Non-Myeloablative HLA-Matched Ex-Vivo T-Cell Depleted Stem Cell Transplantation for Hematologic Malignancies
Our prior experience in the lab and in clinical trials with non-myeloablative HLA-matched
and mismatched transplant strategies have been remarkable for a low transplant related
mortality rate, but a still formidable risk of GVHD and graft rejection. In this trial, we
have incorporated a combination ex-vivo T-cell depletion strategy to prevent GVHD with
vigorous in vivo depletion of host (and to a lesser extent donor) T-cells to prevent graft
Patients will receive non-myeloablative conditioning with cyclophosphamide, thymoglobulin,
fludarabine, and thymic irradiation, followed by a T-cell depleted PBSC infusion.
Cyclosporine will be given for GVHD prophylaxis, and tapered beginning on day 35. Data from
our mouse model and previous clinical trials have demonstrated that this approach can induce
mixed chimerism without GVHD, with the potential for conversion of mixed chimerism to full
donor hematopoiesis following donor leukocyte infusions.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the risks of severe (grade III/IV) GVHD or transplant related mortality at < 100 days following HLA-matched non-myeloablative stem cell transplantation (or following "prophylactic" DLI given for chimerism conversion).
Thomas Spitzer, M.D.
Massachusetts General Hospital, Harvard University
United States: Institutional Review Board
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