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

TY - JOUR

T1 - 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

AU - Peters, Christina

AU - Schrappe, Martin

AU - von Stackelberg, Arend

AU - Schrauder, André

AU - Bader, Peter

AU - Ebell, Wolfram

AU - Lang, Peter

AU - Sykora, Karl-Walter

AU - Schrum, Johanna

AU - Kremens, Bernhard

AU - Ehlert, Karoline

AU - Albert, Michael H

AU - Meisel, Roland

AU - Matthes-Martin, Susanne

AU - Gungor, Tayfun

AU - Holter, Wolfgang

AU - Strahm, Brigitte

AU - Gruhn, Bernd

AU - Schulz, Ansgar

AU - Woessmann, Wilhelm

AU - Poetschger, Ulrike

AU - Zimmermann, Martin

AU - Klingebiel, Thomas

N1 - © 2015 by American Society of Clinical Oncology.

PY - 2015/4/10

Y1 - 2015/4/10

N2 - 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.

AB - 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.

KW - Adolescent

KW - Child

KW - Child, Preschool

KW - Disease-Free Survival

KW - Etoposide

KW - Europe

KW - Female

KW - HLA Antigens

KW - Hematopoietic Stem Cell Transplantation

KW - Histocompatibility

KW - Histocompatibility Testing

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Kaplan-Meier Estimate

KW - Living Donors

KW - Male

KW - Myeloablative Agonists

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Recurrence

KW - Risk Factors

KW - Siblings

KW - Time Factors

KW - Transplantation Conditioning

KW - Transplantation, Homologous

KW - Treatment Outcome

KW - Unrelated Donors

KW - Whole-Body Irradiation

U2 - 10.1200/JCO.2014.58.9747

DO - 10.1200/JCO.2014.58.9747

M3 - SCORING: Journal article

C2 - 25753432

VL - 33

SP - 1265

EP - 1274

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 11

ER -