Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD

OBJECTIVES: Primary * Estimate the probability of grades II-IV acute graft-vs-host disease (GVHD) in patients with acute leukemia or advanced myelodysplastic syndromes treated with CD45RA+ T-cell-depleted allogeneic peripheral blood stem cell transplantation and compare this to relevant historical experience. * Estimate the probability of graft failure in these patients. Secondary * Evaluate immune reconstitution and pathogen-specific T-cell reconstitution in these patients. * Estimate the probability of transplant-related mortality by day 100 in these patients. * Estimate the probability of relapse in these patients. * Estimate the probability and severity of chronic GVHD in these patients. OUTLINE: This is a multicenter study. * Myeloablative conditioning regimen: Patients undergo total body irradiation twice daily for 4 days (Days -10 to -7) Patients also receive thiotepa IV over 4 hours for 2 days (Days -6 and -5) and fludarabine phosphate IV over 30 minutes for 5 days (Days -6 to -2.) * Transplantation: Patients receive a CD34+ enriched allogeneic peripheral blood stem cell (PBSC) product followed by a CD45RA+ T-cell-depleted allogeneic PBSC product on day 0. * Graft-vs-host disease (GVHD) prophylaxis: Patients will receive Tacrolimus as per cohort 1. If the rate of grade II-IV acute GVHD in the first 35 patients is significantly reduced (compared to historical controls), subsequent patients are enrolled in cohort 2. * Cohort 1: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 50, followed by a standard taper in the absence of grade II-IV acute GVHD. * Cohort 2: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 30, followed by a rapid taper in the absence of grade II-IV acute GVHD. Patients are followed actively for at least 1 year post transplant.