Paul V. O'Donnell
M.D., Johns Hopkins University.
Ph.D., Cornell University Graduate School of Medical Sciences.
Allogeneic hematopoietic stem cell transplantation (HSCT) may be curative therapy for a number of hematologic malignancies but this option is often unavailable because of the lack of a suitably matched related or unrelated donor. For several years my research interest has been focused on use of related donors for HSCT who are HLA matched for at least one haplotype. Like many other investigators, my focus in such an approach shifted from myeloablative to nonmyeloablative conditioning for HSCT because of the unacceptable non relapse-related mortality with conventional, myeloablative HSCT. In order to achieve engraftment with acceptable GVHD using haploidentical donors, a novel approach was developed in collaboration with colleagues at the Johns Hopkins Oncology Center. In this approach, higher doses of nonmyeloablative radiochemotherapy were administered pre-transplant to prevent rejection and high-dose cyclophosphamide followed by tacrolimus and MMF were administered after transplant to induce tolerance in the donor lymphocytes by deleting highly alloreactive clones which could cause severe GVHD. An early report on 13 patients transplanted using this approach was published recently [O’Donnell, P.V. et al., Biol Blood and Marrow Transpl 8: 377 (2002)]. A Phase II trial using this approach to treat patients with high-risk hematologic malignancies is currently underway at the Fred Hutchinson Cancer Research Center. Thus far, results are promising with most patients achieving good engraftment within a month of transplant and developing only moderate GVHD which has been responsive to corticosteroids. If possible, we plan to open this protocol at other centers within the existing Nonmyeloablative Transplant Consortium in order to increase accrual.
Clinical expertise and interests include:
1. Hematologic malignancies
2. Allogeneic and autologous HSCT
3. HLA-typing of potential donors
5. Acute GVHD
6. Chronic GVHD
7. Palliative Care
8. Stem cell processing
Standard myeloablative conditioning for patients with high-risk CML or MDS consists of targeted busulfan and cyclophosphamide but non relapse-related mortality at 4-5 months post-transplant is 20-25%. A recent Phase II study of targeted busulfan and fludarabine as myeloablative conditioning for such patients by C. Anasetti and colleagues at this Center and Dresden, Germany showed that full engraftment could be achieved with a non relapse-related mortality of only 7%. No increase in relapse rate was observed compared to historical controls transplanted with the standard conditioning regimen. Encouraged by these results we plan a new Phase II trial of reduced intensity conditioning with targeted busulfan and fludarabine for patients with standard risk hematologic malignancies in an effort to decrease transplant-related morbidity and mortality.
American College of Physicians
American Medical Association
American Society for Blood and Bone Marrow Transplantation
American Society for Clinical Oncology
American Society of Hematology
International Society for Hematotherapy and Graft Engineering
Assistant Member, Memorial Sloan-Kettering Cancer Center
Associate Member, Memorial Sloan-Kettering Cancer Center
Head; Laboratory of Viral Leukemogenesis, Memorial Sloan-Kettering Cancer Center
Research Associate, Memorial Sloan-Kettering Cancer Center
Assistant Professor, Johns Hopkins University, School of Medicine
Assistant Professor, Cornell University, Graduate School of Medical Sciences
Associate Professor, Cornell University, Graduate School of Medical Sciences
Population pharmacokinetic/dynamic model of lymphosuppression after fludarabine administration.. Cancer chemotherapy and pharmacology. 75(1):67-75.. 2015.
Design of a cost-effectiveness analysis alongside a randomized trial of transplantation using umbilical cord blood versus HLA-haploidentical related bone marrow in advanced hematologic cancer.. Journal of comparative effectiveness research. 3(2):135-44.. 2014.
A pilot pharmacologic biomarker study in HLA-haploidentical hematopoietic cell transplant recipients.. Cancer chemotherapy and pharmacology. 72(3):607-18.. 2013.
Alternative transplant donor sources: is there any consensus? Current opinion in oncology. 25(2):173-9.. 2013.
A pilot pharmacologic biomarker study of busulfan and fludarabine in hematopoietic cell transplant recipients.. Cancer chemotherapy and pharmacology. 69(1):263-272.. 2012.
Accurate Targeting of Daily Intravenous Busulfan with 8-Hour Blood Sampling in Hospitalized Adult Hematopoietic Cell Transplant Recipients.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 18(2):265-272.. 2012.
Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation.. Seminars in oncology. 39(6):683-93.. 2012.
Histology and time to progression predict survival for lymphoma recurring after reduced-intensity conditioning and allogeneic hematopoietic cell transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 17(10):1537-45.. 2011.
Development of a population pharmacokinetics-based sampling schedule to target daily intravenous busulfan for outpatient clinic administration.. Journal of clinical pharmacology. 50(11):1292-300.. 2010.
Comparison of matched unrelated and matched related donor myeloablative hematopoietic cell transplantation for adults with acute myeloid leukemia in first remission.. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 24(7):1276-82.. 2010.
Nonmyeloablative HLA-haploidentical bone marrow transplantation with high-dose posttransplantation cyclophosphamide: effect of HLA disparity on outcome.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 16(4):482-9.. 2010.
The contribution of malglycemia to mortality among allogeneic hematopoietic cell transplant recipients.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 15(3):344-51.. 2009.
A novel phenotypic method to determine fludarabine triphosphate accumulation in T-lymphocytes from hematopoietic cell transplantation patients.. Cancer chemotherapy and pharmacology. 63(3):391-401.. 2009.
A limited sampling schedule to estimate individual pharmacokinetic parameters of fludarabine in hematopoietic cell transplant patients.. Clinical cancer research : an official journal of the American Association for Cancer Research. 15(16):5280-7.. 2009.
Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 14(11):1279-87.. 2008.
HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 14(6):641-50.. 2008.