Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia conditioned with busulfan,...

Children with acute lymphoblastic leukemia (ALL) undergoing allogeneic bone marrow transplantation (BMT) using total body irradiation (TBI)-containing conditioning regimens are at risk of substantial late sequelae affecting growth and endocrine functions. This has lead to the use of non-TBI or chemotherapy conditioning regimens for ALL patients in many centers. However, it is unknown whether chemotherapy conditioning results in improved antileukemic efficacy or reduced transplant-related toxicity. We report our experience using a chemotherapy conditioning regimen (busulfan (Bu), cyclophosphamide (CY) and melphalan (Mel)) in 26 consecutively enrolled children with ALL (group I). At a median follow-up of 58 months, event-free survival (EFS) for Bu/CY/Mel-treated patients was 27% (+/- 8.7), while the leukemic relapse rate was 49% (+/- 13). Regimen-related toxicity was severe in these patients: overall treatment-related mortality was 42%, while 50% of patients had interstitial pneumonitis and 35% of patients had severe hemorrhagic cystitis. A historical control group of 25 consecutively enrolled patients, mostly treated with TBI-containing regimens (group II), had an EFS of 36% (+/- 9.6%) and a leukaemic relapse rate of 45% (+/- 11) at a median follow-up of 117 months. We conclude that the Bu/CY/Mel conditioning regimen leads to severe transplant-related toxicity and did not significantly improve leukemic relapse rates.