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Prasad, Vinod K.

Overview:

1. Expanding the role of umbilical cord blood transplants for inherited metabolic disorders.
2. Impact of histocompatibility and other determinants of alloreactivity on clinical outcomes of unrelated cord blood transplants.
3. Studies to analyse the impact of Killer Immunoglobulin receptors on the outcomes of hematopoietic stem cell transplantation utilizing haploidentical, CD34 selected, familial grafts.
4. Propective longitudinal study of serial monitoring of adenovirus in allogenic transpants(SMAART)patients.
5. Use of mesenchymal stem cells for the treatment of GVHD

Positions:

Professor of Pediatrics

Pediatrics, Blood and Marrow Transplantation
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.B.B.S. 1981

M.B.B.S. — Maulana Azad Medical College (India)

Rotating Internship, Pediatrics & Orthopedics

Maulana Azad Medical College (India)

Junior Resident, Pediatrics & Orthopedics

Maulana Azad Medical College (India)

Junior Resident, Pediatrics

Lady Hardinge Medical College (India)

Senior Resident, Pediatrics

Lady Hardinge Medical College (India)

Senior House Officer, Pediatrics

Hospital for Sick Children (UK)

Fellow, Pediatric Hematology Oncology, Pediatrics

Memorial Sloan Kettrng Rad Te

Resident, Pediatrics

Cornell University

News:

Grants:

CMX001-333 Registry

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
Chimerix, Inc.
Role
Principal Investigator
Start Date
February 01, 2016
End Date
January 31, 2020

Bluebird Bio ALD-103

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
Bluebird Bio
Role
Principal Investigator
Start Date
September 01, 2015
End Date
August 31, 2019

Brincidofovir CMX001-304

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
Chimerix, Inc.
Role
Principal Investigator
Start Date
April 18, 2014
End Date
January 31, 2017

CMX001-305 Historical Control

Administered By
Pediatrics, Blood and Marrow Transplantation
AwardedBy
Chimerix, Inc.
Role
Principal Investigator
Start Date
May 01, 2015
End Date
October 06, 2016
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Publications:

Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial.

Adenovirus infection in immunocompromised patients contributes to significant morbidity and mortality, especially after allogeneic hematopoietic cell transplantation (HCT). Brincidofovir (BCV, CMX001) is an orally bioavailable lipid conjugate of cidofovir that has in vitro activity against adenoviruses and other double-stranded DNA viruses. This randomized placebo-controlled phase II trial evaluated pre-emptive treatment with BCV for the prevention of adenovirus disease in pediatric and adult allogeneic HCT recipients with asymptomatic adenovirus viremia. Allogeneic HCT recipients with adenovirus viremia were randomized 1:1:1 to receive oral BCV 100 mg (2 mg/kg if <50 kg) twice weekly (BIW), BCV 200 mg (4 mg/kg if <50 kg) once weekly (QW), or placebo for 6 to 12 weeks, followed by 4 weeks of post-treatment follow-up. For randomization, subjects were stratified by screening absolute lymphocyte count (<300 cells/mm3 versus ≥300 cells/mm3). Assignment to BCV or placebo was double blinded; dose frequency was unblinded. The primary endpoint was the proportion of subjects experiencing treatment failure, defined as either progression to probable or definitive adenovirus disease or confirmed increasing adenovirus viremia (≥1 log10 copies/mL) during randomized therapy. Between June 2011 and December 2012, 48 subjects were randomized to the BCV BIW (n = 14), BCV QW (n = 16), or placebo (n = 18) groups. The proportion of subjects with treatment failure in the BCV BIW group was 21% (odds ratio, .53; 95% confidence interval [CI], .11 to 2.71; P = .45), 38% (odds ratio, 1.23; 95% CI, .30 to 5.05, P = .779) in the BCV QW group, and 33% in the placebo group. All-cause mortality was lower in the BCV BIW (14%) and BCV QW groups (31%) relative to the placebo group (39%), but these differences were not statistically significant. After 1 week of therapy, 8 of 12 subjects (67%) randomized to BCV BIW had undetectable adenovirus viremia (<100 copies/mL), compared with 4 of 14 subjects (29%) randomized to BCV QW and 5 of 15 subjects (33%) randomized to placebo. In a post hoc analysis of subjects with viremia ≥1000 copies/mL at baseline, 6 of 7 BCV BIW subjects (86%) achieved undetectable viremia compared with 2 of 8 placebo subjects (25%; P = .04). Early treatment discontinuation because of adverse events was more common in subjects treated with BCV than with placebo. Diarrhea was the most common event in all groups (57% BCV BIW, 38% BCV QW, 28% placebo), but it led to treatment discontinuation in only 1 subject receiving BCV QW. Events diagnosed as acute graft-versus-host disease, primarily of the gastrointestinal tract, were more frequent in the BCV BIW group (50%) than in the BCV QW (25%) and placebo (17%) groups. There was no evidence of myelotoxicity or nephrotoxicity in BCV-treated subjects. The results of this trial confirm the antiviral activity of BCV against adenoviruses. Further investigation is ongoing to define the optimal treatment strategy for HCT recipients with serious adenovirus infection and disease.

Authors
Grimley, MS; Chemaly, RF; Englund, JA; Kurtzberg, J; Chittick, G; Brundage, TM; Bae, A; Morrison, ME; Prasad, VK
MLA Citation
Grimley, MS, Chemaly, RF, Englund, JA, Kurtzberg, J, Chittick, G, Brundage, TM, Bae, A, Morrison, ME, and Prasad, VK. "Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 23.3 (March 2017): 512-521.
PMID
28063938
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
23
Issue
3
Publish Date
2017
Start Page
512
End Page
521
DOI
10.1016/j.bbmt.2016.12.621

Gallbladder abnormalities in children with metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a lysosomal storage disease that leads to neurological deterioration and visceral involvement, including sulphatide deposition in the gallbladder wall. Using our institution's extensive experience in treating MLD, we examined the incidence of gallbladder abnormalities in the largest cohort of children with MLD to date.We conducted a retrospective review of all children with MLD, adrenoleukodystrophy (ALD), or Krabbe disease who underwent hematopoietic stem cell transplantation (HSCT) at our institution between 1994 and 2015. Baseline characteristics and unadjusted outcomes were compared using the Kruskal-Wallis test for continuous variables and Pearson χ2 test for categorical variables, with significance defined as P < 0.05.In total, 87 children met study criteria: 29 children with MLD and 58 children with ALD or Krabbe disease. Children with MLD were more likely to demonstrate gallbladder abnormalities on imaging, both before HSCT (41.4% versus 5.2%, P < 0.001) and after HSCT (75.9% versus 41.4%, P = 0.002). Consequently, a larger proportion of children with MLD underwent surgical or interventional management of biliary disease (10.3% versus 3.4%, P = 0.03).Children with MLD have a significantly greater incidence of gallbladder abnormalities than children with other lysosomal storage diseases. Biliary disease should be considered in children with MLD who develop abdominal pain, and cholecystectomy should be considered for persistent, symptomatic gallbladder abnormalities.

Authors
Kim, J; Sun, Z; Ezekian, B; Schooler, GR; Prasad, VK; Kurtzberg, J; Rice, HE; Tracy, ET
MLA Citation
Kim, J, Sun, Z, Ezekian, B, Schooler, GR, Prasad, VK, Kurtzberg, J, Rice, HE, and Tracy, ET. "Gallbladder abnormalities in children with metachromatic leukodystrophy." The Journal of surgical research 208 (February 2017): 187-191.
PMID
27993207
Source
epmc
Published In
Journal of Surgical Research
Volume
208
Publish Date
2017
Start Page
187
End Page
191
DOI
10.1016/j.jss.2016.08.081

Extrapulmonary Aspergillus infection in patients with CARD9 deficiency.

Invasive pulmonary aspergillosis is a life-threatening mycosis that only affects patients with immunosuppression, chemotherapy-induced neutropenia, transplantation, or congenital immunodeficiency. We studied the clinical, genetic, histological, and immunological features of 2 unrelated patients without known immunodeficiency who developed extrapulmonary invasive aspergillosis at the ages of 8 and 18. One patient died at age 12 with progressive intra-abdominal aspergillosis. The other patient had presented with intra-abdominal candidiasis at age 9, and developed central nervous system aspergillosis at age 18 and intra-abdominal aspergillosis at age 25. Neither patient developed Aspergillus infection of the lungs. One patient had homozygous M1I CARD9 (caspase recruitment domain family member 9) mutation, while the other had homozygous Q295X CARD9 mutation; both patients lacked CARD9 protein expression. The patients had normal monocyte and Th17 cell numbers in peripheral blood, but their mononuclear cells exhibited impaired production of proinflammatory cytokines upon fungus-specific stimulation. Neutrophil phagocytosis, killing, and oxidative burst against Aspergillus fumigatus were intact, but neither patient accumulated neutrophils in infected tissue despite normal neutrophil numbers in peripheral blood. The neutrophil tissue accumulation defect was not caused by defective neutrophil-intrinsic chemotaxis, indicating that production of neutrophil chemoattractants in extrapulmonary tissue is impaired in CARD9 deficiency. Taken together, our results show that CARD9 deficiency is the first known inherited or acquired condition that predisposes to extrapulmonary Aspergillus infection with sparing of the lungs, associated with impaired neutrophil recruitment to the site of infection.

Authors
Rieber, N; Gazendam, RP; Freeman, AF; Hsu, AP; Collar, AL; Sugui, JA; Drummond, RA; Rongkavilit, C; Hoffman, K; Henderson, C; Clark, L; Mezger, M; Swamydas, M; Engeholm, M; Schüle, R; Neumayer, B; Ebel, F; Mikelis, CM; Pittaluga, S; Prasad, VK; Singh, A; Milner, JD; Williams, KW; Lim, JK; Kwon-Chung, KJ; Holland, SM; Hartl, D; Kuijpers, TW; Lionakis, MS
MLA Citation
Rieber, N, Gazendam, RP, Freeman, AF, Hsu, AP, Collar, AL, Sugui, JA, Drummond, RA, Rongkavilit, C, Hoffman, K, Henderson, C, Clark, L, Mezger, M, Swamydas, M, Engeholm, M, Schüle, R, Neumayer, B, Ebel, F, Mikelis, CM, Pittaluga, S, Prasad, VK, Singh, A, Milner, JD, Williams, KW, Lim, JK, Kwon-Chung, KJ, Holland, SM, Hartl, D, Kuijpers, TW, and Lionakis, MS. "Extrapulmonary Aspergillus infection in patients with CARD9 deficiency." JCI insight 1.17 (October 20, 2016): e89890-.
PMID
27777981
Source
epmc
Published In
JCI insight
Volume
1
Issue
17
Publish Date
2016
Start Page
e89890

Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning.

Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), congenital immune deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation.

Authors
Allewelt, H; El-Khorazaty, J; Mendizabal, A; Taskindoust, M; Martin, PL; Prasad, V; Page, K; Sanders, J; Kurtzberg, J
MLA Citation
Allewelt, H, El-Khorazaty, J, Mendizabal, A, Taskindoust, M, Martin, PL, Prasad, V, Page, K, Sanders, J, and Kurtzberg, J. "Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 22.9 (September 2016): 1627-1635.
PMID
27264632
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
9
Publish Date
2016
Start Page
1627
End Page
1635
DOI
10.1016/j.bbmt.2016.05.024

Bone Marrow Transplantation and Umbilical Cord Blood Transplantation for Inborn Errors of Metabolism

Authors
Prasad, VK
MLA Citation
Prasad, VK. "Bone Marrow Transplantation and Umbilical Cord Blood Transplantation for Inborn Errors of Metabolism." BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY 106.5 (May 2016): 361-361.
Source
wos-lite
Published In
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume
106
Issue
5
Publish Date
2016
Start Page
361
End Page
361

Long-Term Functional Outcomes following Hematopoietic Stem Cell Transplantation for Krabbe Disease

Authors
Allewelt, HB; Page, K; Taskindoust, M; Troy, JD; Wood, S; Parikh, S; Prasad, VK; Kurtzberg, J
MLA Citation
Allewelt, HB, Page, K, Taskindoust, M, Troy, JD, Wood, S, Parikh, S, Prasad, VK, and Kurtzberg, J. "Long-Term Functional Outcomes following Hematopoietic Stem Cell Transplantation for Krabbe Disease." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S102
End Page
S103

Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis

Authors
Patel, S; Allewelt, HB; Martin, PL; Page, K; Driscoll, TA; Prasad, VK; Kurtzberg, J; Parikh, S
MLA Citation
Patel, S, Allewelt, HB, Martin, PL, Page, K, Driscoll, TA, Prasad, VK, Kurtzberg, J, and Parikh, S. "Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S257
End Page
S257

Umbilical Cord Blood Transplantation for Cartilage Hair Hypoplasia: A Single Center Experience Demonstrates Excellent Outcomes Using Myeloablative Preparative Regimens

Authors
Allewelt, HB; Patel, S; Prasad, VK; Kurtzberg, J; Driscoll, TA; Martin, PL; Page, K; Parikh, S
MLA Citation
Allewelt, HB, Patel, S, Prasad, VK, Kurtzberg, J, Driscoll, TA, Martin, PL, Page, K, and Parikh, S. "Umbilical Cord Blood Transplantation for Cartilage Hair Hypoplasia: A Single Center Experience Demonstrates Excellent Outcomes Using Myeloablative Preparative Regimens." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S235
End Page
S235

Effect of Human Mesenchymal Stem Cells (Remestemcel-L) on Clinical Response and Survival Confirmed in a Large Cohort of Pediatric Patients with Severe High-Risk Steroid Refractory Acute Graft Versus Host Disease

Authors
Kurtzberg, J; Prockop, SE; Prasad, VK; Chaudhury, S; Teira, P; Nemecek, ER; Horn, B; Burke, E; Hayes, J; Skerrett, D
MLA Citation
Kurtzberg, J, Prockop, SE, Prasad, VK, Chaudhury, S, Teira, P, Nemecek, ER, Horn, B, Burke, E, Hayes, J, and Skerrett, D. "Effect of Human Mesenchymal Stem Cells (Remestemcel-L) on Clinical Response and Survival Confirmed in a Large Cohort of Pediatric Patients with Severe High-Risk Steroid Refractory Acute Graft Versus Host Disease." March 2016.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
22
Issue
3
Publish Date
2016
Start Page
S59
End Page
S59

Brincidofovir (CMX001) Toxicity: Another Potential Mimicker of Gastrointestinal Graft Versus Host Disease

Authors
Detweiler, CJ; Sung, AD; Saullo, JL; Prasad, VK; Cardona, DM
MLA Citation
Detweiler, CJ, Sung, AD, Saullo, JL, Prasad, VK, and Cardona, DM. "Brincidofovir (CMX001) Toxicity: Another Potential Mimicker of Gastrointestinal Graft Versus Host Disease." February 2016.
Source
wos-lite
Published In
Laboratory Investigation
Volume
96
Publish Date
2016
Start Page
169A
End Page
169A

Brincidofovir (CMX001) Toxicity: Another Potential Mimicker of Gastrointestinal Graft Versus Host Disease

Authors
Detweiler, CJ; Sung, AD; Saullo, JL; Prasad, VK; Cardona, DM
MLA Citation
Detweiler, CJ, Sung, AD, Saullo, JL, Prasad, VK, and Cardona, DM. "Brincidofovir (CMX001) Toxicity: Another Potential Mimicker of Gastrointestinal Graft Versus Host Disease." February 2016.
Source
wos-lite
Published In
Modern Pathology
Volume
29
Publish Date
2016
Start Page
169A
End Page
169A

Survival after mesenchymal stromal cell therapy in steroid-refractory acute graft-versus-host disease: systematic review and meta-analysis.

Graft-versus-host disease (GVHD) is the major limitation of allogeneic haemopoietic stem-cell transplantation (HSCT), for which no approved treatments are available. Use of mesenchymal stromal cells (MSCs) has become standard practice in some European countries, but controversy exists for their benefit. The aim of this meta-analysis was to analyse available evidence for the benefit of MSC treatments in steroid-resistant acute GVHD.We did a systematic review and meta-analysis to assess response to and survival after MSC treatment in patients with steroid-refractory acute GVHD. We searched MEDLINE, Embase, Ovid, and Cochrane Central databases for published studies, and we used ClinicalTrials.gov and other websites to find unpublished studies and conference abstracts. We included prospective and retrospective studies in which MSCs were administered to patients with steroid-refractory acute GVHD. Data were extracted independently by two investigators based on strict selection criteria. A random-effects model was used to pool outcomes across studies because of anticipated heterogeneity. Our primary outcome was survival at 6 months from the first infusion of MSCs.We identified 628 citations with our search, of which 610 were excluded after review and a further five did not contain pertinent data. Thus, our meta-analysis included 13 non-randomised studies at moderate risk of bias, comprising a total of 336 patients. Six studies provided data for the primary outcome analysis (119 patients). Survival at 6 months after MSC treatment was 63% (95% CI 50-74; I(2)=41%). Survival did not differ with respect to age, MSC culture medium, or dose of MSCs delivered.Available evidence suggests that infusion of MSCs could be an acceptable treatment for patients with steroid-refractory acute GVHD. Randomised clinical trials are needed urgently to assess different treatment modalities for steroid-refractory acute GVHD.None.

Authors
Hashmi, S; Ahmed, M; Murad, MH; Litzow, MR; Adams, RH; Ball, LM; Prasad, VK; Kebriaei, P; Ringden, O
MLA Citation
Hashmi, S, Ahmed, M, Murad, MH, Litzow, MR, Adams, RH, Ball, LM, Prasad, VK, Kebriaei, P, and Ringden, O. "Survival after mesenchymal stromal cell therapy in steroid-refractory acute graft-versus-host disease: systematic review and meta-analysis." The Lancet. Haematology 3.1 (January 2016): e45-e52.
PMID
26765648
Source
epmc
Published In
The Lancet. Haematology
Volume
3
Issue
1
Publish Date
2016
Start Page
e45
End Page
e52
DOI
10.1016/s2352-3026(15)00224-0

Durable engraftment and correction of hematological abnormalities in children with congenital amegakaryocytic thrombocytopenia following myeloablative umbilical cord blood transplantation.

The use of HSCT is the only potentially curative treatment for CAMT, but access is limited by the availability of suitable donors. We report five consecutive patients with CAMT who received MAC and partially HLA-mismatched, UCBT (unrelated, n = 4). Median times to neutrophil (>500/μL) and platelet (≥20 000 and ≥50 000/μL) engraftment were 19, 57, and 70 days, respectively. Acute GvHD, grade II, developed in one patient, who subsequently developed limited chronic GvHD. At median follow-up of 14 yr, all patients are alive with sustained donor cell engraftment. To our knowledge, this is the largest single-center series of UCBT for patients with this disease and suggests that UCBT is a successful curative option for patients with CAMT.

Authors
Mahadeo, KM; Tewari, P; Parikh, SH; Driscoll, TA; Page, K; Martin, PL; Kurtzberg, J; Prasad, VK
MLA Citation
Mahadeo, KM, Tewari, P, Parikh, SH, Driscoll, TA, Page, K, Martin, PL, Kurtzberg, J, and Prasad, VK. "Durable engraftment and correction of hematological abnormalities in children with congenital amegakaryocytic thrombocytopenia following myeloablative umbilical cord blood transplantation." Pediatric transplantation 19.7 (November 2015): 753-757.
PMID
26369627
Source
epmc
Published In
Pediatric Transplantation
Volume
19
Issue
7
Publish Date
2015
Start Page
753
End Page
757
DOI
10.1111/petr.12577

Predictors of gastrostomy placement in children with inherited metabolic diseases treated by umbilical cord blood transplantation.

Children with inherited metabolic diseases (IMDs) undergoing umbilical cord blood transplantation (UCBT) who are at risk for post-transplant failure to thrive may benefit from pretransplant gastrostomy tube (GT) placement. Here we sought to determine predictors of posttransplant failure to thrive.A retrospective analysis was performed for IMD patients who underwent UCBT at a single center from 2001 to 2011. Patients who received GTs were compared with controls. Multivariable logistic regression was used to determine significant predictors for GT placement. Recursive partitioning was performed to determine appropriate cut-offs for significant continuous variables.Two hundred and seventeen patients met inclusion criteria of which twenty-three were excluded due to death within one hundred days of transplant. Forty (20.6%) of the remaining patients underwent a surgical GT placement. Multivariable logistic regression demonstrated that weight percentile at time of transplant was significantly associated with GT placement (Adjusted odds ratio (AOR): 0.87 per 10th percentile, p=0.022). Recursive partitioning demonstrated that the 40th weight percentile at time of transplant was an optimal cut-off for predicting GT placement.Patients preparing for umbilical cord transplantation who are below the 40th percentile for weight may benefit from pre-emptive GT placement prior to transplant.

Authors
Gulack, BC; Schweitzer, M; Englum, BR; Kuchibhatla, M; Prasad, VK; Adibe, OO
MLA Citation
Gulack, BC, Schweitzer, M, Englum, BR, Kuchibhatla, M, Prasad, VK, and Adibe, OO. "Predictors of gastrostomy placement in children with inherited metabolic diseases treated by umbilical cord blood transplantation." Journal of pediatric surgery 50.7 (July 2015): 1109-1111.
PMID
25783333
Source
epmc
Published In
Journal of Pediatric Surgery
Volume
50
Issue
7
Publish Date
2015
Start Page
1109
End Page
1111
DOI
10.1016/j.jpedsurg.2014.09.053

Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study.

Mucopolysaccharidosis type I-Hurler syndrome (MPS-IH) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Although hematopoietic cell transplantation (HCT) has been performed in these patients for more than 30 years, large studies on the long-term outcome of patients with MPS-IH after HCT are lacking. The goal of this international study was to identify predictors of the long-term outcome of patients with MPS-IH after successful HCT. Two hundred seventeen patients with MPS-IH successfully engrafted with a median follow-up age of 9.2 years were included in this retrospective analysis. Primary endpoints were neurodevelopmental outcomes and growth. Secondary endpoints included neurologic, orthopedic, cardiac, respiratory, ophthalmologic, audiologic, and endocrinologic outcomes. Considerable residual disease burden was observed in the majority of the transplanted patients with MPS-IH, with high variability between patients. Preservation of cognitive function at HCT and a younger age at transplantation were major predictors for superior cognitive development posttransplant. A normal α-l-iduronidase enzyme level obtained post-HCT was another highly significant predictor for superior long-term outcome in most organ systems. The long-term prognosis of patients with MPS-IH receiving HCT can be improved by reducing the age at HCT through earlier diagnosis, as well as using exclusively noncarrier donors and achieving complete donor chimerism.

Authors
Aldenhoven, M; Wynn, RF; Orchard, PJ; O'Meara, A; Veys, P; Fischer, A; Valayannopoulos, V; Neven, B; Rovelli, A; Prasad, VK; Tolar, J; Allewelt, H; Jones, SA; Parini, R; Renard, M; Bordon, V; Wulffraat, NM; de Koning, TJ; Shapiro, EG; Kurtzberg, J; Boelens, JJ
MLA Citation
Aldenhoven, M, Wynn, RF, Orchard, PJ, O'Meara, A, Veys, P, Fischer, A, Valayannopoulos, V, Neven, B, Rovelli, A, Prasad, VK, Tolar, J, Allewelt, H, Jones, SA, Parini, R, Renard, M, Bordon, V, Wulffraat, NM, de Koning, TJ, Shapiro, EG, Kurtzberg, J, and Boelens, JJ. "Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study." Blood 125.13 (March 2015): 2164-2172.
PMID
25624320
Source
epmc
Published In
Blood
Volume
125
Issue
13
Publish Date
2015
Start Page
2164
End Page
2172
DOI
10.1182/blood-2014-11-608075

Improved Outcomes in Allogeneic Hematopoietic Cell Transplant (allo HCT) Patients Treated with Brincidofovir (CMX001, BCV) for Disseminated Adenovirus (AdV) Disease Compared to Literature: Updated Preliminary Results from the AdVise (CMX001-304) Study

Authors
Grimley, M; Papanicolaou, G; Maron, G; Chittick, G; Brundage, T; Bae, A; Mommeja-Marin, H; Nichols, WG; Prasad, VK
MLA Citation
Grimley, M, Papanicolaou, G, Maron, G, Chittick, G, Brundage, T, Bae, A, Mommeja-Marin, H, Nichols, WG, and Prasad, VK. "Improved Outcomes in Allogeneic Hematopoietic Cell Transplant (allo HCT) Patients Treated with Brincidofovir (CMX001, BCV) for Disseminated Adenovirus (AdV) Disease Compared to Literature: Updated Preliminary Results from the AdVise (CMX001-304) Study." March 2015.
Source
wos-lite
Published In
Bone Marrow Transplantation
Volume
50
Publish Date
2015
Start Page
S29
End Page
S30

Outcomes of Second Unrelated Donor Cord Blood Transplants (UCBT) Performed in Children with Graft Failure of Autologous Recovery Following the First UCBT

Authors
McFarren, A; Smith, PB; Page, K; Allewelt, HB; Parikh, S; Driscoll, TA; Martin, PL; Kurtzberg, J; Prasad, VK
MLA Citation
McFarren, A, Smith, PB, Page, K, Allewelt, HB, Parikh, S, Driscoll, TA, Martin, PL, Kurtzberg, J, and Prasad, VK. "Outcomes of Second Unrelated Donor Cord Blood Transplants (UCBT) Performed in Children with Graft Failure of Autologous Recovery Following the First UCBT." February 2015.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
2
Publish Date
2015
Start Page
S37
End Page
S38

Treatment with Human Mesenchymal Stem Cells (Remestemcel-L) Is Effective in Pediatric Patients with Refractory Acute Graft Versus Host Disease

Authors
Kurtzberg, J; Prockop, SE; Prasad, VK; Chaudhury, S; Teira, P; Nemecek, E; Horn, B; Burke, E; Hayes, J; Skerrett, D
MLA Citation
Kurtzberg, J, Prockop, SE, Prasad, VK, Chaudhury, S, Teira, P, Nemecek, E, Horn, B, Burke, E, Hayes, J, and Skerrett, D. "Treatment with Human Mesenchymal Stem Cells (Remestemcel-L) Is Effective in Pediatric Patients with Refractory Acute Graft Versus Host Disease." February 2015.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
2
Publish Date
2015
Start Page
S338
End Page
S339

Preliminary Results from the AdVise Study Evaluating Brincidofovir (CMX001, BCV) for the Treatment of Disseminated and High-Risk Adenovirus (AdV) Infection

Authors
Grimley, MS; Maron, GM; Prasad, VK; Jacobsohn, DA; Young, J-AH; Chittick, G; Brundage, TM; Mommeja-Marin, H
MLA Citation
Grimley, MS, Maron, GM, Prasad, VK, Jacobsohn, DA, Young, J-AH, Chittick, G, Brundage, TM, and Mommeja-Marin, H. "Preliminary Results from the AdVise Study Evaluating Brincidofovir (CMX001, BCV) for the Treatment of Disseminated and High-Risk Adenovirus (AdV) Infection." February 2015.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
21
Issue
2
Publish Date
2015
Start Page
S108
End Page
S109

Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation.

We examined current outcomes of unrelated donor allogeneic hematopoietic cell transplantation (HCT) to determine the clinical implications of donor-recipient HLA matching. Adult and pediatric patients who had first undergone myeloablative-unrelated bone marrow or peripheral blood HCT for acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome between 1999 and 2011 were included. All had high-resolution typing for HLA-A, -B, -C, and -DRB1. Of the total (n = 8003), cases were 8/8 (n = 5449), 7/8 (n = 2071), or 6/8 (n = 483) matched. HLA mismatch (6-7/8) conferred significantly increased risk for grades II to IV and III to IV acute graft vs host disease (GVHD), chronic GVHD, transplant-related mortality (TRM), and overall mortality compared with HLA-matched cases (8/8). Type (allele/antigen) and locus (HLA-A, -B, -C, and -DRB1) of mismatch were not associated with overall mortality. Among 8/8 matched cases, HLA-DPB1 and -DQB1 mismatch resulted in increased acute GVHD, and HLA-DPB1 mismatch had decreased relapse. Nonpermissive HLA-DPB1 allele mismatch was associated with higher TRM compared with permissive HLA-DPB1 mismatch or HLA-DPB1 match and increased overall mortality compared with permissive HLA-DPB1 mismatch in 8/8 (and 10/10) matched cases. Full matching at HLA-A, -B, -C, and -DRB1 is required for optimal unrelated donor HCT survival, and avoidance of nonpermissive HLA-DPB1 mismatches in otherwise HLA-matched pairs is indicated.

Authors
Pidala, J; Lee, SJ; Ahn, KW; Spellman, S; Wang, H-L; Aljurf, M; Askar, M; Dehn, J; Fernandez Viña, M; Gratwohl, A; Gupta, V; Hanna, R; Horowitz, MM; Hurley, CK; Inamoto, Y; Kassim, AA; Nishihori, T; Mueller, C; Oudshoorn, M; Petersdorf, EW; Prasad, V; Robinson, J; Saber, W; Schultz, KR; Shaw, B; Storek, J; Wood, WA; Woolfrey, AE; Anasetti, C
MLA Citation
Pidala, J, Lee, SJ, Ahn, KW, Spellman, S, Wang, H-L, Aljurf, M, Askar, M, Dehn, J, Fernandez Viña, M, Gratwohl, A, Gupta, V, Hanna, R, Horowitz, MM, Hurley, CK, Inamoto, Y, Kassim, AA, Nishihori, T, Mueller, C, Oudshoorn, M, Petersdorf, EW, Prasad, V, Robinson, J, Saber, W, Schultz, KR, Shaw, B, Storek, J, Wood, WA, Woolfrey, AE, and Anasetti, C. "Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation." Blood 124.16 (October 2014): 2596-2606.
PMID
25161269
Source
epmc
Published In
Blood
Volume
124
Issue
16
Publish Date
2014
Start Page
2596
End Page
2606
DOI
10.1182/blood-2014-05-576041

Optimizing donor selection for public cord blood banking: Influence of maternal, infant, and collection characteristics on cord blood unit quality

Background Banked unrelated donor umbilical cord blood (CB) has improved access to hematopoietic stem cell transplantation for patients without a suitably matched donor. In a resource-limited environment, ensuring that the public inventory is enriched with high-quality cord blood units (CBUs) addressing the needs of a diverse group of patients is a priority. Identification of donor characteristics correlating with higher CBU quality could guide operational strategies to increase the yield of banked high-quality CBUs. Study Design and Methods Characteristics of 5267 CBUs donated to the Carolinas Cord Blood Bank, a public bank participating in the National Cord Blood Inventory, were retrospectively analyzed. Eligible CBUs, collected by trained personnel, were processed using standard procedures. Routine quality and potency metrics (postprocessing total nucleated cell count [post-TNCC], CD34+, colony-forming units [CFUs]) were correlated with maternal, infant, and collection characteristics. Results High-quality CBUs were defined as those with higher post-TNCC (>1.25 × 109) with CD34+ and CFUs in the upper quartile. Factors associated with higher CD34+ or CFU content included a shorter interval from collection to processing (<10 hr), younger gestational age (34-37 weeks; CD34+ and CFUs), Caucasian race, higher birthweight (>3500 g), and larger collection volumes (>80 mL). Conclusions We describe characteristics identifying high-quality CBUs, which can be used to inform strategies for CBU collection for public banks. Efforts should be made to prioritize collections from larger babies born before 38 weeks of gestation. CBUs should be rapidly transported to the processing laboratory. The lower quality of CBUs from non-Caucasian donors highlights the challenges of building a racially diverse public CB inventory. © 2013 American Association of Blood Banks.

Authors
Page, KM; Mendizabal, A; Betz-Stablein, B; Wease, S; Shoulars, K; Gentry, T; Prasad, VK; Sun, J; Carter, S; Balber, AE; Kurtzberg, J
MLA Citation
Page, KM, Mendizabal, A, Betz-Stablein, B, Wease, S, Shoulars, K, Gentry, T, Prasad, VK, Sun, J, Carter, S, Balber, AE, and Kurtzberg, J. "Optimizing donor selection for public cord blood banking: Influence of maternal, infant, and collection characteristics on cord blood unit quality." Transfusion 54.2 (February 1, 2014): 340-352.
Source
scopus
Published In
Transfusion
Volume
54
Issue
2
Publish Date
2014
Start Page
340
End Page
352
DOI
10.1111/trf.12257

Stem-cell transplantation for chronic granulomatous disease.

Authors
Prasad, VK
MLA Citation
Prasad, VK. "Stem-cell transplantation for chronic granulomatous disease." Lancet 383.9915 (February 1, 2014): 390-392.
PMID
24161823
Source
pubmed
Published In
The Lancet
Volume
383
Issue
9915
Publish Date
2014
Start Page
390
End Page
392
DOI
10.1016/S0140-6736(13)62144-3

Unrelated Umbilical Cord Blood Transplant for Diamond-Blackfan Anemia

Authors
McFarren, A; Page, K; Parikh, S; Martin, PL; Driscoll, TA; Kurtzberg, J; Prasad, VK
MLA Citation
McFarren, A, Page, K, Parikh, S, Martin, PL, Driscoll, TA, Kurtzberg, J, and Prasad, VK. "Unrelated Umbilical Cord Blood Transplant for Diamond-Blackfan Anemia." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S177
End Page
S177

Interplay of Recipient-Donor Matching for HLA, Race/Ethnicity and Gender on Long Term Outcomes in 365 Pediatric Recipients of Single 4/6 Matched Unrelated Cord Blood Transplantation (UCBT) after Myeloablative Therapy

Authors
Prasad, VK; Mendizabal, A; Page, K; Parikh, S; Wishnew, J; Driscoll, TA; Martin, PL; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Page, K, Parikh, S, Wishnew, J, Driscoll, TA, Martin, PL, and Kurtzberg, J. "Interplay of Recipient-Donor Matching for HLA, Race/Ethnicity and Gender on Long Term Outcomes in 365 Pediatric Recipients of Single 4/6 Matched Unrelated Cord Blood Transplantation (UCBT) after Myeloablative Therapy." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S87
End Page
S88

Brincidofovir (CMX001) Is Well Tolerated in Highly Immunocompromised Pediatric Patients

Authors
Prasad, VK; Grimley, M; Papanicolaou, G; Yu, LC; Florescu, DF; Brundage, TM; Mommeja-Marin, H; Kurtzberg, J
MLA Citation
Prasad, VK, Grimley, M, Papanicolaou, G, Yu, LC, Florescu, DF, Brundage, TM, Mommeja-Marin, H, and Kurtzberg, J. "Brincidofovir (CMX001) Is Well Tolerated in Highly Immunocompromised Pediatric Patients." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S93
End Page
S93

Predictors of Long-Term Clinical Outcome in Hurler Syndrome Patients after Successful Hematopoietic Cell Transplantation: An International Study

Authors
Aldenhoven, M; Orchard, P; Kurtzberg, J; Wynn, R; O'Meara, A; Veys, P; Fischer, A; Valayannopoulos, V; Neven, B; Rovelli, A; Prasad, VK; Tolar, J; Shapiro, E; Jones, S; Parini, R; Renard, M; Bordon, V; Poe, M; de Koning, T; Wraith, E; Escolar, M; Boelens, J-J
MLA Citation
Aldenhoven, M, Orchard, P, Kurtzberg, J, Wynn, R, O'Meara, A, Veys, P, Fischer, A, Valayannopoulos, V, Neven, B, Rovelli, A, Prasad, VK, Tolar, J, Shapiro, E, Jones, S, Parini, R, Renard, M, Bordon, V, Poe, M, de Koning, T, Wraith, E, Escolar, M, and Boelens, J-J. "Predictors of Long-Term Clinical Outcome in Hurler Syndrome Patients after Successful Hematopoietic Cell Transplantation: An International Study." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S78
End Page
S79

Twice-Weekly Brincidofovir (CMX001) Shows Promising Antiviral Activity in Immunocompromised Transplant Recipients with Asymptomatic Adenovirus Viremia

Authors
Grimley, M; Prasad, VK; Kurtzberg, J; Chemaly, RF; Brundage, TM; Wilson, C; Mommeja-Marin, H
MLA Citation
Grimley, M, Prasad, VK, Kurtzberg, J, Chemaly, RF, Brundage, TM, Wilson, C, and Mommeja-Marin, H. "Twice-Weekly Brincidofovir (CMX001) Shows Promising Antiviral Activity in Immunocompromised Transplant Recipients with Asymptomatic Adenovirus Viremia." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S93
End Page
S93

Late Effects in Infants and Young Children Following Umbilical Cord Blood Transplant Using Busulfan-Based, Myeloablative Non-TBI Conditioning Regimens

Authors
Allewelt, HB; Martin, PL; Prasad, VK; Page, K; Kurtzberg, J
MLA Citation
Allewelt, HB, Martin, PL, Prasad, VK, Page, K, and Kurtzberg, J. "Late Effects in Infants and Young Children Following Umbilical Cord Blood Transplant Using Busulfan-Based, Myeloablative Non-TBI Conditioning Regimens." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S63
End Page
S63

HLA-Mismatch Is Associated with Worse Outcomes after Myeloablative Conditioning and Unrelated Donor Hematopoietic Cell Transplantation: A Cibmtr Analysis

Authors
Pidala, J; Lee, SJ; Spellman, SR; Wang, H; Ahn, KW; Aljurf, MD; Askar, M; Dehn, J; Vina, MAF; Gratwohl, A; Gupta, V; Hanna, R; Hurley, CK; Inamoto, Y; Kassim, AA; Nishihori, T; Oudshoorn, M; Petersdorf, EW; Prasad, VK; Saber, W; Schultz, KR; Wood, WA; Storek, J; Woolfrey, AE; Anasetti, C
MLA Citation
Pidala, J, Lee, SJ, Spellman, SR, Wang, H, Ahn, KW, Aljurf, MD, Askar, M, Dehn, J, Vina, MAF, Gratwohl, A, Gupta, V, Hanna, R, Hurley, CK, Inamoto, Y, Kassim, AA, Nishihori, T, Oudshoorn, M, Petersdorf, EW, Prasad, VK, Saber, W, Schultz, KR, Wood, WA, Storek, J, Woolfrey, AE, and Anasetti, C. "HLA-Mismatch Is Associated with Worse Outcomes after Myeloablative Conditioning and Unrelated Donor Hematopoietic Cell Transplantation: A Cibmtr Analysis." February 2014.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
20
Issue
2
Publish Date
2014
Start Page
S25
End Page
S26

Optimizing donor selection for public cord blood banking: influence of maternal, infant, and collection characteristics on cord blood unit quality.

BACKGROUND: Banked unrelated donor umbilical cord blood (CB) has improved access to hematopoietic stem cell transplantation for patients without a suitably matched donor. In a resource-limited environment, ensuring that the public inventory is enriched with high-quality cord blood units (CBUs) addressing the needs of a diverse group of patients is a priority. Identification of donor characteristics correlating with higher CBU quality could guide operational strategies to increase the yield of banked high-quality CBUs. STUDY DESIGN AND METHODS: Characteristics of 5267 CBUs donated to the Carolinas Cord Blood Bank, a public bank participating in the National Cord Blood Inventory, were retrospectively analyzed. Eligible CBUs, collected by trained personnel, were processed using standard procedures. Routine quality and potency metrics (postprocessing total nucleated cell count [post-TNCC], CD34+, colony-forming units [CFUs]) were correlated with maternal, infant, and collection characteristics. RESULTS: High-quality CBUs were defined as those with higher post-TNCC (>1.25 × 10(9)) with CD34+ and CFUs in the upper quartile. Factors associated with higher CD34+ or CFU content included a shorter interval from collection to processing (<10 hr), younger gestational age (34-37 weeks; CD34+ and CFUs), Caucasian race, higher birthweight (>3500 g), and larger collection volumes (>80 mL). CONCLUSIONS: We describe characteristics identifying high-quality CBUs, which can be used to inform strategies for CBU collection for public banks. Efforts should be made to prioritize collections from larger babies born before 38 weeks of gestation. CBUs should be rapidly transported to the processing laboratory. The lower quality of CBUs from non-Caucasian donors highlights the challenges of building a racially diverse public CB inventory.

Authors
Page, KM; Mendizabal, A; Betz-Stablein, B; Wease, S; Shoulars, K; Gentry, T; Prasad, VK; Sun, J; Carter, S; Balber, AE; Kurtzberg, J
MLA Citation
Page, KM, Mendizabal, A, Betz-Stablein, B, Wease, S, Shoulars, K, Gentry, T, Prasad, VK, Sun, J, Carter, S, Balber, AE, and Kurtzberg, J. "Optimizing donor selection for public cord blood banking: influence of maternal, infant, and collection characteristics on cord blood unit quality." Transfusion 54.2 (February 2014): 340-352.
PMID
23711284
Source
pubmed
Published In
Transfusion
Volume
54
Issue
2
Publish Date
2014
Start Page
340
End Page
352
DOI
10.1111/trf.12257

Stem-cell transplantation for chronic granulomatous disease

Authors
Prasad, VK
MLA Citation
Prasad, VK. "Stem-cell transplantation for chronic granulomatous disease." The Lancet 383.9915 (January 1, 2014): 390-392.
Source
scopus
Published In
The Lancet
Volume
383
Issue
9915
Publish Date
2014
Start Page
390
End Page
392
DOI
10.1016/S0140-6736(13)62144-3

Amino acid substitution at peptide-binding pockets of HLA class I molecules increases risk of severe acute GVHD and mortality

HLA disparity has a negative impact on the outcomes of hematopoietic cell transplantation (HCT). We studied the independent impact of amino acid substitution (AAS) at peptidebinding positions 9, 99, 116, and 156, and killer immunoglobulin-like receptor binding position 77 of HLA-A, B, or C, on the risks for grade 3-4 acute graft-versus-host disease (GVHD), chronic GVHD, treatment-related mortality (TRM), relapse, and overall survival. In multivariate analysis, a mismatch at HLA-C position 116 was associated with increased risk for severe acute GVHD (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.15-1.82, P =.0016). Mismatch at HLA-C position 99 was associated with increased transplantrelated mortality (HR = 1.37, 95% CI = 1.1-1.69, P =.0038). Mismatch at HLA-B position 9 was associated with increased chronic GVHD (HR=2.28, 95%CI =1.36-3.82, P=.0018).No AAS were significantly associated with outcome at HLA-A. Specific AAS pair combinations with a frequency >30 were tested for association with HCT outcomes. Cysteine to tyrosine substitution at position 99 of HLA-C was associated with increased TRM (HR = 1.78, 95% = CI 1.27-2.51, P =.0009). These results demonstrate that donor-recipient mismatch for certainpeptide-binding residues of the HLA class Imoleculeis associated with increased risk for acute and chronic GVHD and death. © 2013 by The American Society of Hematology.

Authors
Pidala, J; Wang, T; Haagenson, M; Spellman, SR; Askar, M; Battiwalla, M; Baxter-Lowe, LA; Bitan, M; Fernandez-Viña, M; Gandhi, M; Jakubowski, AA; Maiers, M; Marino, SR; Marsh, SGE; Oudshoorn, M; Palmer, J; Prasad, VK; Reddy, V; Ringden, O; Saber, W; Santarone, S; Schultz, KR; Setterholm, M; Trachtenberg, E; Turner, EV; Woolfrey, AE; Lee, SJ; Anasetti, C
MLA Citation
Pidala, J, Wang, T, Haagenson, M, Spellman, SR, Askar, M, Battiwalla, M, Baxter-Lowe, LA, Bitan, M, Fernandez-Viña, M, Gandhi, M, Jakubowski, AA, Maiers, M, Marino, SR, Marsh, SGE, Oudshoorn, M, Palmer, J, Prasad, VK, Reddy, V, Ringden, O, Saber, W, Santarone, S, Schultz, KR, Setterholm, M, Trachtenberg, E, Turner, EV, Woolfrey, AE, Lee, SJ, and Anasetti, C. "Amino acid substitution at peptide-binding pockets of HLA class I molecules increases risk of severe acute GVHD and mortality." Blood 122.22 (November 21, 2013): 3651-3658.
PMID
23982174
Source
scopus
Published In
Blood
Volume
122
Issue
22
Publish Date
2013
Start Page
3651
End Page
3658
DOI
10.1182/blood-2013-05-501510

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

Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning.

We report transplantation outcomes of 258 children with Hurler syndrome (HS) after a myeloablative conditioning regimen from 1995 to 2007. Median age at transplant was 16.7 months and median follow-up was 57 months. The cumulative incidence of neutrophil recovery at day 60 was 91%, acute graft-versus-host disease (GVHD) (grade II-IV) at day 100 was 25%, and chronic GVHD and 5 years was 16%. Overall survival and event-free survival (EFS) at 5 years were 74% and 63%, respectively. EFS after HLA-matched sibling donor (MSD) and 6/6 matched unrelated cord blood (CB) donor were similar at 81%, 66% after 10/10 HLA-matched unrelated donor (UD), and 68% after 5/6 matched CB donor. EFS was lower after transplantation in 4/6 matched unrelated CB (UCB) (57%; P = .031) and HLA-mismatched UD (41%; P = .007). Full-donor chimerism (P = .039) and normal enzyme levels (P = .007) were higher after CB transplantation (92% and 98%, respectively) compared with the other grafts sources (69% and 59%, respectively). In conclusion, results of allogeneic transplantation for HS are encouraging, with similar EFS rates after MSD, 6/6 matched UCB, 5/6 UCB, and 10/10 matched UD. The use of mismatched UD and 4/6 matched UCB was associated with lower EFS.

Authors
Boelens, JJ; Aldenhoven, M; Purtill, D; Ruggeri, A; Defor, T; Wynn, R; Wraith, E; Cavazzana-Calvo, M; Rovelli, A; Fischer, A; Tolar, J; Prasad, VK; Escolar, M; Gluckman, E; O'Meara, A; Orchard, PJ; Veys, P; Eapen, M; Kurtzberg, J; Rocha, V; Eurocord, ; Inborn Errors Working Party of European Blood and Marrow Transplant group, ; Duke University Blood and Marrow Transplantation Program, ; Centre for International Blood and Marrow Research,
MLA Citation
Boelens, JJ, Aldenhoven, M, Purtill, D, Ruggeri, A, Defor, T, Wynn, R, Wraith, E, Cavazzana-Calvo, M, Rovelli, A, Fischer, A, Tolar, J, Prasad, VK, Escolar, M, Gluckman, E, O'Meara, A, Orchard, PJ, Veys, P, Eapen, M, Kurtzberg, J, Rocha, V, Eurocord, , Inborn Errors Working Party of European Blood and Marrow Transplant group, , Duke University Blood and Marrow Transplantation Program, , and Centre for International Blood and Marrow Research, . "Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning." Blood 121.19 (May 9, 2013): 3981-3987.
PMID
23493783
Source
pubmed
Published In
Blood
Volume
121
Issue
19
Publish Date
2013
Start Page
3981
End Page
3987
DOI
10.1182/blood-2012-09-455238

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

Challenges and opportunities for international cooperative studies in pediatric hematopoeitic cell transplantation: Priorities of the westhafen intercontinental group

More than 20% of allogeneic hematopoietic cell transplantations (HCTs) are performed in children and adolescents at a large number of relatively small centers. Unlike adults, at least one-third of HCTs in children are performed for rare, nonmalignant indications. Clinical trials to improve HCT outcomes in children have been limited by small numbers and these pediatric-specific features. The need for a larger number of pediatric HCT centers to participate in trials has led to the involvement of international collaborative groups. Representatives of the Pediatric Blood and Marrow Transplant Consortium, European Group for Blood and Marrow Transplantation's Pediatric Working Group, International Berlin-Frankfurt-Munster (iBFm) Stem Cell Transplantation Committee, and Children's Oncology Group's Hematopoietic Stem Cell Transplantation Discipline Committee met on October 3, 2012, in Frankfurt, Germany to develop a consensus on the highest priorities in pediatric HCT. In addition, it explored the creation of an international consortium to develop studies focused on HCT in children and adolescents. This meeting led to the creation of an international HCT network, dubbed the Westhafen Intercontinental Group, to develop worldwide priorities and strategies to address pediatric HCT issues. This review outlines the priorities of need as identified by this consensus group. © 2013 American Society for Blood and Marrow Transplantation.

Authors
Schultz, RKR; Baker, KS; Boelens, JJ; Bollard, CM; Egeler, RM; Cowan, M; Ladenstein, R; Lankester, A; Locatelli, F; Lawitschka, A; Levine, JE; Loh, M; Nemecek, E; Niemeyer, C; Prasad, VK; Rocha, V; Shenoy, S; Strahm, B; Veys, P; Wall, D; Bader, P; Grupp, SA; Pulsipher, MA; Peters, C
MLA Citation
Schultz, RKR, Baker, KS, Boelens, JJ, Bollard, CM, Egeler, RM, Cowan, M, Ladenstein, R, Lankester, A, Locatelli, F, Lawitschka, A, Levine, JE, Loh, M, Nemecek, E, Niemeyer, C, Prasad, VK, Rocha, V, Shenoy, S, Strahm, B, Veys, P, Wall, D, Bader, P, Grupp, SA, Pulsipher, MA, and Peters, C. "Challenges and opportunities for international cooperative studies in pediatric hematopoeitic cell transplantation: Priorities of the westhafen intercontinental group." Biology of Blood and Marrow Transplantation 19.9 (2013): 1279-1287.
PMID
23883618
Source
scival
Published In
Biology of Blood and Marrow Transplantation
Volume
19
Issue
9
Publish Date
2013
Start Page
1279
End Page
1287
DOI
10.1016/j.bbmt.2013.07.006

Effect of HLA-matching recipients to donor noninherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for hematologic malignancy.

Transplantation-related mortality (TRM) is high after HLA-mismatched umbilical cord blood (UCB) transplantation (UCBT). In utero, exposure to noninherited maternal antigen (NIMA) is recognized by the fetus, which induces T regulator cells to that haplotype. It is plausible that UCBTs in which recipients are matched to donor NIMAs may alleviate some of the excess mortality associated with this treatment. To explore this concept, we used marginal matched-pair Cox regression analysis to compare outcomes in 48 NIMA-matched UCBTs (ie, the NIMA of the donor UCB unit matched to the patient) and in 116 non-NIMA-matched UCBTs. All patients had a hematologic malignancy and received a single UCB unit. Cases and controls were matched on age, disease, disease status, transplantation-conditioning regimen, HLA match, and infused cell dose. TRM was lower after NIMA-matched UCBTs compared with NIMA-mismatched UCBTs (relative risk, 0.48; P = .05; 18% versus 32% at 5 years posttransplantation). Consequently, overall survival was higher after NIMA-matched UCBT. The 5-year probability of overall survival was 55% after NIMA-matched UCBTs versus 38% after NIMA-mismatched UCBTs (P = .04). When faced with the choice of multiple HLA-mismatched UCB units containing adequate cell doses, selecting an NIMA-matched UCB unit may improve survival after mismatched UCBT.

Authors
Rocha, V; Spellman, S; Zhang, M-J; Ruggeri, A; Purtill, D; Brady, C; Baxter-Lowe, LA; Baudoux, E; Bergamaschi, P; Chow, R; Freed, B; Koegler, G; Kurtzberg, J; Larghero, J; Lecchi, L; Nagler, A; Navarrette, C; Prasad, V; Pouthier, F; Price, T; Ratanatharathorn, V; van Rood, JJ; Horowitz, MM; Gluckman, E; Eapen, M; Eurocord-European Blood and Marrow Transplant Group and the Center for International Blood and Marrow Transplant Research,
MLA Citation
Rocha, V, Spellman, S, Zhang, M-J, Ruggeri, A, Purtill, D, Brady, C, Baxter-Lowe, LA, Baudoux, E, Bergamaschi, P, Chow, R, Freed, B, Koegler, G, Kurtzberg, J, Larghero, J, Lecchi, L, Nagler, A, Navarrette, C, Prasad, V, Pouthier, F, Price, T, Ratanatharathorn, V, van Rood, JJ, Horowitz, MM, Gluckman, E, Eapen, M, and Eurocord-European Blood and Marrow Transplant Group and the Center for International Blood and Marrow Transplant Research, . "Effect of HLA-matching recipients to donor noninherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for hematologic malignancy." Biol Blood Marrow Transplant 18.12 (December 2012): 1890-1896.
PMID
22814031
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
12
Publish Date
2012
Start Page
1890
End Page
1896
DOI
10.1016/j.bbmt.2012.07.010

Amino Acid Substitution At Peptide-Binding Pockets of HLA Class I Molecules Adversely Impacts Hematopoietic Cell Transplantation Outcomes

Authors
Pidala, J; Wang, T; Haagenson, MD; Spellman, S; Askar, M; Battiwalla, M; Baxter-Lowe, LA; Bitan, M; Fernandez-Vina, M; Gandhi, M; Jakubowski, AA; Maiers, M; Marino, SR; Marsh, SGE; Oudshoorn, M; Palmer, J; Prasad, VK; Reddy, V; Ringden, O; Saber, W; Santarone, S; Schultz, KR; Setterholm, M; Trachtenberg, E; Turner, V; Woolfrey, A; Lee, SJ; Anasetti, C
MLA Citation
Pidala, J, Wang, T, Haagenson, MD, Spellman, S, Askar, M, Battiwalla, M, Baxter-Lowe, LA, Bitan, M, Fernandez-Vina, M, Gandhi, M, Jakubowski, AA, Maiers, M, Marino, SR, Marsh, SGE, Oudshoorn, M, Palmer, J, Prasad, VK, Reddy, V, Ringden, O, Saber, W, Santarone, S, Schultz, KR, Setterholm, M, Trachtenberg, E, Turner, V, Woolfrey, A, Lee, SJ, and Anasetti, C. "Amino Acid Substitution At Peptide-Binding Pockets of HLA Class I Molecules Adversely Impacts Hematopoietic Cell Transplantation Outcomes." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Amino Acid Substitution At Peptide-Binding Pockets of HLA Class I Molecules Adversely Impacts Hematopoietic Cell Transplantation Outcomes

Authors
Pidala, J; Wang, T; Haagenson, MD; Spellman, S; Askar, M; Battiwalla, M; Baxter-Lowe, LA; Bitan, M; Fernandez-Vina, M; Gandhi, M; Jakubowski, AA; Maiers, M; Marino, SR; Marsh, SGE; Oudshoorn, M; Palmer, J; Prasad, VK; Reddy, V; Ringden, O; Saber, W; Santarone, S; Schultz, KR; Setterholm, M; Trachtenberg, E; Turner, V; Woolfrey, A; Lee, SJ; Anasetti, C
MLA Citation
Pidala, J, Wang, T, Haagenson, MD, Spellman, S, Askar, M, Battiwalla, M, Baxter-Lowe, LA, Bitan, M, Fernandez-Vina, M, Gandhi, M, Jakubowski, AA, Maiers, M, Marino, SR, Marsh, SGE, Oudshoorn, M, Palmer, J, Prasad, VK, Reddy, V, Ringden, O, Saber, W, Santarone, S, Schultz, KR, Setterholm, M, Trachtenberg, E, Turner, V, Woolfrey, A, Lee, SJ, and Anasetti, C. "Amino Acid Substitution At Peptide-Binding Pockets of HLA Class I Molecules Adversely Impacts Hematopoietic Cell Transplantation Outcomes." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Myeloablative transplantation using either cord blood or bone marrow leads to immune recovery, high long-term donor chimerism and excellent survival in chronic granulomatous disease.

The curative potential of hematopoietic stem cell transplantation in patients with chronic granulomatous disease depends on availability of a suitable donor, successful donor engraftment, and maintenance of long-term donor chimerism. Twelve consecutive children (median age, 59.5 months; range, 8-140 months) with severe chronic granulomatous disease (serious bacterial/fungal infections pretransplantation; median, 3; range, 2-9) received myeloablative hematopoietic stem cell transplantation using sibling bone marrow ([SibBM]; n = 5), unrelated cord blood (UCB; n = 6), and sibling cord blood (n = 1) at our center between 1997 and 2010. SibBM and sibling cord blood were HLA matched at 6/6, whereas UCB were 5/6 (n = 5) or 6/6 (n = 1). Recipients of SibBM were conditioned with busulfan and cyclophosphamide ± anti-thymocyte globulin (ATG), whereas 6 of 7 cord blood recipients received fludarabine/busulfan/cyclophosphamide/ATG. Seven patients received granulocyte-colony stimulating factor-mobilized granulocyte transfusions from directed donors. The first 2 UCB recipients had primary graft failure but successfully underwent retransplantation with UCB. Highest acute graft-versus-host disease was grade III (n = 1). Extensive chronic graft-vs-host disease developed in 3 patients. All patients are alive with median follow-up of 70.5 months (range, 12-167 months) with high donor chimerism (>98%, n = 10; 94%, n = 1; and 92%, n = 1). Myeloablative hematopoietic stem cell transplantation led to correction of neutrophil dysfunction, durable donor chimerism, excellent survival, good quality of life, and low incidence of graft-vs-host disease regardless of graft source.

Authors
Tewari, P; Martin, PL; Mendizabal, A; Parikh, SH; Page, KM; Driscoll, TA; Malech, HL; Kurtzberg, J; Prasad, VK
MLA Citation
Tewari, P, Martin, PL, Mendizabal, A, Parikh, SH, Page, KM, Driscoll, TA, Malech, HL, Kurtzberg, J, and Prasad, VK. "Myeloablative transplantation using either cord blood or bone marrow leads to immune recovery, high long-term donor chimerism and excellent survival in chronic granulomatous disease." Biol Blood Marrow Transplant 18.9 (September 2012): 1368-1377.
PMID
22326631
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
18
Issue
9
Publish Date
2012
Start Page
1368
End Page
1377
DOI
10.1016/j.bbmt.2012.02.002

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

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

Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal™) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study.

Preliminary studies using directed-donor ex vivo expanded human mesenchymal stem cells (hMSCs) have shown promise in the treatment of acute graft-versus-host disease (aGVHD). However, their production is cumbersome and standardization is difficult. We describe the first experience of using a premanufactured, universal donor, formulation of hMSCs (Prochymal) in children (n = 12; 10 boys; 9 Caucasian; age range: 0.4-15 years) with treatment-resistant grade III and IV aGVHD who received therapy on compassionate use basis between July 2005 and June 2007 at 5 transplant centers. All patients had stage III or IV gut (GI) symptoms and half had additional liver and/or skin involvement. Disease was refractory to steroids in all cases and additionally to a median of 3 other immunosuppressive therapies. The hMSCs (8 × 10(6)cells/kg/dose in 2 patients and 2 × 10(6)cells/kg/dose in the rest) were infused intravenously over 1 hour twice a week for 4 weeks. Partial and mixed responders received subsequent weekly therapy for 4 weeks. HLA or other matching was not needed. The hMSCs were started at a median of 98 days (range: 45-237) posttransplant. A total of 124 doses were administered, with a median of 8 doses (range: 2-21) per patient. Overall, 7 (58%) patients had complete response, 2 (17%) partial response, and 3 (25%) mixed response. Complete resolution of GI symptoms occurred in 9 (75%) patients. Two patients relapsed after initial response and showed partial response to retreatment. The cumulative incidence of survival at 100 days from the initiation of Prochymal therapy was 58%. Five of 12 patients (42%) were still alive after a median follow-up of 611 days (range: 427-1111) in surviving patients. No infusional or other identifiable acute toxicity was seen in any patient. Multiple infusions of hMSCs were well tolerated and appeared to be safe in children. Clinical responses, particularly in the GI system, were seen in the majority of children with severe refractory aGVHD. Given the favorable results observed in a patient population with an otherwise grave prognosis, we conclude that hMSCs hold potential for the treatment of aGVHD, and should be further studied in phase III trials in pediatric and adult patients.

Authors
Prasad, VK; Lucas, KG; Kleiner, GI; Talano, JAM; Jacobsohn, D; Broadwater, G; Monroy, R; Kurtzberg, J
MLA Citation
Prasad, VK, Lucas, KG, Kleiner, GI, Talano, JAM, Jacobsohn, D, Broadwater, G, Monroy, R, and Kurtzberg, J. "Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal™) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study." Biol Blood Marrow Transplant 17.4 (April 2011): 534-541.
PMID
20457269
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
4
Publish Date
2011
Start Page
534
End Page
541
DOI
10.1016/j.bbmt.2010.04.014

VITAMIN D DEFICIENCY IN CHILDREN UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION

Authors
Desai, SR; Tewari, P; Whelan, M; Kurtzberg, J; Prasad, VK
MLA Citation
Desai, SR, Tewari, P, Whelan, M, Kurtzberg, J, and Prasad, VK. "VITAMIN D DEFICIENCY IN CHILDREN UNDERGOING HEMATOPOIETIC 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
S274
End Page
S274
DOI
10.1016/j.bbmt.2010.12.366

DIFFERENTIAL IMPACT OF HLA-A, -B, AND-DRB1 MISMATCHING IN RELATION TO OTHER VARIABLES ON THE OUTCOMES OF MYELOABLATIVE UNRELATED SINGLE DONOR UMBILICAL CORD BLOOD TRANSPLANTATION FROM 4/6 MATCHED UNITS IN CHILDREN AND YOUNG ADULTS

Authors
Prasad, VK; Mendizabal, A; Tewari, P; Page, K; Parikh, SH; Szabolcs, P; Driscoll, TA; Martin, PL; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Tewari, P, Page, K, Parikh, SH, Szabolcs, P, Driscoll, TA, Martin, PL, and Kurtzberg, J. "DIFFERENTIAL IMPACT OF HLA-A, -B, AND-DRB1 MISMATCHING IN RELATION TO OTHER VARIABLES ON THE OUTCOMES OF MYELOABLATIVE UNRELATED SINGLE DONOR UMBILICAL CORD BLOOD TRANSPLANTATION FROM 4/6 MATCHED UNITS IN CHILDREN AND YOUNG ADULTS." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S185
End Page
S186
DOI
10.1016/j.bbmt.2010.12.100

DURABLE ENGRAFTMENT AND CORRECTION OF GENETIC DEFECT IN CHILDREN WITH CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA FOLLOWING MYELOABLATIVE UMBILICAL CORD BLOOD TRANSPLANTATION

Authors
Mahadeo, KM; Parikh, SH; Driscoll, TA; Page, K; Szabolcs, P; Martin, PL; Kurtzberg, J; Prasad, VK
MLA Citation
Mahadeo, KM, Parikh, SH, Driscoll, TA, Page, K, Szabolcs, P, Martin, PL, Kurtzberg, J, and Prasad, VK. "DURABLE ENGRAFTMENT AND CORRECTION OF GENETIC DEFECT IN CHILDREN WITH CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA FOLLOWING MYELOABLATIVE UMBILICAL CORD BLOOD TRANSPLANTATION." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S256
End Page
S256
DOI
10.1016/j.bbmt.2010.12.312

SUPPORTIVE CARE

Authors
Tewari, P; Allison, J; Waters-Pick, B; Cash, JV; Kurtzberg, J; Prasad, VK
MLA Citation
Tewari, P, Allison, J, Waters-Pick, B, Cash, JV, Kurtzberg, J, and Prasad, VK. "SUPPORTIVE CARE." February 2011.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
2
Publish Date
2011
Start Page
S272
End Page
S272
DOI
10.1016/j.bbmt.2010.12.360

Current international perspectives on hematopoietic stem cell transplantation for inherited metabolic disorders.

Inherited metabolic disorders (IMD) or inborn errors of metabolism are a diverse group of diseases arising from genetic defects in lysosomal enzymes or peroxisomal function. These diseases are characterized by devastating systemic processes affecting neurologic and cognitive function, growth and development, and cardiopulmonary status. Onset in infancy or early childhood is typically accompanied by rapid deterioration. Early death is a common outcome. Timely diagnosis and immediate referral to an IMD specialist are essential steps in management of these disorders. Treatment recommendations are based on the disorder, its phenotype including age at onset and rate of progression, severity of clinical signs and symptoms, family values and expectations, and the risks and benefits associated with available therapies such as allogeneic hematopoietic stem cell transplantation (HSCT). This review discusses indications for HSCT and outcomes of HSCT for selected IMD. An international perspective on progress, limitations, and future directions in the field is provided.

Authors
Boelens, JJ; Prasad, VK; Tolar, J; Wynn, RF; Peters, C
MLA Citation
Boelens, JJ, Prasad, VK, Tolar, J, Wynn, RF, and Peters, C. "Current international perspectives on hematopoietic stem cell transplantation for inherited metabolic disorders." Pediatr Clin North Am 57.1 (February 2010): 123-145. (Review)
PMID
20307715
Source
pubmed
Published In
Pediatric Clinics of North America
Volume
57
Issue
1
Publish Date
2010
Start Page
123
End Page
145
DOI
10.1016/j.pcl.2009.11.004

Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions.

Progressive degeneration of the central nervous system leading to the loss of neuromotor, neurophysiological and cognitive abilities is the fundamental clinical problem in patients with many inherited metabolic diseases (IMD). Worldwide experience shows that morbidity, quality of life, and survival in these patients can be improved by allogeneic haematopoietic stem cell transplantation (HSCT), particularly when performed early in the course of the disease. At present, while available for some conditions, exogenous enzyme replacement therapy is unable to correct cognitive and central nervous system disease because of its inability to cross the blood-brain barrier. In contrast, HSCT allows donor-derived, enzyme-producing cells to migrate to the brain and other organs providing a permanent enzyme replacement therapy. HSCT may also mediate non-hematopoietic cell regeneration or repair. Traditionally, bone marrow has been the graft source for IMD patients. However, in the last 5 years many studies utilizing unrelated donor umbilical cord blood (UCB) as a graft source have demonstrated that UCB provides rapid and increased access to transplantation with favourable outcomes. This review describes preclinical studies and past and present clinical treatment approaches and discusses current controversies and future directions of this promising field.

Authors
Prasad, VK; Kurtzberg, J
MLA Citation
Prasad, VK, and Kurtzberg, J. "Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions." Br J Haematol 148.3 (February 2010): 356-372. (Review)
PMID
19919654
Source
pubmed
Published In
British Journal of Haematology
Volume
148
Issue
3
Publish Date
2010
Start Page
356
End Page
372
DOI
10.1111/j.1365-2141.2009.07974.x

Transplant outcomes in mucopolysaccharidoses.

The mucopolysaccharidoses (MPSs) are inherited metabolic disorders (IMDs) caused by single-gene defects leading to progressive cellular accumulation of glycosaminoglycans (GAGs) and damage to multiple organs, including the central nervous, musculoskeletal, cardiorespiratory, and other systems. Hurler syndrome (MPS IH), the most severe form, is the prototypical model. Enzyme replacement therapy (ERT), available for MPS I, II, and VI, is beneficial in some patients. However, ERT does not improve neurocognitive function because of its inability to cross the blood-brain barrier. In contrast, allogeneic hematopoietic stem cell transplantation (HSCT) allows donor-derived, enzyme-producing cells to migrate to the brain and other organs to provide permanent enzyme therapy and thus help somatic organs, improve neurocognitive function and quality of life, and prolong survival, particularly when performed early in the course of the disease. Bone marrow has been the graft source in the past. However, in the last 5 years many patients have been treated with unrelated donor (URD) umbilical cord blood transplant (UCBT), allowing rapid and increased access to transplantation with favorable outcomes. This review describes published and our institutional clinical experiences, discusses the current status of the field, and provides therapy guidelines for patients with MPS.

Authors
Prasad, VK; Kurtzberg, J
MLA Citation
Prasad, VK, and Kurtzberg, J. "Transplant outcomes in mucopolysaccharidoses." Semin Hematol 47.1 (January 2010): 59-69. (Review)
PMID
20109613
Source
pubmed
Published In
Seminars in Hematology
Volume
47
Issue
1
Publish Date
2010
Start Page
59
End Page
69
DOI
10.1053/j.seminhematol.2009.10.008

Transplantation Following Myeloablative Cytoreduction Results in Excellent Survival, Long-Term Engraftment, and Donor Chimerism in Children with Chronic Granulomatous Disease Across Donor and Graft Sources

Authors
Tewari, P; Wood, S; Martin, PL; Parikh, SH; Szabolcs, P; Page, KM; Driscoll, T; Kurtzberg, J; Prasad, VK
MLA Citation
Tewari, P, Wood, S, Martin, PL, Parikh, SH, Szabolcs, P, Page, KM, Driscoll, T, Kurtzberg, J, and Prasad, VK. "Transplantation Following Myeloablative Cytoreduction Results in Excellent Survival, Long-Term Engraftment, and Donor Chimerism in Children with Chronic Granulomatous Disease Across Donor and Graft Sources." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
1319
End Page
1319

Umbilical cord blood transplantation for non-malignant diseases.

Many factors, including lower risk of GVHD, rapid availability of 4/6-6/6 matched cord blood (CB) units and incremental gains in the outcomes, have led to an increasing use of CB transplantation (CBT) to treat many patients who lack fully matched adult BM donors. A large electronically searchable worldwide inventory of publicly banked CB units allows for quicker donor identification and selection. In this review, we examine the current status and cumulative experience of related and unrelated donor CBT for the treatment of non-malignant diseases, including hemoglobinopathies, BM failure syndromes, primary immunodeficiency diseases (PIDs) and inherited metabolic disorders (IMDs), and conclude that CBT offers a promising and effective therapy for these diseases. Future strategies to facilitate earlier diagnosis and to decrease transplant-related risks should further improve the short- and long-term outcomes. Every effort should be made to perform transplantation early in the course of disease before extensive damage to various tissues and organs ensues.

Authors
Prasad, VK; Kurtzberg, J
MLA Citation
Prasad, VK, and Kurtzberg, J. "Umbilical cord blood transplantation for non-malignant diseases." Bone Marrow Transplant 44.10 (November 2009): 643-651. (Review)
PMID
19802020
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
44
Issue
10
Publish Date
2009
Start Page
643
End Page
651
DOI
10.1038/bmt.2009.290

Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic syndrome: a single-center experience.

Myelodysplastic syndromes (MDS) respond poorly to chemotherapy. Between 1995 and 2006, 23 pediatric patients with MDS were transplanted with unrelated donor umbilical cord blood (UUCB) at our center. The median age was 11.1 years (range: 1.1-19.7), median weight was 38.6 kg (range: 9.6-62.6), 61% of patients were male, and median time from diagnosis to transplant was 6.6 months (range: 2.0-61.4). Patients were followed for a median of 5.3 years (range: 1.6-12.4 years) posttransplant. MDS stage was refractory anemia (RA) in 12, refractory anemia with excess blasts (RAEB) in 8, and refractory anemia with excess blasts in transformation (RAEB-T) in 3 patients; 18 (78%) patients had primary MDS. Monosomy 7 was present in 17(74%) patients. Patients with acute myelogenous leukemia (AML) were excluded. Preparative regimen was total body irradiation (TBI) based in 18 (78%) patients. Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine (CsA)/steroids (19 patients) or CsA/mycophenolate mofetil (MMF; 4 patients). Grafts were HLA matched at Class I (A and B) at low resolution and Class II (DRB1) at the allelic level, resulting in 16 (70%) 4/6 and 7 (30%) 5/6 matched transplants. The grafts contained a median of 4.0 x 10(7) (range: 1.7-12.6) total nucleated cells (TNC)/kg precryopreservation; 3.6 x 10(7) (range: 1.0-12.0) TNC/kg and 1.7 x 10(5) (range: 0.2-28.5) CD34+ cells/kg were infused. Cumulative incidence of neutrophil engraftment (absolute neutrophil count [ANC] >500/microL) at day 42 and day 100 was 73.9% (95% confidence interval [CI] 55.1%-92.7%) and 91.3% (95% CI 71.3%-100.0%) respectively, and that of platelet engraftment (50 K) at 180 days was 69.6% (95% CI 49.8%-89.4%). Three patients had graft failure whereas 3 patients (13%) engrafted slowly (after day 42). Three patients developed acute GVHD (aGVHD) grades II-IV with a cumulative incidence at 100 days of 13% (95% CI 0.0%-27.1.0%). Four patients relapsed with a cumulative incidence of relapse at 3 years of 13.0% (95% CI 0.0%-27.1%). Cumulative incidence of nonrelapse mortality (NRM) at 1 year was 27% (95% CI 8.0%-46.0%). Ten patients died: 3 graft failure, 4 relapse, 2 infections (1 adenovirus, 1 toxoplasmosis), and 1 Epstein-Barr virus (EBV) lymphoproliferative disorder. Probabilities of event-free survival (EFS) at 1 and 3 years were 69.6% (95% CI 46.6%-84.2%) and 60.9% (95% CI 38.3%-77.4%), respectively. Factors associated with better EFS were age < or = 11 years (P = .05) and weight < or = 38 kg (P = .03). These results, especially in younger patients with monosomy 7 positive MDS, are equivalent to published matched allogeneic bone marrow data. UUCB should be actively considered for pediatric MDS patients lacking matched related or unrelated adult donors.

Authors
Parikh, SH; Mendizabal, A; Martin, PL; Prasad, VK; Szabolcs, P; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Mendizabal, A, Martin, PL, Prasad, VK, Szabolcs, P, Driscoll, TA, and Kurtzberg, J. "Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic syndrome: a single-center experience." Biol Blood Marrow Transplant 15.8 (August 2009): 948-955.
PMID
19589484
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
8
Publish Date
2009
Start Page
948
End Page
955
DOI
10.1016/j.bbmt.2009.04.010

Risk factor analysis of outcomes after unrelated cord blood transplantation in patients with hurler syndrome.

Allogeneic stem cell transplantation (SCT) is considered effective in preventing disease progression in patients with Hurler syndrome (HS). Unrelated umbilical cord blood (UCB) grafts are suggested as an alternative to bone marrow (BM) or peripheral blood stem cells (PBSC). We studied 93 HS patients receiving an UCB graft to analyze risk factors for outcomes. The median time from diagnosis to transplant was 4.6 months, median follow-up was 29 months, and median number of nucleated CB cells infused was 7.6 x 10(7)/kg. Most of the patients received 1 or 2 HLA disparate grafts, and the most frequently used conditioning regimen was cyclophosphamide + busulfan (Bu/Cy). All patients received anti-T cell antibody. At post transplant day +60, the cumulative incidence of neutrophil engraftment was 85%. A younger age at transplant and a higher CD34(+) dose at infusion were favorably associated with engraftment. With the exception of 2 patients, all engrafted patients achieved full and sustained donor chimerism. The 3-year event-free survival (EFS) and 3-year overall survival (OS) rates were 70% and 77%, respectively. In a multivariate analyses, use of Bu/Cy and a shorter interval from diagnosis to transplant were predictors for improved EFS rate (82% for patients transplanted within 4.6 months after diagnosis compared to 57% for the rest). Improved outcomes from early transplantation and immediate availability of CB unit lead us to conclude that CB transplantation is a beneficial option, which should be considered expediently for children with HS.

Authors
Boelens, JJ; Rocha, V; Aldenhoven, M; Wynn, R; O'Meara, A; Michel, G; Ionescu, I; Parikh, S; Prasad, VK; Szabolcs, P; Escolar, M; Gluckman, E; Cavazzana-Calvo, M; Kurtzberg, J; EUROCORD, Inborn error Working Party of EBMT and Duke University,
MLA Citation
Boelens, JJ, Rocha, V, Aldenhoven, M, Wynn, R, O'Meara, A, Michel, G, Ionescu, I, Parikh, S, Prasad, VK, Szabolcs, P, Escolar, M, Gluckman, E, Cavazzana-Calvo, M, Kurtzberg, J, EUROCORD, and Inborn error Working Party of EBMT and Duke University, . "Risk factor analysis of outcomes after unrelated cord blood transplantation in patients with hurler syndrome." Biol Blood Marrow Transplant 15.5 (May 2009): 618-625.
PMID
19361754
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
5
Publish Date
2009
Start Page
618
End Page
625
DOI
10.1016/j.bbmt.2009.01.020

PERICARDIAL EFFUSION FOLLOWING UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION: ANALYSIS IN A COHORT OF 423 PEDIATRIC PATIENTS TRANSPLANTED AT A SINGLE CENTER

Authors
Hwang, EI; Camitta, MGW; Vinesett, R; Mendizabal, A; Wood, S; Semmel, D; Page, K; Driscoll, TA; Parikh, SH; Szabolcs, P; Kurtzberg, J; Prasad, VK
MLA Citation
Hwang, EI, Camitta, MGW, Vinesett, R, Mendizabal, A, Wood, S, Semmel, D, Page, K, Driscoll, TA, Parikh, SH, Szabolcs, P, Kurtzberg, J, and Prasad, VK. "PERICARDIAL EFFUSION FOLLOWING UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION: ANALYSIS IN A COHORT OF 423 PEDIATRIC PATIENTS TRANSPLANTED AT A SINGLE CENTER." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 73-74.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
73
End Page
74

UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION FROM A SINGLE 4/6 MATCHED UNIT IS AN EFFECTIVE THERAPY FOR CHILDREN WITH MALIGNANT AND NON-MALIGNANT DIAGNOSES: GOOD SURVIVAL, LOW GRAFT FAILURE AND GRAFT-VS-HOST DISEASE IN A SINGLE CENTER ANALYSIS OF 314 PATIENTS

Authors
Prasad, VK; Mendizabal, A; Gill, P; Parikh, SH; Szabolcs, P; Driscoll, TA; Page, K; Wood, S; Semmel, D; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Gill, P, Parikh, SH, Szabolcs, P, Driscoll, TA, Page, K, Wood, S, Semmel, D, Martin, PL, Carter, S, and Kurtzberg, J. "UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION FROM A SINGLE 4/6 MATCHED UNIT IS AN EFFECTIVE THERAPY FOR CHILDREN WITH MALIGNANT AND NON-MALIGNANT DIAGNOSES: GOOD SURVIVAL, LOW GRAFT FAILURE AND GRAFT-VS-HOST DISEASE IN A SINGLE CENTER ANALYSIS OF 314 PATIENTS." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 27-27.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
27
End Page
27

OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN PEDIATRIC PATIENTS WITH PRIMARY AND SECONDARY MYELODYSPLASTIC SYNDROMES

Authors
Parikh, SH; Mendizabal, A; Betz-Stablein, B; Martin, PL; Szabolcs, P; Prasad, VK; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Mendizabal, A, Betz-Stablein, B, Martin, PL, Szabolcs, P, Prasad, VK, Driscoll, TA, and Kurtzberg, J. "OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN PEDIATRIC PATIENTS WITH PRIMARY AND SECONDARY MYELODYSPLASTIC SYNDROMES." BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15.2 (February 2009): 72-72.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
15
Issue
2
Publish Date
2009
Start Page
72
End Page
72

Single Donor 4/6 Matched Banked Unrelated Cord Blood Is An Effective Graft Source for Children Undergoing Myeloablative Transplantation for Malignant and Nonmalignant Disorders: Single Center Analysis of 318 Patients

Authors
Prasad, VK; Gill, P; Vinesett, R; Parikh, SH; Szabolcs, P; Driscoll, TA; Page, KM; Wood, S; Semmel, D; Martin, PL; Kurtzberg, J
MLA Citation
Prasad, VK, Gill, P, Vinesett, R, Parikh, SH, Szabolcs, P, Driscoll, TA, Page, KM, Wood, S, Semmel, D, Martin, PL, and Kurtzberg, J. "Single Donor 4/6 Matched Banked Unrelated Cord Blood Is An Effective Graft Source for Children Undergoing Myeloablative Transplantation for Malignant and Nonmalignant Disorders: Single Center Analysis of 318 Patients." BLOOD 112.11 (November 16, 2008): 690-690.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
690
End Page
690

Differential Impact of Inhibitory and Activating Killer Ig-Like Receptors and HLA Ligand on Outcomes of Transplantation for Myeloid and Lymphoid Malignancies

Authors
Prasad, VK; Chen, D-F; Broadwater, G; Reinsmoen, NL; Clark, A; Chao, NJ; Rizzieri, DA
MLA Citation
Prasad, VK, Chen, D-F, Broadwater, G, Reinsmoen, NL, Clark, A, Chao, NJ, and Rizzieri, DA. "Differential Impact of Inhibitory and Activating Killer Ig-Like Receptors and HLA Ligand on Outcomes of Transplantation for Myeloid and Lymphoid Malignancies." BLOOD 112.11 (November 16, 2008): 1118-1118.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
1118
End Page
1118

Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies.

Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching at enrollment was 6/6 (n = 17), 5/6 (n = 58), 4/6 (n = 111), or 3/6 (n = 5) by low-resolution HLA-A, -B, and high-resolution (HR) DRB1. Retrospectively, 179 pairs were HLA typed by HR. The median precryopreservation total nucleated cell (TNC) dose was 5.1 x 10(7) TNC/kg (range, 1.5-23.7) with 3.9 x 10(7) TNC/kg (range, 0.8-22.8) infused. The median time to engraftment (absolute neutrophil count > 500/mm(3) and platelets 50 000/muL) was 27 and 174 days. The cumulative incidence of neutrophil engraftment by day 42 was 79.9% (95% confidence interval [CI], 75.1%-85.2%); acute grades III/IV GVHD by day 100 was 19.5% (95% CI, 13.9%-25.5%); and chronic GVHD at 2 years was 20.8% (95% CI, 14.8%-27.7%). HR matching decreased the probability of severe acute GVHD. The cumulative incidence of relapse at 2 years was 19.9% (95% CI, 14.8%-25.7%). The probabilities of 6-month and 2-year survivals were 67.4% and 49.5%. Unrelated donor cord blood transplantation from partially HLA-mismatched units can cure many children with leukemias. The study was registered at www.clinicaltrials.gov as #NCT00000603.

Authors
Kurtzberg, J; Prasad, VK; Carter, SL; Wagner, JE; Baxter-Lowe, LA; Wall, D; Kapoor, N; Guinan, EC; Feig, SA; Wagner, EL; Kernan, NA; COBLT Steering Committee,
MLA Citation
Kurtzberg, J, Prasad, VK, Carter, SL, Wagner, JE, Baxter-Lowe, LA, Wall, D, Kapoor, N, Guinan, EC, Feig, SA, Wagner, EL, Kernan, NA, and COBLT Steering Committee, . "Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies." Blood 112.10 (November 15, 2008): 4318-4327.
PMID
18723429
Source
pubmed
Published In
Blood
Volume
112
Issue
10
Publish Date
2008
Start Page
4318
End Page
4327
DOI
10.1182/blood-2007-06-098020

Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes.

Outcomes of 159 young patients with inherited metabolic disorders (IMDs) undergoing transplantation with partially HLA-mismatched unrelated donor umbilical cord blood were studied to investigate the impact of graft and patient characteristics on engraftment, overall survival (OS), and graft-versus-host disease (GVHD). Patients received myeloablative chemotherapy (busulfan, cyclophosphamide, ATG) and cyclosporine-based GVHD prophylaxis. Infused cell doses were high (7.57 x 10(7)/kg) because of the patients' young age (median, 1.5 years) and small size (median, 12 kg). Median follow-up was 4.2 years (range, 1-11 years). The cumulative incidences of neutrophil and platelet engraftment were 87.1% (95% confidence interval [CI], 81.8%-92.4%) and 71.0% (95% CI, 63.7%-78.3%). A total of 97% achieved high (> 90%) donor chimerism. Serum enzyme normalized in 97% of patients with diseases for which testings exist. Grade III/IV acute GVHD occurred in 10.3% (95% CI, 5.4%-15.2%) of patients. Extensive chronic GVHD occurred in 10.8% (95% CI, 5.7%-15.9%) of patients by 1 year. OS at 1 and 5 years was 71.8% (95% CI, 64.7%-78.9%) and 58.2% (95% CI, 49.7%-66.6%) in all patients and 84.5% (95% CI, 77.0%-92.0%) and 75.7% (95% CI, 66.1%-85.3%) in patients with high (80-100) performance score. In multivariate analysis, favorable factors for OS were high pretransplantation performance status, matched donor/recipient ethnicity, and higher infused colony forming units.

Authors
Prasad, VK; Mendizabal, A; Parikh, SH; Szabolcs, P; Driscoll, TA; Page, K; Lakshminarayanan, S; Allison, J; Wood, S; Semmel, D; Escolar, ML; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Parikh, SH, Szabolcs, P, Driscoll, TA, Page, K, Lakshminarayanan, S, Allison, J, Wood, S, Semmel, D, Escolar, ML, Martin, PL, Carter, S, and Kurtzberg, J. "Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes." Blood 112.7 (October 1, 2008): 2979-2989.
PMID
18587012
Source
pubmed
Published In
Blood
Volume
112
Issue
7
Publish Date
2008
Start Page
2979
End Page
2989
DOI
10.1182/blood-2008-03-140830

Posttransplant autoimmune hemolytic anemia and other autoimmune cytopenias are increased in very young infants undergoing unrelated donor umbilical cord blood transplantation.

Autoimmune cytopenias are a recognized complication of hematopoietic stem cell transplant (HSCT), and are considered to be a feature of chronic graft-versus-host disease (cGVHD). We report on a cohort of very young infants (< or =3 months of age) receiving HSCT from unrelated donor umbilical cord blood for genetic disorders who developed posttransplant autoimmune cytopenias at an increased rate compared to older aged controls. These infants received a conditioning regimen consisting of busulfan, cyclophosphamide, and antithymocyte globulin (ATG). All infants received HLA mismatched unrelated umbilical cord blood as graft source. GVHD prophylaxis was either cyclosporine + methylprednisolone (n = 16) or cyclosporine + mycophenolate mofetil (n = 3). Engraftment, acute GVHD (aGVHD) and cGVHD, survival, treatment-related mortality (TRM), and deaths were evaluated. Ten patients developed cGVHD manifesting as autoimmune cytopenias at a median 247 days posttransplant with a cumulative incidence of 44% (95% confidence interval [CI] 21%-68%) and 56% (95% CI 32%-80%) at 1 and 2 years, respectively. In 6 of 10 patients developing autoimmune cytopenias, cGVHD presented as autoimmune cytopenia de novo. The cytopenias observed included anemia (n = 4), thrombocytopenia (n = 1), anemia with thrombocytopenia (n = 3), and pancytopenia (n = 2). No graft factors were identified as being significant to development of cGVHD. All patients responded to treatment with methylprednisolone, azithioprine +/- rituximab. One patient required splenectomy. We hypothesize that posttransplant immunosuppression interferes with normal immune ontogeny creating immune dysregulation and graft directed cell destruction. Alternative strategies to prevent GVHD should be considered for this unique patient population.

Authors
Page, KM; Mendizabal, AM; Prasad, VK; Martin, PL; Parikh, S; Wood, S; Sempowski, GD; Szabolcs, P; Kurtzberg, J
MLA Citation
Page, KM, Mendizabal, AM, Prasad, VK, Martin, PL, Parikh, S, Wood, S, Sempowski, GD, Szabolcs, P, and Kurtzberg, J. "Posttransplant autoimmune hemolytic anemia and other autoimmune cytopenias are increased in very young infants undergoing unrelated donor umbilical cord blood transplantation." Biol Blood Marrow Transplant 14.10 (October 2008): 1108-1117.
PMID
18804040
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
10
Publish Date
2008
Start Page
1108
End Page
1117
DOI
10.1016/j.bbmt.2008.07.006

Pediatric hematopoietic stem cell transplantation and the role of imaging.

The use of hematopoietic stem cell transplantation (HSCT) in the treatment of children afflicted with many potentially fatal malignant and nonmalignant diseases is well recognized. Although outcomes continue to improve and the utility of HSCT is increasing, HSCT remains a complicated process necessitating support from many medical disciplines, including radiology. Importantly, children who undergo HSCT are at risk for the development of specific complications that are linked to the timeline of transplantation, as well as to the relationship between the underlying diagnoses, severe immune deficiency, cytoreductive regimen, and graft-versus-host reactions. An understanding of the complex interplay of the immune status, therapeutic regimen, and disease allows increased diagnostic accuracy. Successful treatment of these high-risk children requires that radiologists who are involved with their care be familiar with broad concepts, as well as with specific problems that frequently occur following HSCT. In this article, the clinical aspects of pediatric HSCT are summarized, including common complications, and imaging features of these complications are described.

Authors
Hollingsworth, CL; Frush, DP; Kurtzburg, J; Prasad, VK
MLA Citation
Hollingsworth, CL, Frush, DP, Kurtzburg, J, and Prasad, VK. "Pediatric hematopoietic stem cell transplantation and the role of imaging." Radiology 248.2 (August 2008): 348-365. (Review)
PMID
18641243
Source
pubmed
Published In
Radiology
Volume
248
Issue
2
Publish Date
2008
Start Page
348
End Page
365
DOI
10.1148/radiol.2482070988

THE USE, SAFETY, AND EFFICACY OF DACLIZUMAB FOR STEROID REFRACTORY GRAFT-VERSUS-HOST-DISEASE (GVHD) AFTER UNRELATED CORD BLOOD TRANSPLANTATION (UCBT)

Authors
Mohamed, A; Niedzwiecki, D; Baker, JH; Vinesett, R; Martin, PL; Driscoll, TA; Prasad, VK; Parikh, S; Kurtzberg, J; Szabolcs, P
MLA Citation
Mohamed, A, Niedzwiecki, D, Baker, JH, Vinesett, R, Martin, PL, Driscoll, TA, Prasad, VK, Parikh, S, Kurtzberg, J, and Szabolcs, P. "THE USE, SAFETY, AND EFFICACY OF DACLIZUMAB FOR STEROID REFRACTORY GRAFT-VERSUS-HOST-DISEASE (GVHD) AFTER UNRELATED CORD BLOOD TRANSPLANTATION (UCBT)." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
77
End Page
77
DOI
10.1016/j.bbmt.2007.12.217

OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN PEDIATRIC PATIENTS WITH MYELODYSPLASTIC SYNDROME

Authors
Parikh, SH; Mendizabal, A; Martin, PL; Szabolcs, P; Prasad, VK; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Mendizabal, A, Martin, PL, Szabolcs, P, Prasad, VK, Driscoll, TA, and Kurtzberg, J. "OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN PEDIATRIC PATIENTS WITH MYELODYSPLASTIC SYNDROME." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
83
End Page
84
DOI
10.1016/j.bbmt.2007.12.233

OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN 159 YOUNG PATIENTS WITH PEROXISOMAL AND LYSOSOMAL STORAGE DISORDERS AT A SINGLE CENTER

Authors
Prasad, VK; Mendizabal, A; Parikh, SH; Szabolcs, P; Driscoll, T; Page, K; Lakshbinarayanan, S; Allison, J; Wood, S; Semmel, D; Escolar, ML; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Mendizabal, A, Parikh, SH, Szabolcs, P, Driscoll, T, Page, K, Lakshbinarayanan, S, Allison, J, Wood, S, Semmel, D, Escolar, ML, Martin, PL, Carter, S, and Kurtzberg, J. "OUTCOMES OF UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN 159 YOUNG PATIENTS WITH PEROXISOMAL AND LYSOSOMAL STORAGE DISORDERS AT A SINGLE CENTER." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
26
End Page
26
DOI
10.1016/j.bbmt.2007.12.071

POST THAW COLONY FORMING UNITS (CFU) IS A STRONG INDEPENDENT PREDICTOR OF ENGRAFTMENT AFTER UNRELATED DONOR UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT)

Authors
Page, KM; Mendizabel, A; Waters-Pick, B; Avrutsky, S; Reese, M; Prasad, VK; Kurtzberg, J
MLA Citation
Page, KM, Mendizabel, A, Waters-Pick, B, Avrutsky, S, Reese, M, Prasad, VK, and Kurtzberg, J. "POST THAW COLONY FORMING UNITS (CFU) IS A STRONG INDEPENDENT PREDICTOR OF ENGRAFTMENT AFTER UNRELATED DONOR UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT)." February 2008.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
14
Issue
2
Publish Date
2008
Start Page
41
End Page
42
DOI
10.1016/j.bbmt.2007.12.116

Emerging trends in transplantation of inherited metabolic diseases.

Allogeneic hematopoietic stem cell transplantation (HSCT) can prolong life and improve its quality in patients with inherited metabolic diseases. HSCT offers a permanent source of enzyme replacement therapy and also might mediate nonhematopoietic cell regeneration or repair. Unrelated cord blood is an exciting newer graft source for treatment of patients with these fatal disorders, providing increased access to donors and significant clinical efficacy, particularly when transplantation is performed in early stages. Pre-transplant performance status is highly predictive of overall survival.

Authors
Prasad, VK; Kurtzberg, J
MLA Citation
Prasad, VK, and Kurtzberg, J. "Emerging trends in transplantation of inherited metabolic diseases." Bone Marrow Transplant 41.2 (January 2008): 99-108. (Review)
PMID
18176609
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
41
Issue
2
Publish Date
2008
Start Page
99
End Page
108
DOI
10.1038/sj.bmt.1705970

RELEVANCE OF INHIBITORY AND ACTIVATING KIR AND HLA LIGAND ON OUTCOMES IN REDUCED INTENSITY HAPLOIDENTICAL PERIPHERAL BLOOD STEM CELL TRANSPLANTS

Authors
Chen, D-F; Prasad, VK; Broadwater, G; Clark, A; Rizzieri, DA; Chao, NJ; Reinsmoen, NL
MLA Citation
Chen, D-F, Prasad, VK, Broadwater, G, Clark, A, Rizzieri, DA, Chao, NJ, and Reinsmoen, NL. "RELEVANCE OF INHIBITORY AND ACTIVATING KIR AND HLA LIGAND ON OUTCOMES IN REDUCED INTENSITY HAPLOIDENTICAL PERIPHERAL BLOOD STEM CELL TRANSPLANTS." 2008.
Source
wos-lite
Published In
Human Immunology
Volume
69
Publish Date
2008
Start Page
S8
End Page
S8
DOI
10.1016/j.humimm.2008.08.018

Correction of chronic granulomatous disease after second unrelated-donor umbilical cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for chronic granulomatous disease (CGD), but many patients lack a suitably matched related donor. We report successful outcomes after mismatched, unrelated-donor umbilical cord blood transplantation (uUCBT) in two boys with X-linked CGD. Both patients experienced autologous recovery after first transplants, required second transplants to achieve durable donor engraftment, and are alive 27 and 15 months post-transplant. Both had invasive fungal disease and received granulocyte transfusions. In conclusion, uUCBT is effective in children with CGD, but immunosuppression in the conditioning regimen may need to be increased to decrease the risk of graft rejection.

Authors
Parikh, SH; Szabolcs, P; Prasad, VK; Lakshminarayanan, S; Martin, PL; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Szabolcs, P, Prasad, VK, Lakshminarayanan, S, Martin, PL, Driscoll, TA, and Kurtzberg, J. "Correction of chronic granulomatous disease after second unrelated-donor umbilical cord blood transplantation." Pediatr Blood Cancer 49.7 (December 2007): 982-984.
PMID
17941061
Source
pubmed
Published In
Pediatric Blood & Cancer
Volume
49
Issue
7
Publish Date
2007
Start Page
982
End Page
984
DOI
10.1002/pbc.21365

Analysis of the cellular components of the graft and clinical characteristics of 159 children with lysosomal and peroxisomal disorders (LSD) undergoing unrelated umbilical cord blood transplantation at a single center

Authors
Prasad, VK; Medizabal, A; Parikh, SH; Szaboles, P; Driscoll, TA; Page, K; Lakshminarayan, S; Allison, J; Wood, S; Semmell, D; Escolar, ML; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Medizabal, A, Parikh, SH, Szaboles, P, Driscoll, TA, Page, K, Lakshminarayan, S, Allison, J, Wood, S, Semmell, D, Escolar, ML, Martin, PL, Carter, S, and Kurtzberg, J. "Analysis of the cellular components of the graft and clinical characteristics of 159 children with lysosomal and peroxisomal disorders (LSD) undergoing unrelated umbilical cord blood transplantation at a single center." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
106A
End Page
106A

Use of mesenchymal stem cells to treat pediatric patients with severe (Grade III-IV) acute graft versus host disease refractory to steroid and other agents on a compassionate use basis

Authors
Prasad, VK; Lucas, KG; Kleiner, GI; Talano, J-AM; Jacobsohn, D; Szaboles, P; Monroy, R; Kurtzberg, J
MLA Citation
Prasad, VK, Lucas, KG, Kleiner, GI, Talano, J-AM, Jacobsohn, D, Szaboles, P, Monroy, R, and Kurtzberg, J. "Use of mesenchymal stem cells to treat pediatric patients with severe (Grade III-IV) acute graft versus host disease refractory to steroid and other agents on a compassionate use basis." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
872A
End Page
873A

Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.

Authors
Beam, D; Poe, MD; Provenzale, JM; Szabolcs, P; Martin, PL; Prasad, V; Parikh, S; Driscoll, T; Mukundan, S; Kurtzberg, J; Escolar, ML
MLA Citation
Beam, D, Poe, MD, Provenzale, JM, Szabolcs, P, Martin, PL, Prasad, V, Parikh, S, Driscoll, T, Mukundan, S, Kurtzberg, J, and Escolar, ML. "Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy." Biol Blood Marrow Transplant 13.6 (June 2007): 665-674.
PMID
17531776
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
6
Publish Date
2007
Start Page
665
End Page
674
DOI
10.1016/j.bbmt.2007.01.082

Outcomes of unrelated umbilical cord blood transplantation in pediatric patients with myelodysplastic syndrome

Authors
Parikh, SH; Mendizabal, A; Martin, PL; Szaboles, P; Prasad, VK; Driscoll, TA; Kurtzberg, J
MLA Citation
Parikh, SH, Mendizabal, A, Martin, PL, Szaboles, P, Prasad, VK, Driscoll, TA, and Kurtzberg, J. "Outcomes of unrelated umbilical cord blood transplantation in pediatric patients with myelodysplastic syndrome." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
64
End Page
65

Outcomes of matched related donor bone marrow transplantation in pediatric patients with myelodysplastic syndrome

Authors
Parikh, SH; Martin, PL; Prasad, VK; Szaboles, P; Driscoll, TA; Kurtzbeig, J
MLA Citation
Parikh, SH, Martin, PL, Prasad, VK, Szaboles, P, Driscoll, TA, and Kurtzbeig, J. "Outcomes of matched related donor bone marrow transplantation in pediatric patients with myelodysplastic syndrome." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
64
End Page
64

Chronic graft-versus host disease (GVHD) in children with mucopolysacharidoses (MPS) two years after unrelated donor umbilical cord blood transplantation (UCBT)

Authors
Szaboles, P; Martin, RL; Parikh, S; Prasad, VK; Vinesett, R; Escolar, ML; Kurtzberg, J
MLA Citation
Szaboles, P, Martin, RL, Parikh, S, Prasad, VK, Vinesett, R, Escolar, ML, and Kurtzberg, J. "Chronic graft-versus host disease (GVHD) in children with mucopolysacharidoses (MPS) two years after unrelated donor umbilical cord blood transplantation (UCBT)." February 2007.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
13
Issue
2
Publish Date
2007
Start Page
67
End Page
67
DOI
10.1016/j.bbmt.2006.12.184

Melphalan containing cytoreduction results in a good overall survival (OS) in pediatric patients with relapse or refractory AML undergoing unrelated umbilical cord blood transplantation (UCBT).

Authors
Prasad, VK; Wu, J; Martin, PL; Driscoll, TA; Parikh, SH; Semmel, D; Moffet, J; Stafford, L; Shonkwiler, A; Carter, S; Szabolcs, P; Kurtzberg, J
MLA Citation
Prasad, VK, Wu, J, Martin, PL, Driscoll, TA, Parikh, SH, Semmel, D, Moffet, J, Stafford, L, Shonkwiler, A, Carter, S, Szabolcs, P, and Kurtzberg, J. "Melphalan containing cytoreduction results in a good overall survival (OS) in pediatric patients with relapse or refractory AML undergoing unrelated umbilical cord blood transplantation (UCBT)." November 16, 2006.
Source
wos-lite
Published In
Blood
Volume
108
Issue
11
Publish Date
2006
Start Page
899A
End Page
899A

Busulfan/melphalan is an effective and well tolerated conditioning regimen for pediatric AML and MDS patients receiving a matched sibling bmt

Authors
Martin, PL; Driscoll, TA; Szabolcs, P; Parikh, SH; Prasad, VK; Kurtzberg, J
MLA Citation
Martin, PL, Driscoll, TA, Szabolcs, P, Parikh, SH, Prasad, VK, and Kurtzberg, J. "Busulfan/melphalan is an effective and well tolerated conditioning regimen for pediatric AML and MDS patients receiving a matched sibling bmt." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
127
End Page
127
DOI
10.1016/j.bbmt.2005.11.389

Single center experience of unrelated umbilical cord blood transplantation (UCBDT) for acute myeloid leukemia (AML) in 97 pediatric patients: Impact of disease status and cytoreductive regimen

Authors
Prasad, VK; Wu, J; Parikh, SH; Driscoll, TA; Szabolcs, P; Martin, PL; Carter, S; Kurtzberg, J
MLA Citation
Prasad, VK, Wu, J, Parikh, SH, Driscoll, TA, Szabolcs, P, Martin, PL, Carter, S, and Kurtzberg, J. "Single center experience of unrelated umbilical cord blood transplantation (UCBDT) for acute myeloid leukemia (AML) in 97 pediatric patients: Impact of disease status and cytoreductive regimen." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
124
End Page
124
DOI
10.1016/j.bbmt.2005.11.381

Impact of donor KIR genotype and recipient hla ligand incompatibility on relapse related mortality and acute graft versus host disease in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myeloid malignancies

Authors
Prasad, VK; Chen, DF; Reinsmoen, NL; Broadwater, G; Chao, NJ; Rizzieri, DA
MLA Citation
Prasad, VK, Chen, DF, Reinsmoen, NL, Broadwater, G, Chao, NJ, and Rizzieri, DA. "Impact of donor KIR genotype and recipient hla ligand incompatibility on relapse related mortality and acute graft versus host disease in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myeloid malignancies." February 2006.
Source
wos-lite
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
2
Publish Date
2006
Start Page
15
End Page
15
DOI
10.1016/j.bbmt.2005.11.050

Transplant outcomes and stabilization of neurological function in young children with MPS III (Sanfilippo syndrome) after unrelated donor umbilical cord blood transplantation.

Authors
Lakshminarayanan, S; Szabolcs, P; Prasad, VK; Parikh, S; Allison, J; Wood, SJ; Escolar, M; Kurtzberg, J
MLA Citation
Lakshminarayanan, S, Szabolcs, P, Prasad, VK, Parikh, S, Allison, J, Wood, SJ, Escolar, M, and Kurtzberg, J. "Transplant outcomes and stabilization of neurological function in young children with MPS III (Sanfilippo syndrome) after unrelated donor umbilical cord blood transplantation." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
580A
End Page
580A

Impact of donor KIR genotype and recipient HLA ligand incompatibility on relapse-related mortality in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myelloid malignanc

Authors
Chen, DF; Prasad, VK; Broadwater, G; Rizzieri, DA; Chao, NJ; Reinsmoen, NL
MLA Citation
Chen, DF, Prasad, VK, Broadwater, G, Rizzieri, DA, Chao, NJ, and Reinsmoen, NL. "Impact of donor KIR genotype and recipient HLA ligand incompatibility on relapse-related mortality in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myelloid malignanc." November 2005.
Source
wos-lite
Published In
Tissue Antigens
Volume
66
Issue
5
Publish Date
2005
Start Page
376
End Page
376

Defibrotide (DF) is effective in the treatment of severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post stem cell transplantation (SCT): Results of a phase II, multicenter, randomized study.

Authors
Richardson, P; Soiffer, RJ; Antin, JH; Jin, Z; Vredenburgh, JJ; Kurtzberg, J; Martin, PL; Hockenbery, D; Steinbach, G; Murray, KF; Vogelsang, GB; Chen, A; Krishnan, A; Prasad, VK; Warren, DL; Momtaz, P; Batchelder, A; Wei, LJ; Rifai, N; Bradwin, G; Iacobelli, M; McDonald, GB; Guinan, EC
MLA Citation
Richardson, P, Soiffer, RJ, Antin, JH, Jin, Z, Vredenburgh, JJ, Kurtzberg, J, Martin, PL, Hockenbery, D, Steinbach, G, Murray, KF, Vogelsang, GB, Chen, A, Krishnan, A, Prasad, VK, Warren, DL, Momtaz, P, Batchelder, A, Wei, LJ, Rifai, N, Bradwin, G, Iacobelli, M, McDonald, GB, and Guinan, EC. "Defibrotide (DF) is effective in the treatment of severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post stem cell transplantation (SCT): Results of a phase II, multicenter, randomized study." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
193A
End Page
193A

Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance.

We describe a case of CMV ventriculoencephalitis in a severely immunocompromised bone marrow transplant recipient who was receiving combination therapy with ganciclovir and foscarnet for treatment of viremia and retinitis. Analysis of sequential viral isolates recovered from the patient's cerebrospinal fluid suggested that disease developed because of the presence of viral resistance and, possibly, low tissue penetration of antiviral agents.

Authors
Seo, SK; Regan, A; Cihlar, T; Lin, DC; Boulad, F; George, D; Prasad, VK; Kiehn, TE; Polsky, B
MLA Citation
Seo, SK, Regan, A, Cihlar, T, Lin, DC, Boulad, F, George, D, Prasad, VK, Kiehn, TE, and Polsky, B. "Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance." Clin Infect Dis 33.9 (November 1, 2001): e105-e108.
PMID
11577375
Source
pubmed
Published In
Clinical Infectious Diseases
Volume
33
Issue
9
Publish Date
2001
Start Page
e105
End Page
e108
DOI
10.1086/323022

Stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts.

We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA), using T cell-depleted two HLA-allele disparate related peripheral blood stem cell transplants (PBSCTs). Patient 1, a 5-year-old male with FA and aplastic anaemia, initially received an HLA two-antigen mismatched unrelated cord blood transplant and failed to engraft. He received fludarabine (Flu) and cyclophosphamide (Cy), followed by a CD34(+) E-rosette(-) (CD34(+)E(-)), T cell-depleted, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCT from his HLA B-DRB1 mismatched father. He received anti-thymocyte globulin (ATG), steroids, FK506 and G-CSF after transplant for rejection and graft-versus-host disease (GVHD) prophylaxis. The patient is now 23 months after SCT with no evidence of GVHD and with full haematopoietic and immune reconstitution. Patient 2, a 10-year-old boy with FA and myelodysplastic syndrome, received single-dose total body irradiation (SDTBI), Flu and Cy followed by a CD34(+)E(-), T-cell-depleted, G-CSF-mobilized PBSCT from his HLA B-DRB1 mismatched sister. He also received ATG, steroids, FK506 and G-CSF after transplant. The patient is now 12 months after SCT in complete remission with no evidence of GVHD. Absolute neutrophil counts (ANC) of > 1 x 10(9)/l were achieved on day 11 and day 10 post transplant respectively. Both patients are fully engrafted. In summary, we report two successful T-cell-depleted stem cell transplants from mismatched related donors for the treatment of Fanconi anaemia, using a fludarabine-based cytoreduction. Both patients experienced minimal toxicity, rapid engraftment and no GVHD.

Authors
Boulad, F; Gillio, A; Small, TN; George, D; Prasad, V; Torok-Castanza, J; Regan, AD; Collins, N; Auerbach, AD; Kernan, NA; O'Reilly, RJ
MLA Citation
Boulad, F, Gillio, A, Small, TN, George, D, Prasad, V, Torok-Castanza, J, Regan, AD, Collins, N, Auerbach, AD, Kernan, NA, and O'Reilly, RJ. "Stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts." Br J Haematol 111.4 (December 2000): 1153-1157.
PMID
11167755
Source
pubmed
Published In
British Journal of Haematology
Volume
111
Issue
4
Publish Date
2000
Start Page
1153
End Page
1157

Rolandic encephalopathy and epilepsia partialis continua following bone marrow transplant.

Epilepsia partialis continua (EPC) is a condition defined by prolonged focal myoclonus. Often resistant to therapy, EPC in children is frequently present in Rasmussen encephalitis, a form of chronic encephalitis of uncertain etiology. We discuss a child who developed bilateral EPC 5 months after a bone marrow transplant. Neuroimaging studies showed signal abnormalities on both sensory-motor areas. An extensive search failed to reveal the etiology of the disorder, but treatment with a broad-spectrum anti-viral agent was associated with resolution of the process. An unidentified infectious agent may be responsible for an encephalitis of the motor strip in immunosuppressed patients.

Authors
Antunes, NL; Boulad, F; Prasad, V; Rosenblum, M; Lis, E; Souweidane, M
MLA Citation
Antunes, NL, Boulad, F, Prasad, V, Rosenblum, M, Lis, E, and Souweidane, M. "Rolandic encephalopathy and epilepsia partialis continua following bone marrow transplant." Bone Marrow Transplant 26.8 (October 2000): 917-919.
PMID
11081396
Source
pubmed
Published In
Bone Marrow Transplantation
Volume
26
Issue
8
Publish Date
2000
Start Page
917
End Page
919
DOI
10.1038/sj.bmt.1702637

The probability of HLA-C matching between patient and unrelated donor at the molecular level: estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles.

BACKGROUND: Recent evidence suggests a more significant role of HLA-C as a target of alloreactions after bone marrow transplantation than previously suspected. Although linkage disequilibrium (LD) between HLA-B and -C serogroups is well documented, the level of LD at the allelic level is not known. In this study, we determine the LD between HLA-B and -C alleles and estimate the probability of molecular HLA-C matching between unrelated individuals who match for both HLA-B alleles. METHODS: The study included 727 haplotypes from 849 individuals who were HLA-A, -B, -C and -DRB1 typed by high-resolution PCR-SSOP technique. Zelterman's statistic was used to test for global LD between HLA loci. LD between specific HLA-B and -C allelic combinations was calculated from their observed and expected frequencies in the study haplotypes. The probability of HLA-C matching for specific HLA-B allele was estimated from contingency table generated from the HLA-B and -C haplotypes. RESULTS: HLA-C was found to exist in LD with HLA-A and -B, as well as -DRB1, loci; however, it was strongest between HLA-B and -C loci. A marked variability in the level of LD between specific HLA-B and -C alleles was noticed. A strong LD was seen in some allele pairs like B*0702-C*w0702, B*3501-Cw*0401, and B*0801-Cw*0701. The overall estimated probability of HLA-C matching between unrelated individuals that match for both HLA-B alleles is 42.25%. For 237 (72.9%) of 325 combinations involving the 25 commonest HLA-B alleles, the estimated probability that the HLA-B-matched unrelated individuals will match for both HLA-C alleles is less than 50%. In addition, a 100% probability of matching for both HLA-C alleles is expected only if both individuals bear either B*0801/ B*0801 or B*4901/B*4901 or B*0801/B*4901. Probability tables for common alleles are presented. CONCLUSIONS: We conclude that, despite matching for both HLA-B alleles by high resolution DNA typing and the presence of a strong LD between HLA-B and HLA-C loci, unrelated individuals are more likely to mismatch rather than match for one or both HLA-C alleles.

Authors
Prasad, VK; Heller, G; Kernan, NA; O'Reilly, RJ; Yang, SY
MLA Citation
Prasad, VK, Heller, G, Kernan, NA, O'Reilly, RJ, and Yang, SY. "The probability of HLA-C matching between patient and unrelated donor at the molecular level: estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles." Transplantation 68.7 (October 15, 1999): 1044-1050.
PMID
10532548
Source
pubmed
Published In
Transplantation
Volume
68
Issue
7
Publish Date
1999
Start Page
1044
End Page
1050

DNA typing for HLA-A and HLA-B identifies disparities between patients and unrelated donors matched by HLA-A and HLA-B serology and HLA-DRB1.

High incidences of graft failure and graft-versus-host disease in the recipients of bone marrow transplantations (BMT) from unrelated donors (URD) may reflect the existence of allelic disparities between the patient and the URD despite apparent HLA identity at HLA-A, HLA-B, and HLA-DRB1 loci. To identify the extent and pattern of allelic disparities at HLA-A and HLA-B loci, 128 patients and 484 potential URD were evaluated by DNA typing. DNA typing for HLA-A, HLA-B, and HLA-DRB1 was performed at Memorial Sloan Kettering Cancer Center. HLA-A and HLA-B serotyping on URD was provided by the registries. By original typing (serology for HLA-A and HLA-B; DNA typing for DRB1) 187, 164, and 133 URD were 6/6, 5/6, and 4/6 matches, respectively. Following DNA typing, however, only 52.9% of the originally 6/6 matched URD remained 6/6, while 38.5%, 7.5%, and 1.1% were found to be 5/6, 4/6, and 3/6 matches. The level of disparity was higher in the originally 5/6 (P <.01) and 4/6 (P <.01) matched URD. A higher level of disparity was seen for HLA-B as compared to HLA-A. In addition, a serotype related variation was also noticed. For example, 24.1% of HLA-A2 and 60.1% of HLA-B35 seromatched URD were genotypically disparate, but no disparities were seen for HLA-A1 and HLA-B8. A higher percentage of HLA-A (67. 4%) compared with HLA-B (35.4%) serologic homozygous URD remained genotypically homozygous (P =.01). The level of allelic disparity was lower (P <.01 for 6/6; P =.02 for 5/6) if the patient had one of the 15 most common haplotypes (A1B8DR3, A2B7DR15, A3B7DR15, etc) in comparison to the rest of the group. Outcome studies will answer the question whether these disparities are associated with a higher rate of immunological complications seen with URD-BMT.

Authors
Prasad, VK; Kernan, NA; Heller, G; O'Reilly, RJ; Yang, SY
MLA Citation
Prasad, VK, Kernan, NA, Heller, G, O'Reilly, RJ, and Yang, SY. "DNA typing for HLA-A and HLA-B identifies disparities between patients and unrelated donors matched by HLA-A and HLA-B serology and HLA-DRB1." Blood 93.1 (January 1, 1999): 399-409.
PMID
9864187
Source
pubmed
Published In
Blood
Volume
93
Issue
1
Publish Date
1999
Start Page
399
End Page
409

HLA-C disparity between patients and unrelated donors matched for HLA-A, -B, and -DRB1 alleles: impact of serological vs. DNA typing for HLA-A and -B loci.

High incidences of graft failure, graft-vs.-host disease (GVHD), and serious infections following unrelated donor (URD) marrow transplantation, despite apparent human leukocyte antigen (HLA) identity, may reflect the presence of molecular disparities, including those for HLA-C alleles between the patient and the URD. The level of these disparities could be significant, because as many as 42 alleles are currently known for HLA-C locus. We studied 84 patients and 251 potential URDs to evaluate 1) the extent of HLA-C disparity between the patient and the URD identified by serology for HLA-A and -B and by DNA typing for -DRB1 and 2) the level of HLA-C disparity between patients and URDs matched by high-resolution DNA typing for HLA-A, -B, and -DRB1. The DNA typing was performed at the Memorial Sloan Kettering Cancer Center, and the serotyping was provided by the registries. Of 251 URDs matched by HLA-A and -B serology and -DRB1 (sA_sB_dnaDRB1 ); 94, 75, and 82 were 6/6, 5/6, and 4/6 matches, respectively. Of 94 sA_sB_dnaDRB1 6/6 URDs, 51 (54.3%) were matched for both HLA-C alleles. In contrast, 31 (41.3%) 5/6 (p=0.12) and 15 (18.3%) 4/6 (p < 0.01) sA_sB_dnaDRB1 URDs were matched for both HLA-C alleles. Following DNA typing for HLA-A and -B, 52 (55.3%) of 94 6/6, 30 (40%) of 75 5/6, and 25 (30.5%) of 82 4/6 sA_sB_dnaDRB1 URDs remained 6/6, 5/6, and 4/6 matches at the DNA level (dnaA_B_DRB1). HLA-C disparities continued to exist in the dnaA_B_DRB1 URD group. Of 54 dnaA_B_DRB1 6/6 URDs, 41 (75.9%) were matched for both HLA-C alleles. Only 45.3% of the 5/6 (p=0.01) and 22.2% of the 4/6 (p < 0.01) dnaA_B_DRB1 URDs were matched for both HLA-C alleles. In the 6/6 category, the frequency of HLA-C matching improved (75.9 vs. 54.3%; p=0.01) following DNA matching for HLA-A and -B. In comparison to mismatching for HLA-B locus, mismatching for either HLA-DRB1 or -A resulted in a lower odds ratio for HLA-C disparity. The presence of a common haplotype in the sA_sB_dnaDRBl (p=0.06) URD category improved the level of HLA-C matching. We identified alleles that are associated with high (B*1501, B*4402, B*5101, DRB1*0101, A*0201, A*1101, A*2301, and A*3201) or low (B*0702, B*0801, B*1302, B*3502, DRB1*0301, DRB1*1104, A*0101, A*3001, and A*6801) probability of HLA-C disparity. Overall, sA_sB_dnaDRB1 as well as dnaA_B_DRB1 matched URDs for non-Caucasian patients were more likely to have HLA-C disparity in comparison to the matched URDs of Caucasian patients. However, a high incidence of HLA-C disparities was identified even in the URDs for Caucasian patients. Whether the disparities demonstrated by this study contribute to the higher immunological complications noted following URD bone marrow transplantation is unclear. Outcome analysis and studies aimed at understanding the functional role of HLA-C may provide an answer.

Authors
Prasad, VK; Kernan, NA; Heller, G; O'Reilly, RJ; Yang, SY
MLA Citation
Prasad, VK, Kernan, NA, Heller, G, O'Reilly, RJ, and Yang, SY. "HLA-C disparity between patients and unrelated donors matched for HLA-A, -B, and -DRB1 alleles: impact of serological vs. DNA typing for HLA-A and -B loci." Biol Blood Marrow Transplant 5.2 (1999): 77-85.
PMID
10371359
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
5
Issue
2
Publish Date
1999
Start Page
77
End Page
85

HI.a-dqb1 disparity between patients and unrelated marrow donors (urd) matched for hla-a. -b, and -drb1 by dna typing

URD and patients matched by HLA-A and -B serology and -DRBI are known to have disparities for HLA-DQBI alleles. We studied 129 patients and 431 URD to examine whether DNA typing for HLA-A, -B, and -DRBI has any influence on the degree of HLA-DQBI matching. The DNA typing was performed by PCR-SSOP method. Of 431 URD, 102, 169, and 160 were 6/6, 5/6, and 4/6 DNA matches, respectively. Of 6/6 URD. 86 (84.3%) were matched for both and the rest (15.7%) were mismatched for one HLA-DQBI allele. In the 5/6 group, 115 (68.0%), 51 (30.2%), and 3 (1.8%) and in the 4/6 group, 86 (53.8%), 61 (38.1%), and 13 (8.1%) URD were matched for both, one, and none of HLA-DQBI alleles, respectively. Compared to the 6/6 group, a higher degree of HLA-DQBI disparity was seen in the 5/6 (pO.OI) and 4/6 (p<0.01) groups. The degree of disparity in the 4/6 was higher than in 5/6 (p<0.01). Next we examined the effect of matching at individual loci. The URD (n=431) were stratified for HLA-A, -B, and -DRBI matching as follows: MA-matched for both HLA-A alleles (n=296); MMA-mismatched for HLA-A alleles (n"135); MB-matched for both HLA-B alleles (n=270); MMBmismatched for HLA-B alleles (n=16l); MD-matched for both HLA-DRBI alleles (n275); and MMD-mismatched for HLA-DRBI alleles (n=56). Within MA group, 194 (65.6%), 88 (29.7%), and 14 (4.7%) and in MMA group, 93 (68.9%), 40 (29.6%). and 2 (1.5%) URD were matched for both, one, and none of HLA-DQBI alleles. In MB group, 180 (66.7%), 77 (28.5%), and 13 (4.8%) and in MMB group, 107 (66.4%), 51 (31.7%), and 3 (1.9%) URD were matched for both, one, and none of HLA-DQBI alleles, respectively. The degree of HLA-DQBI disparity was similar between MA and MMA (p=0.26) as well as between MB and MMB (p-0.27) groups. In MD group, 215 (78.2%), 60 (21.8%), and zero URD and in the MMD group, 72 (46.1%), 68 (43.6%). and 16 (10:3%) URD were matched for both, one, and none of HLA-DQBI alleles. The odds ratio of HLA-DQBI matching for MD vs. MMD group was 4.15. The degree of HLA-DQBI disparity was significantly higher in MMD compared to MD group (p<0.01). We conclude that URD matching for HLA-A, -B, and -DRBI, even by DNA typing, does not guarantee HLA-DQBI matching. Furthermore. DNA matching for HLA-A and -B has no influence on the degree of HLA-DQBI matching. Conversely, the level of HLA-DRBI matching positively influences the degree of HLA-DQBI matching reflecting linkage disequilibrium between the two loci. The outcome studies will determine the clinical importance of the above observations.

Authors
Prasad, VK
MLA Citation
Prasad, VK. "HI.a-dqb1 disparity between patients and unrelated marrow donors (urd) matched for hla-a. -b, and -drb1 by dna typing." Experimental Hematology 26.8 (1998): 691--.
Source
scival
Published In
Experimental Hematology
Volume
26
Issue
8
Publish Date
1998
Start Page
691-

TTP following ITP in an HIV-positive boy.

PURPOSE: To report the previously undescribed development of thrombotic thrombocytopenic purpura (TTP) in a human immunodeficiency virus (HIV)-positive child and discuss the differential diagnosis. PATIENT AND METHODS: Our patient was a 9-year-old boy with vertically acquired HIV infection and a previous history of immune thrombocytopenic purpura (ITP). Initial presentation, difficulty in diagnosis, clinical course, and subsequent outcome are described. RESULTS: Rapid resolution of TTP following plasmapheresis was seen. CONCLUSIONS: Recognition of this treatable though potentially fatal complication in severely ill HIV-infected children requires a high degree of suspicion in view of its diverse clinical manifestations. The long-term outcome may be relatively good.

Authors
Prasad, VK; Kim, IK; Farrington, K; Bussel, JB
MLA Citation
Prasad, VK, Kim, IK, Farrington, K, and Bussel, JB. "TTP following ITP in an HIV-positive boy." J Pediatr Hematol Oncol 18.4 (November 1996): 384-386.
PMID
8888747
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
18
Issue
4
Publish Date
1996
Start Page
384
End Page
386

Progressive glomerular toxicity of ifosfamide in children

Glomerular toxicity following ifosfamide (IFO) is not as well recognized as renal tubular damage. Following a case of ifosfamide-induced renal failure with histological evidence of glomerular changes, we undertook a retrospective study of all IFO-treated children to assess the extent and severity of its glomerular toxicity and to identify possible predisposing factors. Thirty seven children with a follow-up of 6 months or more from the end of chemotherapy were studied. They were a median of 10.8 years old (range 3.25-18.5), had received a median of 54 g/m2 (range 9-135) of IFO, and had a median follow-up of 29 months (range 6-68). The criteria to identify glomerular dysfunction were raised plasma creatinine (P(cr)) values on two occasions or a low glomerular filtration rate (GFR) measured by Tc-99-DTPA clearance. Detailed assessment was carried out to identify other nephrotoxic influences in these children. Subjects in whom glomerular dysfunction could be causally linked to IFO were compared with the rest of the group for a variety of predisposing factors. Of eight children with glomerular dysfunction, two had other nephrotoxic influences and were excluded from further analysis. In six(17.1%) children, glomerular dysfunction appeared to be causally linked to IFO. Their median GFR was 61.9 ml/min/1.73 m2 (range 3385) and P(cr) was 123 μmol/l (range 85-216). Five of the six had normal glomerular function at the end of therapy and the raised P(cr) values were first noted 19, 21, 26, 29, and 36 months later. Children with glomerular toxicity had a significantly longer median follow-up (41.5 vs. 19 months; P=0.04) than the rest of the group, suggesting late onset of this problem. They were older at the time of the study and had received nearly twice the dose of IFO, though the differences in age and dose did not reach statistical significance. The earliest signs of renal toxicity were seen in the index case, who had prior nephrectomy. All affected children had coexistent and preceding tubular toxicity. The inadequacies of tests commonly used to assess glomerular function and the possibility of underestimation of dysfunction are discussed. Glomerular dysfunction following IFO is poorly recognized and evidence from this study of its later onset and progressive nature is a cause for concern. The index case is described with histological findings.

Authors
Prasad, VK; Lewis, IJ; Aparicio, SR; Heney, D; Hale, JP; Bailey, CC; Kinsey, SE
MLA Citation
Prasad, VK, Lewis, IJ, Aparicio, SR, Heney, D, Hale, JP, Bailey, CC, and Kinsey, SE. "Progressive glomerular toxicity of ifosfamide in children." Medical and Pediatric Oncology 27.3 (September 1, 1996): 149-155.
Source
scopus
Published In
Pediatric Blood and Cancer
Volume
27
Issue
3
Publish Date
1996
Start Page
149
End Page
155
DOI
10.1002/(SICI)1096-911X(199609)27:3<149::AID-MPO3>3.0.CO;2-E

Progressive glomerular toxicity of ifosfamide in children.

Glomerular toxicity following ifosfamide (IFO) is not as well recognized as renal tubular damage. Following a case of ifosfamide-induced renal failure with histological evidence of glomerular changes, we undertook a retrospective study of all IFO-treated children to assess the extent and severity of its glomerular toxicity and to identify possible predisposing factors. Thirty-seven children with a follow-up of 6 months or more from the end of chemotherapy were studied. They were a median of 10.8 years old (range 3.25-18.5), had received a median of 54 g/m2 (range 9-135) of IFO, and had a median follow-up of 29 months (range 6-68). The criteria to identify glomerular dysfunction were raised plasma creatinine (Pc) values on two occasions or a low glomerular filtration rate (GFR) measured by Tc-99-DTPA clearance. Detailed assessment was carried out to identify other nephrotoxic influences in these children. Subjects in whom glomerular dysfunction could be causally linked to IFO were compared with the rest of the group for a variety of predisposing factors. Of eight children with glomerular dysfunction, two had other nephrotoxic influences and were excluded from further analysis. In six (17.1%) children, glomerular dysfunction appeared to be causally linked to IFO. Their median GFR was 61.9 ml/min/1.73 m2(range 33-85) and Pc was 123 mumol/l (range 85-216). Five of the six had normal glomerular function at the end of therapy and the raised Pc values were first noted 19, 21, 26, 29, and 36 months later. Children with glomerular toxicity had a significantly longer median follow-up (41.5 vs. 19 months; P = 0.04) than the rest of the group, suggesting late onset of this problem. They were older at the time of the study and had received nearly twice the dose of IFO, though the differences in age and dose did not reach statistical significance. The earliest signs of renal toxicity were seen in the index case, who had had prior nephrectomy. All affected children had coexistent and preceding tubular toxicity. The inadequacies of tests commonly used to assess glomerular function and the possibility of underestimation of dysfunction are discussed. Glomerular dysfunction following IFO is poorly recognized and evidence from this study of its later onset and progressive nature is a cause for concern. The index case is described with histological findings.

Authors
Prasad, VK; Lewis, IJ; Aparicio, SR; Heney, D; Hale, JP; Bailey, CC; Kinsey, SE
MLA Citation
Prasad, VK, Lewis, IJ, Aparicio, SR, Heney, D, Hale, JP, Bailey, CC, and Kinsey, SE. "Progressive glomerular toxicity of ifosfamide in children." Med Pediatr Oncol 27.3 (September 1996): 149-155.
PMID
8699991
Source
pubmed
Published In
Pediatric Blood and Cancer
Volume
27
Issue
3
Publish Date
1996
Start Page
149
End Page
155
DOI
10.1002/(SICI)1096-911X(199609)27:3<149::AID-MPO3>3.0.CO;2-E

Allele assignment for HLA-A, -B, and -C genes to the Tenth International Histocompatibility Workshop cell lines.

Development of DNA typing for Class I HLA alleles has lagged behind that of class II for a variety of technical reasons. Following the recognition of locus specific sequences in the first and the third intron, and acquiring the ability to amplify genomic DNA by intron-based PCR primer, we have devised DNA typing of class I alleles by SSOP and direct sequencing. In this study using these techniques we provide the allelic typing of HLA-A, -B, and -C genes for the B-lymphoblastoid reference cell lines from the Tenth International Histocompatibility Workshop. We also describe some common associations of the C alleles with HLA-A and HLA-B alleles.

Authors
Prasad, VK; Yang, SY
MLA Citation
Prasad, VK, and Yang, SY. "Allele assignment for HLA-A, -B, and -C genes to the Tenth International Histocompatibility Workshop cell lines." Tissue Antigens 47.6 (June 1996): 538-546.
PMID
8813743
Source
pubmed
Published In
Tissue Antigens
Volume
47
Issue
6
Publish Date
1996
Start Page
538
End Page
546

Hepatic focal nodular hyperplasia in infant antenatally exposed to steroids.

Authors
Prasad, VK; Aronson, DC; Gerald, WL; Meyers, PA; La Quaglia, MP
MLA Citation
Prasad, VK, Aronson, DC, Gerald, WL, Meyers, PA, and La Quaglia, MP. "Hepatic focal nodular hyperplasia in infant antenatally exposed to steroids." Lancet 346.8971 (August 5, 1995): 371-. (Letter)
PMID
7623541
Source
pubmed
Published In
The Lancet
Volume
346
Issue
8971
Publish Date
1995
Start Page
371

Treatment of hyperkalaemia using intravenous and nebulised salbutamol.

In 11 children (aged 5-18 years) with end stage chronic renal failure, the effect on plasma potassium of two doses of salbutamol (separated by two hours) given intravenously (4 micrograms/kg) and on a separate date, of salbutamol administered by nebuliser (2.5 mg if the child weighed below 25 kg, 5 mg if above) was observed. Within 30 minutes of the first dose, the mean plasma potassium concentration fell significantly by 0.87 and 0.61 mmol/l after intravenous and nebulised administration respectively. Sixty minutes after the second dose the plasma potassium was significantly reduced by a further 0.28 and 0.53 mmol/l respectively. There was a significant difference between the two methods of administration at 300 minutes after the first dose favouring nebulisation. No major side effects were observed. Nebulised salbutamol should be the first choice emergency treatment of hyperkalaemia.

Authors
McClure, RJ; Prasad, VK; Brocklebank, JT
MLA Citation
McClure, RJ, Prasad, VK, and Brocklebank, JT. "Treatment of hyperkalaemia using intravenous and nebulised salbutamol." Arch Dis Child 70.2 (February 1994): 126-128.
PMID
8129434
Source
pubmed
Published In
Archives of Disease in Childhood
Volume
70
Issue
2
Publish Date
1994
Start Page
126
End Page
128

Ifosfamide enantiomers: pharmacokinetics in children.

Ifosfamide, like other oxazaphosphorine drugs, is chiral and there is some evidence, mainly from animal studies, of stereo-selective differences in metabolism, excretion and cytotoxic activity between the two enantiomers. The pharmacokinetics of racemic ifosfamide (RAC-IFO), R-ifosfamide (R-IFO) and S-ifosfamide (S-IFO) were studied in five children who received intravenous therapy with racemic ifosfamide on 3 consecutive days. The clearance of S-IFO was greater than that of R-IFO. The clearance value at the end of the infusion was faster than the respective rate measured at the beginning of or during the ifosfamide regimens in four children and, therefore, suggests autoinduction of elimination of both enantiomers.

Authors
Prasad, VK; Corlett, SA; Abaasi, K; Heney, D; Lewis, I; Chrystyn, H
MLA Citation
Prasad, VK, Corlett, SA, Abaasi, K, Heney, D, Lewis, I, and Chrystyn, H. "Ifosfamide enantiomers: pharmacokinetics in children." Cancer Chemother Pharmacol 34.5 (1994): 447-449.
PMID
8070015
Source
pubmed
Published In
Cancer Chemotherapy and Pharmacology
Volume
34
Issue
5
Publish Date
1994
Start Page
447
End Page
449

Tetanus neonatorum: clinico-epidemiological profile.

Authors
Kumar, H; Aneja, S; Prasad, VK; Arora, SK; Mullick, DN
MLA Citation
Kumar, H, Aneja, S, Prasad, VK, Arora, SK, and Mullick, DN. "Tetanus neonatorum: clinico-epidemiological profile." Indian Pediatr 25.11 (November 1988): 1054-1057.
PMID
3248877
Source
pubmed
Published In
Indian Pediatrics
Volume
25
Issue
11
Publish Date
1988
Start Page
1054
End Page
1057
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