Reduced-toxicity conditioning regimen with busulfan, fludarabine, rATG, and 400 cGy TBI in pediatric patients undergoing hematopoietic stem cell transplant for high-risk hematologic malignancies

Background Myeloablative conditioning regimens decrease the risk of relapse in pediatric patients undergoing allogeneic hematopoietic stem cell transplant (HCT) for hematologic malignancies, but cause significant toxicities Procedure This prospective study evaluated the use of a reduced-toxicity, myeloablative regimen with dose-adjusted busulfan, fludarabine, antithymocyte globulin and 400 cGy of total body irradiation in 40 patients Overall survival at two- and five-years post-HCT was 67% and 51%, respectively. Relapse occurred in 11 patients (28%) at a median of seven months and was the leading cause of death. Transplant-related mortality was 8% and 13% at 100 days and one-year post-HCT, respectively. Trends toward improved survival were seen in patients transplanted for myeloid disease using bone marrow as stem cell source who achieved a busulfan AUC > 4000 mu mol*min/day with two-year relapse-free survival approaching 80% Conclusions This conditioning regimen is safe and effective in patients with high-risk leukemias, particularly myeloid disease. Larger studies are needed to compare its safety and efficacy to other myeloablative regimens in this population.