Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

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PRIMARY OBJECTIVES: I. To estimate the probability of developing chronic GHVD among patients who receive naive T cell (TN)-depleted peripheral blood stem cell transplant (PBSCT) in each of the following groups: a) Arm A: patients who receive TN-depleted peripheral blood stem cells (PBSC) from a huma...

PRIMARY OBJECTIVES: I. To estimate the probability of developing chronic GHVD among patients who receive naive T cell (TN)-depleted peripheral blood stem cell transplant (PBSCT) in each of the following groups: a) Arm A: patients who receive TN-depleted peripheral blood stem cells (PBSC) from a human leukocyte antigens (HLA) matched related donor (MRD) following high-intensity myeloablative conditioning (total body irradiation [TBI] 1320 cGy, thiotepa, fludarabine phosphate [fludarabine]) and pharmacological immunosuppression with tacrolimus and methotrexate; b) Arm B: patients who receive TN-depleted PBSC from a MRD following lower-intensity myeloablative conditioning (TBI 400 cGy, thiotepa, fludarabine and cyclophosphamide) and pharmacological immunosuppression with tacrolimus and mycophenolate mofetil (MMF); c) Arm C: patients who receive TN-depleted PBSC from a HLA-matched unrelated donor (MUD) following high-intensity myeloablative conditioning (TBI 1320 cGy, thiotepa, fludarabine) and pharmacological immunosuppression with tacrolimus and methotrexate; d) Arm D: patients who receive TN-depleted PBSC from a MUD following lower-intensity myeloablative conditioning (TBI 400 cGy, thiotepa, fludarabine and cyclophosphamide) and pharmacological immunosuppression with tacrolimus and MMF. II. To estimate the probability of acute (a)GVHD grade II-IV following TN-depleted (TND) PBSCT with tacrolimus and methotrexate (Arm A) or MMF (Arm B) GVHD prophylaxis in MRD recipients. III. Estimate the rate of aGVHD grade II-IV following TND PBSCT with tacrolimus and methotrexate (Arm C) or MMF (Arm D) prophylaxis in recipients of MUD hematopoietic cell transplantation (HCT). IV. Estimate the probability of graft failure in recipients of CD45RA positive (+) TN-depleted PBSCT with tacrolimus and methotrexate (MTX) or MMF GVHD prophylaxis. SECONDARY OBJECTIVES: I. Estimate the probability of transplant-related mortality by day 100. II. Estimate the probability of relapse. III. Evaluate immune reconstitution and pathogen-specific immune reconstitution. OUTLINE: Patients are assigned to 1 of 4 treatment arms. CONDITIONING: ARMS A AND C (high-intensity myeloablative conditioning): Patients undergo total body irradiation twice daily (BID) on days -10 to -7. Patients also receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. ARMS B AND D (lower-intensity myeloablative conditioning): Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation once daily (QD) on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with granulocyte colony-stimulating factor (GCSF)-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: ARMS A AND C: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or orally (PO) (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. ARMS B AND D: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on days -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the principal investigator. After completion of study treatment, patients are followed up at 80-100 days, 360 days, and then yearly for up to 5 years.

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