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.

Abstract

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-Frankfurt-Muenster (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 v 0.71 ± 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.

CONCLUSION:

Outcome among high-risk pediatric patients with ALL after hematopoietic stem-cell transplantation was not affected by donor type. Standardized myeloablative conditioning produced a low incidence of treatment-related mortality and effective control of leukemia.

• Authors: Christina Peters, Martin Schrappe, Arend von Stackelberg, André Schrauder, Peter Bader, Wolfram Ebell, Peter Lang, Karl-Walter Sykora, Johanna Schrum, Bernhard Kremens, Karoline Ehlert, Michael H Albert, Roland Meisel, Susanne Matthes-Martin, Tayfun Gungor, Wolfgang Holter, Brigitte Strahm, Bernd Gruhn, Ansgar Schulz, Wilhelm Woessmann, Ulrike Poetschger, Martin Zimmermann, Thomas Klingebiel
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 11 Pg. 1265-74 (Apr 10 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 25753432 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• HLA Antigens
• Myeloablative Agonists
• Etoposide

Topics

• Adolescent
• Child
• Child, Preschool
• Disease-Free Survival
• Etoposide (administration & dosage)
• Europe
• Female
• HLA Antigens (genetics, immunology)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods, mortality)
• Histocompatibility
• Histocompatibility Testing
• Humans
• Infant
• Infant, Newborn
• Kaplan-Meier Estimate
• Living Donors
• Male
• Myeloablative Agonists (administration & dosage)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics, immunology, mortality, pathology, surgery)
• Proportional Hazards Models
• Prospective Studies
• Recurrence
• Risk Factors
• Siblings
• Time Factors
• Transplantation Conditioning (methods)
• Transplantation, Homologous
• Treatment Outcome
• Unrelated Donors
• Whole-Body Irradiation