Klemperer, M; Graham-Pole, J
MLA Citation
Walters, MC, Sullivan, KM, O'Reilly, RJ, Boulad, F, Brockstein, J, Blume, K, Amylon, M, Johnson, FL, Klemperer, M, and Graham-Pole, J. "Bone marrow transplantation for thalassemia. The USA experience." Am J Pediatr Hematol Oncol 16.1 (February 1994): 11-17.
PMID
8311166
Source
pubmed
Published In
American Journal of Pediatric Hematology/Oncology
Volume
16
Issue
1
Publish Date
1994
Start Page
11
End Page
17

Marrow transplant experience for children with severe aplastic anemia.

PURPOSE: The two major factors associated with lack of survival after allogeneic marrow transplant for severe aplastic anemia have been graft rejection and acute graft versus host disease (GVHD). As a result, survival for patients transplanted in the 1970s was approximately 68%. Improved survival during the 1980s was primarily related to the decrease in the incidence of acute GVHD with the use of combination methotrexate and cyclosporine for GVHD prophylaxis. Although the incidence of graft rejection has not changed, the time to graft rejection has been delayed. PATIENTS AND METHODS: One hundred forty children < 18 years of age received a marrow transplant for severe aplastic anemia at the Fred Hutchinson Cancer Research Center between May, 1971 and June, 1991. Four recipients of syngeneic marrow received a simple marrow infusion, 119 recipients of HLA-identical family member marrow received cyclophosphamide (CY), 200 mg/kg; most recipients of alternative donor marrow received CY plus 12.0 Gy fractionated total body irradiation. GVHD prophylaxis was MTX only for 91 recipients of HLA-identical family member marrow, and was MTX plus CSP for all other allogeneic marrow patients. Estimates of graft rejection, acute and chronic GVHD, survival and event-free survival (EFS) were determined by the Kaplan-Meier method. RESULTS: Two recipients of syngeneic marrow achieved engraftment with donor marrow infusion only and two required immunosuppression with CY. Among the 119 recipients of HLA-identical family member marrow the type of GVHD prophylaxis did not influence graft rejection but non-transfused patients had 10% incidence of rejection compared to 22% for transfused patients (p = 0.1). All patients with late graft rejection survive whereas those with early rejection usually do not. The incidence of acute GVHD was 27% and 11% for MTX recipients and MTX plus CSP recipients, respectively (p = 0.11), and the probability of chronic GVHD was 30% and 26%, respectively. Survival is 64% for recipients of MTX and 96% for recipients of MTX plus CSP (p = 0.007), but EFS was 60% and 71%, respectively (p = 0.48). Recipients of partially matched family member or unrelated marrow donor grafts have transplants complicated by infections and GVHD. Growth and development of CY only recipients is normal and several children have been born to these former patients. CONCLUSIONS: High dose CY is usually an effective preparative regimen for children with severe aplastic anemia and an HLA-identical family member marrow donor. Additional immunosuppression with anti-thymocyte globulin may result in a further decrease in graft rejection and improved EFS. Identification of a group of children who are unlikely to respond to immunosuppressive treatment could permit earlier transplantation for patients without HLA-identical family member donors available. Children who receive CY only have normal growth and development.

Authors
Sanders, JE; Storb, R; Anasetti, C; Deeg, HJ; Doney, K; Sullivan, KM; Witherspoon, RP; Hansen, J
MLA Citation
Sanders, JE, Storb, R, Anasetti, C, Deeg, HJ, Doney, K, Sullivan, KM, Witherspoon, RP, and Hansen, J. "Marrow transplant experience for children with severe aplastic anemia." Am J Pediatr Hematol Oncol 16.1 (February 1994): 43-49.
PMID
8311172
Source
pubmed
Published In
American Journal of Pediatric Hematology/Oncology
Volume
16
Issue
1
Publish Date
1994
Start Page
43
End Page
49

Marrow transplantation for chronic myeloid leukemia: A randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide

A prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty- nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY- TBI), and 73 patients received 16 mg/kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TBI and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event- free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence of venocclusive disease of the liver. The 4-year probabilities of survival and event-free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TBI group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY-TBI group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TBI group than in the BU-CY group. In conclusion, the BU-CY regimen was better tolerated than, and associated with survival and relapse probabilities that compare favorably with, the CY-TBI regimen.

Authors
Clift, RA; Buckner, CD; Thomas, ED; Bensinger, WI; Bowden, R; Bryant, E; Deeg, HJ; Doney, KC; Fisher, LD; Hansen, JA; Martin, P; McDonald, GB; Sanders, JE; Schoch, G; Singer, J; Storb, R; Sullivan, KM; Witherspoon, RP; Appelbaum, FR
MLA Citation
Clift, RA, Buckner, CD, Thomas, ED, Bensinger, WI, Bowden, R, Bryant, E, Deeg, HJ, Doney, KC, Fisher, LD, Hansen, JA, Martin, P, McDonald, GB, Sanders, JE, Schoch, G, Singer, J, Storb, R, Sullivan, KM, Witherspoon, RP, and Appelbaum, FR. "Marrow transplantation for chronic myeloid leukemia: A randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide." Blood 84.6 (1994): 2036-2043.
PMID
8081005
Source
scival
Published In
Blood
Volume
84
Issue
6
Publish Date
1994
Start Page
2036
End Page
2043

Treatment of acute graft-versus-host disease with humanized anti-Tac: An antibody that binds to the interleukin-2 receptor

Humanized anti-Tac is a genetically engineered human IgG1 monoclonal antibody specific for Tac, the α subunit of the interleukin-2 (IL-2) receptor, and blocks IL-2-dependent activation of human T lymphocytes. The safety, pharmacokinetics, and immunosuppressive activity of humanized anti- Tac were evaluated in 20 patients who developed acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. Patients had developed acute GVHD at 5 to 26 (median, 14) days after transplantation and had failed to respond to primary therapy with glucocorticoids. Sequential groups of 4 patients each received a single 1-hour infusion of antibody in escalating doses of 0.5, 1.0, or 1.5 mg/kg; 8 additional patients were then treated with 1.5 mg/kg. A second infusion of antibody was administered after 11 to 48 (median, 16) days in 8 patients who had transient improvement of GVHD after the first infusion. Acute side effects, limited to chills in 1 patient and diaphoresis in another, were observed during or shortly after the antibody infusion. Overall improvement of acute GVHD occurred in 8 patients, 6 of whom were treated with a single antibody infusion and 2 with two infusions. Four responses were complete and 4 were partial. Three additional patients had improvement in one organ but progression in another. Responses occurred in 9 of 16 cases with skin disease, 3 of 15 with liver disease, and 6 of 12 with gastrointestinal disease. Two patients survive at 529 and 645 days after antibody treatment. Two patients died after relapse of leukemia. Sixteen patients died of infection or organ failure between 5 and 211 (median, 55) days. The terminal elimination half-life of the antibody was 44 to 363 hours, with a harmonic mean of 79, 88, and 94 hours, respectively, for the three doses studied. Absolute peripheral blood T-lymphocyte counts remained unchanged during the 56 days after infusion of the antibody. A fraction of circulating T cells expressed the α chain of the IL-2 receptor that, in some patients, was bound by antibody in vivo up to 28 days after treatment. No patient developed a measurable antibody response to humanized anti-Tac. Humanized anti-Tac has a long half-life after intravenous injection in humans, superior to any rodent monoclonal antibody specific for human T cells, and does not appear to induce antibody formation in recipients of marrow transplants. Improvement of steroid-refractory GVHD in 40% of patients after only one or two antibody infusions indicates that humanized anti-Tac is immunosuppressive.

Authors
Anasetti, C; Hansen, JA; Waldmann, TA; Appelbaum, FR; Davis, J; Deeg, HJ; Doney, K; Martin, PJ; Nash, R; Storb, R; Sullivan, KM; Witherspoon, RP; Binger, M-H; Chizzonite, R; Hakimi, J; Mould, D; Satoh, H; Light, SE
MLA Citation
Anasetti, C, Hansen, JA, Waldmann, TA, Appelbaum, FR, Davis, J, Deeg, HJ, Doney, K, Martin, PJ, Nash, R, Storb, R, Sullivan, KM, Witherspoon, RP, Binger, M-H, Chizzonite, R, Hakimi, J, Mould, D, Satoh, H, and Light, SE. "Treatment of acute graft-versus-host disease with humanized anti-Tac: An antibody that binds to the interleukin-2 receptor." Blood 84.4 (1994): 1320-1327.
PMID
8049447
Source
scival
Published In
Blood
Volume
84
Issue
4
Publish Date
1994
Start Page
1320
End Page
1327

Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia

Graft rejection has been a problem after marrow grafts for patients with aplastic anemia who were conditioned with cyclophosphamide (CY). Rejection lessened when patients were given the marrow donor's peripheral blood buffy- coat cells in addition to the marrow, but this result was achieved at the price of more chronic graft-versus-host disease (GVHD). Results with second transplants suggested that CY alternating with antithymocyte globulin (ATG) was more immunosuppressive than CY alone. Therefore, the current study explored CY and ATG without buffy-coat cell transfusions in 39 patients with aplastic anemia given marrow transplants from HLA-identical family members (siblings in 38 cases, father in 1 case). We hoped both to minimize the risks of graft rejection and of chronic GVHD and to improve survival. Patients were 2 to 52 years of age (median, 24.5); 87% had received previous transfusions, and 41% had therapy with immunosuppressive agents before transplant. They were administered four daily doses of CY (total, 200 mg/kg) alternating with three doses of ATG (total, 90 mg/kg) followed by an HLA-identical marrow graft. Methotrexate and cyclosporine were administered to prevent GVHD. Two patients rejected their grafts (5%), and both were successfully retransplanted. Acute (grade 2 or 3) GVHD occurred in 15% and chronic GVHD in 34% of patients. The actuarial survival rate at 3 years was 92%, which compares favorably to the 72% survival rate in 39 historical patients who were matched with current patients for age and risk factors for rejection and GVHD. CY/ATG is a well-tolerated and effective conditioning program for marrow grafting in aplastic anemia that, when combined with GVHD prevention by methotrexate/cyclosporine, results in excellent survival.

Authors
Storb, R; Etzioni, R; Anasetti, C; Appelbaum, FR; Buckner, CD; Bensinger, W; Bryant, E; Clift, R; Deeg, HJ; Doney, K; Flowers, M; Hansen, J; Martin, P; Pepe, M; Sale, G; Sanders, J; Singer, J; Sullivan, KM; Thomas, ED; Witherspoon, RP
MLA Citation
Storb, R, Etzioni, R, Anasetti, C, Appelbaum, FR, Buckner, CD, Bensinger, W, Bryant, E, Clift, R, Deeg, HJ, Doney, K, Flowers, M, Hansen, J, Martin, P, Pepe, M, Sale, G, Sanders, J, Singer, J, Sullivan, KM, Thomas, ED, and Witherspoon, RP. "Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia." Blood 84.3 (1994): 941-949.
PMID
8043876
Source
scival
Published In
Blood
Volume
84
Issue
3
Publish Date
1994
Start Page
941
End Page
949

Effect of graft-versus-host disease prophylaxis on relapse in patients transplanted for acute myeloid leukemia

Between November 1978 and September 1988, 184 patients with acute myeloid leukemia in first remission received marrow transplants from HLA-identical siblings after conditioning with 120 mg/kg of cyclophosphamide and 12.0 Gy fractionated total body irradiation. Patients received either cyclosporine (CYA, n = 59), methotrexate (MTX, n = 82), or MTX + CYA (n = 43) as graft-versus-host disease (GVHD) prophylaxis. The probabilities of grades II-IV acute GVHD after CYA, MTX or MTX + CYA were 0.43, 0.48 and 0.28, respectively (p = 0.06). The probability of non-relapse mortality was 0.53, 0.50 and 0.42 at 4 years in patients treated with CYA, MTX, or MTX + CYA, respectively. The probability of relapse was 0.24 in patients receiving CYA, 0.24 in patients receiving MTX and 0.44 in patients receiving MTX + CYA (p = 0.02). The probability of survival at 4 years was 0.54 with CYA, 0.51 with MTX and 0.45 with MTX + CYA. A multivariate analysis of risk factors for relapse examined age, WBC at diagnosis, blast count at diagnosis, percentage of marrow blasts, FAB subtype, the number of remission induction courses to achieve a remission, maintenance therapy, consolidation therapy, marrow cell dose, donor-recipient sex, GVHD prophylaxis regimen and isolation and decontamination in laminar airflow rooms. GVHD prophylaxis with MTX + CYA was independently significantly associated with an increased risk of relapse (relative risk 2.25, p = 0.01). Acute GVHD was associated with increased non-relapse mortality (RR = 3.58, p < 0.0001). The administration of MTX + CYA did not adversely affect survival because patients receiving this regimen experienced less mortality from causes other than relapse when compared with patients receiving either CYA or MTX alone.

Authors
Weaver, CH; Clift, RA; Deeg, HJ; Storb, R; Appelbaum, FR; Bensinger, W; Doney, K; Hansen, JA; Martin, PO; Sanders, J; Sullivan, KM; Thomas, ED; Singer, J; Witherspoon, R; Buckner, CD
MLA Citation
Weaver, CH, Clift, RA, Deeg, HJ, Storb, R, Appelbaum, FR, Bensinger, W, Doney, K, Hansen, JA, Martin, PO, Sanders, J, Sullivan, KM, Thomas, ED, Singer, J, Witherspoon, R, and Buckner, CD. "Effect of graft-versus-host disease prophylaxis on relapse in patients transplanted for acute myeloid leukemia." Bone Marrow Transplantation 14.6 (1994): 885-893.
PMID
7711667
Source
scival
Published In
Bone Marrow Transplantation
Volume
14
Issue
6
Publish Date
1994
Start Page
885
End Page
893

The case for the Clinton plan for health care reform [2]

Authors
Stevens, CD; Harris, CJ; Sullivan, K; Starr, P
MLA Citation
Stevens, CD, Harris, CJ, Sullivan, K, and Starr, P. "The case for the Clinton plan for health care reform [2]." New England Journal of Medicine 330.15 (1994): 1086-1088.
PMID
8127344
Source
scival
Published In
New England Journal of Medicine
Volume
330
Issue
15
Publish Date
1994
Start Page
1086
End Page
1088
DOI
10.1056/NEJM199404143301514

Long-term follow-up of a randomized trial of graft-versus-host disease prevention by methotrexate/cyclosporine versus methotrexate alone in patients given marrow grafts for severe aplastic anemia [1]

Authors
Storb, R; Leisenring, W; Deeg, HJ; Anasetti, C; Appelbaum, F; Bensinger, W; Buckner, CD; Clift, R; Doney, K; Hansen, J; Martin, P; Sanders, J; Stewart, P; Sullivan, K; Thomas, ED; Witherspoon, R
MLA Citation
Storb, R, Leisenring, W, Deeg, HJ, Anasetti, C, Appelbaum, F, Bensinger, W, Buckner, CD, Clift, R, Doney, K, Hansen, J, Martin, P, Sanders, J, Stewart, P, Sullivan, K, Thomas, ED, and Witherspoon, R. "Long-term follow-up of a randomized trial of graft-versus-host disease prevention by methotrexate/cyclosporine versus methotrexate alone in patients given marrow grafts for severe aplastic anemia [1]." Blood 83.9 (1994): 2749-2750.
PMID
8167353
Source
scival
Published In
Blood
Volume
83
Issue
9
Publish Date
1994
Start Page
2749
End Page
2750

The management of chronic graft-versus-host disease

Chronic graft-versus-host disease (GVHD) is a major cause of late morbidity and mortality following allogeneic marrow transplantation. The pathogenesis and clinical features of chronic GVHD resemble those of several autoimmune diseases including progressive systemic sclerosis, systemic lupus erythematous, lichen planus, Sjögren's syndrome, rheumatoid arthritis, and primary biliary cirrhosis. Chronic GVHD retards the tempo of immune reconstitution following allogeneic transplantation and is a major risk factor for late infections. Although in vivo immunosuppression and in vitro depletion of T-cells can reduce the incidence of acute GVHD, improved long-term survival free of chronic GVHD has not been observed. Early treatment of multiorgan extensive chronic GVHD with an alternating-day regimen of cyclosporine and prednisone has led to improved disability-free survival. Functional performance of the long-term survivors receiving combination immunosuppressive therapy remained near normal and the incidence of disabling scleroderma has decreased from over 50% to 6%. However, infections remain a frequent cause of morbidity especially in high-risk patients with advanced age, HLA-nonidentical marrow grafts, progressive onset of chronic GVHD and continued thrombocytopenia. © 1994.

Authors
Siadak, M; Sullivan, KM
MLA Citation
Siadak, M, and Sullivan, KM. "The management of chronic graft-versus-host disease." Blood Reviews 8.3 (1994): 154-160.
Source
scival
Published In
Blood Reviews
Volume
8
Issue
3
Publish Date
1994
Start Page
154
End Page
160
DOI
10.1016/0268-960X(94)90076-T

High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma

Purpose: To evaluate a high-dose treatment regimen of fractionated total- body irradiation (TBI), etoposide, and cyclophosphamide (Cy) followed by autologous stem-cell transplantation (ASCT) in patients with malignant lymphoma. Patients and Methods: Fifty-three patients with non-Hodgkin's lymphoma (NHL; n = 43) or Hodgkin's disease (HD; n = 10) received 12.0 Gy of fractionated TBI, etoposide 60 mg/kg, and Cy 100 mg/kg followed by infusion of autologous hematopoietic stem cells. Results: Thirty-one of 53 patients are alive a median of 643 (range, 177 to 1,144) days after transplant. The 2- year Kaplan-Meier (K-M) estimates of survival, event-free survival (EFS), and relapse for all 53 patients were 54%, 45%, and 43%, respectively. Sixteen of 24 patients with less advanced disease and 10 of 29 patients with more advanced disease survive free of disease for K-M estimates of EFS of 61% and 31%, respectively (P = .006). The K-M estimates of relapse were 34% for patients with less advanced disease and 53% (P = .05) for patients with more advanced disease. The K-M estimates of dying from causes other than relapse were 8% in patients with less versus 25% in patients with more advanced disease (P = .09). Conclusion: These data indicate that approximately 60% of patients transplanted early after failure of initial therapy for malignant lymphoma are projected to be disease-free more than 2 years after treatment with fractionated TBI, etoposide, and Cy and infusion of autologous hematopoietic stem cells. The transplant-related mortality rate is low and relapse is the main cause of treatment failure in patients with less advanced disease. For patients with more advanced disease, the K-M estimates of both transplant-related deaths (25%) and relapse (53%) remain major problems.

Authors
Weaver, CH; Petersen, FB; Appelbaum, FR; Bensinger, WI; Press, O; Martin, P; Sandmaier, B; Deeg, HJ; Hansen, JA; Brunvand, M; Rowley, S; Benyunes, K; Chauncey, T; Fefer, A; Hackman, R; Gooley, T; Schiffman, K; Storb, R; Sullivan, KM; Weiden, P; Witherspoon, R; Buckner, CD
MLA Citation
Weaver, CH, Petersen, FB, Appelbaum, FR, Bensinger, WI, Press, O, Martin, P, Sandmaier, B, Deeg, HJ, Hansen, JA, Brunvand, M, Rowley, S, Benyunes, K, Chauncey, T, Fefer, A, Hackman, R, Gooley, T, Schiffman, K, Storb, R, Sullivan, KM, Weiden, P, Witherspoon, R, and Buckner, CD. "High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma." Journal of Clinical Oncology 12.12 (1994): 2559-2566.
PMID
7989929
Source
scival
Published In
Journal of Clinical Oncology
Volume
12
Issue
12
Publish Date
1994
Start Page
2559
End Page
2566

Marrow transplantation for patients in accelerated phase of chronic myeloid leukemia

The records were reviewed of 58 patients receiving transplants in Seattle with unmanipulated marrow from HLA-identical siblings during the accelerated phase (AP) of chronic myeloid leukemia. Variables examined for association with survival and relapse included the interval from diagnosis to transplant, the reasons for categorization as AP, age, regimen, and cytomegalovirus serology. Four patients relapsed. The 4-year probabilities of survival, relapse-free survival, nonrelapse mortality, and relapse were 0.49, 0.43, 0.51, and 0.12, respectively. After completion of the stepwise multivariate analysis, age less than 38 years and categorization as AP solely on the basis of chromosomal abnormalities emerged as being independently significantly associated with improved survival. The 4-year probability of survival for the 16 patients categorized as AP because of chromosomal abnormalities and receiving transplant less than 1 year from diagnosis was 0.74. The low probability of relapse in these patients suggests that more aggressive preparative regimens are not indicated for patients receiving transplants in AP because of the increased risk of transplant-related mortality.

Authors
Clift, RA; Buckner, CD; Thomas, ED; Bryant, E; Anasetti, C; Bensinger, WI; Bowden, R; Deeg, HJ; Doney, KC; Fisher, LD; Hansen, JA; Martin, P; McDonald, GB; Sanders, JE; Schoch, G; Singer, J; Storb, R; Sullivan, KM; Witherspoon, RP; Appelbaum, FR
MLA Citation
Clift, RA, Buckner, CD, Thomas, ED, Bryant, E, Anasetti, C, Bensinger, WI, Bowden, R, Deeg, HJ, Doney, KC, Fisher, LD, Hansen, JA, Martin, P, McDonald, GB, Sanders, JE, Schoch, G, Singer, J, Storb, R, Sullivan, KM, Witherspoon, RP, and Appelbaum, FR. "Marrow transplantation for patients in accelerated phase of chronic myeloid leukemia." Blood 84.12 (1994): 4368-4373.
PMID
7527674
Source
scival
Published In
Blood
Volume
84
Issue
12
Publish Date
1994
Start Page
4368
End Page
4373

Quality of life of adult long-term survivors of bone marrow transplantation: a qualitative analysis of narrative data.

Recently, clinicians and researchers alike have challenged the long-standing impression that survivors of bone marrow transplantation (BMT) experience a less than optimal quality of life (QOL). Despite the accumulating evidence suggesting that most adult survivors adjust relatively well within two to five years after BMT, little is known about the growing population of recipients living well beyond five years. This paper reports the design and qualitative components of a large study that used a cross-sectional, descriptive, mailed survey design. The aim of the study was to document systematically how 125 adult survivors of BMT (6-18.4 years post-transplant) perceived the quality of their lives. An eight-item, open-ended questionnaire was used to gather information on the reestablishment of life after BMT, demands of recovery, coping strategies, limitations imposed by BMT, current health problems, QOL, and concerns for the future. Content analysis of the verbatim responses indicated that most long-term survivors, despite the persistence of lingering side effects, perceive themselves as cured and well, leading full and meaningful lives. Nursing therapeutics can focus on providing accurate and timely information about the known long-range complications of BMT. Further research is needed to examine the entire issue of social support following BMT and to identify the special care requirements of the recipients (5%) who reported poor physical and mental health.

Authors
Haberman, M; Bush, N; Young, K; Sullivan, KM
MLA Citation
Haberman, M, Bush, N, Young, K, and Sullivan, KM. "Quality of life of adult long-term survivors of bone marrow transplantation: a qualitative analysis of narrative data." Oncol Nurs Forum 20.10 (November 1993): 1545-1553.
PMID
8278280
Source
pubmed
Published In
Oncology Nursing Forum
Volume
20
Issue
10
Publish Date
1993
Start Page
1545
End Page
1553

Marrow transplantation for disorders of hematopoiesis.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Marrow transplantation for disorders of hematopoiesis." Leukemia 7.7 (July 1993): 1098-1099.
PMID
8321033
Source
pubmed
Published In
Leukemia
Volume
7
Issue
7
Publish Date
1993
Start Page
1098
End Page
1099

Long-term survival and cure after marrow transplantation for congenital hypoplastic anaemia (Diamond-Blackfan syndrome).

Four patients with Diamond-Blackfan syndrome (congenital hypoplastic anaemia) whose disease was resistant to corticosteroid treatment and who were red blood cell transfusion-dependent, were given marrow grafts from allogeneic human-leucocyte-antigen (HLA)-identical siblings. The patients were conditioned with regimens including cyclophosphamide and busulfan. Three of four patients had sustained and complete marrow engraftment. One patient showed early signs of haematopoietic recovery but died on day 35 of pulmonary toxicity. The three surviving patients are well with normal haematopoiesis and Karnofsky performance scores of 100%, 3.0, 7.4 and 10.6 years after transplantation. Congenital hypoplastic anaemia can be treated successfully by allogeneic marrow grafts.

Authors
Greinix, HT; Storb, R; Sanders, JE; Deeg, HJ; Doney, KC; Sullivan, KM; Witherspoon, RP
MLA Citation
Greinix, HT, Storb, R, Sanders, JE, Deeg, HJ, Doney, KC, Sullivan, KM, and Witherspoon, RP. "Long-term survival and cure after marrow transplantation for congenital hypoplastic anaemia (Diamond-Blackfan syndrome)." Br J Haematol 84.3 (July 1993): 515-520.
PMID
8217802
Source
pubmed
Published In
British Journal of Haematology
Volume
84
Issue
3
Publish Date
1993
Start Page
515
End Page
520

Recovery after allogeneic marrow transplantation: prospective study of predictors of long-term physical and psychosocial functioning.

No prospective data have documented the physical and psychosocial functioning of patients before and after BMT. In this study 67 allogeneic transplant patients completed standardized self-report measures pre-transplant. Survivors were re-assessed at 90 days (n = 34) and 1 year (n = 31) post-transplant. Telephone interviews established 4-year work history and performance status. Physical function was most impaired at 90 days post-transplant, with a return to pre-transplant levels of functioning by 1 year in most areas. By 2 years post-transplant, 68% of patients had returned to full-time work. Only 9% of 4-year survivors failed to return to full-time occupations. Mean levels of anxiety and depression did not change over the first year. Pre-transplant, 27% of patients reported depression and 41% reported elevated anxiety. Greater emotional distress at 1 year was predicted by pre-transplant family conflict, non-married status and development of less severe chronic GVHD. Impaired physical recovery at 1 year was predicted by more severe chronic GVHD, pre-transplant physical impairment and family conflict. The large majority of long-term survivors returned to full-time employment with normal physical and psychosocial functioning, although recovery took longer than 1 year for approximately 40%. Family relationships were important determinants of physical and emotional recovery.

Authors
Syrjala, KL; Chapko, MK; Vitaliano, PP; Cummings, C; Sullivan, KM
MLA Citation
Syrjala, KL, Chapko, MK, Vitaliano, PP, Cummings, C, and Sullivan, KM. "Recovery after allogeneic marrow transplantation: prospective study of predictors of long-term physical and psychosocial functioning." Bone Marrow Transplant 11.4 (April 1993): 319-327.
PMID
8485479
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
11
Issue
4
Publish Date
1993
Start Page
319
End Page
327

Fatal eosinophilia myalgia syndrome in a marrow transplant patient attributed to total parenteral nutrition with a solution containing tryptophan.

A 16-year-old white male with acute biphenotypic leukemia developed evidence of the eosinophilia myalgia syndrome associated with total parenteral nutritional support with solutions containing tryptophan, which were given during his initial induction chemotherapy and also after autologous marrow transplantation. He developed pronounced eosinophilia and a vasculitic skin rash, myalgias of the abdomen, upper trunk, and neck, and died of respiratory distress with no evidence of an infectious etiology. Autopsy revealed diffuse vasculitis involving the heart, lungs, kidneys, testes, spleen, liver, skin, gut wall and marrow with neuritis of gut wall nerves and ganglia. Thus, the eosinophilia myalgia syndrome can be associated with parenteral tryptophan administration.

Authors
de Oliveira, JS; Auerbach, SB; Sullivan, KM; Sale, GE
MLA Citation
de Oliveira, JS, Auerbach, SB, Sullivan, KM, and Sale, GE. "Fatal eosinophilia myalgia syndrome in a marrow transplant patient attributed to total parenteral nutrition with a solution containing tryptophan." Bone Marrow Transplant 11.2 (February 1993): 163-167.
PMID
8435665
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
11
Issue
2
Publish Date
1993
Start Page
163
End Page
167

Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: The 21-year seattle experience

Purpose: To analyze results of 127 patients undergoing myeloablative therapy followed by marrow transplantation for relapsed or refractory Hodgkin's disease. Patients and Methods: Twenty-three patients had primary refractory disease, 34 were in early first relapse or second complete remission (CR), and 70 had refractory first relapse or disease beyond second CR. Preparative regimens included total-body irradiation (TBI) and chemotherapy (n = 61) or chemotherapy only (n = 66). Sixty-eight patients received autologous marrow, six syngeneic marrow, and 53 allogeneic marrow. Results: The 5-year actuarial probabilities of survival, event-free survival (EFS), relapse, and nonrelapse mortality for the entire group were 21%, 18%, 65%, and 49%, respectively. HLA-identical allogeneic marrow recipients had a statistically lower relapse rate compared with recipients of autologous marrow, but survival, EFS, and nonrelapse mortality rates were not significantly different. In the multivariate analysis, higher performance status and absence of bulky disease predicted for improved EFS and lower relapse rates, while fewer prior treatment regimens predicted for improved EFS and lower nonrelapse mortality rates. Additionally, the univariate analysis showed that patients who underwent transplantation with disease refractory to chemotherapy or beyond second CR had a worse outcome compared with those who had less advanced disease. Conclusion: Outcome with transplantation for patients with Hodgkin's disease is improved if transplantation is performed early after relapse when disease burden is less, tumor chemosensitivity is greater, and the patient is likely to have a better performance status. The use of HLA-matched sibling marrow results in a lower relapse rate and, thus, for some individuals, may be preferable to the use of autologous marrow. © 1993 by American Society of Clinical Oncology.

Authors
Anderson, JE; Litzow, MR; Appelbaum, FR; Schoch, G; Fisher, LD; Buckner, CD; Petersen, FB; Crawford, SW; Press, OW; Sanders, JE; Bensinger, WI; Martin, PJ; Storb, R; Sullivan, KM; Hansen, JA; Thomas, ED
MLA Citation
Anderson, JE, Litzow, MR, Appelbaum, FR, Schoch, G, Fisher, LD, Buckner, CD, Petersen, FB, Crawford, SW, Press, OW, Sanders, JE, Bensinger, WI, Martin, PJ, Storb, R, Sullivan, KM, Hansen, JA, and Thomas, ED. "Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: The 21-year seattle experience." Journal of Clinical Oncology 11.12 (1993): 2342-2350.
PMID
8246023
Source
scival
Published In
Journal of Clinical Oncology
Volume
11
Issue
12
Publish Date
1993
Start Page
2342
End Page
2350

Risk factors for acute graft-versus-host disease associated with cyclosporine and methotrexate prophylaxis [4]

Authors
Russell, N; Rogers, S; Hunter, A; Nash, RA; Pepe, MS; Storb, R; Anasetti, C; Appelbaum, FR; Deeg, HJ; Doney, K; Martin, PJ; Sullivan, KM; Witherspoon, RP
MLA Citation
Russell, N, Rogers, S, Hunter, A, Nash, RA, Pepe, MS, Storb, R, Anasetti, C, Appelbaum, FR, Deeg, HJ, Doney, K, Martin, PJ, Sullivan, KM, and Witherspoon, RP. "Risk factors for acute graft-versus-host disease associated with cyclosporine and methotrexate prophylaxis [4]." Blood 81.7 (1993): 1972-1974.
PMID
8507260
Source
scival
Published In
Blood
Volume
81
Issue
7
Publish Date
1993
Start Page
1972
End Page
1974

Marrow transplantation from unrelated donors for treatment of hematologic malignancies: Effect of mismatching for one HLA locus

One hundred twelve patients less than 36 years old received marrow grafts from unrelated donors as treatment for hematologic malignancy. Seventy donor/recipient pairs were phenotypically identical for HLA-A, -B, and -D, while 42 had a "minor" disparity at one HLA locus. There was an increase in the risk of acute graft-versus-host disease (GVHD) in patients receiving HLA-partially matched grafts compared with those receiving HLA-matched grafts (51 % v 36% probability of grades III-IV acute GVHD). However. in this cohort of patients, there was no significant difference in survival (at 1.5 years, 46% v 51 % for good-risk patients, 44% v 30% for poor-risk patients). This finding suggests that some degree of HLA disparity can be tolerated in young patients transplanted from unrelated donors for malignant disease, thus making transplantation an option available to larger numbers of patients. © 1993 by The American Society of Hematology.

Authors
Beatty, PG; Anasetti, C; Hansen, JA; Longton, GM; Sanders, JE; Martin, PJ; Mickelson, EM; Choo, SY; Petersdorf, EW; Pepe, MS; Appelbaum, FR; Bearman, SI; Buckner, CD; Clift, RA; Petersen, FB; Singer, J; Stewart, PS; Storb, RF; Sullivan, KM; Tesler, MC; Witherspoon, RP; Thomas, ED
MLA Citation
Beatty, PG, Anasetti, C, Hansen, JA, Longton, GM, Sanders, JE, Martin, PJ, Mickelson, EM, Choo, SY, Petersdorf, EW, Pepe, MS, Appelbaum, FR, Bearman, SI, Buckner, CD, Clift, RA, Petersen, FB, Singer, J, Stewart, PS, Storb, RF, Sullivan, KM, Tesler, MC, Witherspoon, RP, and Thomas, ED. "Marrow transplantation from unrelated donors for treatment of hematologic malignancies: Effect of mismatching for one HLA locus." Blood 81.1 (1993): 249-253.
PMID
8417795
Source
scival
Published In
Blood
Volume
81
Issue
1
Publish Date
1993
Start Page
249
End Page
253

Autologous bone marrow transplantation for acute lymphoblastic leukemia

Between December 1979 and February 1991, 89 patients with ALL received autologous BMT. Median patient age was 18.4 years. Ten patients were in first remission, 52 were in second or greater remission and 27 were in relapse at the time of transplant. Conditioning regimens utilized chemotherapy alone (5 patients) or in combination with 10-15.75 Gy total body irradiation (84 patients). Disease-free survival at 1 year is 50% for patients transplanted in first remission, 27% for those in ≥ second remission and 8% for patients in relapse. Pre- and post-transplant variables were evaluated in univariate and multivariate analyses for their effect on survival and relapse. Factors significantly associated with improved survival were being transplanted in first remission and achieving a self-sustained platelet count ≥ 20 x 109/l in a shorter period of time. A decreased relapse rate after transplant was associated with a lower white blood count at diagnosis, being transplanted in first remission and not being transplanted in relapse.

Authors
Doney, K; Buckner, CD; Fisher, L; Petersen, FB; Sanders, J; Appelbaum, FR; Anasetti, C; Badger, C; Bensinger, W; Deeg, HJ; Fefer, A; Martin, P; Petersdorf, E; Schuening, F; Singer, J; Stewart, P; Storb, R; Sullivan, KM; Witherspoon, R; Hansen, JA
MLA Citation
Doney, K, Buckner, CD, Fisher, L, Petersen, FB, Sanders, J, Appelbaum, FR, Anasetti, C, Badger, C, Bensinger, W, Deeg, HJ, Fefer, A, Martin, P, Petersdorf, E, Schuening, F, Singer, J, Stewart, P, Storb, R, Sullivan, KM, Witherspoon, R, and Hansen, JA. "Autologous bone marrow transplantation for acute lymphoblastic leukemia." Bone Marrow Transplantation 12.4 (1993): 315-321.
PMID
8275030
Source
scival
Published In
Bone Marrow Transplantation
Volume
12
Issue
4
Publish Date
1993
Start Page
315
End Page
321

Autologous marrow transplantation for patients with acute myeloid leukemia in untreated first relapse or in second complete remission

Purpose: This study compares outcomes of autologous bone marrow transplantation (ABMT) in patients with acute myeloid leukemia (AML) in untreated first relapse (REL1) or in second complete remission (REM2). Patients and Methods; Forty-seven patients with AML in REL1 (n = 21) or in REM2 (n = 26) were treated with busulfan (BU) and cyclophosphamide (CY) with or without total-body irradiation (TBI) followed by ABMT. All REL1 patients and four REM2 patients had marrow stored during first remission (REM1). Twenty-seven had marrow stored with and 20 without treatment in vitro with 4-hydroperoxycyclophosphamide (4-HC). Eighteen patients received BU and CY and 29 received BU, CY, and TBI. REL1 patients relapsed within a median of 9 months (range, 2 to 26) after marrow harvest and were transplanted a median of 30 days (range, 9 to 87) from detection of relapse. Results: With a median follow-up of 2.1 years (range, 0.4 to 5.3), 19 patients survive in remission (10 of 21 in REL1; nine of 26 in REM2). The actuarial probabilities of relapse-free survival at 2 years for patients transplanted in REL1 and REM2 were 45% ± 22% and 32% ± 18%, respectively (P = .33). The corresponding probabilities of relapse were 30% ± 26% and 44% ± 23%, respectively (P = .45). No conclusions could be drawn about the benefits of adding TBI to BU plus CY. There were no significant differences in neutrophil or platelet recovery or in posttransplant probabilities of relapse and nonrelapse mortality between patients who received marrow treated or not treated with 4-HC. Conclusion: These results suggest that ABMT may produce long-term leukemia-free survival in approximately one third of patients with AML in REL1 or in REM2. There is no apparent clinical advantage in attempting to obtain second remissions in relapsed patients before ABMT if marrow has been cryopreserved during REM1. Although a strategy of transplantation in REL1 has advantages for the patient, such an approach involves the storage of marrow, which may not be used, and is impractical without the coordinated support of the treating physician, the patient, and the marrow transplant center. © 1993 by American Society of Clinical Oncology.

Authors
Petersen, FB; Lynch, MHE; Clift, RA; Appelbaum, FR; Sanders, JE; Bensinger, WI; Benyunes, MC; Doney, K; Fefer, A; Martin, P; Storb, R; Rowley, S; Sullivan, KM; Witherspoon, R; Weiden, P; Thomas, ED; Fisher, L; Hansen, JA; Buckner, CD
MLA Citation
Petersen, FB, Lynch, MHE, Clift, RA, Appelbaum, FR, Sanders, JE, Bensinger, WI, Benyunes, MC, Doney, K, Fefer, A, Martin, P, Storb, R, Rowley, S, Sullivan, KM, Witherspoon, R, Weiden, P, Thomas, ED, Fisher, L, Hansen, JA, and Buckner, CD. "Autologous marrow transplantation for patients with acute myeloid leukemia in untreated first relapse or in second complete remission." Journal of Clinical Oncology 11.7 (1993): 1353-1360.
PMID
8315433
Source
scival
Published In
Journal of Clinical Oncology
Volume
11
Issue
7
Publish Date
1993
Start Page
1353
End Page
1360

High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy

Purpose: To evaluate high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in patients with lymphoid malignancy who had received prior radiation therapy. Patients and Methods: Fifty-seven patients with non-Hodgkin's lymphoma (NHL; n = 23), Hodgkin's disease (HD; n = 32), or acute lymphoblastic leukemia (ALL; n = 2) with a history of previous radiation therapy were treated with cyclophosphamide (Cy; 7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2) (CBV) followed by ABMT. Results: The projected 2-year probabilities of survival, event-free survival (EFS), and relapse were .31, .24, and .76, respectively. For patients with intermediate- and high-grade lymphoma and HD the probabilities were .27, .10, and .14 for EFS and .57, .90, and .77 for relapse. The probability of nonrelapse mortality in the first 100 days post-ABMT was 33%. Idiopathic pneumonia syndrome (IPS) was observed in no patients who received carmustine 300 mg/m2 and 23% of patients who received carmustine 600 mg/m2 (P = .05). Eight-three percent of patients who received mediastinal radiation therapy less than 3 months before transplant developed IPS, compared with 13% who received radiation therapy more than 3 months before transplant (P = .001). Conclusion: ABMT following high-dose CBV resulted in long-term disease-free survival in 25% of patients with lymphoid malignancies who had previously received dose-limiting radiation therapy. Fatal IPS and a high relapse rate were major factors limiting successful outcome following ABMT. The morbidity and mortality rates associated with the administration of carmustine 600 mg/m2 were prohibitively high, especially in patients who received mediastinal radiation immediately before ABMT, and were not associated with a decrease in post-ABMT relapse. © 1993 by American Society of Clinical Oncology.

Authors
Weaver, CH; Appelbaum, FR; Petersen, FB; Clift, R; Singer, J; Press, O; Bensinger, W; Bianco, J; Martin, P; Anasetti, C; Badger, C; Deeg, J; Dony, K; Hansen, JA; Petersdorf, E; Rowley, S; Storb, R; Sullivan, K; Witherspoon, R; Weiden, P; Buckner, CD
MLA Citation
Weaver, CH, Appelbaum, FR, Petersen, FB, Clift, R, Singer, J, Press, O, Bensinger, W, Bianco, J, Martin, P, Anasetti, C, Badger, C, Deeg, J, Dony, K, Hansen, JA, Petersdorf, E, Rowley, S, Storb, R, Sullivan, K, Witherspoon, R, Weiden, P, and Buckner, CD. "High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy." Journal of Clinical Oncology 11.7 (1993): 1329-1335.
PMID
8315430
Source
scival
Published In
Journal of Clinical Oncology
Volume
11
Issue
7
Publish Date
1993
Start Page
1329
End Page
1335

Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome

We treated 93 patients with myelodysplastic syndrome using cyclophosphamide and either total body irradiation (n = 88) or busulfan (n = 5) followed by marrow transplantation. Sixty-five marrow donors were genotypically HLA-identical siblings and 28 were other family members or unrelated donors. Before transplantation all patients had either severe neutropenia or thrombocytopenia or had greater than 5% blasts in the marrow or peripheral blood. The probabilities of disease-free survival, relapse, and nonrelapse mortality at 4 years were 41%, 28%, and 43%, respectively. Multivariate analysis revealed that younger age and shorter disease duration were significantly associated with improved disease-free survival and decreased non-relapse mortality. Relapse was seen only in patients with excess blasts at the time of transplantation (51% at 4 years). Patients younger than age 40 and without excess blasts had a 4-year disease-free survival of 62%. This study confirms that allogeneic marrow transplantation can cure some patients with myelodysplasia. Because of the favorable outcome in younger patients without excess blasts, we recommend that transplantation be considered early for patients younger than age 40, before disease progression or development of life-threatening cytopenias. For older patients and those with excess blasts, changes in the transplant procedure will be necessary to improve out-come. © 1993 by The American Society of Hematology.

Authors
Anderson, JE; Appelbaum, FR; Fisher, LD; Schoch, G; Shulman, H; Anasetti, C; Bensinger, WI; Bryant, E; Buckner, CD; Doney, K; Martin, PJ; Sanders, JE; Sullivan, KM; Thomas, ED; Witherspoon, RP; Hansen, JA; Storb, R
MLA Citation
Anderson, JE, Appelbaum, FR, Fisher, LD, Schoch, G, Shulman, H, Anasetti, C, Bensinger, WI, Bryant, E, Buckner, CD, Doney, K, Martin, PJ, Sanders, JE, Sullivan, KM, Thomas, ED, Witherspoon, RP, Hansen, JA, and Storb, R. "Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome." Blood 82.2 (1993): 677-681.
PMID
8329721
Source
scival
Published In
Blood
Volume
82
Issue
2
Publish Date
1993
Start Page
677
End Page
681

Two Cases of Transfusion-Associated Graft-vs-Host Disease After Open Heart Surgery

Authors
Tanaka, K
MLA Citation
Tanaka, K. "Two Cases of Transfusion-Associated Graft-vs-Host Disease After Open Heart Surgery." Archives of Dermatology 128.11 (November 1, 1992): 1503-1503.
Source
crossref
Published In
Archives of Dermatology
Volume
128
Issue
11
Publish Date
1992
Start Page
1503
End Page
1503
DOI
10.1001/archderm.1992.01680210081012

Allogeneic marrow transplantation during untreated first relapse of acute myeloid leukemia.

PURPOSE: The purpose of this report was to review the Seattle experience in bone marrow transplantation (BMT) for acute myeloid leukemia (AML) during untreated first relapse. PATIENTS AND METHODS: Through 1990, 126 patients were transplanted during untreated first relapse of AML. Several preparative regimens were used, two of which involved more than 20 patients. Regimen 1 (29 patients) consisted of cyclophosphamide (CY) 120 mg/kg and 15.75 Gy of fractionated total-body irradiation (TBI) with methotrexate (MTX) given intermittently during a 102-day period to prevent graft-versus-host disease (GVHD). Regimen 2 (22 patients) consisted of the same CY and TBI treatment and a combination of MTX and cyclosporine (CSP) for GVHD prophylaxis. The remaining 75 patients were treated with 17 other transplant regimens. Outcome was compared for patients who were treated with regimen 1, regimen 2, and any other regimen. RESULTS: The 5-year probabilities of relapse-free survival (RFS), relapse, and nonrelapse mortality for 126 patients were .23, .57, and .44, respectively. With regimen 1, relapse (.26) was significantly less than for regimen 2 (.70; P = .004) or any other regimen (.76; P = .004). Regimen 1 patients developed more acute GVHD (.67) than regimen 2 patients (.26; P = .02) or patients on other regimens (.41; P = .02), and had increased nonrelapse mortality. Nevertheless, regimen 1 patients had a significantly higher 3-year RFS (.38) than those treated with regimen 2 (.18; P = .04) or any other regimen (.20; P = .05). CONCLUSIONS: For patients who received 120 mg/kg CY and 15.75 Gy TBI, relapse incidence was less and survival was better after GVHD prophylaxis with MTX alone than after a combination of MTX and CSP, despite a significantly higher incidence of acute GVHD. The results of treatment with regimen 1 justify future studies of the optimal timing of allogeneic BMT in the treatment of patients with AML.

Authors
Clift, RA; Buckner, CD; Appelbaum, FR; Schoch, G; Petersen, FB; Bensinger, WI; Sanders, J; Sullivan, KM; Storb, R; Singer, J
MLA Citation
Clift, RA, Buckner, CD, Appelbaum, FR, Schoch, G, Petersen, FB, Bensinger, WI, Sanders, J, Sullivan, KM, Storb, R, and Singer, J. "Allogeneic marrow transplantation during untreated first relapse of acute myeloid leukemia." J Clin Oncol 10.11 (November 1992): 1723-1729.
PMID
1403055
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
10
Issue
11
Publish Date
1992
Start Page
1723
End Page
1729
DOI
10.1200/JCO.1992.10.11.1723

Two cases of transfusion-associated graft-vs-host disease after open heart surgery.

BACKGROUND: Some cases of blood transfusion-associated (TA) graft-vs-host disease (GVHD) in immunocompetent patients have been reported, but those dermatologic findings were not precisely mentioned. We describe patients with clinicopathologically TA-GVHD and compare TA-GVHD and acute GVHD after bone marrow transplantation. OBSERVATIONS: Two cases of TA-GVHD after open heart surgery are reported. In both immunocompetent patients, severe erythema multiformelike skin rash developed over the entire body, followed by fever, diarrhea, jaundice, transaminitis, pancytopenia, and marrow alpasia approximately 10 days after operation. The rash in one patient changed from erythema multiformelike to toxic epidermal necrolysis at death. Skin biopsy specimens revealed eosinophilic bodies, basal vacuolation, and exocytosis in the epidermis. Eosinophilic bodies tend to appear in the upper epidermis. Immunohistochemistry studies revealed that infiltrating cells were CD4 and CD8. While acute GVHD in immunosuppressed patients who have undergone bone marrow transplantations often shows lichenoid histologic features, TA-GVHD in our patients who were immunocompetent may resemble severe erythema multiforme or toxic epidermal necrolysis. The difference in TA-GVHD may be related to lack of host modification by immunosuppression. CONCLUSIONS: Irradiation of the blood products should be required in open heart surgery, for TA-GVHD in immunocompetent patients is almost always fatal.

Authors
Tanaka, K; Aki, T; Shulman, HM; Sullivan, KM; Tanaka, A; Nagasako, R
MLA Citation
Tanaka, K, Aki, T, Shulman, HM, Sullivan, KM, Tanaka, A, and Nagasako, R. "Two cases of transfusion-associated graft-vs-host disease after open heart surgery." Arch Dermatol 128.11 (November 1992): 1503-1506.
PMID
1444505
Source
pubmed
Published In
Archives of Dermatology
Volume
128
Issue
11
Publish Date
1992
Start Page
1503
End Page
1506

Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody.

Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival.

Authors
Anasetti, C; Martin, PJ; Storb, R; Appelbaum, FR; Beatty, PG; Davis, J; Doney, K; Hill, HF; Stewart, P; Sullivan, KM
MLA Citation
Anasetti, C, Martin, PJ, Storb, R, Appelbaum, FR, Beatty, PG, Davis, J, Doney, K, Hill, HF, Stewart, P, and Sullivan, KM. "Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody." Transplantation 54.5 (November 1992): 844-851.
PMID
1440852
Source
pubmed
Published In
Transplantation
Volume
54
Issue
5
Publish Date
1992
Start Page
844
End Page
851

Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study.

Thirty-seven patients with advanced hematologic malignancy were entered into a phase I study designed to define a maximum tolerable dose (MTD) of etoposide (VP-16) and cyclophosphamide (CY) combined with 12 Gy fractionated total body irradiation (TBI) as preparation for marrow transplantation from an HLA-identical sibling (n = 13) or with cryopreserved autologous marrow (n = 24). Dose levels ranged from 36 mg/kg of VP-16 combined with 67 mg/kg of CY to 52 mg/kg of VP-16 combined with 103 mg/kg of CY followed by 12 Gy TBI. The MTD for allogeneic marrow recipients was 36 mg/kg of VP-16 + 52 mg/kg of CY followed by 12 Gy TBI and for autologous marrow recipients 44 mg/kg of VP-16 + 103 mg/kg CY followed by 12 Gy TBI. Pulmonary and liver toxicities were dose limiting. All of 31 evaluable patients transplanted in relapse achieved a complete remission. However, in all but three of these patients the disease relapsed 28-899 (median 110) days post-transplant. Currently, six of 24 autologous marrow recipients are surviving, three in remission 256, 340 and 764 days post-transplant. None of 12 allogeneic marrow recipients have survived. In conclusion, a preparative regimen combining 44 mg/kg of VP-16 + 103 mg/kg CY followed by 12 Gy TBI is well tolerated by autologous marrow recipients and 36 mg/kg VP-16 + 67 mg/kg CY followed by 12 Gy TBI is well tolerated by allogeneic marrow recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Petersen, FB; Buckner, CD; Appelbaum, FR; Sanders, JE; Bensinger, WI; Storb, R; Deeg, HJ; Witherspoon, RP; Sullivan, KM; Clift, RA
MLA Citation
Petersen, FB, Buckner, CD, Appelbaum, FR, Sanders, JE, Bensinger, WI, Storb, R, Deeg, HJ, Witherspoon, RP, Sullivan, KM, and Clift, RA. "Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study." Bone Marrow Transplant 10.1 (July 1992): 83-88.
PMID
1515884
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
10
Issue
1
Publish Date
1992
Start Page
83
End Page
88

Long-term follow-up of three controlled trials comparing cyclosporine versus methotrexate for graft-versus-host disease prevention in patients given marrow grafts for leukemia.

Authors
Storb, R; Martin, P; Deeg, HJ; Sanders, JE; Pepe, M; Singer, J; Anasetti, C; Stewart, P; Appelbaum, FR; Sullivan, KM
MLA Citation
Storb, R, Martin, P, Deeg, HJ, Sanders, JE, Pepe, M, Singer, J, Anasetti, C, Stewart, P, Appelbaum, FR, and Sullivan, KM. "Long-term follow-up of three controlled trials comparing cyclosporine versus methotrexate for graft-versus-host disease prevention in patients given marrow grafts for leukemia." Blood 79.11 (June 1, 1992): 3091-3092. (Letter)
PMID
1586751
Source
pubmed
Published In
Blood
Volume
79
Issue
11
Publish Date
1992
Start Page
3091
End Page
3092

Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver.

OBJECTIVE: To determine the safety and efficacy of ursodeoxycholic acid treatment in patients with chronic graft-versus-host disease (GVHD) of the liver. DESIGN: Open-label study in which each patient served as his or her own control. SETTING: Private practice and a university bone marrow transplant center. PATIENTS: Twelve patients with refractory chronic GVHD of the liver were studied after allogeneic bone marrow transplantation. INTERVENTIONS: After baseline data collection, patients were given ursodeoxycholic acid (UDCA, 10 to 15 mg/kg body weight per day) for 6 weeks. After discontinuation of the drug, patients were followed for an additional 6 weeks. Doses of immunosuppressive drugs were unchanged for these 12 weeks. MEASUREMENTS: Signs, symptoms, Karnofsky performance scores, hematocrit, total leukocyte count, absolute neutrophil count, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyltransferase (GGT), total serum bilirubin, prothrombin time, serum creatinine, and blood urea nitrogen were assessed. RESULTS: Serum tests of cholestatic liver injury measured at 2, 4, and 6 weeks showed improvement compared with baseline. At 6 weeks, the percent decrease from baseline in total serum bilirubin was 33% (P less than 0.005); in alkaline phosphatase the decrease was 32% (P less than 0.038); and in AST the decrease was 37% (P less than 0.007). After discontinuation of UDCA therapy, 11 patients were followed for 6 additional weeks. All showed significant worsening in liver function test results. Symptom scores were unchanged throughout the study. One patient with pruritus improved while receiving therapy with UDCA. No adverse effects were observed. CONCLUSION: Therapy with UDCA was safe, well-tolerated, and efficacious in the short-term treatment of refractory chronic GVHD of the liver. Further investigation is needed to evaluate the long-term effects of UDCA therapy.

Authors
Fried, RH; Murakami, CS; Fisher, LD; Willson, RA; Sullivan, KM; McDonald, GB
MLA Citation
Fried, RH, Murakami, CS, Fisher, LD, Willson, RA, Sullivan, KM, and McDonald, GB. "Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver." Ann Intern Med 116.8 (April 15, 1992): 624-629.
PMID
1546861
Source
pubmed
Published In
Annals of internal medicine
Volume
116
Issue
8
Publish Date
1992
Start Page
624
End Page
629

Clinical experience with Tc-99m labeled (N2S2) anti-melanoma antibody fragments and single photon emission computed tomography.

We evaluated the imaging capability of murine Tc-99m-labeled antimelanoma Fab fragments in 12 patients with clinical stage II and III melanoma. Tc-99m-NRX118.7 antimelanoma Fab fragment, 10.0 to 27.2 mCi (370-1, 006 MBq), was injected IV 30 min after irrelevant nonspecific intact antibody and 5 min after intact specific antibody were given. In all patients, whole-body scans and spot views were obtained. Single photon emission computed tomography (SPECT) was additionally performed in eight of the patients. The procedure was well tolerated, and 31 of 38 known foci of melanoma were detected (sensitivity, 82%). SPECT aided in detecting and better localizing lesions in the head, neck, and chest. The specificity of the technique was satisfactory when interpretation was performed with a knowledge of normal sites of accretion and excretion of technetium-99m activity such as the kidneys and gut. In several instances, lesions were discovered by means of the antibody scan before detection by other methods, and in two instances, the lack of visualization on antibody scan of a palpable mass correctly indicated that no melanoma was present in the mass. Scan results in three patients led to alterations in patient care; including preventing aggressive surgical and nonsurgical treatments. Although these data are encouraging, evaluation in additional patients will be essential to determine the clinical utility of this antibody scan in the management of patients with melanoma.

Authors
Wahl, RL; Swanson, NA; Johnson, JW; Natale, R; Petry, NA; Mallette, S; Kasina, S; Reno, J; Sullivan, K; Abrams, P
MLA Citation
Wahl, RL, Swanson, NA, Johnson, JW, Natale, R, Petry, NA, Mallette, S, Kasina, S, Reno, J, Sullivan, K, and Abrams, P. "Clinical experience with Tc-99m labeled (N2S2) anti-melanoma antibody fragments and single photon emission computed tomography." Am J Physiol Imaging 7.2 (April 1992): 48-58.
PMID
1419120
Source
pubmed
Published In
American journal of physiologic imaging
Volume
7
Issue
2
Publish Date
1992
Start Page
48
End Page
58

Marrow transplantation for Fanconi anemia with or without leukemic transformation: an update of the Seattle experience.

Between March 1973 and August 1990, 17 patients with Fanconi anemia (FA) underwent bone marrow transplantation in Seattle. Marrow donors were HLA identical siblings (n = 14), phenotypically HLA identical parents (n = 2) and a one antigen mismatched parent (n = 1). Patients with no evidence of leukemic transformation (n = 12) were conditioned with 140-200 mg/kg cyclophosphamide (CY). Of five patients with leukemic transformation, four received CY (120 mg/kg) plus 12 Gy fractionated total body irradiation and one patient received busulfan (14 mg/kg) and CY (100 mg/kg). All patients engrafted; however, one patient whose sibling donor's cells showed variable results when assayed for chromosome instability required two additional marrow infusions. Toxicity associated with the conditioning regimen included severe oral mucositis (n = 14), hemorrhagic cystitis (n = 11) and diffuse erythroderma (n = 3). Seven of the 12 patients without leukemic transformation are surviving 1-17 years (median = 5 years) after transplant, with an estimated survival probability at 5 years of 65% (95% CI 0.31; 0.85). Two patients developed squamous cell carcinoma of the tongue greater than 10 years post-transplant. One of these patients died at 10.3 years as a result of the malignant process, and the other is disease free more than 12 years post-transplant. Of the five patients with leukemic transformation, one is alive at 8 years. These data demonstrate that marrow transplantation can offer long-term survival for patients with FA, engraftment can be achieved with reduced doses of CY in FA patients, and less toxic preparative regimens are needed for FA patients who have developed leukemic transformation.

Authors
Flowers, ME; Doney, KC; Storb, R; Deeg, HJ; Sanders, JE; Sullivan, KM; Bryant, E; Witherspoon, RP; Appelbaum, FR; Buckner, CD
MLA Citation
Flowers, ME, Doney, KC, Storb, R, Deeg, HJ, Sanders, JE, Sullivan, KM, Bryant, E, Witherspoon, RP, Appelbaum, FR, and Buckner, CD. "Marrow transplantation for Fanconi anemia with or without leukemic transformation: an update of the Seattle experience." Bone Marrow Transplant 9.3 (March 1992): 167-173.
PMID
1511254
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
9
Issue
3
Publish Date
1992
Start Page
167
End Page
173

Mixed leukocyte culture reactivity and graft-versus-host disease in HLA-identical marrow transplantation for leukemia.

The results of pretransplant mixed leukocyte culture (MLC) assays were compared to subsequent risk of graft-versus-host disease (GVHD) in 783 patients receiving marrow transplants from HLA genotypically identical sibling donors. The mean MLC response observed between 1303 normal HLA identical sibling pairs was 0.0 +/- 4.2% RR. The donor anti-recipient MLC reaction, an in vitro response that presumably might be relevant to GVHD, was significantly increased (greater than mean + 2 sd) in 83 (10.6%) of the cases, most often in patients in relapse at the time of testing. No association was found, however, between this increased donor anti-recipient MLC reactivity pretransplant and the incidence or severity of subsequent acute or chronic GVHD. These data suggest that the increased MLC responses sometimes observed between leukemia patients and their HLA identical sibling donors prior to marrow transplantation do not represent genetic differences capable of causing GVHD.

Authors
DeGast, GC; Mickelson, EM; Beatty, PG; Amos, D; Sullivan, KM; Schoch, HG; Thomas, ED; Hansen, JA
MLA Citation
DeGast, GC, Mickelson, EM, Beatty, PG, Amos, D, Sullivan, KM, Schoch, HG, Thomas, ED, and Hansen, JA. "Mixed leukocyte culture reactivity and graft-versus-host disease in HLA-identical marrow transplantation for leukemia." Bone Marrow Transplant 9.2 (February 1992): 87-90.
PMID
1533333
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
9
Issue
2
Publish Date
1992
Start Page
87
End Page
90

Cumulative incidence of secondary solid malignant tumors in aplastic anemia patients given marrow grafts after conditioning with chemotherapy alone.

Authors
Witherspoon, RP; Storb, R; Pepe, M; Longton, G; Sullivan, KM
MLA Citation
Witherspoon, RP, Storb, R, Pepe, M, Longton, G, and Sullivan, KM. "Cumulative incidence of secondary solid malignant tumors in aplastic anemia patients given marrow grafts after conditioning with chemotherapy alone." Blood 79.1 (January 1, 1992): 289-291. (Letter)
PMID
1728317
Source
pubmed
Published In
Blood
Volume
79
Issue
1
Publish Date
1992
Start Page
289
End Page
291

Late complications of allogeneic and autologous marrow transplantation.

Authors
Sullivan, KM; Mori, M; Sanders, J; Siadak, M; Witherspoon, RP; Anasetti, C; Appelbaum, FR; Bensinger, W; Bowden, R; Buckner, CD
MLA Citation
Sullivan, KM, Mori, M, Sanders, J, Siadak, M, Witherspoon, RP, Anasetti, C, Appelbaum, FR, Bensinger, W, Bowden, R, and Buckner, CD. "Late complications of allogeneic and autologous marrow transplantation." Bone Marrow Transplant 10 Suppl 1 (1992): 127-134. (Review)
PMID
1521083
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
10 Suppl 1
Publish Date
1992
Start Page
127
End Page
134

Marrow transplantation following escalating doses of fractionated total body irradiation and cyclophosphamide--a phase I trial.

Thirty-six patients with advanced hematologic malignancy were entered into a Phase I study designed to define the maximum tolerated dose of unshielded total body irradiation delivered from dual 60 Cobalt sources at an exposure rate of 8 cGy/min and given in fractions twice daily for total doses ranging from 12 Gy to 17 Gy. All patients received cyclophosphamide, 120 mg/kg administered over 2 days before total body irradiation. Allogeneic marrow was infused from HLA-identical siblings (n = 29) or one locus HLA incompatible family members (n = 3); three patients received cryopreserved autologous marrow and one patient received syngeneic marrow. The maximum tolerated dose of total body irradiation given as 2 Gy fractions twice a day was 16 Gy. One of eight patients receiving 12 Gy, none of four receiving 14 Gy, three of 20 receiving 16 Gy, and two of four receiving 17 Gy developed severe (Grade 3-4) regimen-related toxicity. The primary dose limiting toxicity was pneumonitis, followed by veno-occlusive disease of the liver, renal impairment, and mucositis. Five patients (14%) are alive, four disease-free 798-1522 days posttransplant. Twenty (56%) relapsed posttransplant. Further investigation of regimens containing 16 Gy of hyperfractionated total body irradiation is warranted to assess anti-tumor efficacy.

Authors
Petersen, FB; Deeg, HJ; Buckner, CD; Appelbaum, FR; Storb, R; Clift, RA; Sanders, JE; Bensinger, WI; Witherspoon, RP; Sullivan, KM
MLA Citation
Petersen, FB, Deeg, HJ, Buckner, CD, Appelbaum, FR, Storb, R, Clift, RA, Sanders, JE, Bensinger, WI, Witherspoon, RP, and Sullivan, KM. "Marrow transplantation following escalating doses of fractionated total body irradiation and cyclophosphamide--a phase I trial." Int J Radiat Oncol Biol Phys 23.5 (1992): 1027-1032.
PMID
1639636
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
23
Issue
5
Publish Date
1992
Start Page
1027
End Page
1032

Photoinactivation of lymphohemopoietic cells: studies in transfusion medicine and bone marrow transplantation.

Ultraviolet (UV) irradiation affects eukaryotic cells in numerous ways. Exposure of blood transfusion products to UVC (200-280 nm) or UVB (280-320 nm) reduces or abrogates their immunogenicity and thereby prevents allosensitization and transfusion refractoriness in several models. Although the exact mechanism is not known, in vitro studies suggest that UV exposure results in a loss of class II histocompatibility antigens from the cell surface, alterations of calcium homeostasis, and a lack of interaction between antigen presenting and responding cells. In the UVB and UVA (320-400 nm) range, lymphocytes appear to be more sensitive than hemopoietic cells. In murine transplant models, UVB irradiation of spleen and marrow cells can be used to prevent the development of graft-versus-host disease while allowing for complete hemopoietic reconstitution. Furthermore, in clinical marrow transplantation, pilot studies of UVA in conjunction with psoralen administration have yielded encouraging results in patients with steroid refractory graft-versus-host disease of the skin. Thus, UV irradiation provides an interesting tool to study cell/cell and donor/host interactions and may have some applications in transfusion medicine and bone marrow transplantation.

Authors
Deeg, HJ; Erickson, K; Storb, R; Sullivan, KM
MLA Citation
Deeg, HJ, Erickson, K, Storb, R, and Sullivan, KM. "Photoinactivation of lymphohemopoietic cells: studies in transfusion medicine and bone marrow transplantation." Blood Cells 18.1 (1992): 151-161. (Review)
PMID
1617189
Source
pubmed
Published In
Blood Cells
Volume
18
Issue
1
Publish Date
1992
Start Page
151
End Page
161

Acute graft-versus-host disease: Analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate

Previous studies of risk factors for acute graft-versus-host disease (GVHD) involved patients receiving predominantly single-agent prophylaxis. Therefore, a retrospective analysis was performed on 446 patients, from a single institution, who received transplants of marrow from HLA-identical siblings and the combination of cyclosporine (CSP) and methotrexate (MTX) to determine risk factors for acute GVHD associated with this more effective form of GVHD prophylaxis. The incidences of Grades II-IV and Grades III-IV (severe) acute GVHD were 35% and 16%, respectively. Increased clinical grades of acute GVHD in patients without advanced malignant disease were associated with a decreased survival. In a multivariate Cox regression analysis, risk factors associated with the onset of Grades II-IV acute GVHD were sex mismatch and donor parity (P = .001), increased dose of total body irradiation (TBI) (P = .001), and reduction to less than 80% of the scheduled dose of MTX (P = .02) or CSP (P = .02). The multivariate analysis indicated a relative risk of 1.37 for acute GVHD in a group defined as having advanced malignant disease at transplant; however, this difference failed to reach conventional levels of statistical significance (P = .07). Reduction of MTX and CSP occurred in up to 36% and 44% of patients, respectively, primarily because of renal or hepatic dysfunction. The periods of increased risk for the onset of acute GVHD were up to 1 week after a reduction of MTX and 2 weeks after a reduction in CSP. When only patients who developed Grades II-IV acute GVHD were considered, the more severe acute GVHD of Grades III-IV was associated with increased patient age of 40 years or greater (P = .05) and dose reductions of CSP (P = .008). Serologic status of patient and donor for cytomegalovirus (CMV), HLA antigens in the A and B loci, and isolation in a laminar air flow room during marrow transplantation, all previously identified as risk factors for acute GVHD, were not confirmed as risk factors in this study population. The toxicity of MTX and CSP and the development of acute GVHD from inadequate immunosuppression because of dose reduction warrants further trials with potentially less toxic immunosuppressive agents. Risk factors for acute GVHD should be considered in clinical management and in the design of clinical trials. © 1992 by The American Society of Hematology.

Authors
Nash, RA; Pepe, MS; Storb, R; Longton, G; Pettinger, M; Anasetti, C; Appelbaum, FR; Bowden, RA; Deeg, HJ; Doney, K; Martin, PJ; Sullivan, KM; Sanders, J; Witherspoon, RP
MLA Citation
Nash, RA, Pepe, MS, Storb, R, Longton, G, Pettinger, M, Anasetti, C, Appelbaum, FR, Bowden, RA, Deeg, HJ, Doney, K, Martin, PJ, Sullivan, KM, Sanders, J, and Witherspoon, RP. "Acute graft-versus-host disease: Analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate." Blood 80.7 (1992): 1838-1845.
PMID
1391947
Source
scival
Published In
Blood
Volume
80
Issue
7
Publish Date
1992
Start Page
1838
End Page
1845

Immunosuppressive therapy of aplastic anemia: Results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high-dose methylprednisolone, and oxymetholone

Sixty-eight patients with moderate (n = 15) or severe (n = 53) aplastic anemia were entered into a prospective, randomized, two-arm treatment study comparing antihuman thymocyte globulin (ATG), lower-dose methylprednisolone (LDM) and oxymetholone to ATG, higher-dose methylprednisolone (HDM), and oxymetholone. There were no differences between the two groups when comparing age, sex, etiology of aplasia, disease duration, severity of aplasia, or pretherapy granulocyte counts. Side effects of LDM and HDM were similar. Of the 64 patients evaluable for response to therapy, 12 of 33 (36%) who received LDM had complete, partial, or minimal responses compared with 15 of 31 patients (48%) who received HDM (P = .33). Actuarial survival at 4 years is 43% for patients in the LDM group and 47% for patients in the HDM group (P = .99). Causes of death included hemorrhage, infection, evolution to acute leukemia, and complications of subsequent bone marrow transplantation. Long-term complications included paroxysmal nocturnal hemoglobinuria (n = 3), evolution to myelodysplasia or acute leukemia (n = 6), and recurrent aplasia (n = 6). We were unable to show a significant difference in toxicity, response rate, or survival for patients treated with ATG, oxymetholone, and LDM compared with patients who received ATG, oxymetholone, and HDM. © 1992 by The American Society of Hematology.

Authors
Doney, K; Pepe, M; Storb, R; Bryant, E; Anasetti, C; Appelbaum, FR; Buckner, CD; Sanders, J; Singer, J; Sullivan, K; Weiden, P; Hansen, JA
MLA Citation
Doney, K, Pepe, M, Storb, R, Bryant, E, Anasetti, C, Appelbaum, FR, Buckner, CD, Sanders, J, Singer, J, Sullivan, K, Weiden, P, and Hansen, JA. "Immunosuppressive therapy of aplastic anemia: Results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high-dose methylprednisolone, and oxymetholone." Blood 79.10 (1992): 2566-2571.
PMID
1586708
Source
scival
Published In
Blood
Volume
79
Issue
10
Publish Date
1992
Start Page
2566
End Page
2571

Phase II trial of recombinant human granulocyte-macrophage colony-stimulating factor in patients undergoing allogeneic bone marrow transplantation from unrelated donors

The safety and possible efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were evaluated in 40 consecutive patients who received transplants from unrelated donors. rhGM-CSF was administered by 2-hour daily intravenous infusion from day 0 to day 20 or day 27 after the marrow infusion. These patients were compared with 78 historical patients who received transplants from unrelated donors who did not receive rhGM-CSF. The rhGM-CSF-treated patients were older (P = .037) and were treated less frequently in laminar air flow rooms (P = .005) than were control patients. However, the rhGM-CSF-treated group had a higher proportion of "good risk" patients with chronic myelogenous leukemia in chronic phase (P = .006) than did the comparison group (P = .017), rendering comparisons of transplant-related complications not meaningful. rhGM-CSF was well tolerated and did not adversely increase the incidence of graft rejection or increase the incidence and severity of acute graft-versus-host disease. The median day the absolute neutrophil count reached 500/mm3 in patients who received rhGM-CSF was day 21, which was not different from that of historical patients. Nevertheless, the numbers of febrile days and septicemic episodes within the first 28 days in patients who received rhGM-CSF were less than in historical patients. The probability of nonrelapse mortality at 1 year in patients who received rhGM-CSF was 22%. In view of the retrospective nature of the control group, we cannot conclusively determine whether rhGM-CSF administration was beneficial. A prospective, randomized controlled study of rhGM-CSF is required to confirm these suggestive data. © 1992 by The American Society of Hematology.

Authors
Nemunaitis, J; Anasetti, C; Storb, R; Bianco, JA; Buckner, CD; Onetto, N; Martin, P; Sanders, J; Sullivan, K; Mori, M; Shannon-Dorcy, K; Bowden, R; Appelbaum, FR; Hansen, J; Singer, JW
MLA Citation
Nemunaitis, J, Anasetti, C, Storb, R, Bianco, JA, Buckner, CD, Onetto, N, Martin, P, Sanders, J, Sullivan, K, Mori, M, Shannon-Dorcy, K, Bowden, R, Appelbaum, FR, Hansen, J, and Singer, JW. "Phase II trial of recombinant human granulocyte-macrophage colony-stimulating factor in patients undergoing allogeneic bone marrow transplantation from unrelated donors." Blood 79.10 (1992): 2572-2577.
PMID
1586709
Source
scival
Published In
Blood
Volume
79
Issue
10
Publish Date
1992
Start Page
2572
End Page
2577

Long-term follow-up of a controlled trial comparing a combination of methotrexate plus cyclosporine with cyclosporine alone for prophylaxis of graft-versus-host disease in patients administered HLA-identical marrow grafts for leukemia [4]

Authors
Storb, R; Pepe, M; Deeg, HJ; Anasetti, C; Appelbaum, FR; Bensinger, W; Buckner, CD; Clift, RA; Doney, K; Hansen, J; Martin, P; Pettinger, M; Sanders, JE; Singer, J; Stewart, P; Sullivan, KM; Thomas, ED; Witherspoon, RP
MLA Citation
Storb, R, Pepe, M, Deeg, HJ, Anasetti, C, Appelbaum, FR, Bensinger, W, Buckner, CD, Clift, RA, Doney, K, Hansen, J, Martin, P, Pettinger, M, Sanders, JE, Singer, J, Stewart, P, Sullivan, KM, Thomas, ED, and Witherspoon, RP. "Long-term follow-up of a controlled trial comparing a combination of methotrexate plus cyclosporine with cyclosporine alone for prophylaxis of graft-versus-host disease in patients administered HLA-identical marrow grafts for leukemia [4]." Blood 80.2 (1992): 560-561.
PMID
1627810
Source
scival
Published In
Blood
Volume
80
Issue
2
Publish Date
1992
Start Page
560
End Page
561

Changing trends in marrow transplantation for aplastic anemia

Authors
Storb, R; Longton, G; Anasetti, C; Appelbaum, FR; Beatty, P; Bensinger, W; Crawford, S; Deeg, HJ; Doney, K; Fefer, A; Hansen, J; Loughran, T; Martin, P; Pepe, M; Petersen, FB; Sanders, JE; Singer, J; Stewart, P; Sullivan, KM
MLA Citation
Storb, R, Longton, G, Anasetti, C, Appelbaum, FR, Beatty, P, Bensinger, W, Crawford, S, Deeg, HJ, Doney, K, Fefer, A, Hansen, J, Loughran, T, Martin, P, Pepe, M, Petersen, FB, Sanders, JE, Singer, J, Stewart, P, and Sullivan, KM. "Changing trends in marrow transplantation for aplastic anemia." Bone Marrow Transplantation 10.SUPPL. 1 (1992): 45-52.
PMID
1521089
Source
scival
Published In
Bone Marrow Transplantation
Volume
10
Issue
SUPPL. 1
Publish Date
1992
Start Page
45
End Page
52

A pilot study of low-dose cyclosporin for graft-versus-host prophylaxis in marrow transplantation

Nineteen patients with leukaemia, preleukaemia, and aplastic anaemia were treated by marrow transplantation from HLA-identical siblings. All were given postgrading immunosuppression with a combination of methotrexate (days 1, 3, 6 and 11) and cyclosporin (days -1 to 180). In an attempt at reducing cyclosporin-associated toxicity, we explored whether the cyclosporin dose during the first 2 weeks could be decreased by 50% (from 3.0 to 1.5 mg/kg/d intravenously) without adversely affecting the incidence, onset, and severity of acute graft-versus-host disease (GVHD) and overall survival. Results from this pilot study were compared to those of a matched cohort of 38 patients given a standard dose of 3.0 mg cyclosporin/kg/d starting on day -1. The cumulative incidence of grade II and III acute GVHD in the 'low dose' cyclosporin group was 4.2% compared to 51% in the 'standard dose' group (P = 0.60). Three-year survival was 63% and 54% respectively (P = 0.59). Patients receiving the reduced cyclosporin dose during the first 14 d appeared to have less hepatotoxicity, and the methotrexate and cyclosporin doses administered were closer to the doses intended per protocol. We suggest that 'low dose' cyclosporin from day -1 to day 15 postgrafting might be as effective as 'standard dose' cyclosporin during that time period for the prevention of acute GVHD.

Authors
Stockschlaeder, M; Storb, R; Pepe, M; Longton, G; McDonald, G; Anasetti, C; Appelbaum, F; Doney, K; Martin, P; Sullivan, K; Witherspoon, R
MLA Citation
Stockschlaeder, M, Storb, R, Pepe, M, Longton, G, McDonald, G, Anasetti, C, Appelbaum, F, Doney, K, Martin, P, Sullivan, K, and Witherspoon, R. "A pilot study of low-dose cyclosporin for graft-versus-host prophylaxis in marrow transplantation." British Journal of Haematology 80.1 (1992): 49-54.
PMID
1536809
Source
scival
Published In
British Journal of Haematology
Volume
80
Issue
1
Publish Date
1992
Start Page
49
End Page
54

Prophylaxis of cytomegalovirus disease in allogeneic bone marrow transplantation [1]

Authors
Grigg, A; Phillips, G; Bowden, RA; Sullivan, K
MLA Citation
Grigg, A, Phillips, G, Bowden, RA, and Sullivan, K. "Prophylaxis of cytomegalovirus disease in allogeneic bone marrow transplantation [1]." Journal of Infectious Diseases 165.5 (1992): 972-973.
PMID
1314874
Source
scival
Published In
Journal of Infectious Diseases
Volume
165
Issue
5
Publish Date
1992
Start Page
972
End Page
973

Busulfan and cyclophosphamide as a preparative regimen for bone marrow transplantation in patients with prior chest radiotherapy.

In a previous study, we reported that patients with hematologic malignancies who had received prior chest radiotherapy had a 32% risk of developing fatal interstitial pneumonia (IP) when prepared for bone marrow transplantation (BMT) with a regimen containing total body irradiation (TBI). To determine if avoidance of TBI would lessen the incidence of fatal IP, 37 patients who had received prior chest radiotherapy in excess of 2000 cGy were prepared with busulfan (BU, 4 mg/kg x 4 days) and cyclophosphamide (CY, 60 mg/kg x 2 days) followed by autologous (n = 15) or allogeneic (n = 22) BMT. Thirty-five of these patients had recurrent or refractory hematologic malignancies and most were heavily pretreated. Results were compared with the group of similar patients (n = 25) previously treated at our institution with a CY/TBI conditioning regimen. Among those treated with BU/CY, two patients (5%) developed fatal interstitial pneumonia, 12 (32%) died of other transplant related toxicities and 13 (35%) died of relapse. Seven (19%) patients remain alive and well. Among those treated with CY/TBI, eight (32%) died of pneumonia, six (24%) died of relapse, nine (36%) died of other causes and two (8%) remain alive and well. The 5% incidence of fatal interstitial pneumonitis in the chemotherapy conditioned group was significantly less than the 32% incidence in the previously treated CY/TBI group (p = 0.005). However, long-term survival and relapse probabilities were not significantly better than seen previously with CY/TBI, although a trend towards improved survival was observed in the BU/CY group. Avoidance of TBI appeared to lower the incidence of fatal pneumonitis in patients with prior chest radiotherapy.

Authors
Van der Jagt, RH; Appelbaum, FR; Petersen, FB; Bigelow, CL; Fisher, LD; Schoch, GH; Buckner, CD; Sanders, JE; Storb, R; Sullivan, KM
MLA Citation
Van der Jagt, RH, Appelbaum, FR, Petersen, FB, Bigelow, CL, Fisher, LD, Schoch, GH, Buckner, CD, Sanders, JE, Storb, R, and Sullivan, KM. "Busulfan and cyclophosphamide as a preparative regimen for bone marrow transplantation in patients with prior chest radiotherapy." Bone Marrow Transplant 8.3 (September 1991): 211-215.
PMID
1958901
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
8
Issue
3
Publish Date
1991
Start Page
211
End Page
215

Introduction to a symposium on sickle cell anemia: current results of comprehensive care and the evolving role of bone marrow transplantation.

Authors
Sullivan, KM; Reid, CD
MLA Citation
Sullivan, KM, and Reid, CD. "Introduction to a symposium on sickle cell anemia: current results of comprehensive care and the evolving role of bone marrow transplantation." Semin Hematol 28.3 (July 1991): 177-179. (Review)
PMID
1887244
Source
pubmed
Published In
Seminars in Hematology
Volume
28
Issue
3
Publish Date
1991
Start Page
177
End Page
179

Chronic graft-versus-host disease and other late complications of bone marrow transplantation.

Authors
Sullivan, KM; Agura, E; Anasetti, C; Appelbaum, F; Badger, C; Bearman, S; Erickson, K; Flowers, M; Hansen, J; Loughran, T
MLA Citation
Sullivan, KM, Agura, E, Anasetti, C, Appelbaum, F, Badger, C, Bearman, S, Erickson, K, Flowers, M, Hansen, J, and Loughran, T. "Chronic graft-versus-host disease and other late complications of bone marrow transplantation." Semin Hematol 28.3 (July 1991): 250-259. (Review)
PMID
1887253
Source
pubmed
Published In
Seminars in Hematology
Volume
28
Issue
3
Publish Date
1991
Start Page
250
End Page
259

Transfusions shortly before HLA-matched marrow transplantation for leukemia are associated with a decrease in chronic graft-versus-host disease.

The effect of random red cell transfusions given shortly before allogeneic bone marrow transplantation (BMT) was evaluated in 969 leukemic patients transplanted from an HLA-identical sibling donor. Patients were divided into two groups: 501 who received a transfusion shortly before BMT, and 468 who did not. Both groups had a similar incidence of acute graft-versus-host disease (GVHD), but the recently-transfused group had a significantly lower incidence of chronic GVHD (35.9% vs 48.9%). These differences remained significant in a multivariate analysis of time to chronic GVHD (p = 0.022), taking into account other differences between the two groups and known risk factors for chronic GVHD.

Authors
deGast, GC; Beatty, PG; Amos, D; Mickelson, EM; Sullivan, KM; Anderson, JE; Giblett, ER; Appelbaum, F; Storb, R; Deeg, HJ
MLA Citation
deGast, GC, Beatty, PG, Amos, D, Mickelson, EM, Sullivan, KM, Anderson, JE, Giblett, ER, Appelbaum, F, Storb, R, and Deeg, HJ. "Transfusions shortly before HLA-matched marrow transplantation for leukemia are associated with a decrease in chronic graft-versus-host disease." Bone Marrow Transplant 7.4 (April 1991): 293-295.
PMID
2070135
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
7
Issue
4
Publish Date
1991
Start Page
293
End Page
295

Intravenous IgG to prevent graft-versus-host disease after bone marrow transplantation.

MLA Citation
"Intravenous IgG to prevent graft-versus-host disease after bone marrow transplantation." The New England journal of medicine 324.9 (February 1991): 631-633. (Letter)
PMID
1992325
Source
epmc
Published In
The New England journal of medicine
Volume
324
Issue
9
Publish Date
1991
Start Page
631
End Page
633

Long-term follow-up of patients who received recombinant human granulocyte-macrophage colony stimulating factor after autologous bone marrow transplantation for lymphoid malignancy.

Twenty-seven patients with lymphoid neoplasia who underwent autologous bone marrow transplant (BMT) and who had received recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) were followed in order to examine the potential long-term consequences of rhGM-CSF. rhGM-CSF (15-240 micrograms/m2/day) was given daily either for 14 or 21 days after marrow infusion. All surviving patients who remained in remission had stable marrow graft function. The actuarial survival rate was 45% and the relapse incidence was 50% at a median of 774 days after autologous BMT. These findings suggest that treatment with rhGM-CSF does not have profound adverse long-term consequences.

Authors
Nemunaitis, J; Singer, JW; Buckner, CD; Mori, T; Laponi, J; Hill, R; Storb, R; Sullivan, KM; Hansen, JA; Appelbaum, FR
MLA Citation
Nemunaitis, J, Singer, JW, Buckner, CD, Mori, T, Laponi, J, Hill, R, Storb, R, Sullivan, KM, Hansen, JA, and Appelbaum, FR. "Long-term follow-up of patients who received recombinant human granulocyte-macrophage colony stimulating factor after autologous bone marrow transplantation for lymphoid malignancy." Bone Marrow Transplant 7.1 (January 1991): 49-52.
PMID
2043878
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
7
Issue
1
Publish Date
1991
Start Page
49
End Page
52

A clinical review: cutaneous manifestations of acute and chronic graft-versus-host disease following bone marrow transplantation.

Authors
Tanaka, K; Sullivan, KM; Shulman, HM; Sale, GE; Tanaka, A
MLA Citation
Tanaka, K, Sullivan, KM, Shulman, HM, Sale, GE, and Tanaka, A. "A clinical review: cutaneous manifestations of acute and chronic graft-versus-host disease following bone marrow transplantation." J Dermatol 18.1 (January 1991): 11-17. (Review)
PMID
2050901
Source
pubmed
Published In
The Journal of Dermatology
Volume
18
Issue
1
Publish Date
1991
Start Page
11
End Page
17

Prophylaxis of graft-versus-host disease by administration of the murine anti-IL-2 receptor antibody 2A3

The efficacy of murine monoclonal IgG1 antibody 2A3 specific for the 55 kD chain of the human IL-2 receptor (CD25) was evaluated for prophylaxis of acute GVHD in patients with advanced leukemia transplanted with unmodified bone marrow from related HLA-haploidentical donors incompatible for two or three HLA loci of the non-shared haplotype. As GVHD prophylaxis, 36 patients (control) received standard cyclosporine and methotrexate (C + M) whereas 11 patients (study) received C + M plus antibody 2A3, 1.0 mg/kg on day -1, and 0.5 mg/kg daily from day 0 through day +19. Antibody administration was not associated with appreciable toxicity and did not adversely affect engraftment. During treatment, cirvulating CD25+ cells appeared saturated by the infused antibody. Patients receiving antibody 2A3 tolerated more cyclosporine than controls (p < 0.001) with lower increase of serum creatinine (p < 0.05) during the first month. Seven of 10 (70%) evaluable study patients developed acute GVHD of grade II-IV with onset at a median of 20 days compared to 27 of 31 (87%) control patients with onset at a median of 13 days (p = 0.11). Trough serum levels of antibody 2A3 ranged from 7.2 to 68.8 mg/l, and lower values correlated with occurrence of acute GVHD. A human anti-mouse immunoglobulin antibody response was detected in four patients but was not associated with lower levels of antibody 2A3 in the serum. Two study patients and two controls have survived more than 1 year (p = 0.92). These findings suggest that administration of antibody 2A3 suppressed and delayed activation of alloantigen-specific T cells but did not result in their elimination.

Authors
Anasetti, C; Martin, PJ; Storb, R; Appelbaum, FR; Beatty, PG; Calori, E; Davis, J; Doney, K; Reichert, T; Stewart, P; Sullivan, KM; Thomas, ED; Witherspoon, RP; Hansen, JA
MLA Citation
Anasetti, C, Martin, PJ, Storb, R, Appelbaum, FR, Beatty, PG, Calori, E, Davis, J, Doney, K, Reichert, T, Stewart, P, Sullivan, KM, Thomas, ED, Witherspoon, RP, and Hansen, JA. "Prophylaxis of graft-versus-host disease by administration of the murine anti-IL-2 receptor antibody 2A3." Bone Marrow Transplantation 7.5 (1991): 375-381.
PMID
2070147
Source
scival
Published In
Bone Marrow Transplantation
Volume
7
Issue
5
Publish Date
1991
Start Page
375
End Page
381

Seroconversion for hepatitis C virus antibody in bone marrow recipients treated with immune globulin [3]

Authors
Horst, H-A; Schmitz, N; Glinike, C; Loffler, H; Laufs, R; Sullivan, KM; McDonald, GB; Meyers, JD; Shulman, HM
MLA Citation
Horst, H-A, Schmitz, N, Glinike, C, Loffler, H, Laufs, R, Sullivan, KM, McDonald, GB, Meyers, JD, and Shulman, HM. "Seroconversion for hepatitis C virus antibody in bone marrow recipients treated with immune globulin [3]." New England Journal of Medicine 325.2 (1991): 132-133.
PMID
1646961
Source
scival
Published In
New England Journal of Medicine
Volume
325
Issue
2
Publish Date
1991
Start Page
132
End Page
133

Treatment of adult acute lymphoblastic leukemia with allogeneic bone marrow transplantation. Multivariate analysis of factors affecting acute graft-versus-host disease, relapse, and relapse-free survival

Between February 1972 and December 1987, 192 adults (≥ 18 years old) with acute lymphoblastic leukemia were transplanted using genotypically HLA-identical marrow donors. Median patient age was 23 years. Eighty-nine patients were in marrow remission and 103 were in relapse. Conditioning regimens included chemotherapy alone (three patients) or in combination with 9.2-17.5 Gy total body irradiation (189 patients). Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate and/or cyclosporine. Seventy-nine patients developed grades II-IV acute GVHD and 28 of 122 patients who survived at least 100 days developed chronic GVHD. Relapse-free survival at 5 years was 21% for patients transplanted in first remission, 15% for those in ≥ 2nd remission, and 12% for those transplanted in relapse. Patient and donor characteristics were evaluated in multivariate analyses for their effect on development of acute GVHD, survival, relapse, and relapse-free survival. An increased risk of developing acute GVHD was associated with increasing donor age. Variables significantly associated with both increased survival and relapse-free survival included transplantation in first remission, younger patient age, and not developing interstitial pneumonia. A decreased probability of relapse was associated with transplantation in first remission, male patient sex, and grades II-IV acute GVHD.

Authors
Doney, K; Fisher, LD; Appelbaum, FR; Buckner, CD; Storb, R; Singer, J; Fefer, A; Anasetti, C; Beatty, P; Bensinger, W; Clift, R; Hansen, J; Hill, R; Jr, TPL; Martin, P; Petersen, FB; Sanders, J; Sullivan, KM; Stewart, P
MLA Citation
Doney, K, Fisher, LD, Appelbaum, FR, Buckner, CD, Storb, R, Singer, J, Fefer, A, Anasetti, C, Beatty, P, Bensinger, W, Clift, R, Hansen, J, Hill, R, Jr, TPL, Martin, P, Petersen, FB, Sanders, J, Sullivan, KM, and Stewart, P. "Treatment of adult acute lymphoblastic leukemia with allogeneic bone marrow transplantation. Multivariate analysis of factors affecting acute graft-versus-host disease, relapse, and relapse-free survival." Bone Marrow Transplantation 7.6 (1991): 453-459.
PMID
1873592
Source
scival
Published In
Bone Marrow Transplantation
Volume
7
Issue
6
Publish Date
1991
Start Page
453
End Page
459

Effects of treatment regimens on post marrow transplant relapse

Authors
Buckner, CD; Clift, RA; Appelbaum, FR; Storb, R; Fefer, A; Petersen, FB; Sanders, JE; Sullivan, K; Thomas, ED; Hansen, JA
MLA Citation
Buckner, CD, Clift, RA, Appelbaum, FR, Storb, R, Fefer, A, Petersen, FB, Sanders, JE, Sullivan, K, Thomas, ED, and Hansen, JA. "Effects of treatment regimens on post marrow transplant relapse." Seminars in Hematology 28.3 SUPPL. 4 (1991): 32-34.
PMID
1780749
Source
scival
Published In
Seminars in Hematology
Volume
28
Issue
3 SUPPL. 4
Publish Date
1991
Start Page
32
End Page
34

Graft-versus-host disease prophylaxis with methotrexate/cyclosporine in children with severe aplastic anemia treated with cyclophosphamide and HLA-identical marrow grafts [1]

Authors
Storb, R; Sanders, JE; Pepe, M; Anasetti, C; Appelbaum, FR; Buckner, CD; Deeg, HJ; Doney, K; Hansen, J; Martin, P; Stewart, P; Sullivan, KM; Thomas, ED; Witherspoon, RP
MLA Citation
Storb, R, Sanders, JE, Pepe, M, Anasetti, C, Appelbaum, FR, Buckner, CD, Deeg, HJ, Doney, K, Hansen, J, Martin, P, Stewart, P, Sullivan, KM, Thomas, ED, and Witherspoon, RP. "Graft-versus-host disease prophylaxis with methotrexate/cyclosporine in children with severe aplastic anemia treated with cyclophosphamide and HLA-identical marrow grafts [1]." Blood 78.4 (1991): 1144-1145.
PMID
1868246
Source
scival
Published In
Blood
Volume
78
Issue
4
Publish Date
1991
Start Page
1144
End Page
1145

Intravenous IgG to prevent graft-versus-host disease after bone marrow transplantation (Reply)

Authors
Sullivan, KM; Kopecky, KJ; Buckner, CD; Storb, R
MLA Citation
Sullivan, KM, Kopecky, KJ, Buckner, CD, and Storb, R. "Intravenous IgG to prevent graft-versus-host disease after bone marrow transplantation (Reply)." New England Journal of Medicine 324.9 (1991): 632-633.
Source
scival
Published In
New England Journal of Medicine
Volume
324
Issue
9
Publish Date
1991
Start Page
632
End Page
633

Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies

Less than 40% of the patients who could benefit from marrow transplantation have an HLA-matched relative who can serve as a donor. For this reason, several centers have explored marrow transplantation from other categories of donors. This retrospective study analyzes the results of marrow transplantation for 52 patients receiving grafts from HLA-A,B,DR,Dw-phenotypically matched, MLC-compatible, unrelated volunteer donors compared to a disease, disease-stage, and age-matched cohort of 104 patients transplanted from HLA-genotypically identical sibling donors. The patients transplanted from unrelated donors had an increased incidence of grade II-IV acute graft-versus-host disease compared to patients transplanted from related donors (79% vs. 36%, P<<0.001). However, the probability of relapse-free survival appears similar in the two groups (P = 0.39 over all, with estimates of 41% vs. 46% at 1 year). We conclude from this preliminary data that marrow transplantation from HLA-matched unrelated donors should be considered in most, if not all, circumstances where transplantation from an HLA-matched sibling would be indicated if such a donor were available.

Authors
Beatty, PG; Hansen, JA; Longton, GM; Thomas, ED; Sanders, JE; Martin, PJ; Bearman, SI; Anasetti, C; Petersdorf, EW; Mickelson, EM; Pepe, MS; Appelbaum, FR; Buckner, CD; Clift, RA; Petersen, FB; Stewart, PS; Storb, RF; Sullivan, KM; Tesler, MC; Witherspoon, RP
MLA Citation
Beatty, PG, Hansen, JA, Longton, GM, Thomas, ED, Sanders, JE, Martin, PJ, Bearman, SI, Anasetti, C, Petersdorf, EW, Mickelson, EM, Pepe, MS, Appelbaum, FR, Buckner, CD, Clift, RA, Petersen, FB, Stewart, PS, Storb, RF, Sullivan, KM, Tesler, MC, and Witherspoon, RP. "Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies." Transplantation 51.2 (1991): 443-447.
PMID
1994541
Source
scival
Published In
Transplantation
Volume
51
Issue
2
Publish Date
1991
Start Page
443
End Page
447

Allogeneic marrow transplantation in patients with chronic myeloid leukemia in the chronic phase: A randomized trial of two irradiation regimens

A randomized trial was performed to compare two regimens of total body irradiation in patients with chronic myeloid leukemia treated by allogeneic marrow transplantation while in the chronic phase. All patients received cyclophosphamide 120 mg/kg followed by total body irradiation and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease. Fifty-seven patients were randomized to receive 2.0 Gy fractions of irradiation daily for 6 days and 59 were randomized to receive 2.25 Gy fractions daily for 7 days. The probabilities of relapse at 4 years were 0.25 for the 12.0 Gy group and 0.00 for the 15.75 Gy group (P = .008). The actuarial probabilities of survival and relapse-free survival at 4 years were 0.60 and 0.58 among the patients who received 12.0 Gy compared with 0.66 and 0.66 for those who received 15.75 Gy. The 4-year probabilities of transplant-related mortality were 0.24 and 0.34 respectively (P = .13) while the probability of moderate to severe acute graft-versus-host disease was 0.33 for the 12.0 Gy group and 0.44 for the 15.75 Gy group (P = .15). The lower relapse probability in the patients receiving the higher dose of total body irradiation did not result in improved survival because mortality from causes other than relapse was increased. © 1991 by The American Society of Hematology.

Authors
Clift, RA; Buckner, CD; Appelbaum, FR; Bryant, E; Bearman, SI; Petersen, FB; Fisher, LD; Anasetti, C; Beatty, P; Bensinger, WI; Doney, K; Hill, RS; McDonald, GB; Martin, P; Meyers, J; Sanders, J; Singer, J; Stewart, P; Sullivan, KM; Witherspoon, R; Storb, R; Hansen, JA; Thomas, ED
MLA Citation
Clift, RA, Buckner, CD, Appelbaum, FR, Bryant, E, Bearman, SI, Petersen, FB, Fisher, LD, Anasetti, C, Beatty, P, Bensinger, WI, Doney, K, Hill, RS, McDonald, GB, Martin, P, Meyers, J, Sanders, J, Singer, J, Stewart, P, Sullivan, KM, Witherspoon, R, Storb, R, Hansen, JA, and Thomas, ED. "Allogeneic marrow transplantation in patients with chronic myeloid leukemia in the chronic phase: A randomized trial of two irradiation regimens." Blood 77.8 (1991): 1660-1665.
PMID
2015394
Source
scival
Published In
Blood
Volume
77
Issue
8
Publish Date
1991
Start Page
1660
End Page
1665

Marrow transplantation for severe aplastic anemia and thalassemia major

Authors
Storb, R; Anasetti, C; Appelbaum, F; Bensinger, W; Buckner, CD; Clift, R; Deeg, HJ; Doney, K; Hansen, J; Loughran, T; Martin, P; Pepe, M; Petersen, F; Sanders, J; Singer, J; Stewart, P; Sullivan, KM; Witherspoon, R; Thomas, ED
MLA Citation
Storb, R, Anasetti, C, Appelbaum, F, Bensinger, W, Buckner, CD, Clift, R, Deeg, HJ, Doney, K, Hansen, J, Loughran, T, Martin, P, Pepe, M, Petersen, F, Sanders, J, Singer, J, Stewart, P, Sullivan, KM, Witherspoon, R, and Thomas, ED. "Marrow transplantation for severe aplastic anemia and thalassemia major." Seminars in Hematology 28.3 (1991): 235-239.
PMID
1887251
Source
scival
Published In
Seminars in Hematology
Volume
28
Issue
3
Publish Date
1991
Start Page
235
End Page
239

Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation.

BACKGROUND: Graft-versus-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Since intravenous immunoglobulin has shown benefit in several immunodeficiency and autoimmune disorders, we studied its antimicrobial and immunomodulatory role after marrow transplantation. METHODS: In a randomized trial of 382 patients, transplant recipients given immunoglobulin (500 mg per kilogram of body weight weekly to day 90, then monthly to day 360 after transplantation) were compared with controls not given immunoglobulin. By chance, the immunoglobulin group included more patients with advanced-stage neoplasms; otherwise, the study groups were balanced for prognostic factors. RESULTS: Control patients seronegative for cytomegalovirus who received seronegative blood products remained seronegative, but seronegative patients who received immunoglobulin and screened blood had a passive transfer of cytomegalovirus antibody (median titer, 1:64). Among the 61 seronegative patients who could be evaluated, none contracted interstitial pneumonia; among the 308 seropositive patients evaluated, 22 percent of control patients and 13 percent of immunoglobulin recipients had this complication (P = 0.021). Control patients had an increased risk of gram-negative septicemia (relative risk = 2.65, P = 0.0039) and local infection (relative risk = 1.36, P = 0.029) and received 51 more units of platelets than did immunoglobulin recipients. Neither survival nor the risk of relapse was altered by immunoglobulin. However, among patients greater than or equal to 20 years old, there was a reduction in the incidence of acute GVHD (51 percent in controls vs. 34 percent in immunoglobulin recipients; P = 0.0051) and a decrease in deaths due to transplant-related causes after transplantation of HLA-identical marrow (46 percent vs. 30 percent; P = 0.023). CONCLUSIONS: Passive immunotherapy with intravenous immunoglobulin decreases the risk of acute GVHD, associated interstitial pneumonia, and infections after bone marrow transplantation.

Authors
Sullivan, KM; Kopecky, KJ; Jocom, J; Fisher, L; Buckner, CD; Meyers, JD; Counts, GW; Bowden, RA; Peterson, FB; Witherspoon, RP
MLA Citation
Sullivan, KM, Kopecky, KJ, Jocom, J, Fisher, L, Buckner, CD, Meyers, JD, Counts, GW, Bowden, RA, Peterson, FB, and Witherspoon, RP. "Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation." N Engl J Med 323.11 (September 13, 1990): 705-712.
PMID
2167452
Source
pubmed
Published In
The New England journal of medicine
Volume
323
Issue
11
Publish Date
1990
Start Page
705
End Page
712
DOI
10.1056/NEJM199009133231103

What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants?

One hundred forty-seven consecutive patients with leukemia, myelodysplastic syndrome, or aplastic anemia were treated by marrow grafts from genotypically HLA-identical siblings (n = 122) or HLA-haploidentical family members (n = 25). Haploidentical recipients differed from their donors for no more than one HLA locus on the nonshared haplotype. All were given postgrafting immunosuppression with a combination of methotrexate and cyclosporine. In a randomized study we explored whether prednisone administered from day 0 through 35 along with methotrexate/cyclosporine could improve prevention of acute graft-versus-host disease (GVHD). The GVHD incidence in patients not given prednisone was comparable with that previously reported with methotrexate/cyclosporine. Unexpectedly, significant increases in acute and also chronic GVHD were seen in HLA-identical recipients administered prednisone, but not in the small number of patients administered HLA-nonidentical grafts. However, the resultant increase in transplant-related mortality in patients administered prednisone was offset by an increase in leukemic relapse in patients not administered prednisone, presumably related to the absence of a graft-versus-leukemia effect. Therefore, overall disease-free survival of the two groups of patients was comparable, with slightly more than 50% of the patients being alive at more than 2 years after transplantation. We speculated that prednisone adversely affected GVHD prophylaxis, interfering with methotrexate's cell cycle-dependent suppression of donor lymphocyte proliferation in response to host antigens. In a pilot study we explored whether beginning prednisone on day 15, after completion of methotrexate administration, would avoid this adverse effect. The GVHD incidence in patients administered methotrexate/cyclosporine along with "late" prednisone was comparable with that in patients not administered prednisone. We conclude that methotrexate/cyclosporine is effective in decreasing the incidence of grade II through IV GVHD, and that the addition of prednisone to this regimen is not beneficial in recipients of HLA-identical marrow grafts.

Authors
Storb, R; Pepe, M; Anasetti, C; Appelbaum, FR; Beatty, P; Doney, K; Martin, P; Stewart, P; Sullivan, KM; Witherspoon, R
MLA Citation
Storb, R, Pepe, M, Anasetti, C, Appelbaum, FR, Beatty, P, Doney, K, Martin, P, Stewart, P, Sullivan, KM, and Witherspoon, R. "What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants?." Blood 76.5 (September 1, 1990): 1037-1045.
PMID
2203481
Source
pubmed
Published In
Blood
Volume
76
Issue
5
Publish Date
1990
Start Page
1037
End Page
1045

Durable complete remission of acute nonlymphocytic leukemia associated with discontinuation of immunosuppression following relapse after allogeneic bone marrow transplantation. A case report of a probable graft-versus-leukemia effect.

Authors
Higano, CS; Brixey, M; Bryant, EM; Durnam, DM; Doney, K; Sullivan, KM; Singer, JW
MLA Citation
Higano, CS, Brixey, M, Bryant, EM, Durnam, DM, Doney, K, Sullivan, KM, and Singer, JW. "Durable complete remission of acute nonlymphocytic leukemia associated with discontinuation of immunosuppression following relapse after allogeneic bone marrow transplantation. A case report of a probable graft-versus-leukemia effect." Transplantation 50.1 (July 1990): 175-177.
PMID
2368144
Source
pubmed
Published In
Transplantation
Volume
50
Issue
1
Publish Date
1990
Start Page
175
End Page
177

Cyclosporine treatment of chronic graft-versus-host disease following allogeneic bone marrow transplantation.

Authors
Sullivan, KM; Siadak, MF; Witherspoon, RP
MLA Citation
Sullivan, KM, Siadak, MF, and Witherspoon, RP. "Cyclosporine treatment of chronic graft-versus-host disease following allogeneic bone marrow transplantation." Transplant Proc 22.3 (June 1990): 1336-1338. (Review)
PMID
2190396
Source
pubmed
Published In
Transplantation Proceedings
Volume
22
Issue
3
Publish Date
1990
Start Page
1336
End Page
1338

Prevalence of nutrition-related problems among long-term survivors of allogeneic marrow transplantation.

The nutritional status and prevalence of nutrition-related problems in 192 adult and child allogeneic marrow transplant recipients were evaluated 1 year after transplant in a retrospective chart review. Among these patients, 63% exhibited evidence of chronic graft-versus-host disease (GVHD) at the time of nutrition evaluation, including 44% with extensive disease who were receiving immunosuppressive therapy. Oral sensitivity was observed in 23% of all patients reviewed, and frank stomatitis occurred in 8%. The frequency of xerostomia was 18%; anorexia, 8%; reflux symptoms, 7%; diarrhea, 7%; steatorrhea, 5%; dysgeusia, 3%; and limited exercise tolerance because of dyspnea or joint contractures, 4%. Weight loss 3 to 12 months after transplant was experienced by 28%. Nutrition-related problems, changes in anthropometric indexes indicative of suboptimal nutritional status, and inadequate energy intake were observed more frequently in patients with extensive chronic GVHD than in patients without GVHD or in those with limited GVHD. Our findings indicate a high prevalence of nutrition problems among recipients of allogeneic marrow transplantation 1 year after transplant and, further, suggest the need for ongoing, community-based nutrition monitoring after discharge from a transplant center.

Authors
Lenssen, P; Sherry, ME; Cheney, CL; Nims, JW; Sullivan, KM; Stern, JM; Moe, G; Aker, SN
MLA Citation
Lenssen, P, Sherry, ME, Cheney, CL, Nims, JW, Sullivan, KM, Stern, JM, Moe, G, and Aker, SN. "Prevalence of nutrition-related problems among long-term survivors of allogeneic marrow transplantation." J Am Diet Assoc 90.6 (June 1990): 835-842.
PMID
2345257
Source
pubmed
Published In
Journal of the American Dietetic Association
Volume
90
Issue
6
Publish Date
1990
Start Page
835
End Page
842

Comparative trials of chemotherapy and bone marrow transplantation in acute nonlymphocytic leukemia.

Authors
Sullivan, KM; Appelbaum, FR
MLA Citation
Sullivan, KM, and Appelbaum, FR. "Comparative trials of chemotherapy and bone marrow transplantation in acute nonlymphocytic leukemia." Rinsho Ketsueki 31.5 (May 1990): 527-533. (Review)
PMID
2118573
Source
pubmed
Published In
Rinsho ketsueki/The Japanese journal of clinical hematology
Volume
31
Issue
5
Publish Date
1990
Start Page
527
End Page
533

Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle.

Between October 1979 and January 1988, 101 patients with malignant lymphoma who failed initial induction treatment or relapsed received high-dose combination chemotherapy or chemoradiotherapy followed by infusion of autologous bone marrow. Twenty-eight of the 101 patients survive, 18 of whom are disease-free for a median of 26 (range, 12 to 66) months. The 5-year actuarial probabilities of survival, event-free survival (EFS), and relapse from transplantation were 20%, 11%, and 84%, respectively. Multivariate analysis showed that the likelihood of EFS was decreased among patients transplanted with a Karnofsky score of less than 80%. Recurrent lymphoma after transplant was the most important cause of treatment failure with 36 of 62 relapses occurring within 100 days from marrow infusion. Early, but not late relapse, was more frequent in patients transplanted for advanced lymphoma, and both early and late relapses were increased among patients with impaired pretransplant clinical performance or high-grade histology of lymphoma. Ten patients who relapsed post-transplant are alive, seven in remission. Further improvement of these results will require earlier transplantation, improved preparative regimens, or early posttransplant therapy.

Authors
Petersen, FB; Appelbaum, FR; Hill, R; Fisher, LD; Bigelow, CL; Sanders, JE; Sullivan, KM; Bensinger, WI; Witherspoon, RP; Storb, R
MLA Citation
Petersen, FB, Appelbaum, FR, Hill, R, Fisher, LD, Bigelow, CL, Sanders, JE, Sullivan, KM, Bensinger, WI, Witherspoon, RP, and Storb, R. "Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle." J Clin Oncol 8.4 (April 1990): 638-647.
PMID
2313333
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
8
Issue
4
Publish Date
1990
Start Page
638
End Page
647
DOI
10.1200/JCO.1990.8.4.638

Previous donor pregnancy as a risk factor for acute graft-versus-host disease in patients with aplastic anaemia treated by allogeneic marrow transplantation.

To determine if previous donor pregnancies influence the development of acute graft-versus-host disease (GVHD) we evaluated data from 136 patients with aplastic anaemia greater than 15 years of age and given marrow grafts from HLA-identical sibling donors. Of the 136 marrow donors, 30 were parous females (previous history of pregnancy), 30 were nulliparous females (no history of pregnancy or abortions), and 76 were males. The cumulative incidence of grade II-IV GVHD was 57%, 21% and 46% for patients with parous, nulliparous and male donors, respectively. A multivariate analysis of the data confirmed that the risk of grade II-IV acute GVHD was significantly increased among patients receiving marrow from parous females as compared to those from nulliparous females (relative risk = 2.5, P = 0.02). There was no statistically significant difference in the incidence of acute GVHD, however, between patients with parous donors and male donors (relative risk = 1.3, P = 0.26). Male patients given grafts from parous donors showed a higher incidence of acute GVHD (63%) than female patients (45%), though this difference was not statistically significant. The 5-year probability of survival was 47% for patients with parous donors, 68% for patients with nulliparous donors and 70% for those with male donors. We confirm that prior donor pregnancy represents an important factor in selecting marrow donors or designing clinical protocols for GVHD prophylaxis.

Authors
Flowers, ME; Pepe, MS; Longton, G; Doney, KC; Monroe, D; Witherspoon, RP; Sullivan, KM; Storb, R
MLA Citation
Flowers, ME, Pepe, MS, Longton, G, Doney, KC, Monroe, D, Witherspoon, RP, Sullivan, KM, and Storb, R. "Previous donor pregnancy as a risk factor for acute graft-versus-host disease in patients with aplastic anaemia treated by allogeneic marrow transplantation." Br J Haematol 74.4 (April 1990): 492-496.
PMID
2346728
Source
pubmed
Published In
British Journal of Haematology
Volume
74
Issue
4
Publish Date
1990
Start Page
492
End Page
496

Secondary cancers after bone marrow transplantation.

Authors
Lishner, M; Lang, R
MLA Citation
Lishner, M, and Lang, R. "Secondary cancers after bone marrow transplantation." The New England journal of medicine 322.12 (March 1990): 853-. (Letter)
PMID
2308621
Source
epmc
Published In
The New England journal of medicine
Volume
322
Issue
12
Publish Date
1990
Start Page
853

Self-administration of morphine in bone marrow transplant patients reduces drug requirement.

Bone marrow transplant recipients were randomly assigned to receive morphine by either continuous infusion (32 patients) or self-administration of small boluses (patient-controlled analgesia (PCA), 26 patients) for control of chemoradiotherapy-induced oral mucositis pain. All patients received morphine for a minimum of 9 days and most required morphine for at least 14 days. Patients rated their pain and side-effect intensity daily using visual analogue scales. Patient pain ratings did not differ between the groups although PCA patients used only 53% as much morphine as the continuous infusion group. Tolerance did not develop in the PCA group; in patients receiving continuous infusion morphine dosage continued to increase throughout the study while pain scores remained constant, indicating that tolerance had developed. Nausea, alertness and respiratory rate measurements did not differ between groups. PCA appeared more effective than the hospital staff determined treatment at delivering the least amount of morphine required to produce maximal pain relief. Patients self-administering morphine did not appear to restrict morphine intake in order to minimize opioid side-effects.

Authors
Hill, HF; Chapman, CR; Kornell, JA; Sullivan, KM; Saeger, LC; Benedetti, C
MLA Citation
Hill, HF, Chapman, CR, Kornell, JA, Sullivan, KM, Saeger, LC, and Benedetti, C. "Self-administration of morphine in bone marrow transplant patients reduces drug requirement." Pain 40.2 (February 1990): 121-129.
PMID
2308758
Source
pubmed
Published In
PAIN
Volume
40
Issue
2
Publish Date
1990
Start Page
121
End Page
129

Recognition, incidence, and management of oral graft-versus-host disease.

Acute and chronic graft-versus-host disease (GVHD) are significant complications of allogeneic bone marrow transplantation that occur when immunologically active T-cell lymphocytes are transplanted into an immunosuppressed recipient who is genetically disparate from the marrow donor. Oral GVHD lesions closely resemble those seen with a number of autoimmune connective tissue disease, including lichen planus, systemic sclerosis, lupus erythematosus, and Sjögren's syndrome. Mucosal erythema, atrophy, and ulceration are noted clinically; lichen planus-like lesions are the most distinctive oral lesions. Salivary gland changes include changes in both flow rate and sialochemistry. Oral involvement ranges between 33% and 75% for patients with acute GVHD and upwards of 80% for those with chronic GVHD. Management of oral GVHD lesions depends on successful systemic therapy, although topical steroids can be of help in some instances.

Authors
Schubert, MM; Sullivan, KM
MLA Citation
Schubert, MM, and Sullivan, KM. "Recognition, incidence, and management of oral graft-versus-host disease." NCI Monogr 9 (1990): 135-143. (Review)
PMID
2188151
Source
pubmed
Published In
NCI Monographs
Issue
9
Publish Date
1990
Start Page
135
End Page
143

Supportive care of the marrow transplant recipient: the Seattle Experience.

It is now almost 2 decades after the first successful human marrow transplants from HLA-identical siblings for the treatment of life-threatening hematologic diseases. Results have improved, especially for patients transplanted earlier in the course of disease. However, major problems remain in supporting patients through the transplant. More effective and less toxic conditioning regimens are needed. Acceleration of hematopoietic and immunologic reconstitution by use of various cytokines holds promise for decreasing infectious morbidity and mortality. Improved regimens to control acute and chronic GVHD and prevent opportunistic infections will play a major role in the advancement of supportive care of the marrow transplant recipient.

Authors
Sullivan, KM; Meyers, J; Petersen, FB; Bowden, R; Counts, GC; Banaji, M; Schubert, M; Clark, J; Clift, RA; Appelbaum, FR
MLA Citation
Sullivan, KM, Meyers, J, Petersen, FB, Bowden, R, Counts, GC, Banaji, M, Schubert, M, Clark, J, Clift, RA, and Appelbaum, FR. "Supportive care of the marrow transplant recipient: the Seattle Experience." Haematol Blood Transfus 33 (1990): 539-545. (Review)
PMID
2182446
Source
pubmed
Published In
Haematology and blood transfusion
Volume
33
Publish Date
1990
Start Page
539
End Page
545

Chronic graft-versus-host disease.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Chronic graft-versus-host disease." Cancer Treat Res 50 (1990): 79-98. (Review)
PMID
1976359
Source
pubmed
Published In
Cancer Treatment and Research
Volume
50
Publish Date
1990
Start Page
79
End Page
98

Secondary cancers after bone marrow transplantation (I: Reply)

Authors
Witherspoon, RP; Fisher, LD; Sullivan, KM; Storb, R; Thomas, ED
MLA Citation
Witherspoon, RP, Fisher, LD, Sullivan, KM, Storb, R, and Thomas, ED. "Secondary cancers after bone marrow transplantation (I: Reply)." New England Journal of Medicine 322.12 (1990): 853--.
Source
scival
Published In
New England Journal of Medicine
Volume
322
Issue
12
Publish Date
1990
Start Page
853-

Value of day 100 screening studies for predicting the development of chronic graft-versus-host disease after allogeneic bone marrow transplantation

We prospectively evaluated 169 patients with a number of screening studies performed between 71 to 121 days after allogeneic marrow transplantation to detect the development of chronic graft-versus-host disease (GVHD). Group 1 patients (n = 78) were asymptomatic and had normal physical examinations at the time of screening and, with a minimum of 8 years follow-up, have not developed chronic GVHD. Group 2 patients (n = 38) had signs and symptoms of chronic GVHD at time of testing. Group 3 patients (n = 53) were similar to those in group 1 in having no clinically evident GVHD at the time of testing, but later developed clinical chronic GVHD. Using time to an event analysis, we compared patients in groups 1 and 3 to determine which of 17 clinical and laboratory factors evaluated at screening accurately predicted the development of subsequent chronic GVHD. Multivariate analyses showed several factors to have independent predictive value. In the first model, results of oral biopsies were excluded since these were done only in one half of the patients. Predictive factors in this analysis included: (1) histologic findings of GVHD on skin biopsy, relative risk 3.23 (95% confidence interval 1.75 to 5.94), P = .0002; and (2) history of grade II through IV acute GVHD, relative risk 3.12 (95% confidence interval 1.72 to 5.64), P = .0002. When oral biopsy results were included in the second model, independent risk factors included: (1) histologic findings of GVHD on skin biopsy, relative risk 5.96 (95% confidence interval 1.95 to 18.19), P = .0017; and (2) low numbers of immunoglobulin A (IgA)-bearing plasma cells detected by direct immunofluorescence in salivary gland areas on oral biopsy, relative risk 11.53 (95% confidence interval 2.51 to 52.03), P = .0017. Our study demonstrates the value of day 100 screening studies for predicting subsequent development of clinical chronic GVHD. © 1990 by The American Society of Hematology.

Authors
Jr, TPL; Sullivan, K; Morton, T; Beckham, C; Schubert, M; Witherspoon, R; Sale, G; Sanders, J; Fisher, L; Shulman, H; Thomas, ED; Storb, R
MLA Citation
Jr, TPL, Sullivan, K, Morton, T, Beckham, C, Schubert, M, Witherspoon, R, Sale, G, Sanders, J, Fisher, L, Shulman, H, Thomas, ED, and Storb, R. "Value of day 100 screening studies for predicting the development of chronic graft-versus-host disease after allogeneic bone marrow transplantation." Blood 76.1 (1990): 228-234.
PMID
2194590
Source
scival
Published In
Blood
Volume
76
Issue
1
Publish Date
1990
Start Page
228
End Page
234

A phase I-II study evaluating the murine anti-IL-2 receptor antibody 2A3 for treatment of acute graft-versus-host disease

A murine IgG1 antibody specific for the IL-2-binding site on the human lymphocyte IL-2 receptor β chain (CD25) was evaluated in 11 patients who developed acute graft-versus-host disease following allogeneic marrow transplantation. All patients had received cyclosporine and methotrexate for prophylaxis of GVHD, either alone (4 cases), or in combination with antithymocyte globulin (4 cases) or with prednisone (3 cases). Patients had developed GVHD at 7-53 days (median 12) after transplantation and had failed treatment with corticosteroids for 3-44 days (median 19). Residual GVHD was of grade II severity in 4 patients, grade III in 5 patients, and grade IV in 2 patients. Sequential patients received monoclonal antibody in escalating doses from 0.1 mg/kg/day to 1.0 mg/kg/day for 7 days. Side effects were fewer, respiratory distress, hypertension, hypotension, and chills occurring in 11 of 72 (14%) antibody infusions. Trough antibody levels greater than 6 μg/ml were achieved in patients treated with 0.5 or 1.0 mg/kg/day. Four of eight evaluable patients had an IgM antibody response, and one had an IgG response to the murine immunoglobulin. Clinical response of GVHD was evaluated in 10 patients who received the entire course of the antibody treatment. Among 7 patients treated within 40 days from transplantation, one patient had a complete response in the skin as the only involved organ, and 3 patients had a partial response, 2 in the skin and one in the gastrointestinal tract. No responses were achieved with liver disease at anytime or in any organ in patients treated beyond 40 days after transplantation. Since administration of this antibody was well tolerated and some efficacy was observed in patients with acute GVHD treated early after transplantation, there is a rationale for testing this antibody as an agent for prophylaxis of GVHD.

Authors
Anasetti, C; Martin, PJ; Hansen, JA; Appelbaum, FR; Beatty, PG; Doney, K; Harkonen, S; Jackson, A; Reichert, T; Stewart, P; Storb, R; Sullivan, KM; Thomas, ED; Warner, N; Witherspoon, RP
MLA Citation
Anasetti, C, Martin, PJ, Hansen, JA, Appelbaum, FR, Beatty, PG, Doney, K, Harkonen, S, Jackson, A, Reichert, T, Stewart, P, Storb, R, Sullivan, KM, Thomas, ED, Warner, N, and Witherspoon, RP. "A phase I-II study evaluating the murine anti-IL-2 receptor antibody 2A3 for treatment of acute graft-versus-host disease." Transplantation 50.1 (1990): 49-54.
PMID
2368150
Source
scival
Published In
Transplantation
Volume
50
Issue
1
Publish Date
1990
Start Page
49
End Page
54

Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: A randomized trial of two irradiation regimens

A randomized trial of 12.0 Gy versus 15.75 Gy of total body irradiation (TBI) was performed in patients with acute myeloid leukemia undergoing allogeneic marrow transplantation while in first complete remission. All patients received 120 mg/kg cyclophosphamide followed by TBI and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease (GVHD). Thirty-four patients received 2.0-Gy fractions of irradiation daily for 6 days and 37 received 2.25-Gy fractions daily for 7 days. The 3-year actuarial probabilities for relapse-free survival were 0.58 for the patients who received 12.0 Gy and 0.59 for those who received 15.75 Gy. The 3-year probabilities of relapse were 0.35 for the 12.0 Gy group and 0.12 for the 15.75 Gy group (P = .06). The 3-year probabilities of transplant-related mortality were 0.12 and 0.32, respectively (P = .04). The probability of moderate to severe acute GVHO was 0.21 for the 12.0 Gy group and 0.48 for the 15.75 Gy group (P = .02). Patients exposed to the higher irradiation dose received less immunoprophylaxis against, and had a higher incidence of, acute GVHD. The increased dose of TBI significantly reduced the probability of relapse but did not improve survival because of increased mortality from causes other than relapse. © 1990 by The American Society of Hematology.

Authors
Clift, RA; Buckner, CD; Appelbaum, FR; Bearman, SI; Petersen, FB; Fisher, LD; Anasetti, C; Beatty, P; Bensinger, WI; Doney, K; Hill, RS; McDonald, GB; Martin, P; Sanders, J; Singer, J; Stewart, P; Sullivan, KM; Witherspoon, R; Storb, R; Hansen, JA; Thomas, ED
MLA Citation
Clift, RA, Buckner, CD, Appelbaum, FR, Bearman, SI, Petersen, FB, Fisher, LD, Anasetti, C, Beatty, P, Bensinger, WI, Doney, K, Hill, RS, McDonald, GB, Martin, P, Sanders, J, Singer, J, Stewart, P, Sullivan, KM, Witherspoon, R, Storb, R, Hansen, JA, and Thomas, ED. "Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: A randomized trial of two irradiation regimens." Blood 76.9 (1990): 1867-1871.
PMID
2224134
Source
scival
Published In
Blood
Volume
76
Issue
9
Publish Date
1990
Start Page
1867
End Page
1871

Staging non-small cell carcinoma of the lung using technetium-99m-labeled monoclonal antibodies

A technetium-labeled monoclonal antibody was administered to 52 patients with non-small cell lung carcinoma, either to stage the mediastinum preoperatively or to detect distant metastases. Results from planar and tomographic imaging are compared to CT and histologic confirmation. Differences in detection rates and predictive values between imaging modalities are discussed. The authors conclude that imaging with a technetium-labeled monoclonal antibody is safe and accurate and may be useful for staging patients with either operable or inoperable non-small cell lung cancer.

Authors
Friedman, S; Sullivan, K; Salk, D; Nelp, WB; Griep, RJ; Johnson, DH; Blend, MJ; Aye, R; Suppers, V; Abrams, PG
MLA Citation
Friedman, S, Sullivan, K, Salk, D, Nelp, WB, Griep, RJ, Johnson, DH, Blend, MJ, Aye, R, Suppers, V, and Abrams, PG. "Staging non-small cell carcinoma of the lung using technetium-99m-labeled monoclonal antibodies." Hematology/Oncology Clinics of North America 4.6 (1990): 1069-1078.
PMID
1962776
Source
scival
Published In
Hematology/Oncology Clinics of North America
Volume
4
Issue
6
Publish Date
1990
Start Page
1069
End Page
1078

A retrospective analysis of therapy for acute graft-versus-host disease: Initial treatment

We have reviewed results of therapy in 740 patients with grades II-IV acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was with glucocorticoids (n = 531), cyclosporine (n = 170), antithymocyte globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n = 633) or in combination (n = 107). Parameters of GVHD severity in each organ were recorded weekly, and evaluation of response was made using values at the initiation of secondary treatment or, for patients without such treatment, using values on day 29 of primary treatment or the last recorded value before death, whichever occurred first. Minimal criteria for improvement or progression were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease. Overall complete or partial responses were seen in 44% of patients. Multivariate analyses were carried out to identify patient, disease or treatment factors associated with likelihood of overall improvement and likelihood of response in at least one organ. A similar analysis was also carried out to identify covariates associated with time to treatment failure (defined as initiation of secondary therapy or death not due to relapse of malignancy). In all three models, GVHD prophylaxis using cyclosporine combined with methotrexate was associated with favorable GVHD treatment outcome compared to prophylaxis with either agent alone, and treatment with glucocorticoids or cyclosporine was more successful than treatment with ATG. Other factors associated with unfavorable outcome in the model of time to treatment failure and also entered in one of the response models were recipient HLA disparity with the donor, presence of a liver complication other than GVHD, and early onset of GVHD. Results of this analysis indicate that glucocorticoids represent the best initial therapy available for treatment of acute GVHD, although much room for improvement remains. © 1990 by The American Society of Hematology.

Authors
Martin, PJ; Schoch, G; Fisher, L; Byers, V; Anasetti, C; Appelbaum, FR; Beatty, PG; Doney, K; McDonald, GB; Sanders, JE; Sullivan, KM; Storb, R; Thomas, ED; Witherspoon, RP; Lomen, P; Hannigan, J; Hansen, JA
MLA Citation
Martin, PJ, Schoch, G, Fisher, L, Byers, V, Anasetti, C, Appelbaum, FR, Beatty, PG, Doney, K, McDonald, GB, Sanders, JE, Sullivan, KM, Storb, R, Thomas, ED, Witherspoon, RP, Lomen, P, Hannigan, J, and Hansen, JA. "A retrospective analysis of therapy for acute graft-versus-host disease: Initial treatment." Blood 76.8 (1990): 1464-1472.
PMID
2207321
Source
scival
Published In
Blood
Volume
76
Issue
8
Publish Date
1990
Start Page
1464
End Page
1472

HLA-identical transplantation in the leukemias without T-cell depletion

Authors
Storb, R; Appelbaum, F; Buckner, CD; Clift, R; Beatty, CPA; Bianco, J; Doney, K; Hansen, J; Martin, P; al, E
MLA Citation
Storb, R, Appelbaum, F, Buckner, CD, Clift, R, Beatty, CPA, Bianco, J, Doney, K, Hansen, J, Martin, P, and al, E. "HLA-identical transplantation in the leukemias without T-cell depletion." Bone Marrow Transplantation 6.SUPPL. 1 (1990): 80-84.
Source
scival
Published In
Bone Marrow Transplantation
Volume
6
Issue
SUPPL. 1
Publish Date
1990
Start Page
80
End Page
84

Gynecological abnormalities following allogeneic bone marrow transplantation

Forty-four post-pubertal women were studied 261-4628 days after allogeneic transplantation to determine the nature and degree of gynecological abnormalities following bone marrow transplantation. Evaluations included pelvic examinations, exfoliative cytology, serum gonadotropin levels, direct preparations for micro-organisms, and microbial cultures. Pelvic abnormalities were detected in 35 of 44 (80%) women and resembled atrophic changes known to occur after ovarian failure. Findings included reduced vaginal elasticity and rugal folds, pale tissues, small vaginal, uterine and cervical size, atrophic vulvovaginitis, introital stenosis, and loss of pubic hair. Atrophic abnormalities were noted in 33 of 36 recipients of total body irradiation (TBI) compared to two of eight women not prepared with TBI (p = 0.02). Vasomotor symptoms were reported in 67% of TBI recipients compared to 38% of those not given TBI. Elevated serum gonadotropin levels suggested that TBI had caused the ovarian failure. Recognition of these gynecological abnormalities can lead to earlier hormone replacement, alleviating unnecessary discomfort and improving the well-being of the marrow transplant recipient.

Authors
Schubert, MA; Sullivan, KM; Schubert, MM; Nims, J; Hansen, M; Sanders, JE; O'Quigley, J; Witherspoon, RP; Buckner, CD; Storb, R; Thomas, ED
MLA Citation
Schubert, MA, Sullivan, KM, Schubert, MM, Nims, J, Hansen, M, Sanders, JE, O'Quigley, J, Witherspoon, RP, Buckner, CD, Storb, R, and Thomas, ED. "Gynecological abnormalities following allogeneic bone marrow transplantation." Bone Marrow Transplantation 5.6 (1990): 425-430.
PMID
2369683
Source
scival
Published In
Bone Marrow Transplantation
Volume
5
Issue
6
Publish Date
1990
Start Page
425
End Page
430

Bone marrow transplantation for patients with myelodysplasia: Pretreatment variables and outcome

Study Objective: To determine the efficacy of allogeneic bone marrow transplantation for severe myelodysplasia, and to identify variables predictive of outcome. Design: Case series study. Setting: A referral-based bone marrow transplant center. Patients: Consecutive series of 59 patients with myelodysplasia or closely related disorders and either life-threatening cytopenia or a progressive increase in marrow blast percentage. Intervention: Patients were treated with high-dose cyclophosphamide and total body irradiation followed by allogeneic bone marrow transplantation from either an HLA-identical (n = 45) or HLA-partially matched (n = 14) donor. Measurements and Main Results: The product-limit estimate for disease-free survival 3 years after transplant is 45% (95% CI, 32% to 59%). The commonest causes of death after transplant were disease recurrence, interstitial pneumonia, and graft-versus-host disease, accounting for eight deaths each. In a univariate analysis, younger patients, those with shorter disease duration, and those whose disease was characterized by an abnormal cytogenetic karyotype had better survival and disease-free survival than the group as a whole. In a multivariate analysis, younger age and abnormal karyotype were independent predictors of improved disease-free survival and overall survival. Patients who received transplants when they had fewer blasts in their bone marrow had a decreased chance for disease recurrence when compared with patients with excess blasts. Conclusions: Bone marrow transplantation offers a potential cure for many patients with myelodysplasia. Best results can be expected in younger patients who receive transplants relatively early in their disease course.

Authors
Appelbaum, FR; Barrall, J; Storb, R; Fisher, LD; Schoch, G; Ramberg, RE; Shulman, H; Anasetti, C; Bearman, SI; Beatty, P; Bensinger, WI; Buckner, CD; Clift, RA; Hansen, JA; Martin, P; Petersen, FB; Sanders, JE; Singer, J; Stewart, P; Sullivan, KM; Witherspoon, RP; Thomas, ED
MLA Citation
Appelbaum, FR, Barrall, J, Storb, R, Fisher, LD, Schoch, G, Ramberg, RE, Shulman, H, Anasetti, C, Bearman, SI, Beatty, P, Bensinger, WI, Buckner, CD, Clift, RA, Hansen, JA, Martin, P, Petersen, FB, Sanders, JE, Singer, J, Stewart, P, Sullivan, KM, Witherspoon, RP, and Thomas, ED. "Bone marrow transplantation for patients with myelodysplasia: Pretreatment variables and outcome." Annals of Internal Medicine 112.8 (1990): 590-597.
Source
scival
Published In
Annals of internal medicine
Volume
112
Issue
8
Publish Date
1990
Start Page
590
End Page
597

Intravenous immune globulin prophylaxis in recipients of a marrow transplant.

Bone marrow transplantation is a worldwide activity involving more than 250 transplant centers in more than 40 countries. The ultimate success of the procedure depends in large measure on supportive care of the transplant recipient. A major component of this supportive care is the prevention of opportunistic infections. This article reviews the nature of immunoglobulin class and subclass deficiency after marrow transplantation and the role of intravenous immune globulin in preventing infections and associated complications.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Intravenous immune globulin prophylaxis in recipients of a marrow transplant." J Allergy Clin Immunol 84.4 Pt 2 (October 1989): 632-638. (Review)
PMID
2551949
Source
pubmed
Published In
Journal of Allergy and Clinical Immunology
Volume
84
Issue
4 Pt 2
Publish Date
1989
Start Page
632
End Page
638

Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia.

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA-identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.

Authors
Sullivan, KM; Weiden, PL; Storb, R; Witherspoon, RP; Fefer, A; Fisher, L; Buckner, CD; Anasetti, C; Appelbaum, FR; Badger, C
MLA Citation
Sullivan, KM, Weiden, PL, Storb, R, Witherspoon, RP, Fefer, A, Fisher, L, Buckner, CD, Anasetti, C, Appelbaum, FR, and Badger, C. "Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia." Blood 73.6 (May 1, 1989): 1720-1728.
PMID
2653460
Source
pubmed
Published In
Blood
Volume
73
Issue
6
Publish Date
1989
Start Page
1720
End Page
1728

Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms.

The occurrence of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation for leukemia is thought to decrease the probability of recurrence. To study this effect (called adoptive immunotherapy) we modified the prophylaxis of GVHD in patients with advanced hematologic neoplasms (mostly leukemia) who received bone marrow transplants. Patients under 30 years of age were randomly assigned to one of three regimens of post-transplantation immunosuppression: Group I (n = 44) received a standard course of methotrexate for 102 days after transplantation, Group II (n = 40) received an abbreviated (11-day) course of methotrexate, and Group III (n = 25) received the standard course of methotrexate plus viable buffy-coat cells from the marrow donors. All 109 patients received cyclophosphamide (60 mg per kilogram of body weight on each of two days), total-body irradiation (2.25 Gy daily for seven days), and unmodified marrow from HLA-identical sibling donors. The frequency of GVHD of Grades II through IV was 25 percent in Group I, 59 percent in Group II, and 82 percent in Group III (P = 0.0001). The incidence of chronic GVHD, however, did not differ significantly among the groups (33, 51, and 44 percent, respectively), nor did the five-year probability of recurrence of disease (38, 45, and 33 percent, respectively). However, mortality from causes other than cancer was 34 percent in Group I, 45 percent in Group II, and 64 percent in Group III (I vs. III, P = 0.024); the deaths were due primarily to infections complicating the course of GVHD. With a median follow-up of 5.1 years (range, 3.9 to 7.4), disease-free survival was 41 percent in Group I, 30 percent in Group II, and 24 percent in Group III (the differences were not statistically significant). We conclude that abbreviating methotrexate prophylaxis or infusing donor buffy-coat cells increased the incidence of acute GVHD and related mortality without altering the incidence of chronic GVHD or the recurrence of malignant disease.

Authors
Sullivan, KM; Storb, R; Buckner, CD; Fefer, A; Fisher, L; Weiden, PL; Witherspoon, RP; Appelbaum, FR; Banaji, M; Hansen, J
MLA Citation
Sullivan, KM, Storb, R, Buckner, CD, Fefer, A, Fisher, L, Weiden, PL, Witherspoon, RP, Appelbaum, FR, Banaji, M, and Hansen, J. "Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms." N Engl J Med 320.13 (March 30, 1989): 828-834.
PMID
2648143
Source
pubmed
Published In
The New England journal of medicine
Volume
320
Issue
13
Publish Date
1989
Start Page
828
End Page
834
DOI
10.1056/NEJM198903303201303

Assessment and management of donor pain following marrow harvest for allogeneic bone marrow transplantation.

We studied the time course and intensity of pain of multiple bone marrow aspirations in 30 healthy adult marrow donors receiving acetaminophen with codeine for analgesia immediately after marrow harvesting for allogeneic bone marrow transplantation. Upon discharge, donors were supplied with acetaminophen (315 mg) plus codeine (30 mg) tablets and instructed to use one or two tablets up to every 4 h as needed for pain control. Donors used analgesic medication for a mean (+/- SE) of 3.3 +/- 0.5 days (range = 1-13 days) and reported less than complete pain relief. Subjects reported more pain at time of medication than between doses, indicating that the analgesic was at least partially effective. Male donors tended to report more pain and use more analgesic than did females. We conclude that donors self-regulate their analgesic usage to achieve maximal relief and that incomplete relief with acetaminophen plus codeine may be due to limited efficacy of this analgesic preparation. Our findings suggest that donor pain management may be improved by use of more powerful analgesics.

Authors
Hill, HF; Chapman, CR; Jackson, TL; Sullivan, KM
MLA Citation
Hill, HF, Chapman, CR, Jackson, TL, and Sullivan, KM. "Assessment and management of donor pain following marrow harvest for allogeneic bone marrow transplantation." Bone Marrow Transplant 4.2 (March 1989): 157-161.
PMID
2650785
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
4
Issue
2
Publish Date
1989
Start Page
157
End Page
161

Chemoradiotherapy toxicity during bone marrow transplantation: time course and variation in pain and nausea.

Chemoradiotherapy-induced toxicity following unmodified allogeneic marrow grafting was studied. Patients with hematologic malignancy (n = 157) received cyclophosphamide (120 mg/kg) followed by single or fractionated total body irradiation (TBI); aplastic anemia patients (n = 41) received only cyclophosphamide (200 mg/kg). Physicians rated mucositis, pain and nausea daily as (0) none, (1) mild, (2) moderate, (3) severe, (4) life threatening. Oral mucositis pain began several days prior to transplant, peaked during the second week after transplant, and declined thereafter. Patients with hematologic malignancies (maximum mean rating of 1.6, day 11) experienced more pain than aplastic anemia patients (maximum mean rating of 0.7, day 6). Nausea peaked before transplant and gradually declined. Nausea was higher (p less than 0.001) in patients with aplastic anemia (maximum mean rating of 1.3, day -2) than with hematologic malignancies (maximum mean rating of 0.9, day -6). There was no significant difference between single dose 1000 cGy and 6-day 1200 cGy irradiation. Recipients of 1575 cGy rather than 1200 cGy TBI had significantly (p less than 0.01) higher levels of pain (mean rating 1.25 and 0.82, respectively) and nausea (mean rating 1.27 and 0.72, respectively). Additional research is needed to determine the predictors, consequences and best methods of controlling these toxicities.

Authors
Chapko, MK; Syrjala, KL; Schilter, L; Cummings, C; Sullivan, KM
MLA Citation
Chapko, MK, Syrjala, KL, Schilter, L, Cummings, C, and Sullivan, KM. "Chemoradiotherapy toxicity during bone marrow transplantation: time course and variation in pain and nausea." Bone Marrow Transplant 4.2 (March 1989): 181-186.
PMID
2650788
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
4
Issue
2
Publish Date
1989
Start Page
181
End Page
186

Congress review: progress and prospects in bone marrow transplantation.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Congress review: progress and prospects in bone marrow transplantation." Transplant Proc 21.1 Pt 3 (February 1989): 2919-2922. (Review)
PMID
2650396
Source
pubmed
Published In
Transplantation Proceedings
Volume
21
Issue
1 Pt 3
Publish Date
1989
Start Page
2919
End Page
2922

Long-term results of allogeneic bone marrow transplantation.

Authors
Sullivan, KM; Witherspoon, RP; Storb, R; Buckner, CD; Sanders, J; Thomas, ED
MLA Citation
Sullivan, KM, Witherspoon, RP, Storb, R, Buckner, CD, Sanders, J, and Thomas, ED. "Long-term results of allogeneic bone marrow transplantation." Transplant Proc 21.1 Pt 3 (February 1989): 2926-2928. (Review)
PMID
2650398
Source
pubmed
Published In
Transplantation Proceedings
Volume
21
Issue
1 Pt 3
Publish Date
1989
Start Page
2926
End Page
2928

Marrow transplantation for malignant plasma cell disorders: summary of the Seattle experience.

28 patients with plasma cell malignancies received marrow transplants from identical twins (N = 8), HLA-identical family members (N = 15), HLA partially-matched relatives (N = 3) or cryopreserved autologous marrow (N = 2). Treatment regimens included cyclophosphamide (CY) and total body irradiation (TBI) for 15 patients and busulphan (BU) and CY for 13 patients. 3 of 8 twins are alive, 2 without disease at 24 and 34 months, and 1 is alive and well at 116 months without evidence of disease except for at small residual monoclonal protein spike. 12 of the 18 allografted patients died of transplant-related causes and 2 died of progressive disease. 4 of 18 allograft recipients are alive; 2 are free of disease at 16 and 15 months, 1 is alive at 6 months without disease except for persistent monoclonal Kappa protein. 1 patient is alive with residual marrow involvement and a persistent IGA lambda monoclonal protein at 7 months. 1 of the 2 autograft recipients is alive 2 months after transplant and is not yet evaluable for tumor response and the other patient died early of transplant-related complications. Both CY + TBI and BU + CY resulted in remissions in patients with advanced plasma cell malignancies. However, the optimal treatment regimen and timing of transplantation remain to be determined.

Authors
Buckner, CD; Fefer, A; Bensinger, WI; Storb, R; Durie, BG; Appelbaum, FR; Petersen, FB; Weiden, P; Clift, RA; Sanders, JE
MLA Citation
Buckner, CD, Fefer, A, Bensinger, WI, Storb, R, Durie, BG, Appelbaum, FR, Petersen, FB, Weiden, P, Clift, RA, and Sanders, JE. "Marrow transplantation for malignant plasma cell disorders: summary of the Seattle experience." European journal of haematology. Supplementum 51 (January 1989): 186-190.
PMID
2697590
Source
epmc
Published In
European journal of haematology. Supplementum
Volume
51
Publish Date
1989
Start Page
186
End Page
190

Engraftment in 86 with patients lymphoid malignancy after autologous marrow transplantation.

The kinetics of marrow engraftment was retrospectively analysed in 55 patients with malignant lymphoma (ML) and 31 patients with acute lymphoblastic leukemia (ALL) after marrow-ablative therapy followed by autologous bone marrow transplantation. Thirty-eight percent of patients with ML, most of whom were transplanted in relapse and 13% of patients with ALL, mostly transplanted in remission, showed failed or delayed engraftment. Analysis of the total patient group showed that failure to recover platelet counts was significantly correlated with detection of disease in the marrow early after transplantation (p less than 0.001). Platelet recovery was also correlated with survival (p = 0.0001), disease-free survival (p = 0.0001), and the probability of relapse (p = 0.02). In those patients achieving engraftment, multivariate regression analysis failed to reveal any single in vitro test of marrow nucleated cell or progenitor cell numbers that significantly influenced time to achieve recovery of either granulocyte or platelet counts.

Authors
Hill, RS; Mazza, P; Amos, D; Buckner, CD; Appelbaum, FR; Martin, P; Still, BJ; Sica, S; Berenson, R; Bensinger, W
MLA Citation
Hill, RS, Mazza, P, Amos, D, Buckner, CD, Appelbaum, FR, Martin, P, Still, BJ, Sica, S, Berenson, R, and Bensinger, W. "Engraftment in 86 with patients lymphoid malignancy after autologous marrow transplantation." Bone Marrow Transplant 4.1 (January 1989): 69-74.
PMID
2647189
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
4
Issue
1
Publish Date
1989
Start Page
69
End Page
74

Intravenous immune globulin prophylaxis in recipients of a marrow transplant

Bone marrow transplantation is a worldwide activity involving more than 250 transplant centers in more than 40 countries.1 The ultimate success of the procedure depends in large measure on supportive care of the transplant recipient. A major component of this supportive care is the prevention of opportunistic infections. This article reviews the nature of immunoglobulin class and subclass deficiency after marrow transplantation and the role of intravenous immune globulin in preventing infections and associated complications. © 1989.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Intravenous immune globulin prophylaxis in recipients of a marrow transplant." The Journal of Allergy and Clinical Immunology 84.4 PART 2 (1989): 632-639.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
84
Issue
4 PART 2
Publish Date
1989
Start Page
632
End Page
639

Technetium-99m labeled NR-LU-10 monoclonal antibody (MoAb) in assessing patients with carcinoma of the lung

Authors
Vansant, J; Johnson, D; Sandler, M; McCook, B; Hainsworth, J; Sonin, A; Clanton, J; Sullivan, K; Salk, D; Abrams, P
MLA Citation
Vansant, J, Johnson, D, Sandler, M, McCook, B, Hainsworth, J, Sonin, A, Clanton, J, Sullivan, K, Salk, D, and Abrams, P. "Technetium-99m labeled NR-LU-10 monoclonal antibody (MoAb) in assessing patients with carcinoma of the lung." Journal of Nuclear Medicine 30.11 (1989): 1Ab-.
Source
scival
Published In
Journal of Nuclear Medicine
Volume
30
Issue
11
Publish Date
1989
Start Page
1Ab

Graft-versus-host disease prevention by methotrexate combined with cyclosporin compared to methotrexate alone in patients given marrow grafts for severe aplastic anaemia: long-term follow-up of a controlled trial

Forty-six patients with aplastic anaemia (median age 23 years) were given cyclophosphamide followed by infusion of marrow from an HLA-identical family member. To evaluate postgrafting prophylaxis for graft-versus-host disease (GVHD), the patients were entered into a randomized prospective trial comparing a combination of methotrexate and cyclosporin (n = 22) to methotrexate alone (n = 24). Methotrexate/cyclosporin significantly reduced the incidence and severity of acute GVHD and improved early survival. This report updates the results of the randomized trial with follow-up ranging from 3 to more than 6 years. The methotrexate/cyclosporin regimen did not interfere with sustained engraftment, and there were no significant differences in the incidence of early or late graft rejection among the two treatment groups (10% v 4%). The incidence of chronic GVHD was higher among methotrexate/cyclosporin-treated patients (58% v 36%; P = 0.18). Two patients in each treatment group still require treatment for chronic GVHD, while treatment is no longer needed in the other patients. Projected 4-year survival is 72% in patients given methotrexate/cyclosporin compared to 58% in patients given methotrexate alone (P = 0.16). Having achieved a reduction in the incidence of acute GVHD and associated early mortality without impairing engraftment, it is clear that future progress in marrow grafting for aplastic anaemia must come in the area of chronic GVHD.

Authors
Storb, R; Deeg, HJ; Pepe, M; Doney, K; Appelbaum, F; Beatty, P; Bensinger, W; Buckner, CD; Clift, R; Hansen, J; Hill, R; Longton, G; Anasetti, C; Martin, P; Loughran, TP; Sanders, J; Singer, J; Stewart, P; Sullivan, KM
MLA Citation
Storb, R, Deeg, HJ, Pepe, M, Doney, K, Appelbaum, F, Beatty, P, Bensinger, W, Buckner, CD, Clift, R, Hansen, J, Hill, R, Longton, G, Anasetti, C, Martin, P, Loughran, TP, Sanders, J, Singer, J, Stewart, P, and Sullivan, KM. "Graft-versus-host disease prevention by methotrexate combined with cyclosporin compared to methotrexate alone in patients given marrow grafts for severe aplastic anaemia: long-term follow-up of a controlled trial." British Journal of Haematology 72.4 (1989): 567-572.
PMID
2673331
Source
scival
Published In
British Journal of Haematology
Volume
72
Issue
4
Publish Date
1989
Start Page
567
End Page
572

Intravenous immune globulin prophylaxis in recipients of a marrow transplant

Bone marrow transplantation is a worldwide activity involving more than 250 transplant centers in more than 40 countries. The ultimate success of the procedure depends in large measure on supportive care of the transplant recipient. A major component of this supportive care is the prevention of opportunistic infections. This article reviews the nature of immunoglobulin class and subclass deficiency after marrow transplantation and the role of intravenous immune globulin in preventing infections and associated complications.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Intravenous immune globulin prophylaxis in recipients of a marrow transplant." Journal of Allergy and Clinical Immunology 84.4 II SUPPL. (1989): 632-639.
Source
scival
Published In
Journal of Allergy and Clinical Immunology
Volume
84
Issue
4 II SUPPL.
Publish Date
1989
Start Page
632
End Page
639

Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma

Ninety-five patients transplanted for malignant lymphoma were retrospectively evaluated for regimen-related toxicity (RRT) and early posttransplant survival. Nineteen patients developed life-threatening (grade 3) or fatal (grade 4) RRT in one or more organs. Grade 3 or 4 RRT was more common in patients with advanced disease versus those transplanted earlier in their course (P = .008), and was more common in patients with advanced disease conditioned with cytarabine (Ara-C)/total body irradiation (TBI) versus those prepared with cyclophosphamide (CY)/TBI (P = .033). There was no significant difference in the incidence of grade 3 or 4 toxicity in autologous, histocompatibility locus antigen (HLA)-identical, or HLA-mismatched marrow recipients. Grade 3 or 4 RRT tended to be more common and 100-day survival worse in patients with a Karnofsky performance status of less than 90 (P = .063 and .0002, respectively). Patients receiving 20 Gy or more of mediastinal irradiation before coming to transplant had more idiopathic or cytomegalovirus (CMV) interstitial pneumonitis than those who received less than 20 Gy (30% v 9%, P = .027). The probability of survival decreased with the number of organs in which toxicity was observed (P = .0001). Severe or fatal toxicities directly related to the preparative regimen are a significant problem in the treatment of patients with advanced malignant lymhoma and can be reduced by carrying out transplantation earlier in the course of the disease.

Authors
Bearman, SI; Appelbaum, FR; Back, A; Petersen, FB; Buckner, CD; Sullivan, KM; Schoch, HG; Fisher, L; Thomas, ED
MLA Citation
Bearman, SI, Appelbaum, FR, Back, A, Petersen, FB, Buckner, CD, Sullivan, KM, Schoch, HG, Fisher, L, and Thomas, ED. "Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma." Journal of Clinical Oncology 7.9 (1989): 1288-1294.
PMID
2671286
Source
scival
Published In
Journal of Clinical Oncology
Volume
7
Issue
9
Publish Date
1989
Start Page
1288
End Page
1294

High-dose cytosine arabinoside, total body irradiation and marrow transplantation for advanced malignant lymphoma

Twenty-four patients with advanced malignant lymphoma including Hodgkin's disease (HD, n = 1), intermediate grade non-Hodgkin's lymphoma (IGL, n = 12) and high-grade non-Hodgkin's lymphoma (HGL, n = 11) were prepared for syngeneic (n = 2), allogeneic (n = 11) or autologous (n = 11) marrow transplantation with cytosine arabinoside, 3 g/m2 every 12 h for 12 doses (HDAC) and total body irradiation, 200 cGy daily for 6 days (TBI) to determine toxicity and efficacy. Eight patients (33%) died from early regimen related toxicity and all eight had a Karnofsky performance score ≤80 at the start of treatment. The actuarial probability of disease-free survival was 17% with a 65% probability of relapse at 4 years after transplantation. Four patients are surviving 2-4 years post-transplant, three transplanted for IGL and one for HD. None of the patients transplanted for HGL survived. The results of this phase II study suggests that HDAC followed by TBI and marrow infusion offers no apparent advantage over cyclophosphamide + TBI for patients with relapsed advanced malignant lymphoma. Earlier transplantation currently is the only demonstrated method of achieving better results.

Authors
Petersen, FB; Appelbaum, FR; Bigelow, CL; Buckner, CD; Clift, RA; Sanders, JE; Storb, R; Sullivan, KM; Weiden, PL; Fefer, A; Thomas, ED
MLA Citation
Petersen, FB, Appelbaum, FR, Bigelow, CL, Buckner, CD, Clift, RA, Sanders, JE, Storb, R, Sullivan, KM, Weiden, PL, Fefer, A, and Thomas, ED. "High-dose cytosine arabinoside, total body irradiation and marrow transplantation for advanced malignant lymphoma." Bone Marrow Transplantation 4.5 (1989): 483-488.
PMID
2676043
Source
scival
Published In
Bone Marrow Transplantation
Volume
4
Issue
5
Publish Date
1989
Start Page
483
End Page
488

Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia

To determine the incidence of secondary cancers after bone marrow transplantation, we reviewed the records of all patients at our center who received allogeneic, syngeneic, or autologous transplants for leukemia (n = 1926) or aplastic anemia (n = 320). Thirty-five patients were given a diagnosis of secondary cancer between 1.5 months and 13.9 years (median, 1.0 year) after transplantation. Sixteen patients had non-Hodgkin's lymphomas, 6 had leukemias, and 13 had solid tumors (including 3 each with glioblastoma, melanoma, and squamous-cell carcinoma). There were 1.2 secondary cancers per 100 exposure-years during the first year after transplantation (95 percent confidence interval, 0.7 to 2.0). The rate declined to 0.4 (95 percent confidence interval, 0.2 to 0.7) after one year. The age-adjusted incidence of secondary cancer was 6.69 times higher than that of primary cancer in the general population. In a multivariate model, the predictors (and relative risks) of any type of secondary cancer were acute graft-versus-host disease treated with either antithymocyte globulin (relative risk, 4.2) or an anti-CD3 monoclonal antibody (13.6) and total-body irradiation (3.9). Two additional factors were associated with secondary non-Hodgkin's lymphomas: T-lymphocyte depletion of donor marrow (12.4) and HLA mismatch (3.8). We conclude that recipients of bone marrow transplantation have a low but significant risk of a secondary cancer, particularly non-Hodgkin's lymphoma.

Authors
Witherspoon, RP; Fisher, LD; Schoch, G; Martin, P; Sullivan, KM; Sanders, J; Deeg, HJ; Doney, K; Thomas, D; Storb, R; Thomas, ED
MLA Citation
Witherspoon, RP, Fisher, LD, Schoch, G, Martin, P, Sullivan, KM, Sanders, J, Deeg, HJ, Doney, K, Thomas, D, Storb, R, and Thomas, ED. "Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia." New England Journal of Medicine 321.12 (1989): 784-789.
PMID
2671734
Source
scival
Published In
New England Journal of Medicine
Volume
321
Issue
12
Publish Date
1989
Start Page
784
End Page
789

Growth and development after bone marrow transplantation.

Authors
Sanders, JE; Buckner, CD; Sullivan, K; Doney, K; Appelbaum, F; Witherspoon, R; Anasetti, C; Storb, R; Thomas, ED
MLA Citation
Sanders, JE, Buckner, CD, Sullivan, K, Doney, K, Appelbaum, F, Witherspoon, R, Anasetti, C, Storb, R, and Thomas, ED. "Growth and development after bone marrow transplantation." Progress in clinical and biological research 309 (1989): 375-382.
PMID
2675106
Source
scival
Published In
Progress in clinical and biological research
Volume
309
Publish Date
1989
Start Page
375
End Page
382

Long-term complications of bone marrow transplantation.

Authors
Sullivan, KM; Buckner, CD; Sanders, JE; Anasetti, C; Appelbaum, FR; Clark, J; Doney, K; Meyers, J; Sale, G; Storb, R
MLA Citation
Sullivan, KM, Buckner, CD, Sanders, JE, Anasetti, C, Appelbaum, FR, Clark, J, Doney, K, Meyers, J, Sale, G, and Storb, R. "Long-term complications of bone marrow transplantation." Progress in clinical and biological research 309 (1989): 367-374.
PMID
2675105
Source
scival
Published In
Progress in clinical and biological research
Volume
309
Publish Date
1989
Start Page
367
End Page
374

Deletion of immunosuppressive prophylaxis after marrow transplantation increases hyperacute graft-versus-host disease but does not influence chronic graft-versus-host disease or relapse in patients with advanced leukemia

Sixteen patients < 30 years of age with advanced leukemia who were given unmodified marrow grafts from HLA-identical siblings without posttransplant immunosuppression were compared to 44 age- and disease-matched controls who received methotrexate (MTX) to prevent graft-versus-host disease (GVHD). All 60 patients were prepared with cyclophosphamide (60 mg/kg x 2) and total body irradiation (2.25 Gy daily x 7). Grade 2-4 acute GVHD developed in all 15 engrafted patients not given immunosuppression compared to 10 of 44 engrafted MTX recipients (p < 0.0001). The onset of Grade 2-4 GVHD was hyperacute (median d 8) compared to a median onset at d 18 in the MTX group (p = 0.005). Treatment of hyperacute GVHD with prednisone ± cyclosporine or ATG + cyclosporine produced sustained improvement in 6, response with subsequent flare in 4, and no response in 4 patients. Despite the prevalence of hyperacute GVHD in patients not given immunosuppression, there was no statistically significant difference in the probability of chronic GVHD (31% versus 33%), interstitial pneumonia (47% versus 22%), or recurrent leukemia (41% versus 38%) compared to the MTX recipients. Six patients not given immunosuppression and 19 given MTX survive with a median follow-up of 4.4 (range 3.2-6.4) yr after transplant. The probability of death from causes other than recurrent malignancy was 58% in the no-immunosuppresion and 34% in the MTX group (p = 0.1). Actuarial 3-yr relapse-free survival is 25% and 41%, respectively (p = 0.3). We conclude that deletion of immunosuppression after unmodified HLA-identical marrow transplantation leads to an increase in hyperacute GVHD without apparent influence on chronic GVHD or relapse. Although nonrelapse mortality was higher and relapse-free survival was lower in patients not given immunosuppression, differences did not reach statistical significance in this study.

Authors
Sullivan, KM; Storb, R; Witherspoon, RP; Weiden, PL; Anasetti, C; Appelbaum, FR; Beatty, P; Buckner, CD; Deeg, HJ; Doney, K; Fisher, L; Loughran, TP; Martin, P; Meyers, J; McDonald, GB; Sanders, J; Shulman, H; Stewart, P; Thomas, ED
MLA Citation
Sullivan, KM, Storb, R, Witherspoon, RP, Weiden, PL, Anasetti, C, Appelbaum, FR, Beatty, P, Buckner, CD, Deeg, HJ, Doney, K, Fisher, L, Loughran, TP, Martin, P, Meyers, J, McDonald, GB, Sanders, J, Shulman, H, Stewart, P, and Thomas, ED. "Deletion of immunosuppressive prophylaxis after marrow transplantation increases hyperacute graft-versus-host disease but does not influence chronic graft-versus-host disease or relapse in patients with advanced leukemia." Clinical Transplantation 3.1 (1989): 5-11.
Source
scival
Published In
Clinical Transplantation
Volume
3
Issue
1
Publish Date
1989
Start Page
5
End Page
11

Long term effects and quality of life in children and adults after marrow transplantation

These studies of late effects associated with marrow transplant preparative regimens demonstrate the need for continued long-term follow-up of these patients. Sequential studies of growth and development in children demonstrate that few endocrine function abnormalities occur after high dose CY, but multiple endocrine abnormalities occur after TBI containing regimens. Children may have decreased growth rates and abnormal development of secondary teeth. Most young adult patients who received CY only have normal gonadal function recovery and may be fertile. Neuropsychological abnormalities, cataracts and secondary malignancies may also develop. Although the marrow transplant preparative regimen may not be the treatment modality solely responsible for the various observed abnormalities, transplant recipients need to be evaluated carefully for many years to determine onset of abnormalities and to initiate appropriate therapeutic interventions which may improve the quality of life of these unique patients.

Authors
Sanders, J; Sullivan, K; Witherspoon, R; Doney, K; Anasetti, C; Beatty, P; Petersen, FB
MLA Citation
Sanders, J, Sullivan, K, Witherspoon, R, Doney, K, Anasetti, C, Beatty, P, and Petersen, FB. "Long term effects and quality of life in children and adults after marrow transplantation." Bone Marrow Transplantation 4.SUPPL. 4 (1989): 27-29.
PMID
2697434
Source
scival
Published In
Bone Marrow Transplantation
Volume
4
Issue
SUPPL. 4
Publish Date
1989
Start Page
27
End Page
29

Marrow transplantation for malignant plasma cell disorders: Summary of the Seattle experience

28 patients with plasma cell malignancies received marrow transplants from identical twins(N = 8), HLA-identical family members (N = 15), HLA partially-matched relatives (N = 3) or cryopreserved autologous marrow (N = 2). Treatment regimens included cyclophosphamide (CY) and total body irradiation (TBI) for 15 patients and busulphan (BU) and CY for 13 ptients. 3 of 8 twins are alive, 2 without disease at 24 and 34 months, and 1 is alive and well at 116 months without evidence of disease except for at small residual monoclonal protein spike. 12 of 18 allografted patients died of transplant-related causes and 2 died of progressive disease. 4 of 18 allograft receipients are alive; 2 are free of disease at 16 and 15 monthsm 1 is alive at 6 months without disease except for persistent monoclonal Kappa protein. 1 patient is alive with residual marrow involvement and a persistent IGA lambda monoclonal protein at 7 months. 1 of the 2 autograft recipients is alive 2 months after transplant and is not yet evaluable for tumor response and the other patient died early of transplant-related complications. Both CY + TBI and BU + CY resulted in remissions in patients with advanced plasma cell malignancies. However, the optimal treatment regimen and timing of transplantation remain to be determined.

Authors
Buckner, CD; Fefer, A; Bensinger, WI; Storb, R; Durie, BG; Appelbaum, FR; Petersen, FB; Weiden, P; Clift, RA; Sanders, JE; Sullivan, KM; Witherspoon, RP; Hill, R; Martin, P; Thomas, ED
MLA Citation
Buckner, CD, Fefer, A, Bensinger, WI, Storb, R, Durie, BG, Appelbaum, FR, Petersen, FB, Weiden, P, Clift, RA, Sanders, JE, Sullivan, KM, Witherspoon, RP, Hill, R, Martin, P, and Thomas, ED. "Marrow transplantation for malignant plasma cell disorders: Summary of the Seattle experience." European Journal of Haematology, Supplement 43.51 (1989): 186-190.
Source
scival
Published In
European Journal of Haematology, Supplement
Volume
43
Issue
51
Publish Date
1989
Start Page
186
End Page
190

Chronic graft-versus-host disease, obliterative bronchiolitis, and graft-versus-leukemia effect: Case histories

Authors
Sullivan, KM; Shulman, HM
MLA Citation
Sullivan, KM, and Shulman, HM. "Chronic graft-versus-host disease, obliterative bronchiolitis, and graft-versus-leukemia effect: Case histories." Transplantation Proceedings 21.3 SUPPL. 1 (1989): 51-62.
PMID
2662536
Source
scival
Published In
Transplantation Proceedings
Volume
21
Issue
3 SUPPL. 1
Publish Date
1989
Start Page
51
End Page
62

Current status of bone marrow transplantation

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Current status of bone marrow transplantation." Transplantation Proceedings 21.3 SUPPL. 1 (1989): 41-50.
PMID
2662535
Source
scival
Published In
Transplantation Proceedings
Volume
21
Issue
3 SUPPL. 1
Publish Date
1989
Start Page
41
End Page
50

Minimal risk of chronic renal dysfunction in marrow transplant recipients treated with cyclosporine for 6 months

To determine whether 6 months of cyclosporine therapy is associated with chronic renal dysfunction, we evaluated serum creatinine concentrations 1 year post-transplant in 82 marrow transplant recipients randomized to receive either cyclosporine (n = 40) or methotrexate (n = 42) as graft-versus-host disease (GVHD) prophylaxis. Nine patients in the methotrexate group were later given cyclosporine as treatment for acute or chronic GVHD (methotrexate → cyclosporine). Cyclosporine prophylaxis was started on the day before marrow infusion, given at full doses until day 50, then gradually tapered and discontinued by day 180. Methotrexate prophylaxis was started on day 1 and given intermittently until day 102. Patients in the cyclosporine and methotrexate → cyclosporine groups had significantly higher mean serum creatinine values during the first 100 days post-transplant than methotrexate-treated patients, but by 1 year mean serum creatinine values were not significantly different between the three groups. Serum creatinine values at 1 year were also not significantly different from baseline values in each of the groups. None of the patients who had their cyclosporine discontinued by day 180 developed chronic renal dysfunction, defined as a doubling of the baseline serum creatinine at 1 year. We conclude that chronic renal dysfunction occurs rarely in marrow transplant recipients treated with 6 months of cyclosporine and when it does occur, it appears to have minimal clinical significance.

Authors
Yee, GC; McGuire, TR; Pierre, BAS; Self, SG; Zager, RA; Sullivan, KM; Deeg, HJ
MLA Citation
Yee, GC, McGuire, TR, Pierre, BAS, Self, SG, Zager, RA, Sullivan, KM, and Deeg, HJ. "Minimal risk of chronic renal dysfunction in marrow transplant recipients treated with cyclosporine for 6 months." Bone Marrow Transplantation 4.6 (1989): 691-694.
PMID
2684309
Source
scival
Published In
Bone Marrow Transplantation
Volume
4
Issue
6
Publish Date
1989
Start Page
691
End Page
694

Busulfan, cyclophosphamide and fractionated total body irradiation as a preparatory regimen for marrow transplantation in patients with advanced hematological malignancies: A phase I study

Thirty-six patients with advanced hematologic malignancy were entered into a phase I study designed to define a tolerable dose of busulfan (BU) and cyclophosphamide (CY) combined with 12 Gy of fractionated total body irradiation (TBI) as preparation for marrow transplantation from HLA-identical siblings, 0-1 locus HLA-non-identical family members or autologous cryopreserved marrow. Five of 18 evaluable patients prepared with 8.7 mg/kg of BU and 69 mg/kg CY + TBI developed severe regimen related toxicity (RRT) while none of 15 patients treated with 6.9 mg/kg of BU and 47 mg/kg of CY + TBI developed severe RRT. Ten of the 15 evaluable patients treated on the lower dose level are alive, nine disease-free, 262-737 days (median, 547) post-transplant with a 87% and 67% actuarial probability of survival at 3 and 18 months respectively. Six of the 18 patients treated on the higher dose level are alive disease-free 273-1039 days (median, 668) post-transplant with a 56% and 27% actuarial probability of survival at 3 and 18 months respectively. Eighteen patients were transplanted with allogeneic marrow for chronic myelogenous leukemia beyond chronic phase and acute non-lymphocytic leukemia beyond first remission or in relapse other than first untreated relapse and only one has relapsed post-transplant. It was concluded that a transplant preparative regimen combining 6.9 mg/kg of BU with 47 mg/kg of CY followed by 12 Gy fractionated TBI is well tolerated. The high proability of surviving this regimen and the low early relapse rate in patients with advanced myeloid malignancies is encouraging.

Authors
Petersen, FB; Buckner, CD; Appelbaum, FR; Clift, RA; Sanders, JE; Bensinger, WI; Storb, R; Witherspoon, RP; Sullivan, KM; Bearman, SI; Flournoy, N; Thomas, ED
MLA Citation
Petersen, FB, Buckner, CD, Appelbaum, FR, Clift, RA, Sanders, JE, Bensinger, WI, Storb, R, Witherspoon, RP, Sullivan, KM, Bearman, SI, Flournoy, N, and Thomas, ED. "Busulfan, cyclophosphamide and fractionated total body irradiation as a preparatory regimen for marrow transplantation in patients with advanced hematological malignancies: A phase I study." Bone Marrow Transplantation 4.6 (1989): 617-623.
PMID
2684307
Source
scival
Published In
Bone Marrow Transplantation
Volume
4
Issue
6
Publish Date
1989
Start Page
617
End Page
623

Congress review: Progress and prospects in bone marrow transplantation

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Congress review: Progress and prospects in bone marrow transplantation." Transplantation Proceedings 21.1 III (1989): 2919-2922.
Source
scival
Published In
Transplantation Proceedings
Volume
21
Issue
1 III
Publish Date
1989
Start Page
2919
End Page
2922

Factors predicting chronic graft-versus-host disease and survival after marrow transplantation for aplastic anemia

The cumulative incidence of chronic graft-versus-host disease (GVHD) was 48% among 165 patients with severe aplastic anemia who had been discharged from Seattle 3 months after they were treated with marrow grafts from HLA-identical siblings. Estimated 10-year survival was 85%. Preceding acute GVHD had a dominating influence on the development of chronic GVHD. Almost all patients with grades II-IV and 67% of those with grade I acute GVHD developed chronic GVHD. Among patients without previous acute GVHD, three factors were independently correlated with an increased risk of de novo chronic GVHD: increasing patient age, the infusion of buffy coat cells in addition to the marrow, and corticosteroid therapy before transplantation. For example, patients below and above age 20 years who had neither buffy coat cell transfusions nor preceding corticosteroid therapy had an incidence of chronic GVHD of only 4-8%, while those with either buffy coat cell transfusions or corticosteroids or both had incidence rates of 33-70%. The development of chronic GVHD significantly influenced survival. Among 83 patients without chronic GVHD, only one died (on day 150 with interstitial pneumonia), compared to 23 deaths among 82 patients with chronic GVHD. For results of marrow grafting for aplastic anemia to improve, better prevention of chronic GVHD is needed.

Authors
Niederwieser, D; Pepe, M; Storb, R; Witherspoon, R; Longton, G; Sullivan, K
MLA Citation
Niederwieser, D, Pepe, M, Storb, R, Witherspoon, R, Longton, G, and Sullivan, K. "Factors predicting chronic graft-versus-host disease and survival after marrow transplantation for aplastic anemia." Bone Marrow Transplantation 4.2 (1989): 151-156.
PMID
2650784
Source
scival
Published In
Bone Marrow Transplantation
Volume
4
Issue
2
Publish Date
1989
Start Page
151
End Page
156

Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma

We analyzed the relevance of HLA compatibility to sustained marrow engraftment in 269 patients with hematologic neoplasms who underwent bone marrow transplantations. Each patient received marrow from a family member who shared one HLA haplotype with the patient but differed to a variable degree for the HLA-A, B, and D antigens of the haplotype not shared. These 269 patients were compared with 930 patients who received marrow from siblings with identical HLA genotypes. All patients were treated with cyclophosphamide and total-body irradiation followed by the infusion of unmodified donor marrow cells. The rate of graft failure was 12.3 percent among the recipients of marrow from a donor with only one identical haplotype, as compared with 2.0 percent among recipients of marrow from a sibling with the same HLA genotype (both haplotypes inherited from the same parents) (P < 0.0001). The incidence of graft failure correlated with the degree of donor HLA incompatibility. Graft failure occurred in 3 of 43 transplants (7 percent) from donors who were phenotypically HLA-matched with their recipient (haplotypes similar, but not inherited from the same parents), in 11 of 121 donors (9 percent) incompatible for one HLA locus, in 18 of 86 (21 percent) incompatible for two loci, and in 1 of 19 (5 percent) incompatible for three loci (P = 0.028). In a multivariate binary logistic regression analysis, independent risk factors associated with graft failure were donor incompatibility for HLA-B and D (relative risk = 2.1; 95 percent confidence interval, 1.7 to 2.5; P = 0.0004) and a positive crossmatch for anti-donor lymphocytotoxic antibody (relative risk = 2.3; 95 percent confidence interval, 1.8 to 2.8; P = 0.0038). Residual host lymphocytes were detected in 11 of 14 patients with graft failure, suggesting that the mechanism for graft failure could be host-mediated immune rejection. We conclude that donor HLA incompatibility and prior alloimmunization are significant risk factors for graft failure, and that a more effective immunosuppressive regimen than those currently used is needed for consistent achievement of sustained engraftment of marrow transplanted from donors who are not HLA-identical siblings.

Authors
Anasetti, C; Amos, D; Beatty, PG; Appelbaum, FR; Bensinger, W; Buckner, CD; Clift, R; Doney, K; Martin, PJ; Mickelson, E; Nisperos, B; O'Quigley, J; Ramberg, R; Sanders, JE; Stewart, P; Storb, R; Sullivan, KM; Witherspoon, RP; Thomas, ED; Hansen, JA
MLA Citation
Anasetti, C, Amos, D, Beatty, PG, Appelbaum, FR, Bensinger, W, Buckner, CD, Clift, R, Doney, K, Martin, PJ, Mickelson, E, Nisperos, B, O'Quigley, J, Ramberg, R, Sanders, JE, Stewart, P, Storb, R, Sullivan, KM, Witherspoon, RP, Thomas, ED, and Hansen, JA. "Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma." New England Journal of Medicine 320.4 (1989): 197-204.
PMID
2643045
Source
scival
Published In
New England Journal of Medicine
Volume
320
Issue
4
Publish Date
1989
Start Page
197
End Page
204

Long-term results of allogeneic bone marrow transplantation

Authors
Sullivan, KM; Witherspoon, RP; Storb, R; Buckner, CD; Sanders, J; Thomas, ED
MLA Citation
Sullivan, KM, Witherspoon, RP, Storb, R, Buckner, CD, Sanders, J, and Thomas, ED. "Long-term results of allogeneic bone marrow transplantation." Transplantation Proceedings 21.1 III (1989): 2926-2928.
Source
scival
Published In
Transplantation Proceedings
Volume
21
Issue
1 III
Publish Date
1989
Start Page
2926
End Page
2928

Graft-v-host disease is associated with autoimmune-like thrombocytopenia

Persistent thrombocytopenia after allogenic marrow transplantation is associated with poor patient survival. To identify the mechanisms of the thrombocytopenia, we studied platelet and fibrinogen kinetics and antiplatelet antibodies in 20 patients between 60 and 649 days (median 90) after transplantation. Seventeen patients had isolated thrombocytopenia (< 100 x 109 platelets/L): the marrow cellularity was normal in five patients and slightly reduced in 12, and there was no discrepancy between thrombopoiesis and myeloerythropoiesis. Three patients had pancytopenia following marrow graft rejection (two) and relapse of leukemia (one). Only three patients had evidence of increased platelet production, indicating that in most cases there is a poor marrow response to thrombocytopenia early after marrow grafting. There was no correlation between platelet count and splenic pooling, suggesting that hypersplenism was an unlikely mechanism of the thrombocytopenia. Although there was a direct relationship between platelet count and platelet survival, the reduction in platelet survival was greater than what could be explained by the fixed platelet removal found in thrombopenic patients; this suggests increased platelet destruction. Seven patients had intercurrent infections that reduced both platelet and fibrinogen survivals. In addition, platelet antibodies bound to autologous or marrow donor platelets were present in five of the 12 patients studied. Patients with antiplatelet antibodies had lower platelet counts (30 ± 10 x 109/L v. 49.1 ± 28.7 x 109/L, P < 0.05) and platelet survivals (1.32 ± 0.92 days v. 3.58 ± 2.02 days, P < 0.05) than patients without antiplatelet antibodies. Furthermore, platelet-bound autoantibodies were present in five of six patients with grade II-IV acute or chronic graft-versus-host disease (GVHD), but were not present in six patients free of GVHD (P < 0.01). We conclude that persistent thrombocytopenia after marrow transplantation is most often secondary to increased platelet destruction mediated by multiple mechanisms and that platelet autoantibodies are found in patients with acute or chronic GVHD.

Authors
Anasetti, C; Rybka, W; Sullivan, KM; Banaji, M; Slichter, SJ
MLA Citation
Anasetti, C, Rybka, W, Sullivan, KM, Banaji, M, and Slichter, SJ. "Graft-v-host disease is associated with autoimmune-like thrombocytopenia." Blood 73.4 (1989): 1054-1058.
PMID
2920206
Source
scival
Published In
Blood
Volume
73
Issue
4
Publish Date
1989
Start Page
1054
End Page
1058

Obstructive lung disease after allogeneic marrow transplantation. Clinical presentation and course

To describe the clinical presentation and progression of obstructive lung disease after marrow transplantation, we examined a sequential sample of 35 patients who had allogeneic marrow transplantation between January 1980 and January 1987, were 16 years or older, had normal pulmonary function tests before transplantation, and developed airflow obstruction defined as FEV1/FVC less than 70% and FEV1 less than 80% predicted 50 days or more after transplantation. Cases were selected from 1029 adult (older than 16 years) patients who underwent allogeneic marrow transplantation during the same period. Patients with airflow obstruction presented with symptoms of cough, dyspnea, or wheezing, or a combination. In 80% the chest radiograph was normal. Airflow obstruction was diagnosed within 1.5 years after transplantation in 33 of 35 patients. Clinical, extensive, chronic graft-versus-host disease was present in 24 patients. Only 4 patients had a complete response to primary therapy of chronic graft-versus-host disease: Serum IgG and IgA levels were decreased in 15 and 25 patients, respectively. The FEV1 declined rapidly (decrease in FEV1 > 30% between tests) in 21 patients, but 14 patients with slowly progressive or reversible disease were identified. Mortality was 65% at 3 years after transplant, a significantly higher value (P = 0.016) than the 3-year mortality rate of 44% in a comparison group of 412 concurrent patients with chronic graft-versus-host disease who were 16 years or older, survived more than 80 days after transplantation, and had normal pulmonary function. We concluded that obstructive lung disease after marrow transplantation may be variable with respect to time of onset and rate of progression. Obstructive lung disease was frequently associated with serum immunoglobulin deficiency and clinical, extensive, chronic graft-versus-host disease that was not readily responsive to treatment. Mortality was high but long-term survivors were identified.

Authors
Clark, JG; Crawford, SW; Madtes, DK; Sullivan, KM
MLA Citation
Clark, JG, Crawford, SW, Madtes, DK, and Sullivan, KM. "Obstructive lung disease after allogeneic marrow transplantation. Clinical presentation and course." Annals of Internal Medicine 111.5 (1989): 368-376.
PMID
2669592
Source
scival
Published In
Annals of Internal Medicine
Volume
111
Issue
5
Publish Date
1989
Start Page
368
End Page
376

Donor buffy coat cell infusion after marrow transplantation for aplastic anemia.

Authors
Anasetti, C; Storb, R; Longton, G; Witherspoon, R; Doney, K; Sullivan, KM; Thomas, ED
MLA Citation
Anasetti, C, Storb, R, Longton, G, Witherspoon, R, Doney, K, Sullivan, KM, and Thomas, ED. "Donor buffy coat cell infusion after marrow transplantation for aplastic anemia." Blood 72.3 (1988): 1099-1100.
PMID
3046681
Source
scival
Published In
Blood
Volume
72
Issue
3
Publish Date
1988
Start Page
1099
End Page
1100

Growth and development in children after bone marrow transplantation

Authors
Sanders, JE; Buckner, CD; Sullivan, KM; Doney, K; Appelbaum, F; Witherspoon, R; Storb, R; Thomas, ED
MLA Citation
Sanders, JE, Buckner, CD, Sullivan, KM, Doney, K, Appelbaum, F, Witherspoon, R, Storb, R, and Thomas, ED. "Growth and development in children after bone marrow transplantation." Hormone Research 30.2-3 (1988): 92-97.
PMID
3074032
Source
scival
Published In
Hormone Research
Volume
30
Issue
2-3
Publish Date
1988
Start Page
92
End Page
97

Allogeneic marrow transplantation for children with juvenile chronic myelogenous leukemia

Fourteen children between the ages of 2 and 5 years with juvenile chronic myelogenous leukemia were given cyclophosphamide, total-body irradiation, and marrow transplants. Unmodified marrow was given to six patients who received marrow from HLA-identical siblings and eight patients who received marrow from family members HLA identical for one haplotype but mismatched for one to three loci on the nonshared haplotype. Five patients died of transplant-related complications, and three relapsed at 48, 81, and 1,670 days posttransplant and died of leukemia. Six patients survive in continuous remission from 0.5 to 11.5 years posttransplant.

Authors
Sanders, JE; Buckner, CD; Thomas, ED; Fleischer, R; Sullivan, KM; Appelbaum, FA; Storb, R
MLA Citation
Sanders, JE, Buckner, CD, Thomas, ED, Fleischer, R, Sullivan, KM, Appelbaum, FA, and Storb, R. "Allogeneic marrow transplantation for children with juvenile chronic myelogenous leukemia." Blood 71.4 (1988): 1144-1146.
PMID
3281722
Source
scival
Published In
Blood
Volume
71
Issue
4
Publish Date
1988
Start Page
1144
End Page
1146

High-dose cytarabine and total body irradiation with or without cyclophosphamide as a preparative regimen for marrow transplantation for acute leukemia

Twenty-nine patients were conditioned for allogeneic marrow transplant with cytarabine (ara-C) (3 g/m2 every 12 hours for 12 doses) and total body irradiation (TBI) (200 cGy daily for six days) with or without cyclophosphamide (CY) (60 mg/kg) to determine toxicity and efficacy. Four patients had chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, and 25 patients had acute leukemia, 24 at stages later than first remission. Three patients (10%) had fatal regimen-related toxicity and another 10% experienced severe toxicity in at least one organ system. The addition of CY to the ara-C and TBI regimen was not associated with an increase in the frequency of severe toxicity. Twenty-five of 29 patients engrafted eight to 33 days posttransplant: three died early before engraftment, and one patient failed to engraft. Ten of 29 patients are alive without disease, and the actuarial probability of disease-free survival for the entire group at 3 years is 33%. Three of ten patients with acute nonlymphocytic leukemia (ANL), six of 15 with acute lymphocytic leukemia (ALL), and one of four with CML are alive and disease free 25 to 42 months (median, 30 months) after transplant. High-dose ara-C (HDara-C) and TBI with or without CY can be administered with approximately the same toxicity as CY plus TBI. Phase III studies appear warranted to determine if these newer regimens provide improved results compared with currently used regimens.

Authors
Riddell, S; Appelbaum, FR; Buckner, CD; Stewart, P; Clift, R; Sanders, J; Storb, R; Sullivan, K; Thomas, ED
MLA Citation
Riddell, S, Appelbaum, FR, Buckner, CD, Stewart, P, Clift, R, Sanders, J, Storb, R, Sullivan, K, and Thomas, ED. "High-dose cytarabine and total body irradiation with or without cyclophosphamide as a preparative regimen for marrow transplantation for acute leukemia." Journal of Clinical Oncology 6.4 (1988): 576-582.
PMID
3282031
Source
scival
Published In
Journal of Clinical Oncology
Volume
6
Issue
4
Publish Date
1988
Start Page
576
End Page
582

Second marrow transplants in patients with leukemia who relapse after allogeneic marrow transplantation

Twenty-six patients with recurrent leukemia following allogeneic marrow transplantation received a second marrow transplant between 1.5 and 78 months (median 26) after the inital transplant. Preparative regimens for second transplant included multi-agent chemotherapy with total body irradiation, 2.0-10.0 Gy (five patients), dimethylbusulfan alone (one patient), and dimethylbusulfan or busulfan plus cyclophosphamide (20 patients). One patient died before engraftment of infection and 18 died after engraftment from veno-occlusive disease (4), infection (2), idiopathic pneumonia (3), cytomegalovirus pneumonia (3), leukemia (5) and encephalopathy (1). Seven patients (27%) survive 12-38 months (median 26); five (19%) are disease-free and two have recurrent leukemia. Two of the five disease-free survivors have chronic graft-versus-host disease. All of the surviving patients received dimethylbusulfan or busulfan plus cyclophosphamide and six of the seven surviving patients were among 11 patients transplanted more than 2 years after the first transplant whereas only one was among the 15 transplanted in less than 2 years. Those who have second marrow transplants one or more years after their initital transplant are more likely to benefit, while those who are less than 1 year from initial transplant appear to benefit the least.

Authors
Sanders, JE; Buckner, CD; Clift, RA; Fefer, A; McGuffin, R; Storb, R; Appelbaum, F; Bensinger, W; Beatty, P; Doney, K; Durnam, D; Martin, P; Sullivan, K; Stewart, P; Witherspoon, RP; Thomas, ED
MLA Citation
Sanders, JE, Buckner, CD, Clift, RA, Fefer, A, McGuffin, R, Storb, R, Appelbaum, F, Bensinger, W, Beatty, P, Doney, K, Durnam, D, Martin, P, Sullivan, K, Stewart, P, Witherspoon, RP, and Thomas, ED. "Second marrow transplants in patients with leukemia who relapse after allogeneic marrow transplantation." Bone Marrow Transplantation 3.1 (1988): 11-19.
PMID
3048466
Source
scival
Published In
Bone Marrow Transplantation
Volume
3
Issue
1
Publish Date
1988
Start Page
11
End Page
19

Ovarian function following marrow transplantation for aplastic anemia or leukemia

One hundred eighty-seven women between 13 and 49 years of age had ovarian function evaluated from 1 to 15 years (median, 4) after marrow transplant for aplastic anemia or leukemia. Among 43 women transplanted for aplastic anemia following 200 mg/kg cyclophosphamide (CY), all 27 < 26 years of age, but only five of 16 > 26 years of age recovered normal ovarian function. Nine of the 43 have had 12 pregnancies, resulting in eight live births, and two elective and two spontaneous abortions. All eight children are normal. Nine of 144 women transplanted for leukemia following 120 mg/kg CY and 9.20 to 15.75 Gy total body irradiation (TBI) recovered ovarian function. Two of these nine have had three pregnancies, resulting in two spontaneous and one elective abortion. The probability of having ovarian failure was 0.35 by 7 years for patients receiving CY alone and was 1.00 at 1 year for patients receiving CY plus TBI (P < .0001). By 7 years after transplant the probabilities of having normal ovarian function were 0.92 after CY alone and 0.24 after CY plut TBI (P < .0001). Multivariate analysis showed that TBI was the only factor significantly influencing ovarian failure and that both TBI and greater patient age at transplant were significantly associated with a decreased probability of recovering normal ovarian function. These data demonstrate that after high-dose CY, recovery of ovarian function occurs in younger women and in a minority of older women, but after CY and TBI, recovery occurs in only a few younger women and none of the older women.

Authors
Sanders, JE; Buckner, CD; Amos, D; Levy, W; Appelbaum, FR; Doney, K; Storb, R; Sullivan, KM; Witherspoon, RP; Thomas, ED
MLA Citation
Sanders, JE, Buckner, CD, Amos, D, Levy, W, Appelbaum, FR, Doney, K, Storb, R, Sullivan, KM, Witherspoon, RP, and Thomas, ED. "Ovarian function following marrow transplantation for aplastic anemia or leukemia." Journal of Clinical Oncology 6.5 (1988): 813-818.
PMID
3130466
Source
scival
Published In
Journal of Clinical Oncology
Volume
6
Issue
5
Publish Date
1988
Start Page
813
End Page
818

Cyclosporine v methotrexate for graft-v-host disease prevention in patients given marrow grafts for leukemia: Long-term follow-up of three controlled trials

One hundred seventy-nine patients with acute nonlymphoblastic leukemia in first remission (n = 75), chronic myelocytic leukemia in chronic or accelerated phase (n = 48) or leukemia in advanced stage (n = 56) were given HLA-identical marrow grafts and randomized to receive methotrexate or cyclosporine for prevention of graft-v-host disease (GVHD). The current report updates the three prospective trials with follow-ups ranging from 3.2 to 6.2 years after marrow grafting. Results were analyzed separately for each individual study and for all three studies combined. Overall, 40% of patients given cyclosporine and 55% of those given methotrexate developed acute GVHD (P = .13); the incidence of chronic GVHD was 42% and 48%, respectively (P = .67). Twenty-two percent of cyclosporine-treated patients and 30% of methotrexate-treated patients developed interstitial pneumonia of any etiology (P =.25), and the figures for cytomegalovirus pneumonia were 18% and 20%, respectively (P = .41). The overall incidence of leukemic relapse was 31% in cyclosporine-treated patients and 36% in methotrexate-treated patients (P = .75). The probabilities of survival for cyclosporine-v-methotrexate-treated patients were comparable for all three study groups: 52% v 48% in patients with acute nonlymphoblastic leukemia (P = .42), 55% v 60% for those with chronic myelocytic leukemia (P = .61), 12% and 12% for those with advanced leukemia (P = .93), and 39% v 38% overall (P = .72). We conclude that cyclosporine and methotrexate are comparable regarding the likelihood of acute/chronic GVHD, interstitial pneumonia, leukemic relapse, and long-term survival.

Authors
Storb, R; Deeg, HJ; Fisher, L; Appelbaum, F; Buckner, CD; Bensinger, W; Clift, R; Doney, K; Irle, C; McGuffin, R; Martin, P; Sanders, J; Schoch, G; Singer, J; Stewart, P; Sullivan, K; Witherspoon, R; Thomas, ED
MLA Citation
Storb, R, Deeg, HJ, Fisher, L, Appelbaum, F, Buckner, CD, Bensinger, W, Clift, R, Doney, K, Irle, C, McGuffin, R, Martin, P, Sanders, J, Schoch, G, Singer, J, Stewart, P, Sullivan, K, Witherspoon, R, and Thomas, ED. "Cyclosporine v methotrexate for graft-v-host disease prevention in patients given marrow grafts for leukemia: Long-term follow-up of three controlled trials." Blood 71.2 (1988): 293-298.
PMID
3276360
Source
scival
Published In
Blood
Volume
71
Issue
2
Publish Date
1988
Start Page
293
End Page
298

HLA-identical marrow transplantation during accelerated-phase chronic myelogenous leukemia: Analysis of survival and remission duration

Results of HLA-identical allogeneic marrow transplantation were analyzed for 66 patients with accelerated-phase chronic myelogenous leukemia (CML). Multivariate proportional hazards regression models were used to determine disease-related and transplant-related factors associated with posttransplant mortality and relapse. The projected 5-year survival rate was estimated at 18% by the product-limit method. The major causes of death were interstitial pneumonia, infection, and relapse. Splenomegaly at initial diagnosis and longer time interval from diagnosis to transplant were associated with decreased overall survival and event-free survival. Sixteen patients have relapsed between 17 and 1,569 days (median, 486) posttransplant. The use of T-cell-depleted marrow and older age of the donor or recipient were associated with an increased probability of leukemic relapse. Ten of the 16 relapses occured among the 15 patients who received T-cell-depleted marrow. The actuarial relapse risk 2.5 years posttransplant was 100% in patients administered T-cell-depleted marrow as compared with 25% in patients administered unmodified marrow. The data in this report emphasize the increased risks and relatively poor results that occur when marrow transplantation is deferred until after signs of acceleration appear. When compared with results for patients who received transplants during chronic phase, the poor results seen here in patients administered unmodified marrow system primarily from increased transplant-related mortality rather than increased relapse risk. The strikingly increased relapse rate associated with the use of T-cell depletion would discourage its use for graft-v-host disease prevention in patients who receive transplants for CML.

Authors
Martin, PJ; Clift, RA; Fisher, LD; Buckner, CD; Hansen, JA; Appelbaum, FR; Doney, KC; Sullivan, KM; Witherspoon, RP; Storb, R; Thomas, ED
MLA Citation
Martin, PJ, Clift, RA, Fisher, LD, Buckner, CD, Hansen, JA, Appelbaum, FR, Doney, KC, Sullivan, KM, Witherspoon, RP, Storb, R, and Thomas, ED. "HLA-identical marrow transplantation during accelerated-phase chronic myelogenous leukemia: Analysis of survival and remission duration." Blood 72.6 (1988): 1978-1984.
PMID
3058233
Source
scival
Published In
Blood
Volume
72
Issue
6
Publish Date
1988
Start Page
1978
End Page
1984

Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants

Results of a previous study suggested that the risk of graft failue after transplantation of HLA-identical T cell-depleted marrow may be influenced by the preparative regimen. Subsequent clinical trials were carried out to clarify this relationship and to determine whether post-transplant immunosuppression could have an effect on graft durability. Two factors were found to be associated with graft failure. Patients with hematologic malignancy given a preparative regimen of cyclophosphamide (120 mg/kg) and 15.75 Gy fractionated total body irradiation (TBI) had a 27% cumulative incidence of graft failure, which was less than the 69% incidence seen previously in patients given cyclophosphamide and 12.0 Gy fractioned TBI (p < 0.05, log-rank test). Patients with acute leukemia had a higher risk of graft failure than patients with chronic myelogenous leukemia (p < 0.005). The incidence of graft failure was not influenced by post-transplant immunosuppression with cyclosporine, methotrexate or a combination of cyclosporine plus methotrexate or by the omission of all post-transplant immunosuppression. Similarly, graft failure was not associated with the complement lot used for marrow treatment, the recovery of BFU-E or CFU-GM, or with the number of nucleated cells or T cells in the graft. The effect of primary diagnosis and the inverse relationship between the amount of pretransplant TBI and the graft failure rate suggested that a host factor may have been involved in a presuably immune-mediated rejection. This observation further leads to the inference that certain T cells present in donor marrow can suppress host immunity or help to maintain function of the graft.

Authors
Martin, PJ; Hansen, JA; Torok-Storb, B; Durnam, D; Przepiorka, D; O'Quigley, J; Sanders, J; Sullivan, KM; Witherspoon, RP; Deeg, HJ; Appelbaum, FR; Stewart, P; Weiden, P; Doney, K; Buckner, CD; Clift, R; Storb, R; Thomas, ED
MLA Citation
Martin, PJ, Hansen, JA, Torok-Storb, B, Durnam, D, Przepiorka, D, O'Quigley, J, Sanders, J, Sullivan, KM, Witherspoon, RP, Deeg, HJ, Appelbaum, FR, Stewart, P, Weiden, P, Doney, K, Buckner, CD, Clift, R, Storb, R, and Thomas, ED. "Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants." Bone Marrow Transplantation 3.5 (1988): 445-456.
PMID
3056552
Source
scival
Published In
Bone Marrow Transplantation
Volume
3
Issue
5
Publish Date
1988
Start Page
445
End Page
456

Transfer of specific immunity in marrow recipients given HLA-mismatched, T cell-depleted, or HLA-identical marrow grafts

The transfer of tetanus toxoid (TT) and diphtheria toxoid (DT) specific immunity was evaluated in 209 short-term (< 120 days postgrafting) and 257 long-term (> 198 days postgrafting) non-boosted recipients after HLA-identical, HLA non-identical and HLA-identical T cell-depleted marrow transplantation. TT or DT immunizations were not given to donors in the 6 months prior to transplant and the recipients received no immunizations post-transplantation. In 209 short-term recipients, 94% and 74% of recipients had detectable anti-TT and anti-DT titers respectively. In long-term recipients, 110 of 210 (52%) who received HLA-identical grafts, 17 of 38 (45%) who received HLA-non-identical grafts, and seven of seven (100%) who received HLA-identical T cell-depleted grafts had anti-TT titers; and 86 of 212 (40%) who received HLA-identical grafts, 11 of 38 (29%) who received HLA-non-identical grafts, and four of seven (57%) received HLA-identical T cell-depleted grafts had anti-DT titers. When compared to non-boosted normal donor and control subjects, the magnitudes of anti-TT and anti-DT titers from the recipients were comparable to controls. These data show that transferred specific immunity is detectable in long-term recipients of T-cell-depleted or HLA-non-identical grafts without immunizations of donors or recipients before or after transplantation.

Authors
Lum, LG; Noges, JE; Beatty, P; Martin, PJ; Deeg, J; Doney, KC; Loughran, T; Sullivan, KM; Witherspoon, RP; Thomas, ED; Storb, R
MLA Citation
Lum, LG, Noges, JE, Beatty, P, Martin, PJ, Deeg, J, Doney, KC, Loughran, T, Sullivan, KM, Witherspoon, RP, Thomas, ED, and Storb, R. "Transfer of specific immunity in marrow recipients given HLA-mismatched, T cell-depleted, or HLA-identical marrow grafts." Bone Marrow Transplantation 3.5 (1988): 399-406.
PMID
3056548
Source
scival
Published In
Bone Marrow Transplantation
Volume
3
Issue
5
Publish Date
1988
Start Page
399
End Page
406

Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: Prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation

We conducted a randomized, double-blind comparison of prednisone and placebo (group I) v prednisone and azathioprine (1.5 mg/kg/day) (group II) as early treatment of extensive chronic graft-v-host disease (GVHD). Patients with platelet counts <100,000/μL were placed into therapy with prednisone alone (group III). All three groups received identical doses of prednisone (1 mg/kg every other day) and one double-strength trimethoprim-sulfamethoxazole (TMP-SMX) tablet twice daily. Between January 1980 and December 1983, 179 previously untreated patients were enrolled and 164 were evaluable. Patients randomized to group I (n = 63) and group II (n = 63) were well matched for prognostic factors; those placed into group III (n = 38) had more frequent acute GVHD and progressive onset of chronic GVHD. Median duration of therapy was 2 years. Complications included diabetes (5%), aseptic necrosis (5%) and infection. For groups I, II, and III, the respective incidence of infection was disseminated varicella, 11%, 24%, 34%; bacteremia, 6%, 11%, 34%; and interstitial pneumonia, 5%, 14%, 18%. Recurrent malignancy was the most frequent cause of death and did not differ significantly across the groups. Nonrelapse mortality, however, did differ: 21% in group I, 40% in group II, and 58% in group III (I v II, P = .003, I v III, P = .001). Forty patients in group I, 30 in group II, and 10 in group III survive with a minimum follow-up of 3.8 years. Karnofsky performance scores for 68 survivors are 90% to 100%, scores for seven survivors are 70% to 89% and scores for five survivors are <70%. Actuarial survival at 5 years after transplant is 61% in group I, 47% in group II, and 26% in group III (I v II, P = .03; I v III, P = .0001). Treatment with prednisone alone results in fewer infections and better survival than prednisone and azathioprine in standard-risk chronic GVHD. Treatment with prednisone alone is less effective in high-risk patients with thrombocytopenia, and other strategies are required.

Authors
Sullivan, KM; Witherspoon, RP; Storb, R; Weiden, P; Flournoy, N; Dahlberg, S; Deeg, HJ; Sanders, JE; Doney, KC; Appelbaum, FR; McGuffin, R; McDonald, GB; Meyers, J; Schubert, MM; Gauvreau, J; Shulman, HM; Sale, GE; Anasetti, C; Loughran, TP
MLA Citation
Sullivan, KM, Witherspoon, RP, Storb, R, Weiden, P, Flournoy, N, Dahlberg, S, Deeg, HJ, Sanders, JE, Doney, KC, Appelbaum, FR, McGuffin, R, McDonald, GB, Meyers, J, Schubert, MM, Gauvreau, J, Shulman, HM, Sale, GE, Anasetti, C, and Loughran, TP. "Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: Prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation." Blood 72.2 (1988): 546-554.
PMID
3042041
Source
scival
Published In
Blood
Volume
72
Issue
2
Publish Date
1988
Start Page
546
End Page
554

Predictive facts and prevention of acute graft-versus-host disease: The Seattle experience

Authors
Storb, R; Anasetti, C; Appelbaum, FR; Beatty, P; Deeg, HJ; Doney, K; Martin, P; Sullivan, K; Witherspoon, R; Thomas, ED
MLA Citation
Storb, R, Anasetti, C, Appelbaum, FR, Beatty, P, Deeg, HJ, Doney, K, Martin, P, Sullivan, K, Witherspoon, R, and Thomas, ED. "Predictive facts and prevention of acute graft-versus-host disease: The Seattle experience." Bone Marrow Transplantation 3.SUPPL. 1 (1988): 7-10.
Source
scival
Published In
Bone Marrow Transplantation
Volume
3
Issue
SUPPL. 1
Publish Date
1988
Start Page
7
End Page
10

Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease

Therapy of chronic graft-v-host disease (GVHD) has been unsatisfactory in patients with platelet counts <100,000/μL. Surival at 5 years after marrow transplant is only 26% in such patients treated with trimethoprim-sulfamethoxazole (TMP-SMX) and every other day with prednisone. Since October 1982, 61 patients with high-risk extensive chronic GVHD were treated with a new alternating-day regimen of prednisone (1 mg/kg every other day) and oral cyclosporine (6 mg/kg every 12 hours every other day) with one double-strength TMP-SMX tablet twice daily. Forty patients (group I) received primary treatment of thrombocytopenic chronic GVHD (median platelet count 35 [range 7 to 87] x 103/μL). Twenty-one patients (group II) received salvage treatment after failing initial prednisone ± azathioprine. Twenty-one patients in group I and 15 in group II survive with a minimum of 2 years and a median of 3.7 years follow-up. At 4 years after transplant, actuarial survival is 51% (group I) and 67% (group II). Causes of death included interstitial pneumonia (six), relapse (five), GVHD without infection (five), infection (four), organ failure (three), and hemorrhage (two). Mortality increased with the progressive type onset of chronic GVHD and treatment failure. Toxicity included hypertension (13), nephrotoxicity (nine), nausea (seven), aseptic necrosis (five), neurologic abnormalities (four), and diabetes (three). Median cyclosporine levels at four and 36 hours were 296 and 64 ng/mL, respectively. Four patients required permanent discontinuation of cyclosporine, but none required renal dialysis. Karnofsky performance scores for 25 survivors are 90% to 100%, scores for six survivors are 70% to 89%, and scores for five survivors are <70%. Alternating-day cyclosporine and prednisone has acceptable toxicity and appears to improve survival in patients with high-risk chronic GVHD.

Authors
Sullivan, KM; Witherspoon, RP; Storb, R; Deeg, HJ; Dahlberg, S; Sanders, JE; Appelbaum, FR; Doney, KC; Weiden, P; Anasetti, C; Loughran, TP; Hill, R; Shields, A; Yee, G; Shulman, H; Nims, J; Strom, S; Thomas, ED
MLA Citation
Sullivan, KM, Witherspoon, RP, Storb, R, Deeg, HJ, Dahlberg, S, Sanders, JE, Appelbaum, FR, Doney, KC, Weiden, P, Anasetti, C, Loughran, TP, Hill, R, Shields, A, Yee, G, Shulman, H, Nims, J, Strom, S, and Thomas, ED. "Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease." Blood 72.2 (1988): 555-561.
PMID
3042042
Source
scival
Published In
Blood
Volume
72
Issue
2
Publish Date
1988
Start Page
555
End Page
561

Use of thymic grafts or thymic factors to augment immunologic recovery after bone marrow transplantation: Brief report with 2 to 12 years' follow-up

Thymus tissue implants, thymic epithelial cells obtained from third party donors sharing one HLA-A and -B locus with the recipient, or the thymic hormones thymosin fraction 5 and thymopentin were given to recipients of HLA-identical sibling bone marrow to prevent chronic graft-versus-host disease (GVHD) and accelerate immunologic reconstitution. The clinical courses of 17 patients receiving thymus tissue and 18 patients receiving thymic hormones were reported initially 5 years ago and showed no difference in the incidence of chronic GVHD or immunologic recovery from those of concurrent or historical controls. We report here for the first time nine new patients who received thymus tissue implants with modifications of the culture method to lower the number of lymphocytes in the transplanted tissue with the intent of reducing rejection of the thymus tissue grafts. The clinical outcomes and immunologic functions of these nine patients were similar to those of the recipients of the earlier thymus tissue implants. With follow-up now ranging from 2.2 to 12.3 years (median 6.7) for the total group, 16 patients are alive. Seven never developed chronic GVHD. Nine were treated for chronic GVHD, seven of whom recovered and are leading normal lives, one has chronic pulmonary insufficiency, and one is disabled from chronic GVHD. We conclude that thymus tissue grafts or thymic epithelial cells partially HLA-matched to the recipient, thymosin fraction 5, or thymopentin used as described were not effective in reducing the incidence of chronic GVHD, improving immunologic recovery or altering long-term survival.

Authors
Witherspoon, RP; Sullivan, KM; Lum, LG; Goehle, S; Atkinson, MK; Ochs, HD; Doney, KC; Hansen, JA; Sanders, JE; Storb, R
MLA Citation
Witherspoon, RP, Sullivan, KM, Lum, LG, Goehle, S, Atkinson, MK, Ochs, HD, Doney, KC, Hansen, JA, Sanders, JE, and Storb, R. "Use of thymic grafts or thymic factors to augment immunologic recovery after bone marrow transplantation: Brief report with 2 to 12 years' follow-up." Bone Marrow Transplantation 3.5 (1988): 425-435.
PMID
3056551
Source
scival
Published In
Bone Marrow Transplantation
Volume
3
Issue
5
Publish Date
1988
Start Page
425
End Page
435

Graft-versus-host disease: allo- and autoimmunity after bone marrow transplantation.

Authors
Shulman, HM; Sullivan, KM
MLA Citation
Shulman, HM, and Sullivan, KM. "Graft-versus-host disease: allo- and autoimmunity after bone marrow transplantation." Concepts in immunopathology 6 (1988): 141-165.
PMID
3292049
Source
scival
Published In
Concepts in immunopathology
Volume
6
Publish Date
1988
Start Page
141
End Page
165

The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation.

The results are presented of allogeneic transplantation for 363 patients with acute non-lymphoblastic leukemia treated in Seattle from May 1973 through December 1985. The probabilities of surviving disease-free for 5 years for patients transplanted in first remission, in second remission, in untreated first relapse or in chemotherapy-resistant first relapse were 46%, 28%, 30%, and 21%, respectively. The corresponding probabilities of relapse within 5 years were 25%, 37%, 36% and 56%, respectively. Prognostic factors predictive of survival after marrow transplantation for patients transplanted in first remission included age, donor sex and the number of circulating blasts at the time of diagnosis. Acute graft-versus-host disease (GVHD) had a major adverse effect on survival, but chronic GVHD decreased the risk of relapse for patients transplanted in first remission.

Authors
Clift, RA; Buckner, CD; Thomas, ED; Kopecky, KJ; Appelbaum, FR; Tallman, M; Storb, R; Sanders, J; Sullivan, K; Banaji, M
MLA Citation
Clift, RA, Buckner, CD, Thomas, ED, Kopecky, KJ, Appelbaum, FR, Tallman, M, Storb, R, Sanders, J, Sullivan, K, and Banaji, M. "The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation." Bone Marrow Transplantation 2.3 (1987): 243-258.
PMID
3332174
Source
scival
Published In
Bone Marrow Transplantation
Volume
2
Issue
3
Publish Date
1987
Start Page
243
End Page
258

Transfusion effect on graft-versus-host disease and leukemic relapse in HLA-matched bone marrow transplantation.

Authors
Gast, GCD; Beatty, PG; Amos, D; Sullivan, K; Anderson, JE; Thomas, ED; Hansen, JA
MLA Citation
Gast, GCD, Beatty, PG, Amos, D, Sullivan, K, Anderson, JE, Thomas, ED, and Hansen, JA. "Transfusion effect on graft-versus-host disease and leukemic relapse in HLA-matched bone marrow transplantation." Transplantation proceedings 19.1 Pt 3 (1987): 2700--.
PMID
3274581
Source
scival
Published In
Transplantation proceedings
Volume
19
Issue
1 Pt 3
Publish Date
1987
Start Page
2700-

The effect of prophylactic intravenous immune globulin on the incidence of septicemia in marrow transplant recipients.

Ninety-seven patients randomized to receive (45 patients) or not to receive (52 patients) intravenous cytomegalovirus immune globulin before and after allogeneic marrow transplantation were evaluated retrospectively for the occurrence of bacterial and fungal septicemia in the first 100 days post-transplant. In a proportional hazards regression test, infection prevention regimens, immunoglobulin administration, age and occurrence of acute graft-versus-host disease were tested simultaneously for the occurrence of septicemia in the pre- and post-engraftment period. Of these factors, only patients receiving immunoglobulin had significantly fewer episodes of septicemia following engraftment with 11 (26%) patients in the globulin group having 14 episodes compared to 22 (42%) patients in the control group having 27 episodes (p = 0.039). None of the patients experienced complications with the immunoglobulin infusions. These results suggest that the administration of intravenous immunoglobulin may be a practical and effective method to decrease the incidence of septicemia following marrow transplantation.

Authors
Petersen, FB; Bowden, RA; Thornquist, M; Meyers, JD; Buckner, CD; Counts, GW; Nelson, N; Newton, BA; Sullivan, KM; McIver, J
MLA Citation
Petersen, FB, Bowden, RA, Thornquist, M, Meyers, JD, Buckner, CD, Counts, GW, Nelson, N, Newton, BA, Sullivan, KM, and McIver, J. "The effect of prophylactic intravenous immune globulin on the incidence of septicemia in marrow transplant recipients." Bone Marrow Transplantation 2.2 (1987): 141-147.
PMID
2844338
Source
scival
Published In
Bone Marrow Transplantation
Volume
2
Issue
2
Publish Date
1987
Start Page
141
End Page
147

Immunoglobulin therapy in bone marrow transplantation

Following ablative treatment with supralethal doses of chemotherapy and total body irradiation, patients demonstrate multiple immunologic deficiencies after bone marrow transplantation. Immune function usually recovers and the risk of infection decreases within six to 12 months. However, patients in whom chronic graft-versus-host disease (GVHD) develops have persisting B and T cell abnormalities, and in vivo and in vitro studies show impaired immunoglobulin regulation and function despite normal levels of serum immunoglobulin G. This review summarizes 12 published clinical trials of immunoglobulin therapy to correct immunodeficiency and prevent infection after marrow grafting. In five controlled studies, cytomegalovirus infection developed in a total of 52 of 172 (30 percent) immunoglobulin recipients and 71 of 165 (43 percent) control patients not given globulin. In four controlled trials, interstitial pneumonia developed in a total of 21 of 127 (17 percent) immunoglobulin recipients and 40 of 94 (43 percent) control patients. Three randomized trials reported a reduced rate of GVHD or post-engraftment septicemia in immunoglobulin recipients. However, methods of immunoglobulin preparation, antibody titer, and dose and schedule of prophylaxis varied widely in these studies, as did other critical patient, transplant regimen, and supportive care factors. Accordingly, data should be interpreted with caution. Ongoing controlled clinical trials will further define the proper role of immunoglobulin therapy in bone marrow transplantation. © 1987.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Immunoglobulin therapy in bone marrow transplantation." The American Journal of Medicine 83.4 SUPPL. 1 (1987): 34-45.
PMID
2823602
Source
scival
Published In
The American Journal of Medicine
Volume
83
Issue
4 SUPPL. 1
Publish Date
1987
Start Page
34
End Page
45

Marrow transplantation for patients with acute lymphoblastic leukemia in first marrow remission

Forty-six patients with acute lymphoblastic leukemia (ALL) in first marrow remission underwent allogeneic marrow transplantation between August 1976 and June 1985. Thirty-four patients had no extramedullary disease after remission induction and 12 had extramedullary relapses prior to or at the time of marrow grafting. The conditioning regimen included cyclophosphamide followed by total body irradiation, 9.2-15.75 Gy, administered as a single dose or in six or seven daily fractions. Marrow donors were genotypically HLA-identical siblings. Methotrexate was given as prophylaxis for graft-versus-host disease (GVHD). Forty-four patients had marrow engraftment. The incidence of grades II-IV acute GVHD was 52%. Clinical chronic GVHD occurred in 21 patients. Eighteen patients are alive 1-9 years (median = 4.2 years) after marrow grafting, 15 of whom are in continuous complete remission. The estimates probability of relapse within 2 years (± standard error) is 41±9% and the probability of relapse-free survival at 5 years is 28±7%. Major causes of death were recurrent leukemia, acute GVHD and interstitial pneumonia. Actuarial probabilities of survival, relapse and disease-free survival were not significantly different between those patients who did and those who did not have extramedullary disease after attaining first marrow remission.

Authors
Doney, K; Buckner, CD; Kopecky, KJ; Sanders, JE; Appelbaum, FR; Clift, R; Sullivan, K; Witherspoon, R; Storb, R; Thomas, ED
MLA Citation
Doney, K, Buckner, CD, Kopecky, KJ, Sanders, JE, Appelbaum, FR, Clift, R, Sullivan, K, Witherspoon, R, Storb, R, and Thomas, ED. "Marrow transplantation for patients with acute lymphoblastic leukemia in first marrow remission." Bone Marrow Transplantation 2.4 (1987): 355-363.
PMID
3332183
Source
scival
Published In
Bone Marrow Transplantation
Volume
2
Issue
4
Publish Date
1987
Start Page
355
End Page
363

Risk factors for airflow obstruction in recipients of bone marrow transplants

Obstructive lung disease is a complication of bone marrow transplantation. To identify risk factors we analyzed pulmonary function tests of 281 adult patients 1 year after marrow transplantation. The forced expiratory volume at 1 second divided by the forced vital capacity (FEV1/FVC) was used to measure airflow rates. Factors associated with a lower year-1 FEV1/FVC (%) included increased age (p<0.0001), male gender (p=0.02), cigarette smoking (p=0.01), lower FEV1/FVC before transplantation (p<0.0001), HLA-nonincidental grafts (p=0.001), chronic graft-versus-host disease (p=0.0002), and immunosuppressive therapy with methotrexate (p=0.01). There was no significant association between the year-1 FEV1/FVC and underlying disease, dose of conditioning irradiation, or development of acute graft-versus-host disease. Linear multivariate regression analysis, after controlling for the FEV1/FVC before transplantation, shows both chronic graft-versus-host disease and administration of methotrexate independently associated with decrements in the year-1 FEV1/FVC. The combined occurrence of chronic graft-versus-host disease and methotrexate also was strongly associated with decreases in the year-1 FEV1/FVC, indicating an interaction of these risk factors.

Authors
Clark, JG; Schwartz, DA; Flournoy, N; Sullivan, KM; Crawford, SW; Thomas, ED
MLA Citation
Clark, JG, Schwartz, DA, Flournoy, N, Sullivan, KM, Crawford, SW, and Thomas, ED. "Risk factors for airflow obstruction in recipients of bone marrow transplants." Annals of Internal Medicine 107.5 (1987): 648-656.
PMID
3310793
Source
scival
Published In
Annals of Internal Medicine
Volume
107
Issue
5
Publish Date
1987
Start Page
648
End Page
656

Treatment of malignant lymphoma in 100 patients with chemotherapy, total body irradiation and marrow transplantation

Between July 1970 and January 1985, 100 patients with malignant lymphoma were treated with high-dose chemoradiotherapy and bone marrow transplantation. Twenty-eight of the 100 are alive and the actuarial probability of disease-free survival 5 years from transplantation is 22%. The most common reason for treatment failure was disease recurrence, with an actuarial probability of 60%. A proportional hazards regression analysis showed that the likelihood of disease-free survival was less in those patients transplanted in resistant relapse and in those previously treated with chest radiotherapy. Neither disease histology (Hodgkin's disease, high-grade lymphoma or intermediate-grade lymphoma), nor source of marrow (syngeneic, allogeneic, or autologous) significantly influenced either disease-free survival or probability of relapse. The use of high-dose chemoradiotherapy and marrow transplantation appears to offer a better chance for long-term survival than any other form of therapy for young patients with disseminated malignant lymphoma whose disease has progressed after initial combination chemotherapy. The best results with marrow transplantation were obtained in patients transplanted in early relapse or second remission who had not received prior chest radiotherapy.

Authors
Appelbaum, FR; Sullivan, KM; Buckner, CD; Clift, RA; Deeg, HJ; Fefer, A; Hill, R; Mortimer, J; Neiman, PE; Sanders, JE; Singer, J; Stewart, P; Storb, R; Thomas, ED
MLA Citation
Appelbaum, FR, Sullivan, KM, Buckner, CD, Clift, RA, Deeg, HJ, Fefer, A, Hill, R, Mortimer, J, Neiman, PE, Sanders, JE, Singer, J, Stewart, P, Storb, R, and Thomas, ED. "Treatment of malignant lymphoma in 100 patients with chemotherapy, total body irradiation and marrow transplantation." Journal of Clinical Oncology 5.9 (1987): 1340-1347.
PMID
3305793
Source
scival
Published In
Journal of Clinical Oncology
Volume
5
Issue
9
Publish Date
1987
Start Page
1340
End Page
1347

Prophylactic use of human leukocyte interferon after allogeneic marrow transplantation

Study Objective: To determine the efficacy of prophylactic interferon for prevention of cytomegalovirus infection and relapse of leukemia after allogeneic marrow transplantation. Design: Randomized trial with intermittent interferon administration to day 80 after transplantation. Setting: Marrow transplantation units of a cancer research center. Patients: Consecutive patients with acute lymphocytic leukemia in remission at the time of transplantation. Thirty-nine patients received interferon, and 40 were control patients. Interventions: Partially purified human leukocyte interferon given every 3 days beginning after marrow engraftment and continuing to day 80 after transplantation. After initial safety testing, the starting and minimum dose was 6 x 104 units/kg of body weight, with dose escalations determined by the circulating neutrophil count. Transplant conditioning and post-transplantation prophylaxis of graft-versus-host disease with methotrexate followed standard procedures. Measurements and Main Results: No difference was observed in the probability or severity of cytomegalovirus infection or in the probability or severity of graft-versus-host disease. Relapse of leukemia occurred in 9 interferon recipients and 21 control patients, with a minimum follow-up of 4 years among surviving patients. The probability of relapse among all interferon recipients was 0.36 (95% confidence interval [CI], 0.56 to 0.17) and among all control patients was 0.74 (95% CI, 0.91 to 0.58) (p = 0.04 by log-rank test). Among patients who received transplants in first or second remission, the probability of relapse among interferon recipients was 0.19 (95% CI, 0.37 to 0.02) compared with 0.71 (95% CI, 0.97 to 0.51) among control patients (p = 0.008 by log-rank test). Survival rates did not differ between interferon recipients and control patients. Transient decreases in leukocyte count and anorexia and nausea occurred among interferon recipients. Six interferon recipients, all of whom had received chemoradiotherapy of the central nervous system before transplantation, developed leukoencephalopathy after transplantation. Conclusions: These data suggest that interferon given after transplantation reduces the risk for subsequent relapse of leukemia. The effect of longer administration and of administration in patients with other underlying diseases will require additional trials. No effect was observed on cytomegalovirus infection, either because interferon was not initiated until a median of 18 days after transplantation or because of a lesser effect among marrow allograft recipients.

Authors
Meyers, JD; Flournoy, N; Sanders, JE; McGuffin, RW; Newton, BA; Fisher, LD; Lum, LG; Appelbaum, FR; Doney, K; Sullivan, KM; Storb, R; Buckner, CD; Thomas, ED
MLA Citation
Meyers, JD, Flournoy, N, Sanders, JE, McGuffin, RW, Newton, BA, Fisher, LD, Lum, LG, Appelbaum, FR, Doney, K, Sullivan, KM, Storb, R, Buckner, CD, and Thomas, ED. "Prophylactic use of human leukocyte interferon after allogeneic marrow transplantation." Annals of Internal Medicine 107.6 (1987): 809-816.
PMID
2825571
Source
scival
Published In
Annals of Internal Medicine
Volume
107
Issue
6
Publish Date
1987
Start Page
809
End Page
816

Adoptively transferred immunity persists in human marrow graft recipients.

This study was designed to determine if antibodies (Abs) to recall antigens (Ags) were produced after bone marrow transplantation (BMT). Sera from marrow recipients (recipients) were tested for Abs to recall Ags post-grafting, and T and B cells from recipients were tested for their ability to produce anti-tetanus toxoid antibody (anti-TT) using in vitro biosynthesis assays. Neither the donors nor recipients received booster immunizations with recall Ags before or after BMT. Serum Ab titers to tetanus toxoid (TT), diphtheria toxoid (DT), and measles virus (MV) were in the normal range for the majority of 235 short-term recipients (less than 100 days postgrafting) and for the majority of 149 long-term (greater than 6 months postgrafting) recipients. Anti-TT was produced in vitro by peripheral blood lymphocytes (PBL) from 6 of 14 long-term recipients after TT stimulation. In another system, purified B cells from 9 of 21 long-term recipients also produced anti-TT after Epstein-Barr virus (EBV) stimulation. The presence of Ab titers to TT, DT, and MV in the serum of recipients and the production of in vitro anti-TT by T and B cells from recipients show that Ag-specific memory was transferred via the marrow inoculum. These data show that adoptively transferred immunity persists in recipients for years postgrafting.

Authors
Lum, LG; Seigneuret, MC; Shiobara, S; Noges, J; Munn, N; Shough, N; Jin, NR; Beatty, P; Martin, P; Sullivan, K
MLA Citation
Lum, LG, Seigneuret, MC, Shiobara, S, Noges, J, Munn, N, Shough, N, Jin, NR, Beatty, P, Martin, P, and Sullivan, K. "Adoptively transferred immunity persists in human marrow graft recipients." Progress in clinical and biological research 244 (1987): 449-460.
PMID
2821549
Source
scival
Published In
Progress in clinical and biological research
Volume
244
Publish Date
1987
Start Page
449
End Page
460

Second marrow transplants in patients with aplastic anemia rejecting the first graft: Use of a conditioning regimen including cyclophosphamide and antithymocyte globulin

Sixteen (11%) of 146 consecutive patients with severe aplastic anemia prepared for engraftment with cyclophosphamide (200 mg/kg) rejected marrow grafts from their HLA-identical siblings. They were given a second marrow transplant from either the same (n = 13) or a second (n = 3) HLA-identical sibling between 23 and 743 (median 86) days after the first transplant. The preparation for the second transplant included cyclophosphamide, 50 mg/kg, on each of four successive days. Twelve hours after each of the first three doses of cyclophosphamide, antithymocyte globulin, 30 mg/kg/dose, was infused. One of the 16 patients died from infection too early after the second transplant to be evaluated, two have failure of engraftment and died with infection, one rejected the second graft and is surviving almost 5 years later with full autologous marrow recovery, and 12 had successful and sustained second grafts. Of these 12, six are surviving between 11 months and 7 3/4 years. Four of the six had no graft-v-host disease (GVHD), while two have chronic GVHD requiring treatment. Five have Karnofsky scores of 100% and one of 90%. Six of the 12 patients with sustained grafts died between 63 days and 38 months after transplantation, four with infections (related in two patients to chronic GVHD), one with acute GVHD, and one with hemorrhage. The average interval from first to second transplant was 308 days during the past five years, compared to 61 days in earlier patients. Five of seven recent patients are surviving, compared to two of nine earlier patients. In conclusion, successful second transplants after cyclophosphamide and antithymocyte globulin are possible in most patients with aplastic anemia who have rejected their first marrow grafts; however, mortality remains high, with only 40% of the patients becoming long-term survivors.

Authors
Storb, R; Weiden, PL; Sullivan, KM; Appelbaum, FR; Beatty, P; Buckner, CD; Clift, RA; Doney, KC; Hansen, J; Martin, PJ
MLA Citation
Storb, R, Weiden, PL, Sullivan, KM, Appelbaum, FR, Beatty, P, Buckner, CD, Clift, RA, Doney, KC, Hansen, J, and Martin, PJ. "Second marrow transplants in patients with aplastic anemia rejecting the first graft: Use of a conditioning regimen including cyclophosphamide and antithymocyte globulin." Blood 70.1 (1987): 116-121.
PMID
3297199
Source
scival
Published In
Blood
Volume
70
Issue
1
Publish Date
1987
Start Page
116
End Page
121

Graft versus leukemia effect in man: the relapse rate of acute leukemia is lower after allogeneic than after syngeneic marrow transplantation.

To determine whether allogeneic bone marrow transplantation (BMT) is associated with a graft vs leukemia (GVL) effect in man, the relapse rate of acute leukemia after allogeneic BMT was compared with that occurring after syngeneic (genetically identical twin) BMT. The patients had ALL or ANL in second or subsequent complete remission (CR) or in relapse. The allogeneic and syngeneic marrow recipients were comparable in diagnosis, age, and interval from diagnosis to BMT and received comparable chemoradiotherapy regimens. Allogeneic marrow recipients, however, received, in addition, GVH disease prophylaxis, most often methotrexate and, more recently, cyclosporine or both. All patients treated by the Seattle team from 1970-1986 are included. Leukemic recurrence was observed in 62% of 785 allogeneic recipients and 75% of 53 syngeneic recipients (p less than 0.0001). The results confirm the circumstantial evidence for a GVL effect exerted by allogeneic marrow. Analyses are in progress to determine whether a GVL effect exists in subsets of patients as a function of their particular diagnosis or status at the time of BMT.

Authors
Fefer, A; Sullivan, KM; Weiden, P; Buckner, CD; Schoch, G; Storb, R; Thomas, ED
MLA Citation
Fefer, A, Sullivan, KM, Weiden, P, Buckner, CD, Schoch, G, Storb, R, and Thomas, ED. "Graft versus leukemia effect in man: the relapse rate of acute leukemia is lower after allogeneic than after syngeneic marrow transplantation." Progress in clinical and biological research 244 (1987): 401-408.
PMID
3310002
Source
scival
Published In
Progress in clinical and biological research
Volume
244
Publish Date
1987
Start Page
401
End Page
408

Graft-versus-leukemia in man: relationship of acute and chronic graft-versus-host disease to relapse of acute leukemia following allogeneic bone marrow transplantation.

To study the effect of acute and chronic graft-versus-host disease (GVHD) on recurrent leukemia, we analysed data on patients with acute leukemia receiving allogeneic marrow transplants in Seattle between 1970 and 1986. Four hundred fifty-four patients survived in remission 150 days after HLA-identical transplant and 114 currently survive five to fifteen years after marrow grafting. At the time of transplant, 252 patients had acute nonlymphocytic leukemia in remission or relapse and 202 had acute lymphocytic leukemia in remission or relapse. According to Kaplan-Meier estimates, recurrence of leukemia following transplantation was observed in 28% of patients developing moderate to severe (grade II-IV) acute GVHD and 48% of patients with no or mild (grade O-I) acute GVHD (p = 0.0028). Relapse was observed in 34% of patients developing clinical extensive chronic GVHD and 45% of patients free of chronic GVHD (p = 0.0001). The incidence of recurrent leukemia was 28% in recipients developing both acute and chronic GVHD and 52% in patients free of both acute and chronic GVHD (p = 0.0001). These data confirm an apparent graft-versus-leukemia effect in patients developing GVHD after allogeneic marrow grafting. Current studies are aimed at determining the influence of such apparent adoptive immunotherapy within the different categories of leukemia and methods to manipulate and augment the clinical benefit of this observation.

Authors
Sullivan, KM; Fefer, A; Witherspoon, R; Storb, R; Buckner, CD; Weiden, P; Schoch, G; Thomas, ED
MLA Citation
Sullivan, KM, Fefer, A, Witherspoon, R, Storb, R, Buckner, CD, Weiden, P, Schoch, G, and Thomas, ED. "Graft-versus-leukemia in man: relationship of acute and chronic graft-versus-host disease to relapse of acute leukemia following allogeneic bone marrow transplantation." Progress in clinical and biological research 244 (1987): 391-399.
PMID
3310001
Source
scival
Published In
Progress in clinical and biological research
Volume
244
Publish Date
1987
Start Page
391
End Page
399

Marrow transplantation for acute nonlymphocytic leukemia following therapy for Hodgkin's disease

Authors
Sargur, M; Buckner, CD; Appelbaum, FR; Stewart, P; Deeg, HJ; Weiden, PL; Sullivan, KM; Fefer, A; Thomas, ED
MLA Citation
Sargur, M, Buckner, CD, Appelbaum, FR, Stewart, P, Deeg, HJ, Weiden, PL, Sullivan, KM, Fefer, A, and Thomas, ED. "Marrow transplantation for acute nonlymphocytic leukemia following therapy for Hodgkin's disease." Journal of Clinical Oncology 5.5 (1987): 731-734.
PMID
3553436
Source
scival
Published In
Journal of Clinical Oncology
Volume
5
Issue
5
Publish Date
1987
Start Page
731
End Page
734

Direct ultrastructural evidence of target-directed polarization by cytotoxic lymphocytes in lesions of human graft-vs-host disease

Cytotoxic lymphocytes are thought to kill target cells by means of potent cytotoxic granules that congregate near the microtubular organizing center and the Golgi apparatus at one pole of the killer cell. We searched for evidence of this type of polarization in 12 lip biopsy specimens from patients with acute and/or chronic graft-vs-host disease (GVHD) compared with two lip specimens from normal individuals. Lymphocytes with such polarization were found in contact with epithelial cells of the squamous mucosa in all 12 cases of GVHD, and cells of the cuboidal minor salivary duct epithelium were found in two of 11 evaluable cases. The data add support to the hypothesis that cytolytic lymphocytes attack epithelial cells in GVHD.

Authors
Sale, GE; Gallucci, BB; Schubert, MM; Sullivan, KM; Thomas, ED
MLA Citation
Sale, GE, Gallucci, BB, Schubert, MM, Sullivan, KM, and Thomas, ED. "Direct ultrastructural evidence of target-directed polarization by cytotoxic lymphocytes in lesions of human graft-vs-host disease." Archives of Pathology and Laboratory Medicine 111.4 (1987): 333-336.
PMID
3493751
Source
scival
Published In
Archives of Pathology and Laboratory Medicine
Volume
111
Issue
4
Publish Date
1987
Start Page
333
End Page
336

Treatment of aplastic anemia with antithymocyte globulin, high-dose corticosteroids, and androgens

A total of 46 patients with aplastic anemia (34 severe; 12 moderate) were treated with antihuman thymocyte globulin (ATG), high-dose methylprednisolone, and oxymetholone. Early symptoms of ATG toxicity included fever, rash, and bronchospasm. Signs of serum sickness also developed in 23 patients. Complications associated with high doses of steroids were hyperglycemia, hypertension, fluid retention, gastrointestinal hemorrhage, and aseptic necrosis of the hip. Other morbidity possibly associated with steroid administration included seizures, arrhythmias, and headache with papilledema. Studies of elevated liver function necessitated discontinuation of androgen therapy in eight patients. A complete or partial hematological response was noted in 19 patients (41%). Of these, three have had recurrent cytopenias, of whom one has developed a myelodysplastic syndrome. There are currently 34 patients surviving, and 12 who have died. Actuarial survival at three years is 65%. These response and survival data are comparable to those of previous trials usig ATG and androgens without high-dose steroids. A prospective, randomized trial is needed to determine whether the addition of high-dose corticosteroids to ATG does significantly increase the rate and frequency of response in order to justify the toxicity of this additional immunosuppressive therapy in the treatment of aplastic anemia.

Authors
Doney, K; Storb, R; Buckner, CD; McGuffin, R; Witherspoon, R; Deeg, HJ; Appelbaum, FR; Sullivan, KM; Thomas, ED
MLA Citation
Doney, K, Storb, R, Buckner, CD, McGuffin, R, Witherspoon, R, Deeg, HJ, Appelbaum, FR, Sullivan, KM, and Thomas, ED. "Treatment of aplastic anemia with antithymocyte globulin, high-dose corticosteroids, and androgens." Experimental Hematology 15.3 (1987): 239-242.
PMID
3493172
Source
scival
Published In
Experimental Hematology
Volume
15
Issue
3
Publish Date
1987
Start Page
239
End Page
242

Treatment of marrow graft recipients with thymopentin

Authors
Witherspoon, RP; Navari, R; Storb, R; Sullivan, KM; Doney, K; Beatty, P; Lum, LG; Thomas, ED
MLA Citation
Witherspoon, RP, Navari, R, Storb, R, Sullivan, KM, Doney, K, Beatty, P, Lum, LG, and Thomas, ED. "Treatment of marrow graft recipients with thymopentin." Bone Marrow Transplantation 1.4 (1987): 365-371.
PMID
3332144
Source
scival
Published In
Bone Marrow Transplantation
Volume
1
Issue
4
Publish Date
1987
Start Page
365
End Page
371

Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia.

We treated 93 patients who had acute nonlymphoblastic leukemia in the first remission or chronic myelocytic leukemia in the chronic phase (median age, 30 years) with high-dose cyclophosphamide and fractionated total-body irradiation, followed by infusion of marrow from an HLA-identical sibling. To evaluate postgrafting prophylaxis for graft versus host disease, we studied these patients in a sequential, prospective, randomized trial that compared the effect of a combination of methotrexate and cyclosporine (n = 43) with that of cyclosporine alone (n = 50). All patients had evidence of sustained engraftment. A significant reduction in the cumulative incidence of grades II to IV acute graft versus host disease was observed in the patients who received both methotrexate and cyclosporine (33 percent), as compared with those who were given cyclosporine alone (54 percent) (P = 0.014). Seven patients who received cyclosporine alone acquired grade IV acute graft versus host disease, as compared with none who received both methotrexate and cyclosporine. Thirty-five of the 43 patients given both methotrexate and cyclosporine and 31 of the 50 patients given cyclosporine are alive as of this writing, at 4 months to 2 years (median, 15 months); the actuarial survival rates in the two groups at 1.5 years were 80 percent and 55 percent, respectively (P = 0.042). We conclude that the combination of methotrexate and cyclosporine is superior to cyclosporine alone in the prevention of acute graft versus host disease after marrow transplantation for leukemia, and that this therapy may have a beneficial effect on long-term survival.

Authors
Storb, R; Deeg, HJ; Whitehead, J; Appelbaum, F; Beatty, P; Bensinger, W; Buckner, CD; Clift, R; Doney, K; Farewell, V
MLA Citation
Storb, R, Deeg, HJ, Whitehead, J, Appelbaum, F, Beatty, P, Bensinger, W, Buckner, CD, Clift, R, Doney, K, and Farewell, V. "Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia." The New England journal of medicine 314.12 (March 1986): 729-735.
PMID
3513012
Source
epmc
Published In
The New England journal of medicine
Volume
314
Issue
12
Publish Date
1986
Start Page
729
End Page
735
DOI
10.1056/nejm198603203141201

Acute and chronic graft-versus-host disease in man.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Acute and chronic graft-versus-host disease in man." International journal of cell cloning 4 Suppl 1 (January 1986): 42-93. (Review)
PMID
2943828
Source
epmc
Published In
International Journal of Cell Cloning
Volume
4 Suppl 1
Publish Date
1986
Start Page
42
End Page
93

Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation.

Seventy-five patients with acute nonlymphoblastic leukemia (ANL) in first remission were treated with cyclophosphamide, 60 mg/kg on each of two consecutive days followed by total body irradiation (TBI) at an exposure rate of 4-6 cGy/min from two opposing 60Co sources. The first 22 patients were given 9.2 Gy of TBI as a single dose. Subsequently 53 patients were randomized to receive either 10 Gy single dose TBI (n = 27) or 6 x 2 Gy fractionated TBI (n = 26). All patients received marrow transplants from HLA-identical siblings and all had sustained engraftment. Patients given 10 Gy of TBI had more early toxicity, especially veno-occlusive disease of the liver, than patients given 9.2 or 6 x 2 Gy of TBI. Idiopathic interstitial pneumonitis appeared to be more frequent in patients given 9.2 or 10 Gy single-dose TBI than in patients given 6 x 2 Gy fractionated TBI. Patients have now been followed from 5 to 9 years. Survival (+/- 95% confidence limits) at 5 years is 54 +/- 31% among patients given 9.2 Gy single dose TBI, 33 +/- 31% among patients given 10 Gy single dose TBI, and 54 +/- 26% among patients given 6 x 2 Gy fractionated TBI (P = 0.04). These results indicate that about half the patients with ANL transplanted while in first chemotherapy-induced remission can be expected to become long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Deeg, HJ; Sullivan, KM; Buckner, CD; Storb, R; Appelbaum, FR; Clift, RA; Doney, K; Sanders, JE; Witherspoon, RP; Thomas, ED
MLA Citation
Deeg, HJ, Sullivan, KM, Buckner, CD, Storb, R, Appelbaum, FR, Clift, RA, Doney, K, Sanders, JE, Witherspoon, RP, and Thomas, ED. "Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation." Bone Marrow Transplantation 1.2 (1986): 151-157.
PMID
3332129
Source
scival
Published In
Bone Marrow Transplantation
Volume
1
Issue
2
Publish Date
1986
Start Page
151
End Page
157

Acute and chronic graft-versus-host disease in man

Allogeneic bone marrow transplantation offers the hope of cure of heretofore untreatable diseases. Graft-versus-host disease is a complication of this medical progress and impedes application of marrow grafting to a wider range of hematologic disorders. It also presents the physician with complex clinical problems not even described in previous years. New knowledge of the immunopathogenesis of acute and chronic GVHD has been derived. The data assist the investigator in understanding control of the immune response and discrimination between self and non-self. Improvements in the diagnosis, supportive care and immunosuppressive prophylaxis and treatment of GVHD have been described over the last decade. Continuation and consolidation of these incremental advances hold promise for considerable progress in the control of graft-versus-host disease in man.

Authors
Sullivan, KM
MLA Citation
Sullivan, KM. "Acute and chronic graft-versus-host disease in man." International Journal of Cell Cloning 4.SUPPL. 1 (1986): 42-93.
Source
scival
Published In
International Journal of Cell Cloning
Volume
4
Issue
SUPPL. 1
Publish Date
1986
Start Page
42
End Page
93

Second marrow infusion for poor graft function after allogeneic marrow transplantation

Authors
Bolger, GB; Sullivan, KM; Storb, R; Witherspoon, RP; Weiden, PL; Stewart, P; Sanders, J; Meyers, JD; Martin, PJ; Doney, KC
MLA Citation
Bolger, GB, Sullivan, KM, Storb, R, Witherspoon, RP, Weiden, PL, Stewart, P, Sanders, J, Meyers, JD, Martin, PJ, and Doney, KC. "Second marrow infusion for poor graft function after allogeneic marrow transplantation." Bone Marrow Transplantation 1.1 (1986): 21-30.
PMID
3332116
Source
scival
Published In
Bone Marrow Transplantation
Volume
1
Issue
1
Publish Date
1986
Start Page
21
End Page
30

Hyperacute graft-v-host disease in patients not given immunosuppression after allogeneic marrow transplantation

Sixteen patients with leukemia in relapse or second to third remission, 5 to 27 years old (median, 17), were given cyclophosphamide (60 mg/kg x 2) and total body irradiation (2.25 Gy for each of seven days) followed by unmodified marrow grafts from HLA-identical siblings. Patients did not receive posttransplant immunosuppression and were followed a median of nine months (range, 5-17). Prompt engraftment was sustained in 12 patients with a median time of 16 days (range, 10 to 63) to achieve 500 neutrophils/mm3. One patient failed to engraft, one had delayed engraftment, and two had late poor graft function. All 15 with engraftment developed moderate to life-threatening graft-v-host disease (GVHD, eight grade II and seven grade III-IV). This syndrome was hyperacute (median onset eight days [range, 7 to 29] posttransplant) and manifest by severe skin disease (14 patients at stage 3 and one at stage 4), fever (ten patients), and liver (four patients, stage 3-4) or gut (four patients, stage 3-4) involvement. Serial tissue biopsies confirmed acute GVHD in 13 of 15 patients. Ten were treated with antithymocyte globulin and cyclosporine (four survive), and four with corticosteroids (two survive). Actuarial survival to 17 months was 37%. Causes of death included interstitial pneumonia (four), infection (three), graft failure (one), venocclusive disease (one), and relapse of leukemia (one). Age-matched controls receiving standard methotrexate after transplant had comparable relapse-free survival but only a 25% incidence of grade II-IV acute GVHD (P < .0001). We conclude that deleting posttransplant immunosuppression is associated with frequent and severe hyperacute GVHD, infectious complications, and occasional poor graft function.

Authors
Sullivan, KM; Deeg, HJ; Sanders, J; Klosterman, A; Amos, D; Shulman, H; Sale, G; Martin, P; Witherspoon, R; Appelbaum, F
MLA Citation
Sullivan, KM, Deeg, HJ, Sanders, J, Klosterman, A, Amos, D, Shulman, H, Sale, G, Martin, P, Witherspoon, R, and Appelbaum, F. "Hyperacute graft-v-host disease in patients not given immunosuppression after allogeneic marrow transplantation." Blood 67.4 (1986): 1172-1175.
PMID
3513869
Source
scival
Published In
Blood
Volume
67
Issue
4
Publish Date
1986
Start Page
1172
End Page
1175

Intestinal and hepatic complications of human bone marrow transplantation. Part II

Authors
McDonald, GB; Shulman, HM; Sullivan, KM; Spencer, GD
MLA Citation
McDonald, GB, Shulman, HM, Sullivan, KM, and Spencer, GD. "Intestinal and hepatic complications of human bone marrow transplantation. Part II." Gastroenterology 90.3 (1986): 770-784.
PMID
3510940
Source
scival
Published In
Gastroenterology
Volume
90
Issue
3
Publish Date
1986
Start Page
770
End Page
784

Intestinal and hepatic complications of human bone marrow transplantation. Part I

Authors
McDonald, GB; Shulman, HM; Sullivan, KM; Spencer, GD
MLA Citation
McDonald, GB, Shulman, HM, Sullivan, KM, and Spencer, GD. "Intestinal and hepatic complications of human bone marrow transplantation. Part I." Gastroenterology 90.2 (1986): 460-477.
PMID
3510147
Source
scival
Published In
Gastroenterology
Volume
90
Issue
2
Publish Date
1986
Start Page
460
End Page
477

Early and late interstitial pneumonia following human bone marrow transplantation

Interstitial pneumonia is a major determinant of early and late morbidity and mortality following bone marrow transplantation. Among 952 patients receiving allogeneic marrow grafts in Seattle, 35% developed interstitial pneumonia within 100 days of transplant. Development of early cytomegalovirus (CMV) or idiopathic interstitial pneumonia was infrequent in patients with aplastic anemia prepared only with cyclophosphamide. Use of total body irradiation (TBI) in the transplant preparation, increasing patient age, pretransplant seropositivity for CMV antibody and post-transplant development of graft-versus-host disease (GVHD) all increased the risk of CMV pneumonia. Late interstitial pneumonia was studied in patients with chronic GVHD. Among 198 patients with extensive chronic GVHD, 31 episodes of interstitial pneumonia (seven idiopathic, six CMV, six pneumocystis, five miscellaneous and four unknown causes, and three varicella-zoster) were observed 3-24 months after transplant. In untreated patients with chronic GVHD, 15% developed late interstitial pneumonia. Patients with chronic GVHD who received prednisone ± azathioprine as immunosuppressive therapy and trimethoprim sulfamethoxazole for infection prophylaxis had an 8% incidence of interstitial pneumonia. Patients with chronic GVHD given immunosuppressive treatment without trimethoprim sulfamethoxazole prophylaxis had a 28% incidence of interstitial pneumonia. Trimethoprim sulfamethoxazole significantly reduced the incidence of late interstitial pneumonia in patients with chronic GVHD (p = 0.001).

Authors
Sullivan, KM; Meyers, JD; Flournoy, N; Storb, R; Thomas, ED
MLA Citation
Sullivan, KM, Meyers, JD, Flournoy, N, Storb, R, and Thomas, ED. "Early and late interstitial pneumonia following human bone marrow transplantation." International Journal of Cell Cloning 4.SUPPL. 1 (1986): 107-121.
PMID
3018098
Source
scival
Published In
International Journal of Cell Cloning
Volume
4
Issue
SUPPL. 1
Publish Date
1986
Start Page
107
End Page
121

Antithymocyte globulin followed by cyclosporine for the treatment of acute GVHD in patients given HLA-identical or -nonidentical marrow grafts

Graft-v-host disease (GVHD) remains a major complication after allogeneic marrow transplantation. Between 30% and 60% of patients given unmanipulated marrow from an HLA-identical sibling donor and 80% of patients transplanted from an HLA-nonidentical donor and given postgrafting immunosuppression with a single agent develop acute GVHD requiring therapy. We carried out a study in which patients with acute GVHD were given ATG followed by CsA with or without the addition of MP. Two thirds of patients responded to therapy, and long-term survival was better than in patients treated in the past with single-agent therapy. This report presents follow-up data on the patient population observed now for 15 to 30 months after transplantation.

Authors
Deeg, HJ; Doney, K; Sullivan, KM
MLA Citation
Deeg, HJ, Doney, K, and Sullivan, KM. "Antithymocyte globulin followed by cyclosporine for the treatment of acute GVHD in patients given HLA-identical or -nonidentical marrow grafts." Transplantation Proceedings 18.4 (1986): 791-793.
Source
scival
Published In
Transplantation Proceedings
Volume
18
Issue
4
Publish Date
1986
Start Page
791
End Page
793

Myasthenia gravis after allogeneic bone marrow transplantation: Relationship to chronic graft-versus-host disease

Three patients with chronic graft-versus-host disease (GVHD) developed myasthenia gravis (MG) 762 to 1,180 days after allogeneic bone marrow transplantation. Symptoms of MG were observed after taper or discontinuation of immunosuppressive treatment of chronic GVHD. All patients developed antibodies to acetylcholine receptor, and one had antibody formation to striated muscle. One patient died of complications of treatment of MG. The severity of disease underscores the importance of the differential diagnosis and the need for prompt therapy of this late complication after human bone marrow transplantation.

Authors
Bolger, GB; Sullivan, KM; Spence, AM; Appelbaum, FR; Johnston, R; Sanders, JE; Deeg, HJ; Witherspoon, RP; Doney, KC; Nims, J
MLA Citation
Bolger, GB, Sullivan, KM, Spence, AM, Appelbaum, FR, Johnston, R, Sanders, JE, Deeg, HJ, Witherspoon, RP, Doney, KC, and Nims, J. "Myasthenia gravis after allogeneic bone marrow transplantation: Relationship to chronic graft-versus-host disease." Neurology 36.8 (1986): 1087-1091.
PMID
3526178
Source
scival
Published In
Neurology
Volume
36
Issue
8
Publish Date
1986
Start Page
1087
End Page
1091

Selection of patients with Hodgkin's disease and non-Hodgkin's lymphoma for bone marrow transplantation

Despite substantial progress in curative therapy of malignant lymphomas, some patients fail current treatment and die of refractory disease. Although high-dose chemotherapy and supralethal total body irradiation followed by bone marrow transplantation may salvage and cure a proportion of these refractory patients, treatment of such end-stage patients with marrow grafting often fails because of resistant disease or transplant-related complications. Using the analogy of transplantation in the early phases of acute and chronic leukemias, results of marrow transplant in Hodgkin's disease and non-Hodgkin's lymphoma might be improved if performed earlier in the course of the malignancy. The following collaborative report by the Seattle and Stanford groups examines current results of conventional lymphoma therapy to define subgroups of patients with 'high-risk' lymphoma from whom early marrow transplant might be offered to control otherwise incurable disease.

Authors
Sullivan, KM; Appelbaum, FR; Horning, SJ; Rosenberg, SA; Thomas, ED
MLA Citation
Sullivan, KM, Appelbaum, FR, Horning, SJ, Rosenberg, SA, and Thomas, ED. "Selection of patients with Hodgkin's disease and non-Hodgkin's lymphoma for bone marrow transplantation." International Journal of Cell Cloning 4.SUPPL. 1 (1986): 94-106.
PMID
3528333
Source
scival
Published In
International Journal of Cell Cloning
Volume
4
Issue
SUPPL. 1
Publish Date
1986
Start Page
94
End Page
106

Decreased incidence of marrow graft rejection in patients with severe aplastic anemia: Changing impact of risk factors

Patients with severe aplastic anemia were conditioned with cyclophosphamide (200 mg/kg) and given marrow grafts from HLA-identical family members. Among 233 patients transplanted, 225 survied ≥14 days and could be evaluated for engraftment. Forty-four of the 225 rejected their graft; 33 of these died and 11 survive. One hundred eighty-one patients had sustained engraftment; of these, 46 died and 135 survived. Binary logistic regression analyses revealed five risk factors for graft rejection: (a) year of transplant, (b) a large number of platelet transfusions, (c) a positive relative response in mixed leukocyte culture, (d) a low marrow cell dose, and (e) omission of donor buffy coat cell infusion for transfused patients. These data show that patients transplanted recently had a lower likelihood of graft rejection than did patients transplanted in earlier years. Conceivably, this was related to changes in transfusion practices, but other factors as yet unidentified are likely to be involved. The data confirm that the largest possible number of marrow cells should be transplanted. Although the difference in the incidence of graft rejection between untransfused and transfused patients was not significant, it should be noted that transfused patients were given buffy coat cells. Because the addition of buffy coat cells results in a higher incidence of chronic graft-v-host disease (GVHD), its is still desirable to transplant patients with marrow alone early in their course before they have been transfused.

Authors
Deeg, HJ; Self, S; Storb, R; Doney, K; Appelbaum, FR; Witherspoon, RP; Sullivan, KM; Sheehan, K; Sanders, J; Mickelson, E
MLA Citation
Deeg, HJ, Self, S, Storb, R, Doney, K, Appelbaum, FR, Witherspoon, RP, Sullivan, KM, Sheehan, K, Sanders, J, and Mickelson, E. "Decreased incidence of marrow graft rejection in patients with severe aplastic anemia: Changing impact of risk factors." Blood 68.6 (1986): 1363-1368.
PMID
3535930
Source
scival
Published In
Blood
Volume
68
Issue
6
Publish Date
1986
Start Page
1363
End Page
1368

Marrow transplantation for severe aplastic anemia. Long-term outcome in fifty 'untransfused' patients

Fifty patients with severe aplastic anemia had no transfusions of blood products until just before marrow transplantation from HLA-identical family members. Of the 50, 42 are still alive 1 to 12 years after transplantation (median, 7 years). By actuarial standards, the 10-year probability of survival is 82%. Of the 42 surviving patients, 37 have Karnofsky performance status scores of 100% and 5 with chronic graft-versus-host disease have scores ranging form 50% to 90% (median, 80%). The 8 deaths were caused by early infection in 1, graft rejection in 1, acute graft-versus-host disease in 3, and chronic graft-versus-host disease in 3. All deaths occurred within two years after transplantation. The incidence of graft failure was 10%. Acute graft-versus-host disease developed in 14 of 44 patients at risk and chronic graft-versus-host disease, in 15 of 41. Risk factors for development of chronic graft-versus-host disease included increased age (p=0.008) and presence of acute graft-versus-host disease (p=0.001). The only factor associated with increased risk of death was development of acute graft-versus-host disease (p=0.05). Results of this study extend our previous findings that patients with severe aplastic anemia who have transplants before the onset of transfusion-induced sensitization have an excellent probability of long-term survival and a normal life.

Authors
Anasetti, C; Doney, KC; Storb, R; Meyers, JD; Farewell, VT; Buckner, CD; Appelbaum, FR; Sullivan, KM; Clift, RA; Deeg, HJ
MLA Citation
Anasetti, C, Doney, KC, Storb, R, Meyers, JD, Farewell, VT, Buckner, CD, Appelbaum, FR, Sullivan, KM, Clift, RA, and Deeg, HJ. "Marrow transplantation for severe aplastic anemia. Long-term outcome in fifty 'untransfused' patients." Annals of Internal Medicine 104.4 (1986): 461-466.
PMID
3006565
Source
scival
Published In
Annals of internal medicine
Volume
104
Issue
4
Publish Date
1986
Start Page
461
End Page
466

Bone marrow transplantation in patients aged 45 years and older

Increasing age has been reported to be a poor prognostic factor for survival after bone marrow transplantation. We evaluated causes of death and frequency and type of complications after marrow grafting in 24 syngeneic and 39 allogeneic recipients who were 45 to 68 years old at the time of transplant. Most patients were in an advanced stage of hematologic malignancy. Among patients given syngeneic transplants, actuarial disease-free survival at 7 years is 20%. The major causes of death were relapse of leukemia and idiopathic interstitial pneumonia. Among allogeneic recipients, 9 (23%) are currently alive, and actuarial disease-free survival at 7 years is 11%. Cytomegalovirus pneumonia and septicemia were the most frequent causes of death. Patients over 50 years of age had the poorest survival rate (1/13), but many of these were transplanted in an advanced stage of their disease. However, among 12 patients transplanted while in remission or at an early stage of their disease, 5 are surviving 65 to 1,160 days after transplantation, with an actuarial survival rate of 22% at 3 years. This is in contrast to those who received their transplant in relapse: 2 out of 20 patients (10%) became long-term survivors, with a probability of survival of 15% at 3 years. The actuarial incidence of grade II through IV acute graft-v-host disease (GVHD) was 30% for allogeneic recipients 45 to 50 years of age. This was not significantly different from the incidence in younger patients. In patients 51 to 62 years of age, the actuarial incidence of acute GVHD was 79%; however, this group included three partially HLA-mismatched transplants. Ten of 15 patients surviving at least 3 months developed chronic GVHD. These results suggest that marrow transplantation is feasible and should be considered in patients over 45 years, especially if recipients are in good clinical condition and are at an early stage of their disease, such as the chronic phase of chronic myelogenous leukemia and preleukemia. For patients more than 50 years of age, allogeneic marrow grafting cannot presently be considered first-line therapy.

Authors
Klingemann, H-G; Storb, R; Fefer, A; Deeg, HJ; Appelbaum, FR; Buckner, CD; Cheever, MA; Greenberg, PD; Stewart, PS; Sullivan, KM
MLA Citation
Klingemann, H-G, Storb, R, Fefer, A, Deeg, HJ, Appelbaum, FR, Buckner, CD, Cheever, MA, Greenberg, PD, Stewart, PS, and Sullivan, KM. "Bone marrow transplantation in patients aged 45 years and older." Blood 67.3 (1986): 770-776.
PMID
3511986
Source
scival
Published In
Blood
Volume
67
Issue
3
Publish Date
1986
Start Page
770
End Page
776

Severe aplastic anemia associated with chronic mucocutaneous candidiasis. Immunologic and hematologic reconstitution after allogeneic bone marrow transplantation

Chronic mucocutaneous candidiasis (CMC) is typically associated with the inability of T lymphocytes to proliferate and produce lymphokines in response to Candida antigen. A 7-year-old girl with CMC developed severe aplastic anemia and, after conditioning with cyclophosphamide, 200 mg/kg, underwent bone marrow transplantation from her HLA-identical sister. Engraftment was prompt and complete. The patient is surviving more than 3 years after transplantation with normal donor-derived hemopoiesis and immune function. Manifestations of CMC have resolved completely and she has not received antifungal therapy for more than 2 years.

Authors
Deeg, HJ; Lum, LG; Sanders, J; Levy, GJ; Sullivan, KM; Beatty, P; Thomas, ED; Storb, R
MLA Citation
Deeg, HJ, Lum, LG, Sanders, J, Levy, GJ, Sullivan, KM, Beatty, P, Thomas, ED, and Storb, R. "Severe aplastic anemia associated with chronic mucocutaneous candidiasis. Immunologic and hematologic reconstitution after allogeneic bone marrow transplantation." Transplantation 41.5 (1986): 583-586.
PMID
3518164
Source
scival
Published In
Transplantation
Volume
41
Issue
5
Publish Date
1986
Start Page
583
End Page
586

Development of bullous pemphigoid after allogeneic bone marrow transplantation: Report of a case

Authors
Ueda, M; Mori, T; Shiobara, S; Harada, M; Yoshida, T; Matsuda, T; Hattori, K; Mizoguchi, H; Sullivan, KM; Witherspoon, RP
MLA Citation
Ueda, M, Mori, T, Shiobara, S, Harada, M, Yoshida, T, Matsuda, T, Hattori, K, Mizoguchi, H, Sullivan, KM, and Witherspoon, RP. "Development of bullous pemphigoid after allogeneic bone marrow transplantation: Report of a case." Transplantation 42.3 (1986): 320-322.
PMID
3529534
Source
scival
Published In
Transplantation
Volume
42
Issue
3
Publish Date
1986
Start Page
320
End Page
322

Growth and development following marrow transplantation for leukemia

One hundred forty-two patients between the ages of 1 and 17 years who survived disease-free more than 1 year after marrow transplantation for hematologic malignancy had growth and development evaluations from one to 14 years posttransplant (median 4 years). Prior to transplant all children received multiagent chemotherapy and 55 also received central nervous system irradiation, but none had growth and development evaluations. Marrow transplant preparation included high-dose chemotherapy and total body irradiation (TBI) given as a single dose of 9.2 to 10.0 Gy (79 patients) or as fractionated doses of 2.0 to 2.25 Gy/d for six to seven days (63 patients). After transplant abnormal thyroid function was present in 39%. Stimulated 11-desoxycortisol levels were subnormal in 24% of patients evaluated. Growth hormone (GH) deficiency was present in 17 of 25 children who received previous cranial irradiation. Partial GH deficiency was present in 4 of 25 who received previous cranial irradiation and in 6 of 18 who had not received cranial irradiation. Height velocity was decreased in all patients. After transplant, height was significantly influenced by chronic graft-v-host disease and single-dose TBI. Sixty-eight percent had delayed development of secondary sexual characteristics. Gonadal failure occurred in nearly all who were postpubertal at transplant. While it is not possible to determine how many of these endocrine abnormalities occurred as a result of treatment administered prior to transplantation, these data do demonstrate that children who become long-term survivors after marrow transplantation for hematologic malignancy have endocrine abnormalities that adversely affect growth and development.

Authors
Sanders, JE; Pritchard, S; Mahoney, P; Amos, D; Buckner, CD; Witherspoon, RP; Deeg, HJ; Doney, KC; Sullivan, KM; Appelbaum, FR
MLA Citation
Sanders, JE, Pritchard, S, Mahoney, P, Amos, D, Buckner, CD, Witherspoon, RP, Deeg, HJ, Doney, KC, Sullivan, KM, and Appelbaum, FR. "Growth and development following marrow transplantation for leukemia." Blood 68.5 (1986): 1129-1135.
PMID
3533180
Source
scival
Published In
Blood
Volume
68
Issue
5
Publish Date
1986
Start Page
1129
End Page
1135

Infection with varicella-zoster virus after marrow transplantation

Infection with varicella-zoster virus (VZV) occurred in 231 (16.6%) of 1,394 patients undergoing marrow transplantation in Seattle, Washington, between 1969 and 1982. The probability of VZV infection was 30% by one year after transplant. Eighty percent of infections occurred within the first nine months after transplant, and of these cases 45% had cutaneous or visceral dissemination. Twenty-three deaths were associated with VZV infection, all within the initial nine months after transplant. Postherpetic neuralgia, scarring, and bacterial superinfection were also significantly more frequent among patients with VZV in the first nine months after transplant (32%) than among patients with later infection (19%; P < .05). By multivariate analysis, allogeneic transplant, acute or chronic graft-vs.-host disease, patient age between 10 and 29 years, diagnosis other than chronic myelogenous leukemia, and posttransplant use of antithymocyte globulin were each risk factors for VZV infection. Among infected patients, the only significant risk factor for VZV dissemination or death was acute graft-vs.-host disease (P < .03 and P < .0002, respectively).

Authors
Locksley, RM; Flournoy, N; Sullivan, KM; Meyers, JD
MLA Citation
Locksley, RM, Flournoy, N, Sullivan, KM, and Meyers, JD. "Infection with varicella-zoster virus after marrow transplantation." Journal of Infectious Diseases 152.6 (1985): 1172-1181.
PMID
3905982
Source
scival
Published In
Journal of Infectious Diseases
Volume
152
Issue
6
Publish Date
1985
Start Page
1172
End Page
1181

Allogeneic marrow transplantation in the treatment of MOPP-resistant Hodgkin's disease

Eight patients with disseminated Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Two patients remain alive in unmaintained complete remission (CR) at 38 and 39 months after transplant. In the other six patients, reasons for failure included relapse of lymphoma (two patients), or death due to complications of the transplant procedure, including Legionnaire's disease, disseminated zoster, graft-v-host disease, and aspiration pneumonia secondary to severe mucositis. These results demonstrate that some patients with MOPP-resistant Hodgkin's disease can obtain prolonged CR following intensive chemoradiotherapy and allogeneic marrow transplantation.

Authors
Appelbaum, FR; Sullivan, KM; Thomas, ED; Buckner, CD; Clift, RA; Deeg, HJ; Neiman, PE; Sanders, JE; Stewart, P; Storb, R
MLA Citation
Appelbaum, FR, Sullivan, KM, Thomas, ED, Buckner, CD, Clift, RA, Deeg, HJ, Neiman, PE, Sanders, JE, Stewart, P, and Storb, R. "Allogeneic marrow transplantation in the treatment of MOPP-resistant Hodgkin's disease." Journal of Clinical Oncology 3.11 (1985): 1490-1494.
PMID
2414410
Source
scival
Published In
Journal of Clinical Oncology
Volume
3
Issue
11
Publish Date
1985
Start Page
1490
End Page
1494

Mycobacterial pulmonary infections after allogeneic bone marrow transplantation.

Authors
Sullivan, KM; Meyers, JD; Clark, J
MLA Citation
Sullivan, KM, Meyers, JD, and Clark, J. "Mycobacterial pulmonary infections after allogeneic bone marrow transplantation." American Journal of Medicine 79.1 (1985): A107-A120.
PMID
3893120
Source
scival
Published In
American Journal of Medicine
Volume
79
Issue
1
Publish Date
1985
Start Page
A107
End Page
A120

Treatment of acute graft-versus-host disease after allogeneic marrow transplantation. Randomized study comparing corticosteroids and cyclosporine

Seventy-seven patients (age 12 to 46 years) who underwent allogeneic marrow transplantation for hematologic malignancy or aplastic anemia and who had grade II to IV acute graft-versus-host disease despite methotrexate prophylaxis were randomly assigned to receive methylprednisolone 2 mg/kg per day intravenously (n = 39) or cyclosporine (n = 38) either 12 to 15 mg/kg per day orally or 3 to 5 mg/kg per day intravenously. In both groups, clinical and histologic evidence of graft-versus-host disease was detected at medians of 16 and 25 days, respectively. Drugs were given for a minimum of 14 days unless significant deterioration occurred. If graft-versus-host disease did not improve with this therapy, treatment with a second agent was Initiated. Treatment responses were scored after reviewing clinical and laboratory data collected before, during, and after the 14-day treatment period. Possible scores were as follows: -1, worse; 0, no change; +1, improvement in one organ system (skin, liver, gut) with no deterioration in the other two; +2, complete resolution of all Involved systems. The median response score among 39 methylprednisolone-treated patients was 0. Sixteen patients (41 percent) showed response to treatment, 11 with partial and five with complete response. The median response score among 38 cyclosporine-treated patients was +1. Twenty-three patients (61 percent) showed response to treatment, 15 with partial and eight with complete response (p = 0.039). Twenty patients receiving methylprednisolone and 18 receiving cyclosporine required additional therapy. The incidence of chronic graft-versus-host disease was similar In both groups. It developed in all nonresponding patients at risk who had received secondary therapy. Among responding patients (scores +1 or +2) who were not given additional treatment, chronic graft-versus-host disease developed in eight of 11 (72 percent) receiving methylprednisolone and five of ten (50 percent) receiving cyclosporine. Survival beyond 17 months was similar In the two groups (28 percent and 24 percent, respectively). These data suggest that cyclosporine is a useful agent for the treatment of acute graft-versus-host disease, comparable in its efficacy to methylprednisolone. © 1985.

Authors
Kennedy, MS; Deeg, HJ; Storb, R; Doney, K; Sullivan, KM; Witherspoon, RP; Appelbaum, FR; Stewart, P; Sanders, J; Buckner, CD; Martin, P; Weiden, P; Thomas, ED
MLA Citation
Kennedy, MS, Deeg, HJ, Storb, R, Doney, K, Sullivan, KM, Witherspoon, RP, Appelbaum, FR, Stewart, P, Sanders, J, Buckner, CD, Martin, P, Weiden, P, and Thomas, ED. "Treatment of acute graft-versus-host disease after allogeneic marrow transplantation. Randomized study comparing corticosteroids and cyclosporine." The American Journal of Medicine 78.6 PART 1 (1985): 978-983.
PMID
3893112
Source
scival
Published In
The American Journal of Medicine
Volume
78
Issue
6 PART 1
Publish Date
1985
Start Page
978
End Page
983

Marrow transplantation for leukemia following fractionated total body irradiation. A comparative trial of methotrexate and cyclosporine

Fifty-six patients, 30-47 yr of age, with leukemia in relapse received allogeneic marrow transplants from HLA-identical siblings. All patients were treated with cyclophosphamide (120 mg/kg) and 7 daily fractions of 2.25 Gy of total body irradiation (TBI) for seven consecutive days. Nine patients (16%) are currently alive and free of disease 324-845 days from transplantation. The actuarial relapse and survival rates at 2 yr were 56% and 9.5% respectively. These data were not remarkably different from those in previous studies using 10 Gy of TBI administered as a single dose. Thirty patients were randomized to receive methotrexate (MTX) and 26 to receive cyclosporine (CSP) as postgrafting prophylaxis for acute graft-versus-host disease (GVHD). The probability of developing significant acute GVHD by day 100 post-transplant was 71% for patients in the MTX group and 45% for patients in the CSP group (p < 0.05). The probability of relapse was 37% for patients in the MTX group and 70% for patients in the CSP group (p < 0.05). Transplant-related deaths were more frequent in the MTX group and leukemic deaths were more frequent in the CSP group although this may have been related to an uneven distribution of high-risk patients. Long-term disease-free survival was comparable. Patients in the MTX group had more severe mucositis, more alveolar pneumonias and possibly more deaths due to complications of acute and chronic GVHD. Patients in the CSP group had a higher incidence of hypertension, neurological complications and renal dysfunction. © 1985.

Authors
Irle, C; Deeg, HJ; Buckner, CD; Kennedy, M; Clift, R; Storb, R; Appelbaum, FR; Beatty, P; Bensinger, W; Doney, K; Cheever, M; Fefer, A; Greenberg, P; Hill, R; Martin, P; McGuffin, R; Sanders, J; Stewart, P; Sullivan, K; Witherspoon, R; Thomas, ED
MLA Citation
Irle, C, Deeg, HJ, Buckner, CD, Kennedy, M, Clift, R, Storb, R, Appelbaum, FR, Beatty, P, Bensinger, W, Doney, K, Cheever, M, Fefer, A, Greenberg, P, Hill, R, Martin, P, McGuffin, R, Sanders, J, Stewart, P, Sullivan, K, Witherspoon, R, and Thomas, ED. "Marrow transplantation for leukemia following fractionated total body irradiation. A comparative trial of methotrexate and cyclosporine." Leukemia Research 9.10 (1985): 1255-1261.
PMID
3906282
Source
scival
Published In
Leukemia Research
Volume
9
Issue
10
Publish Date
1985
Start Page
1255
End Page
1261

Graft versus host disease-related secretory immunoglobulin A deficiency in bone marrow transplant recipients. Findings in labial saliva

Graft versus host disease dependent decreases in salivary IgA levels were sought in labial gland saliva samples from bone marrow transplant recipients. Transplantation-associated, irradiation-related effects were also present, but these could be avoided if analyses were performed at 1 year or later after transplantation. Sampling of minor gland saliva eliminated the possibility of contamination with IgA-rich serum transudates arising from gingival or mucosal pathways which obscured results from previous studies using whole saliva samples. Patients with active extensive clinical disease had significantly depressed levels of salivary IgA. Since labial saliva is a principal source of total salivary IgA, the present findings may explain why patients with graft versus host disease are susceptible to infection via the sinobronchial portal.

Authors
Izutsu, KT; Menard, TW; Schubert, MM; Ensign, WY; Sullivan, K; Truelove, EL; Thomas, ED
MLA Citation
Izutsu, KT, Menard, TW, Schubert, MM, Ensign, WY, Sullivan, K, Truelove, EL, and Thomas, ED. "Graft versus host disease-related secretory immunoglobulin A deficiency in bone marrow transplant recipients. Findings in labial saliva." Laboratory Investigation 52.3 (1985): 292-297.
PMID
3883055
Source
scival
Published In
Laboratory Investigation
Volume
52
Issue
3
Publish Date
1985
Start Page
292
End Page
297

Treatment of human acute graft-versus-host disease with antithymocyte globulin and cyclosporine with or without methylprednisolone

Forty-eight patients with hematologic malignancies treated by allogeneic marrow transplantation developed acute graft-versus-host disease (GVHD), grades II-IV, despite prophylaxis with methotrexate. They were treated with a combination of antithymocyte globulin (ATG) and cyclosporine (CsA), with or without the addition of methylprednisolone (MP). Thirty patients had received HLA-identical and 18 HLA-nonidentical transplants. Median onset of GVHD was day 13 (range 8-60) for patients with HLA-nonidentical grafts and day 18 (range 7-48) for patients given HLA-identical grafts (P = 0.01). Forty-five patients could be evaluated for response on day 7 of therapy. Among these, 13 of 27 given ATG/CSP and 6 of 18 given ATG/CSP/MP improved. Among 33 patients evaluable on day 14 of therapy 13 of 19 given ATG/CSP and 5 of 14 given ATG/CSP/MP showed improvement of GVHD. Patients given HLA-nonidentical grafts responded somewhat (although not significantly) less frequently than patients given HLA-identical grafts. Chronic GVHD developed in 16 of 18 evaluable patients given ATG/CSP and in 5 of 6 given ATG/CSP/MP. Viral, bacterial, and fungal infections were the major cause of death in both groups. Interstitial pneumonitis was more frequent among patients given ATG/CSP/MP. Survival beyond 6 months was 67% among patients treated with ATG/CSP and 25% with ATG/CSP/MP. These data indicate that a regimen of ATG/CSP is of value in the treatment of acute GVHD. The addition of MP was not beneficial and resulted in decreased survival - presumably because of excessive immunosuppression and associated complications.

Authors
Deeg, HJ; Jr, TPL; Storb, R; Kennedy, MS; Sullivan, KM; Doney, K; Appelbaum, FR; Thomas, ED
MLA Citation
Deeg, HJ, Jr, TPL, Storb, R, Kennedy, MS, Sullivan, KM, Doney, K, Appelbaum, FR, and Thomas, ED. "Treatment of human acute graft-versus-host disease with antithymocyte globulin and cyclosporine with or without methylprednisolone." Transplantation 40.2 (1985): 162-166.
PMID
3895622
Source
scival
Published In
Transplantation
Volume
40
Issue
2
Publish Date
1985
Start Page
162
End Page
166

Marrow transplant experience in children with acute lymphoblastic leukemia: An analysis of factors associated with survival, relapse, and graft-versus-host disease

One hundred fourteen children with acute lymphoblastic leukemia were treated with allogeneic marrow transplantation from HLA-identical siblings after conditioning with cyclophosphamide and total body irradiation. Methotrexate was given posttransplantation for prophylaxis of graft-versus-host disease. The minimum follow-up after transplantation was 2 years. Sixteen of 51 patients transplanted in marrow remission survive from 2.1 to 8.9 years (median 2.7), 13 in continuous remission, one in remission following testicular relapse, and two after marrow relapse. Sixty-three were transplanted in relapse and eight survived 3-10 years (median 5.7), five in continuous remission, and three in remission following testicular relapse. In a multivariate analysis, factors significantly related to increased survival were marrow remission at transplant (p < 0.007) and chronic graft-versus-host disease (p < 0.005). Factors associated with increased relapse were marrow relapse at transplant (p < 0.002) and absence of significant graft-versus-host disease (p < 0.004). The development of acute graft-versus-host disease was associated with high marrow cell doses (p < 0.04). These data suggest that some children with acute lymphoblastic leukemia and a poor prognosis with conventional chemotherapy may be cured with marrow transplantation.

Authors
Sanders, JE; Flournoy, N; Thomas, ED; Buckner, CD; Lum, LG; Clift, RA; Appelbaum, FR; Sullivan, KM; Stewart, P; Deeg, HJ
MLA Citation
Sanders, JE, Flournoy, N, Thomas, ED, Buckner, CD, Lum, LG, Clift, RA, Appelbaum, FR, Sullivan, KM, Stewart, P, and Deeg, HJ. "Marrow transplant experience in children with acute lymphoblastic leukemia: An analysis of factors associated with survival, relapse, and graft-versus-host disease." Medical and Pediatric Oncology 13.4 (1985): 165-172.
PMID
3892260
Source
scival
Published In
Pediatric Blood and Cancer
Volume
13
Issue
4
Publish Date
1985
Start Page
165
End Page
172
DOI
10.1002/mpo.2950130402

Association between cyclosporin neurotoxicity and hypomagnesaemia.

The serum magnesium levels of all 12 allogeneic bone-marrow transplant recipients who experienced the neurotoxic effects of cyclosporin (CyA) were more than two standard deviations below the normal range. The neurological events seemed to segregate into three separate syndromes. 7 patients had grand-mal seizures, which occurred within the first several weeks of CyA therapy (median onset 12 days). At the time of their first seizure all 7 patients had hypomagnesaemia, which had developed rapidly over the preceding 1-3 weeks. 3 patients had four episodes of cerebellar ataxia, tremor, and depression. These subacute episodes developed after prolonged CyA therapy (median onset 67 days). Each episode was associated with hypomagnesaemia. 2 patients had a transient episode of expressive aphasia following a long period of hypomagnesaemia. In all cases symptoms resolved or did not recur with adequate magnesium replacement. These data suggest that CyA neurotoxicity is associated with hypomagnesaemia and may be treated or prevented with magnesium replacement.

Authors
Thompson, CB; June, CH; Sullivan, KM; Thomas, ED
MLA Citation
Thompson, CB, June, CH, Sullivan, KM, and Thomas, ED. "Association between cyclosporin neurotoxicity and hypomagnesaemia." Lancet (London, England) 2.8412 (November 1984): 1116-1120.
PMID
6150182
Source
epmc
Published In
The Lancet
Volume
2
Issue
8412
Publish Date
1984
Start Page
1116
End Page
1120
DOI
10.1016/s0140-6736(84)91556-3

Recovery of in vivo cellular immunity after human marrow grafting. Influence of time postgrafting and acute graft-versus-host disease.

Three hundred thirty-two marrow graft recipients and 241 healthy marrow donors were studied by skin testing with recall and neoantigens. Two hundred thirty patients with leukemia and seventy-eight patients with aplastic anemia received allogeneic HLA-identical sibling marrow. Twenty-four patients with leukemia received syngeneic marrow. The conditioning regimen prior to marrow infusion consisted of 120 mg/kg cyclophosphamide and 9.2-15.75 Gy total-body irradiation (leukemia) or 200 mg/kg cyclophosphamide (aplastic anemia). The patients were skin-tested with the neoantigens dinitrochlorobenzene (DNCB), keyhole limpet hemocyanin, and a battery of five recall antigens around 100, 150, 365, 730, 1095, 1460, and 1825 days after grafting. A binary logistic regression analysis was used to investigate the factors thought to influence immunocompetence. At 3 months postgrafting, the proportion of patients positive to DNCB was equal to that of normal marrow donors, but thereafter it was lower until 2 years. The proportion of patients positive to keyhole limpet hemocyanin was lower than normal regardless of the time after grafting. The proportion of patients positive to recall antigens was lower than that of normal marrow donors until 4 years after grafting. Patients with a history of acute graft-versus-host disease had the lowest probability of a positive reaction to recall antigens. None of the other factors was significantly associated with an increased or reduced level of response.

Authors
Witherspoon, RP; Matthews, D; Storb, R; Atkinson, K; Cheever, M; Deeg, HJ; Doney, K; Kalbfleisch, J; Noel, D; Prentice, R
MLA Citation
Witherspoon, RP, Matthews, D, Storb, R, Atkinson, K, Cheever, M, Deeg, HJ, Doney, K, Kalbfleisch, J, Noel, D, and Prentice, R. "Recovery of in vivo cellular immunity after human marrow grafting. Influence of time postgrafting and acute graft-versus-host disease." Transplantation 37.2 (February 1984): 145-150.
PMID
6420960
Source
epmc
Published In
Transplantation
Volume
37
Issue
2
Publish Date
1984
Start Page
145
End Page
150

Oral Manifestations of Chronic Graft-v-Host Disease

Sixty patients were studied 180 to 500 days after allogeneic marrow transplantation to determine if late oral abnormalities were associated with the presence of chronic graft-v-host disease (GVHD). Lip and intraoral mucosal surfaces were evaluated for color, keratinization, atrophy, and erythema. Subjective complaints of oral pain and xerostomia were also recorded. Abnormalities were scored on a scale of 0 to 3 and tested for association with GVHD by χ < sup > 2 < /sup > test. Oral manifestations most strongly associated with chronic GVHD included atrophy and erythema or lichenoid lesions of the buccal and labial mucosa and oral pain. Oral manifestations resembled several naturally occurring autoimmune disorders. Recognition of these changes can aid in the clinical diagnosis and assessment of established chronic GVHD. © 1984, American Medical Association. All rights reserved.

Authors
Schubert, MM; Sullivan, KM; Morton, TH; Izutsu, KT; Peterson, DE; Flournoy, N; Truelove, EL; Sale, GE; Buckner, CD; Storb, R; Thomas, ED
MLA Citation
Schubert, MM, Sullivan, KM, Morton, TH, Izutsu, KT, Peterson, DE, Flournoy, N, Truelove, EL, Sale, GE, Buckner, CD, Storb, R, and Thomas, ED. "Oral Manifestations of Chronic Graft-v-Host Disease." Archives of Internal Medicine 144.8 (January 1, 1984): 1591-1595.
Source
scopus
Published In
Archives of internal medicine
Volume
144
Issue
8
Publish Date
1984
Start Page
1591
End Page
1595
DOI
10.1001/archinte.1984.00350200087014

Association between cyclosporin neurotoxicity and hypomagnesaemia

The serum magnesium levels of all 12 allogeneic bone-marrow transplant recipients who experienced the neurotoxic effects of cyclosporin (CyA) were more than two standard deviations below the normal range. The neurological events seemed to segregate into three separate syndromes. 7 patients had grand-mal seizures, which occurred within the first several weeks of CyA therapy (median onset 12 days). At the time of their first seizure all 7 patients had hypomagnesaemia, which had developed rapidly over the preceding 1-3 weeks. 3 patients had four episodes of cerebellar ataxia, tremor, and depression. These subacute episodes developed after prolonged CyA therapy (mean onset 67 days). Each episode was associated with hypomagnesaemia. 2 patients had a transient episode of expressive aphasia following a long period of hypomagnesaemia. In all cases symptoms resolved or did not recur with adequate magnesium replacement. These data suggest that CyA neurotoxicity is associated with hypomagnesaemia and may be treated or prevented with magnesium replacement.

Authors
Thompson, CB; June, CH; Sullivan, KM; Thomas, ED
MLA Citation
Thompson, CB, June, CH, Sullivan, KM, and Thomas, ED. "Association between cyclosporin neurotoxicity and hypomagnesaemia." Lancet 2.8412 (1984): 1116-1120.
Source
scival
Published In
Lancet
Volume
2
Issue
8412
Publish Date
1984
Start Page
1116
End Page
1120

Radiographic features of esophageal involvement in chronic graft-vs.-host disease

Chronic graft-vs.-host disease (GVHD) is an important late complication of allogeneic bone-marrow transplantation. It resembles several naturally occurring autoimmune diseases and involves the skin, mouth, eyes, liver, and esophagus. The radiographic findings of 14 symptomatic patients with chronic GVHD involving the esophagus were reviewed and found to include webs, ringlike narrowings, and tapering strictures in the mid and upper esophagus. Esophagoscopy revealed characteristic desquamation in the 13 patients studied, but barium studies detected this lesion in only one patient. Knowledge of the site and characteristics of esophageal involvement with chronic GVHD assists the radiologic evaluation of this disorder.

Authors
McDonald, GB; Sullivan, KM; Plumley, TF
MLA Citation
McDonald, GB, Sullivan, KM, and Plumley, TF. "Radiographic features of esophageal involvement in chronic graft-vs.-host disease." American Journal of Roentgenology 142.3 (1984): 501-506.
PMID
6607634
Source
scival
Published In
American Journal of Roentgenology
Volume
142
Issue
3
Publish Date
1984
Start Page
501
End Page
506

Marrow transplantation for aplastic anemia

Authors
Storb, R; Thomas, ED; Buckner, CD; Appelbaum, FR; Clift, RA; Deeg, HJ; Doney, K; Hansen, JA; Prentice, RL; Sanders, JE; Stewart, P; Sullivan, KM; Witherspoon, RP
MLA Citation
Storb, R, Thomas, ED, Buckner, CD, Appelbaum, FR, Clift, RA, Deeg, HJ, Doney, K, Hansen, JA, Prentice, RL, Sanders, JE, Stewart, P, Sullivan, KM, and Witherspoon, RP. "Marrow transplantation for aplastic anemia." Seminars in Hematology 21.1 (1984): 27-35.
PMID
6367054
Source
scival
Published In
Seminars in Hematology
Volume
21
Issue
1
Publish Date
1984
Start Page
27
End Page
35

Cataracts after total body irradiation and marrow transplantation: A sparing effect of dose fractionation

We examined 277 patients, who have been followed for 1 to 12 years after marrow transplantation, for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, usually cyclophosphamide 50 mg/kg × 4 intravenously, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing 60Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients), usually at increments of 2 to 2.25 Gy/day for 6 to 7 days for cumulative doses of 12 to 15.75 Gy. To date, 86 patients have developed cataracts. Kaplan-Meer product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, and 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only (p < 0.00005), suggesting a significant sparing effect with use of TBI dose fractionation. Additional significant risk factors included the chronic use of steroids post-transplant (highly associated with the presence of chronic graft-versus-host disease), and the diagnoses of acute lymphoblastic or chronic myelogenous leukemia. © 1984.

Authors
Deeg, HJ; Flournoy, N; Sullivan, KM; Sheehan, K; Buckner, CD; Sanders, JE; Storb, R; Witherspoon, RP; Thomas, ED
MLA Citation
Deeg, HJ, Flournoy, N, Sullivan, KM, Sheehan, K, Buckner, CD, Sanders, JE, Storb, R, Witherspoon, RP, and Thomas, ED. "Cataracts after total body irradiation and marrow transplantation: A sparing effect of dose fractionation." International Journal of Radiation Oncology, Biology, Physics 10.7 (1984): 957-964.
PMID
6378850
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
10
Issue
7
Publish Date
1984
Start Page
957
End Page
964

Late complications after marrow transplantation

Authors
Sullivan, KM; Deeg, HJ; Sanders, JE; Shulman, HM; Witherspoon, RP; Doney, K; Appelbaum, FR; Schubert, MM; Stewart, P; Springmeyer, S; McDonald, GB; Storb, R; Thomas, ED
MLA Citation
Sullivan, KM, Deeg, HJ, Sanders, JE, Shulman, HM, Witherspoon, RP, Doney, K, Appelbaum, FR, Schubert, MM, Stewart, P, Springmeyer, S, McDonald, GB, Storb, R, and Thomas, ED. "Late complications after marrow transplantation." Seminars in Hematology 21.1 (1984): 53-63.
PMID
6367058
Source
scival
Published In
Seminars in Hematology
Volume
21
Issue
1
Publish Date
1984
Start Page
53
End Page
63

Rapidly progressive air-flow obstruction in marrow transplant recipients. Possible association between obliterative bronchiolitis and chronic graft-versus-host disease

Severe obstructive airways disease developed in 4 young nonsmoking adults after marrow transplantation. They were free of respiratory disease until symptoms developed 277 to 600 days after transplant. Pulmonary function testing showed that the mean forced expiratory volume in one second was 35% of predicted (range, 23 to 49%). All patients had active or inactive extensive chronic graft-versus-host disease that included oral mucositis, esophagitis, sinusitis, and oral and ocular sicca. Three patients had subnormal serum IgA levels. Bronchitis was apparent during fiberoptic bronchoscopy in 3 patients. An open-lung biopsy specimen from 1 patient showed obliterative bronchiolitis. Treatment has included bronchodilators and corticosteroids without objective benefit. The disorder stabilized in all 4 patients, but a severe reduction in air flow persisted. Awareness of this complication may lead to earlier diagnosis and more effective treatment.

Authors
Ralph, DD; Springmeyer, SC; Sullivan, KM; Hackman, RC; Storb, R; Thomas, ED
MLA Citation
Ralph, DD, Springmeyer, SC, Sullivan, KM, Hackman, RC, Storb, R, and Thomas, ED. "Rapidly progressive air-flow obstruction in marrow transplant recipients. Possible association between obliterative bronchiolitis and chronic graft-versus-host disease." American Review of Respiratory Disease 129.4 (1984): 641-644.
PMID
6370061
Source
scival
Published In
American Review of Respiratory Disease
Volume
129
Issue
4
Publish Date
1984
Start Page
641
End Page
644

Allogeneic marrow transplantation

Authors
Sullivan, KM; Storb, R
MLA Citation
Sullivan, KM, and Storb, R. "Allogeneic marrow transplantation." Cancer Investigation 2.1 (1984): 27-38.
PMID
6367899
Source
scival
Published In
Cancer Investigation (Informa)
Volume
2
Issue
1
Publish Date
1984
Start Page
27
End Page
38
DOI
10.3109/07357908409020284

Oral manifestations of chronic graft-v-host disease

Sixty patients were studied 180 to 500 days after allogeneic marrow transplantation to determine if late oral abnormalities were associated with the presence of chronic graft-v-host disease (GVHD). Lip and intraoral mucosal surfaces were evaluated for color, keratinization, atrophy, and erythema. Subjective complaints of oral pain and xerostomia were also recorded. Abnormalities were scored on a scale of 0 to 3 and tested for association with GVHD by χ2 test. Oral manifestations most strongly associated with chronic GVHD included atrophy and erythema or lichenoid lesions of the buccal and labial mucosa and oral pain. Oral manifestations resembled several naturally occurring autoimmune disorders. Recognition of these changes can aid in the clinical diagnosis and assessment of established chronic GVHD.

Authors
Schubert, MM; Sullivan, KM; Morton, TH; Izutsu, KT; Peterson, DE; Flournoy, N; Truelove, EL; Sale, GE; Buckner, CD; Storb, R
MLA Citation
Schubert, MM, Sullivan, KM, Morton, TH, Izutsu, KT, Peterson, DE, Flournoy, N, Truelove, EL, Sale, GE, Buckner, CD, and Storb, R. "Oral manifestations of chronic graft-v-host disease." Archives of Internal Medicine 144.8 (1984): 1591-1595.
PMID
6380439
Source
scival
Published In
Archives of internal medicine
Volume
144
Issue
8
Publish Date
1984
Start Page
1591
End Page
1595
DOI
10.1001/archinte.144.8.1591

Prophylaxis of infection in patients with aplastic anemia receiving allogeneic marrow transplants

One hundred one patients with severe aplastic anemia underwent allogeneic marrow transplantation and received one of three forms of infection prophylaxis: oral nonabsorbable antibiotics and isolation and decontamination in a laminar airflow room (36 patients); prophylactic granulocyte transfusions from a single family member donor (33 patients); or conventional treatment in single rooms with hand-washing and mask precautions (31 patients). During the period of granulocytopenia, patients in the laminar airflow rooms acquired fewer infections than either of the other groups, but this difference was statistically significant only when compared with the group receiving conventional treatment. Patients in the laminar airflow rooms had significantly fewer infections after engraftment as compared with the other two groups. Incidence of interstitial pneumonia and graft rejection was not different among the three groups. Acute graft-versus-host disease occurred later (Day 47) in the group in the laminar airflow rooms as compared with the group receiving prophylactic granulocyte transfusions (Day 23) or the group receiving conventional treatment (Day 20). The incidence of grades II to IV acute graft-versus-host disease was less in the patients in the laminar airflow rooms but only reached borderline significance (p = 0.08) when compared with the conventionally treated patients. The survival at Day 100 was 92 percent for the group in the laminar airflow rooms, 79 percent for the group receiving prophylactic granulocyte transfusions, and 64 percent for the group receiving conventional treatment. © 1984.

Authors
Navari, RM; Buckner, CD; Clift, RA; Storb, R; Sanders, JE; Stewart, P; Sullivan, KM; Williams, B; Counts, GW; Meyers, JD; Thomas, ED
MLA Citation
Navari, RM, Buckner, CD, Clift, RA, Storb, R, Sanders, JE, Stewart, P, Sullivan, KM, Williams, B, Counts, GW, Meyers, JD, and Thomas, ED. "Prophylaxis of infection in patients with aplastic anemia receiving allogeneic marrow transplants." The American Journal of Medicine 76.4 (1984): 564-572.
PMID
6424464
Source
scival
Published In
The American Journal of Medicine
Volume
76
Issue
4
Publish Date
1984
Start Page
564
End Page
572

Murine monoclonal anti-T cell antibodies for treatment of steroid-resistant acute graft-versus-host disease

Four different murine monoclonal anti-T cell antibodies were administered to 15 patients with severe steroid resistant graft versus host disease (GVHD) in a phase I clinical trial in order to evaluate feasibility and toxicity. Antibodies 9.6 (IgG2a and 35.1 (IgG2a bind to separate epitopes on the E receptor (Tp50); antibody 10.2 (IgG2a) binds to the murine Lyt-1 homolog (Tp67); and antibody 12.1 (IgG2a) binds to a cell surface antigen with a molecular weight of approximately 100,000 daltons (Tp100). A total of 151 infusions were given, ranging in dose from one to 20 mg, each administered over a one to four hour period. One patient received a total of 259 mg of antibody over a period of 45 days. Six infusions (4%) in two patient were associated with fever or fever and chills. By decreasing the infusion rate, subsequent infusions to these two patients were accomplished without additional reactions. Although most of the patients treated with monoclonal antibodies required platelet support, the number of platelet units given was not significantly different from similar patients not receiving monoclonal antibodies. Six of ten patients receiving intermediate to high doses (5-20 mg) antibody therapy had evidence of at least partial improvement in GVHD in at least one involved organ system. None of the patients became immunized to mouse immunoglobulin. Our results suggest that therapy of GVHD with murine monoclonal anti-T cell antibodies is feasible and that these antibodies apparently can be administered to marrow transplant patients without significant toxicity. Further studies are required to determine which antibodies or combinations of antibodies have optimal anti-GVHD effect. © 1984.

Authors
Remlinger, K; Martin, PJ; Hansen, JA; Doney, KC; Smith, A; Deeg, HJ; Sullivan, K; Storb, R; Thomas, ED
MLA Citation
Remlinger, K, Martin, PJ, Hansen, JA, Doney, KC, Smith, A, Deeg, HJ, Sullivan, K, Storb, R, and Thomas, ED. "Murine monoclonal anti-T cell antibodies for treatment of steroid-resistant acute graft-versus-host disease." Human Immunology 9.1 (1984): 21-35.
PMID
6198309
Source
scival
Published In
Human Immunology
Volume
9
Issue
1
Publish Date
1984
Start Page
21
End Page
35

Marrow harvesting from normal donors

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.

Authors
Buckner, CD; Clift, RA; Sanders, JE; Stewart, P; Bensinger, WI; Doney, KC; Sullivan, KM; Witherspoon, RP; Deeg, HJ; Appelbaum, FR
MLA Citation
Buckner, CD, Clift, RA, Sanders, JE, Stewart, P, Bensinger, WI, Doney, KC, Sullivan, KM, Witherspoon, RP, Deeg, HJ, and Appelbaum, FR. "Marrow harvesting from normal donors." Blood 64.3 (1984): 630-634.
PMID
6380620
Source
scival
Published In
Blood
Volume
64
Issue
3
Publish Date
1984
Start Page
630
End Page
634

Marrow transplantation in hepatitis-associated aplastic anemia

Seventeen patients who developed aplastic anemia in association with viral hepatitis were transplanted with sibling marrow. Of the 16 HLA-identical recipients, 14 were conditioned with cyclophosphamide, 200 mg/kg, and two receive 10 Gy total body irradiation. One HLA-nonidentical recipient received 123 mg/kg cyclophosphamide and 10 Gy total body irradiation. Of the 14 patients conditioned with cyclophosphamide alone, one died on day 49 after graft rejection, and 13 had sustained engraftment. Six of the 13 developed acute graft-versus-host disease (GVHD), which led to death from opportunistic infections 84, 97, and 130 days after transplantation in three patients. Four of the 13 developed chronic GVHD, two without preceding acute GVHD. Currently, ten of the 14 cyclophosphamide-conditioned patients are alive 0.9-12.4 (median 5.9) years from transplantation. The two HLA-identical recipients conditioned for grafting with total body irradiation died after failure of engraftment, and one also developed concomitant hepatic venocclusive disease. The mismatched recipient conditioned with radiation and cyclophosphamide died of severe GVHD 18 days posttransplant. We conclude that survival, graft rejection, and incidence of acute and chronic GVHD after marrow transplantation for hepatitis-associated aplastic anemia are similar to those of patients transplanted for aplastic anemia of other etiologies. Previous hepatic damage from viral hepatitis and liver function abnormalities existing at the time of grafting do not appear to increase the risk of posttransplant morbidity and mortality from hepatocellular damage or venocclusive disease in cyclophosphamide-conditioned patients.

Authors
Witherspoon, RP; Storb, R; Shulman, H; Buckner, CD; Deeg, HJ; Clift, RA; Sanders, JE; Doney, K; McDonald, G; Sullivan, KM
MLA Citation
Witherspoon, RP, Storb, R, Shulman, H, Buckner, CD, Deeg, HJ, Clift, RA, Sanders, JE, Doney, K, McDonald, G, and Sullivan, KM. "Marrow transplantation in hepatitis-associated aplastic anemia." American Journal of Hematology 17.3 (1984): 269-278.
PMID
6383025
Source
scival
Published In
American Journal of Hematology
Volume
17
Issue
3