Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young children, total body irradiation (TBI) is associated with severe late sequelae. In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of 2 TBI-free conditioning regimens in children aged <4 years with ALL. Patients received fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo) before HSCT. From 2013 to 2021, 191 children received transplantation and were observed for ≥6 months (median follow-up: 3 years). The 3-year OS was 0.63 (95% confidence interval [95% CI], 0.52-0.72) and 0.76 (95% CI, 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (P = .075), respectively. Three-year EFS was 0.52 (95% CI, 0.41-0.61) and 0.51 (95% CI, 0.39-0.62), respectively (P = .794). Cumulative incidence of nonrelapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI, 0.02-0.12) vs 0.03 (95% CI: <0.01-0.09) (P = .406) and 0.42 (95% CI, 0.31-0.52) vs 0.45 (95% CI, 0.34-0.56) (P = .920), respectively. Grade >1 acute graft-versus-host disease (GVHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% of those receiving Flu/Thio/Treo (P = .049), whereas grade 3/4 occurred in 10% and 9%, respectively (P = .813). The 3-year incidence of chronic GVHD was 0.07 (95% CI, 0.03-0.13) vs 0.05 (95% CI, 0.02-0.11), respectively (P = .518). In conclusion, both chemotherapeutic conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure. This trial was registered at www.clinicaltrials.gov as #NCT01949129.

CANSEARCH Research Platform for Pediatric Oncology and Hematology Faculty of Medicine Department of Pediatrics Gynecology and Obstetrics University of Geneva Switzerland

Copenhagen University Hospital Rigshospitalet Department for Pediatric Hematology and Oncology Copenhagen Denmark

Department of Hematology Oncology Immunology Gene Therapy and Stem Cell Transplantation University Children's Hospital Zürich Eleonore Foundation and Children's Research Center Zürich Switzerland

Department of Paediatric Oncology University Hospital Leuven Leuven Belgium

Department of Pediatric Hematology and Oncology Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino Gesù Catholic University of the Sacred Heart Rome Italy

Department of Pediatric Hematology and Oncology Motol University Hospital Prague Czech Republic

Department of Pediatric Hematology and Oncology Oslo University Hospital Oslo Norway

Department of Pediatric Oncology Hematology and Transplantology Poznań University of Medical Sciences Poznań Poland

Division of Pediatric Oncology and Cellular Therapy Alberta Children's Hospital Calgary Alberta Canada

Division of Pediatric Oncology and Hematology Department of Women Child and Adolescent University Geneva Hospitals Geneva Switzerland

Goethe University University Hospital Department of Pediatrics Division for Stem Cell Transplantation Immunology and Intensive Care Medicine Frankfurt Germany

Hospital de Pediatría Prof Dr Juan P Garrahan Buenos Aires Buenos Aires Argentina

Medical Park Antalya Hospital Antalya Turkey

Pediatric Hematology and Immunology Department Robert Debré Hospital Groupe Hospitalo Universitaire Assistance Publique Hôpitaux de Paris Nord Université Paris Cité Paris France

Pediatric Hematology and Stem Cell Transplantation Department Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases Budapest Hungary

Schneider Children's Medical Center of Israel and Sackler Faculty of Medicine Tel Aviv University Petah Tikva Israel

St Anna Children's Cancer Research Institute Vienna Austria

St Anna Children's Hospital University Vienna Vienna Austria

Università degli Studi di Milano Fondazione FONDAZIONE MONZA E BRIANZA PER IL BAMBINO E LA SUA MAMMA Department for Pediatric Hematology and Oncology Monza Italy

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Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM

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ClinicalTrials.gov
NCT01949129