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Sung, Anthony D

Overview:

I am dedicated to the treatment of hematologic malignancies through cellular therapies such as hematopoietic stem cell transplantation (HCT). My research focuses on strategies to reduce complications of HCT and ranges from preclinical studies using murine models of HCT to Phase 1 and Phase 2 clinical trials. Areas of interest include the role of the microbiota (the trillions of bacteria living in and on our bodies), nutrition, and exercise in modulating HCT outcomes such as graft-versus-host disease (GVHD) and infections. In addition to advancing new pharmacological and cellular immunotherapies in support of these goals, we also are developing mobile health technologies (mHealth) to monitor patients at home, both as part of our innovative home transplant program as well as to improve follow up care of all our patients when they return home after transplant.

Positions:

Assistant Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2008

M.D. — Harvard University

Residency, Osler Medical Housestaff Training Program

Johns Hopkins University School of Medicine

Fellowship, Hematology Oncology

Duke University School of Medicine

News:

Grants:

Mitigators of Radiation-Induced Endovascular Injury: Targeting Tie2 and Thrombocytopenia

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
June 06, 2017
End Date
May 31, 2022

Microbiota-focused strategies to mitigate GVHD

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
MD Anderson Cancer Center
Role
Principal Investigator
Start Date
August 15, 2015
End Date
May 31, 2018

Duke CTSA (KL2)

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Scholar
Start Date
September 26, 2013
End Date
April 30, 2018

Prevention of Gastrointestinal Toxicity from total body irradation or high dose Chemo with SOM230

Administered By
Duke Cancer Institute
AwardedBy
Novartis Pharmaceuticals Corporation
Role
Principal Investigator
Start Date
December 01, 2013
End Date
December 31, 2017
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Publications:

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

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

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

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

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

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

Do We Need Full Donor Chimerism? How Alloreactive Cell Therapies without Substantial Engraftment Might Treat Hematologic Cancers.

"Alloreactive cell therapy without substantial engraftment"; (ACT-WiSE) refers to adoptive transfer of natural ("non-engineered") human leukocyte antigen-mismatched lymphocytes to mediate anti-neoplastic alloreactivity in recipients without employing pharmacologic immunosuppression. By definition, ACT-WiSE entails subsequent rejection of most, if not all, donor cells. Macrochimerism is transient and microchimerism may be either short-lived or persistent. This strategy harnesses the anticancer potency of alloreactivity without incurring significant risk of graft-versus-host disease. "Microtransplantation" refers to a form of ACT-WiSE where the donor cell product contains hematopoietic progenitor cells. Microtransplantation therefore accelerates hematopoietic recovery and its immunomodulatory effects may differ from other forms of ACT-WiSE. Recent studies suggest that various forms of ACT-WiSE, including microtransplantation, may improve chemosensitivity in patients with myeloid malignancies, resulting in higher complete remission rates and increased survival. Microtransplantation has also demonstrated promising pilot results in relapsed or refractory Non-Hodgkin and Hodgkin lymphoma. ACT-WiSE and microtransplantation may establish a new class of allogeneic cell therapy of particular relevance to persons not considered candidates for traditional allogeneic hematopoietic cell transplantation (AHCT). Open questions include the optimal timing and cell dose of ACT-WiSE, which donor factors contribute to efficacy, and whether these remissions are durable after eradication of donor cells. We extrapolate from lessons learned in the course of traditional and haploidentical AHCT to propose ways of optimizing ACT-WiSE. We divide these into donor-related strategies (including rational donor selection and boosting NK-cell and T-cell alloreactivity) and patient- related strategies (that may favor development of autologous NK-cell and T-cell mediated anticancer cytotoxicity in the post-ACT-WiSE window).

Authors
Krakow, EF; Ai, H-S; Shaffer, B; Delisle, J-S; Hu, K-X; Sung, AD
MLA Citation
Krakow, EF, Ai, H-S, Shaffer, B, Delisle, J-S, Hu, K-X, and Sung, AD. "Do We Need Full Donor Chimerism? How Alloreactive Cell Therapies without Substantial Engraftment Might Treat Hematologic Cancers." Current drug targets 18.3 (January 2017): 281-295. (Review)
PMID
25738297
Source
epmc
Published In
Current Drug Targets
Volume
18
Issue
3
Publish Date
2017
Start Page
281
End Page
295
DOI
10.2174/1389450116666150304103849

Reply to Strahilevitz and Shapira.

Authors
Sung, A; Horwitz, M
MLA Citation
Sung, A, and Horwitz, M. "Reply to Strahilevitz and Shapira." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (December 12, 2016).
PMID
27956457
Source
epmc
Published In
Clinical Infectious Diseases
Publish Date
2016

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

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

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

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

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

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

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

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

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

Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF vs G-CSF alone

Chemotherapy plus G-CSF (C+G) and G-CSF alone are two of the most common methods used to mobilize CD34 + cells for autologous hematopoietic SCT (AHSCT). In order to compare and determine the real-world outcomes and costs of these strategies, we performed a retrospective study of 226 consecutive patients at 11 medical centers (64 lymphoma, 162 multiple myeloma), of whom 55% of lymphoma patients and 66% of myeloma patients received C+G. Patients with C+G yielded more CD34 + cells/day than those with G-CSF alone (lymphoma: average 5.51 × 10 6 cells/kg on day 1 vs 2.92 × 10 6 cells/kg, P=0.0231; myeloma: 4.16 × 10 6 vs 3.69 × 10 6 cells/kg, P < 0.00001) and required fewer days of apheresis (lymphoma: average 2.11 vs 2.96 days, P=0.012; myeloma: 2.02 vs 2.83 days, P=0.0015), although nearly all patients ultimately reached the goal of 2 × 10 6 cells/kg. With the exception of higher rates of febrile neutropenia in myeloma patients with C+G (17% vs 2%, P < 0.05), toxicities and other outcomes were similar. Mobilization with C+G cost significantly more (lymphoma: median $10 300 vs $7300, P < 0.0001; myeloma: $8800 vs $5600, P < 0.0001), although re-mobilization adds $6700 for drugs alone. Our results suggest that although both C+G and G-CSF alone are effective mobilization strategies, C+G may be more cost-effective for patients at high risk of insufficient mobilization.

Authors
Sung, AD; Grima, DT; Bernard, LM; Brown, S; Carrum, G; Holmberg, L; Horwitz, ME; Liesveld, JL; Kanda, J; McClune, B; Shaughnessy, P; Tricot, GJ; Chao, NJ
MLA Citation
Sung, AD, Grima, DT, Bernard, LM, Brown, S, Carrum, G, Holmberg, L, Horwitz, ME, Liesveld, JL, Kanda, J, McClune, B, Shaughnessy, P, Tricot, GJ, and Chao, NJ. "Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF vs G-CSF alone." Bone Marrow Transplantation 48.11 (November 1, 2013): 1444-1449.
Source
scopus
Published In
Bone Marrow Transplantation
Volume
48
Issue
11
Publish Date
2013
Start Page
1444
End Page
1449
DOI
10.1038/bmt.2013.80

Acute graft-versus-host disease: are we close to bringing the bench to the bedside?

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplant (AHSCT) associated with significant morbidity and mortality. This review focuses on the pathophysiology, prevention, and treatment of acute GVHD. Specifically, we explain how new discoveries in immunology have expanded our understanding of GVHD, in which tissue damage from chemotherapy or radiation results in cytokine release, activating T cells, resulting in proliferation and differentiation, trafficking to target organs, and tissue destruction and inflammation. Insights into the mechanisms of this disease relate directly to the development of preventive strategies and therapies, such as immunosuppression, calcineurin inhibitors, T-cell depletion, CCR5 antagonists, gut decontamination, extracorporeal photopheresis, and more. Understanding the immunobiology of GVHD and developing effective preventions and treatments are critical to the continuing success of AHSCT.

Authors
Sung, AD; Chao, NJ
MLA Citation
Sung, AD, and Chao, NJ. "Acute graft-versus-host disease: are we close to bringing the bench to the bedside?." Best practice & research. Clinical haematology 26.3 (September 2013): 285-292. (Review)
PMID
24309532
Source
epmc
Published In
Best Practice & Research: Clinical Haematology
Volume
26
Issue
3
Publish Date
2013
Start Page
285
End Page
292
DOI
10.1016/j.beha.2013.10.009

New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation.

Minimal residual disease (MRD) is a complex topic that has been studied extensively in hematologic malignancies given its clinical implications related to prognosis. However, methods to monitor and treat MRD, especially after stem cell transplantation, are not well defined and vary in different disease processes. Alternative transplant strategies, such as reduced-intensity conditioning, have altered the way we assess and address MRD after transplantation. Development of new diagnostic tools have allowed for higher sensitivity and specificity of testing. Both targeted chemotherapeutic agents and immunotherapies have been developed to treat MRD in hopes of improving patient outcomes. This article aims to address ways to define and manipulate MRD specifically after stem cell transplantation.

Authors
Rein, LA; Sung, AD; Rizzieri, DA
MLA Citation
Rein, LA, Sung, AD, and Rizzieri, DA. "New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation." International journal of hematologic oncology 2.1 (February 2013).
PMID
24303095
Source
epmc
Published In
International Journal of Hematologic Oncology
Volume
2
Issue
1
Publish Date
2013
DOI
10.2217/ijh.13.4

Concise review: acute graft-versus-host disease: immunobiology, prevention, and treatment.

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplant (AHSCT) associated with significant morbidity and mortality. This review focuses on the pathophysiology, clinical features, prevention, and treatment of acute GVHD. Specifically, we explain how new discoveries in immunology have expanded our understanding of GVHD, in which tissue damage from chemotherapy or radiation results in cytokine release, which activates T cells, resulting in proliferation and differentiation, trafficking to target organs, and tissue destruction and inflammation. Insights into the mechanisms of this disease relate directly to the development of preventive strategies and therapies, such as immunosuppression, T-cell depletion, calcineurin inhibitors, CCR5 antagonists, gut decontamination, extracorporeal photopheresis, and more. We also discuss how GVHD affects the gut, liver, and skin, as well as diagnosis, grading, and scoring. We end by examining future directions of treatment, including new immunomodulators and biomarkers. Understanding the immunobiology of GVHD and developing effective preventions and treatments are critical to the continuing success of AHSCT.

Authors
Sung, AD; Chao, NJ
MLA Citation
Sung, AD, and Chao, NJ. "Concise review: acute graft-versus-host disease: immunobiology, prevention, and treatment." Stem cells translational medicine 2.1 (January 2013): 25-32. (Review)
PMID
23283494
Source
epmc
Published In
Stem cells translational medicine
Volume
2
Issue
1
Publish Date
2013
Start Page
25
End Page
32
DOI
10.5966/sctm.2012-0115

Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF vs G-CSF alone

Chemotherapy plus G-CSF (C+G) and G-CSF alone are two of the most common methods used to mobilize CD34+ cells for autologous hematopoietic SCT (AHSCT). In order to compare and determine the real-world outcomes and costs of these strategies, we performed a retrospective study of 226 consecutive patients at 11 medical centers (64 lymphoma, 162 multiple myeloma), of whom 55% of lymphoma patients and 66% of myeloma patients received C+G. Patients with C+G yielded more CD34+ cells/day than those with G-CSF alone (lymphoma: average 5.51 × 106 cells/kg on day 1 vs 2.92 × 106 cells/kg, P=0.0231; myeloma: 4.16 × 106 vs 3.69 × 106 cells/kg, P<0.00001) and required fewer days of apheresis (lymphoma: average 2.11 vs 2.96 days, P=0.012; myeloma: 2.02 vs 2.83 days, P=0.0015), although nearly all patients ultimately reached the goal of 2 × 106 cells/kg. With the exception of higher rates of febrile neutropenia in myeloma patients with C+G (17% vs 2%, P<0.05), toxicities and other outcomes were similar. Mobilization with C+G cost significantly more (lymphoma: median $10 300 vs $7300, P<0.0001; myeloma: $8800 vs $5600, P<0.0001), although re-mobilization adds $6700 for drugs alone. Our results suggest that although both C+G and G-CSF alone are effective mobilization strategies, C+G may be more cost-effective for patients at high risk of insufficient mobilization.Bone Marrow Transplantation advance online publication, 10 June 2013; doi:10.1038/bmt.2013.80.

Authors
Sung, AD; Grima, DT; Bernard, LM; Brown, S; Carrum, G; Holmberg, L; Horwitz, ME; Liesveld, JL; Kanda, J; McClune, B; al, E
MLA Citation
Sung, AD, Grima, DT, Bernard, LM, Brown, S, Carrum, G, Holmberg, L, Horwitz, ME, Liesveld, JL, Kanda, J, McClune, B, and al, E. "Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF vs G-CSF alone." Bone Marrow Transplantation (2013).
PMID
23749109
Source
scival
Published In
Bone Marrow Transplantation
Publish Date
2013
DOI
10.1038/bmt.2013.80

Risk assessment in human immunodeficiency virus-associated acute myeloid leukemia.

CD4 count ≤200×10(6) cells/L has been identified as a predictor of short survival in HIV-associated acute myeloid leukemia (HIV-AML), but karyotype, which is the best predictor of survival in AML, has not been evaluated in HIV-AML patients. A retrospective cohort of 31 patients was created from 9 local cases and 22 published cases. HIV-AML karyotypes were heterogeneous and were similar in distribution to those in HIV-negative AML. Among intensively treated patients, most achieved complete remission, but succumbed to infectious complications, mostly non-opportunistic, during consolidation therapy. Median survival for intensively-treated patients with CD4 counts ≤200×10(6) cells/L was 8.5 months, compared to 48 months for those with >200×10(6) CD4 cells/L (p=0.03). In contrast, AML karyotype did not predict survival (p=0.43), albeit with small numbers in each karyotype group. Thus, CD4 count is a strong predictor of short survival in HIV-AML patients regardless of karyotype. Studies evaluating innovative strategies for infection prophylaxis and for improving immune reconstitution are needed.

Authors
Evans, MW; Sung, AD; Gojo, I; Tidwell, M; Greer, J; Levis, M; Karp, J; Baer, MR
MLA Citation
Evans, MW, Sung, AD, Gojo, I, Tidwell, M, Greer, J, Levis, M, Karp, J, and Baer, MR. "Risk assessment in human immunodeficiency virus-associated acute myeloid leukemia." Leukemia & lymphoma 53.4 (April 2012): 660-664.
PMID
21942284
Source
epmc
Published In
Leukemia & Lymphoma (Informa)
Volume
53
Issue
4
Publish Date
2012
Start Page
660
End Page
664
DOI
10.3109/10428194.2011.624228

Role of allogeneic transplantation for FLT3/ITD acute myeloid leukemia: outcomes from 133 consecutive newly diagnosed patients from a single institution.

Acute myelogenous leukemia (AML) patients with FLT3/ITD mutations have an inferior survival compared to AML patients with wild-type (WT) FLT3, primarily because of an increased relapse rate. Allogeneic transplantation represents a postremission therapy that is effective at reducing the risk of relapse for many cases of poor-risk AML. Whether or not allogeneic transplantation in first complete remission (CR) can improve outcomes for patients with FLT3/ITD AML remains controversial. Our institution has adopted a policy of pursuing allogeneic transplantation, including the use of alternate donors, for FLT3/ITD AML patients in remission. As part of an instituional review board-approved study, we performed a review of the clinical data from November 1, 2004, to October 31, 2008, on all adult patients under the age of 60 presenting in consecutive fashion to the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins with newly diagnosed non-M3 AML. We followed their outcomes through August 1, 2010. During the study period, 133 previously untreated AML patients between the ages of 20 and 59 were diagnosed and received induction and consolidation therapy at our institution. Of these 133 patients, 31 (23%) harbored an FLT3/ITD mutation at diagnosis. The median overall survival (OS) from the time of diagnosis for the FLT3/ITD AML patients was compared to the OS of the entire cohort and found to be comparable (19.3 months versus 15.5 months, P = .56). Historically, OS for FLT3/ITD AML patients is significantly worse than for AML patients lacking this mutation. However, the OS for the 31 FLT3/ITD patients reported here was comparable to the 102 patients with WT FLT3 over the same 4-year time period. One difference that might have contributed to the surprising outcomes for the FLT3/ITD group is our aggressive pursuit of allogeneic bone marrow transplant (BMT) in CR1 within this group (60% of FLT3/ITD versus 17% with WT). Our single-institution study of consecutively treated AML patients supports the hypothesis that allogeneic transplant in early CR1 improves the long-term outcomes for FLT3/ITD AML.

Authors
DeZern, AE; Sung, A; Kim, S; Smith, BD; Karp, JE; Gore, SD; Jones, RJ; Fuchs, E; Luznik, L; McDevitt, M; Levis, M
MLA Citation
DeZern, AE, Sung, A, Kim, S, Smith, BD, Karp, JE, Gore, SD, Jones, RJ, Fuchs, E, Luznik, L, McDevitt, M, and Levis, M. "Role of allogeneic transplantation for FLT3/ITD acute myeloid leukemia: outcomes from 133 consecutive newly diagnosed patients from a single institution." Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 17.9 (September 2011): 1404-1409.
PMID
21324374
Source
epmc
Published In
Biology of Blood and Marrow Transplantation
Volume
17
Issue
9
Publish Date
2011
Start Page
1404
End Page
1409
DOI
10.1016/j.bbmt.2011.02.003

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

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

Crying: experiences and attitudes of third-year medical students and interns.

BACKGROUND: The medical socialization process is emotionally stressful for trainees; anecdotally, crying is a frequent response. PURPOSES: To understand the experiences and attitudes related to crying among 3rd-year medical students and interns. METHODS: Web-based survey distributed to all 3rd-year medical students and interns at two medical schools and affiliated internal medicine residency programs. RESULTS: Participation rates were 208/307 (68%) students and 93/126 (74%) interns. Sixty-nine percent of students and 74% of interns self-reported crying for reasons related to medicine. For both, the most common cause was "burnout." Although there were no significant differences in crying between students and interns (p =.38), twice as many women cried as men (93% vs. 44%, p <.001). Seventy-three percent of students and 68% of interns thought discussion of physicians' crying was inadequate. CONCLUSIONS: Crying is common among medical students and interns, especially women. Many consider it unprofessional to cry in front of patients and colleagues. Trainees want more discussions of crying.

Authors
Sung, AD; Collins, ME; Smith, AK; Sanders, AM; Quinn, MA; Block, SD; Arnold, RM
MLA Citation
Sung, AD, Collins, ME, Smith, AK, Sanders, AM, Quinn, MA, Block, SD, and Arnold, RM. "Crying: experiences and attitudes of third-year medical students and interns." Teaching and learning in medicine 21.3 (July 2009): 180-187.
PMID
20183336
Source
epmc
Published In
Teaching and Learning in Medicine
Volume
21
Issue
3
Publish Date
2009
Start Page
180
End Page
187
DOI
10.1080/10401330903014111

Unicameral bone cyst: a retrospective study of three surgical treatments.

Between 1979 and 2004, 167 patients younger than 20 years were treated surgically for humeral or femoral unicameral bone cysts with either injection of corticosteroids (steroids), curettage plus bone grafting (curettage), or a combination injection of steroids, demineralized bone matrix, and bone marrow aspirate (SDB) at Children's Hospital of Boston and Massachusetts General Hospital (mean followup, 7.3 years; range, 1 month-27 years). Outcomes included treatment failure (defined clinically as subsequent pathologic fracture or need for retreatment to prevent pathologic fracture) and complications. Information was obtained from medical records and by telephone questionnaire. After one treatment, 84% of cysts treated with steroids experienced failed treatment versus 64% with curettage and 50% with SDB. For unicameral bone cysts requiring retreatment (regardless of first treatment), 76% retreated with steroids had failed treatment versus 63% with curettage and 71% with SDB. Curettage was associated with the lowest rate of posttreatment pathologic fractures and highest rate of pain and other complications. Multivariate logistic regression indicated treatment with steroids alone and younger age were independent predictors of failure. We believe SDB is a reasonable first treatment for unicameral bone cysts in the humerus and femur in patients younger than 20 years, being less invasive yet comparable to curettage in preventing recurrence.

Authors
Sung, AD; Anderson, ME; Zurakowski, D; Hornicek, FJ; Gebhardt, MC
MLA Citation
Sung, AD, Anderson, ME, Zurakowski, D, Hornicek, FJ, and Gebhardt, MC. "Unicameral bone cyst: a retrospective study of three surgical treatments." Clinical orthopaedics and related research 466.10 (October 2008): 2519-2526.
PMID
18679761
Source
epmc
Published In
Clinical Orthopaedics and Related Research ®
Volume
466
Issue
10
Publish Date
2008
Start Page
2519
End Page
2526
DOI
10.1007/s11999-008-0407-0

Hepatocellular carcinoma with intracavitary cardiac involvement: a case report and review of the literature.

A 71-year-old man with hepatocellular carcinoma (HCC) presented with intracavitary cardiac involvement detected incidentally on surveillance computed tomography. Tumor with associated thrombus was found to extend from the liver through the inferior vena cava into the right atrium. This intracardiac mass prolapsed intermittently into the right ventricle, causing functional tricuspid stenosis. The mass was resected but recurred after 4 months, eventually causing refractory right-sided heart failure. This case illustrates how intracavitary cardiac involvement of HCC can develop insidiously and confer significant hemodynamic compromise. A review of the published research, including postmortem studies, demonstrates that the frequency of intracardiac mass lesions in HCC is not insignificant. In conclusion, early detection and diagnosis may have increasing importance in the advent of new therapies for treating advanced HCC.

Authors
Sung, AD; Cheng, S; Moslehi, J; Scully, EP; Prior, JM; Loscalzo, J
MLA Citation
Sung, AD, Cheng, S, Moslehi, J, Scully, EP, Prior, JM, and Loscalzo, J. "Hepatocellular carcinoma with intracavitary cardiac involvement: a case report and review of the literature." The American journal of cardiology 102.5 (September 2008): 643-645.
PMID
18721529
Source
epmc
Published In
The American Journal of Cardiology
Volume
102
Issue
5
Publish Date
2008
Start Page
643
End Page
645
DOI
10.1016/j.amjcard.2008.04.042
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