Prospective study of nonmyeloablative, HLA-mismatched unrelated BMT with high-dose posttransplantation cyclophosphamide

blood or marrow transplantation (BMT) candidates may lack HLA-matched, related haploidentical, and unrelated umbilical cord options. Barriers to partially HLA-mismatched, unrelated donor (mMUD) BMT include excess graft-versus-host disease (GVHD), graft failure, and death. We prospectively studied nonmyeloablative (NMA) mMUD BMT with high-dose posttransplantation cyclophosphamide (PTCy) for patients with hematologic malignancies. Three transplants were performed with busulfan/fludarabine conditioning, with subsequent change to fludarabine/Cy/total body irradiation (flu/Cy/TBI). Twenty mMUD transplants are reported using flu/Cy/TBI, T-cell replete bone marrow grafts, and PTCy, mycophenolate mofetil, and sirolimus or tacrolimus (1 patient) for GVHD prophylaxis. The median patient age was 56. Of these unrelated grafts, 45% had >= 2 mismatched HLA loci, 25% had >= 3 mismatched loci, and 50% had HLA-Cmismatches. No graft failure or grades 3-4 acute GVHD occurred. The median times to neutrophil recovery (>= 500/mu L) and platelet recovery (>= 20000/mu L) were 19 days and 31 days, respectively. Full-donor chimerism was achieved in 95% of evaluable patients by day 60. The 180-day probability of grades 2-4 acute GVHD (all grade 2) was 25%, and the 1-year probability of any chronic GVHD was 16% (none severe). The 2-year nonrelapse mortality probability was 6%. With 4-year median follow-up, the 1-year progression-free and overall survival probabilitieswere 65% and 75%, respectively. NMA, T-cell repletemMUD BMT is thus a potentially viable option for patients without other suitable donors.