Stem-Cell Transplantation in Children With Acute Lymphoblastic Leukemia: A Prospective International Multicenter Trial Comparing Sibling Donors With Matched Unrelated Donors—The ALL-SCT-BFM-2003 Trial

Purpose Although hematopoietic stem-cell transplantation is widely performed in children with high-risk acute lymphoblastic leukemia (ALL), the influence of donor types is poorly understood. Thus, transplantation outcomes were compared in the prospective multinational Berlin-FrankfurtMuenster (BFM) study group trial: ALL-SCT-BFM 2003 (Allogeneic Stem Cell Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia). Patients and Methods After conditioning with total-body irradiation and etoposide, 411 children with high-risk ALL received highly standardized stem-cell transplantations during the first or later remissions. Depending on donor availability, grafts originated from HLA-genoidentical siblings or from HLA-matched unrelated donors who were identified and matched by high-resolution allelic typing and were compatible in at least 9 of 10 HLA loci. Results Four-year event-free survival ( standard deviation [SD]) did not differ between patients with transplantations from unrelated or sibling donors (0.67 0.03 v0.71 0.05; P.405), with cumulative incidences of nonrelapse mortality ( SD) of 0.10 0.02 and 0.03 0.02 (P .017) and relapse rates ( SD) of 0.22 0.02 and 0.24 0.04 (P.732), respectively. Among recipients of transplantations from unrelated donors, no significant differences in event-free survival, overall survival, or nonrelapse mortality were observed between 9/10 and 10/10 matched grafts or between peripheral blood stem cells and bone marrow. The absence of chronic graft-versus-host disease had no effect on event-free survival. Engraftment was faster after bone marrow transplantation from siblings and was associated with fewer severe infections and pulmonary complications.