Hematopoietic cell transplant outcomes after myeloablative conditioning with fludarabine, busulfan, low dose total body irradiation and rabbit antithymocyte globulin.

Optimal conditioning and graft-vs-host disease (GVHD) prophylaxis for hematopoietic cell transplantation (HCT) are unknown. Here we report on outcomes after low-toxicity, myeloablative conditioning consisting of fludarabine, busulfan, and 4 Gy total body irradiation, in combination with Thymoglobulin and posttransplant methotrexate and cyclosporine. We retrospectively studied 700 patients with hematologic malignancies who received blood stem cells from 7 to 8/8 HLA matched unrelated or related donors. Median follow up of surviving patients was 5 years. At 5 years, overall survival (OS), relapse-free survival (RFS), and chronic GVHD/relapse-free survival (cGRFS) were 58%, 55%, and 40%. Risk factors for poor OS, RFS as well as cGRFS were 1. high to very high disease risk index (DRI), 2. high recipient age, and 3. cytomegalovirus (CMV) seropositive recipient with seronegative donor (D-R+). The latter risk factor applied particularly to patients with lymphoid malignancies. Neither donor other than HLA matched sibling (7-8/8 unrelated) nor one HLA allele mismatch were risk factors for poor OS, RFS, or cGRFS. In conclusion, the above regimen results in excellent long-term outcomes. The outcomes are negatively impacted by older age, high or very high DRI, and CMV D-R+ serostatus, but not by donor unrelatedness or one HLA allele mismatch.