Ph.D., Cornell University Graduate School of Medical Sciences
M.D., Johns Hopkins University
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.
Hematologic maglignancies, Allogeneic HSCT from mismatched, related (haploidentical) donors, immunotherapy, acute GVHD, chronic GVHD, palliative care, stem cell processing.
Double Cord Versus Haploidentical Transplants (BMT CTN #1101)
A Multi-Center, Phase III, Randomized Trial of Reduced Intensity (RIC) Conditioning and Transplantation of Double Unrelated Umbilical Cord Blood (dUCB) Versus HLA-Haploidentical Related Bone Marrow (Haplo-BM) for Patients With Hematologic Malignancies (BMT CTN #1101)