The superiority of total body irradiation (TBI)-based vs chemotherapy conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL) has been established in the international, prospective phase-3 FORUM study, randomizing 417 patients aged 4-18 years in complete remission (CR), who received allo-HSCT from HLA-matched sibling or unrelated donors. Because of the unavailability of TBI in some regions and to accommodate individual contraindications, this study reports the prespecified comparison of outcomes of patients receiving busulfan (BU)- or treosulfan (TREO)-based regimens from 2013 to 2018. Overall, 180 and 128 patients received BU/thiotepa (THIO)/fludarabine (FLU) or TREO/THIO/FLU, respectively. Data were analyzed as of February 2023, with a median follow-up of 4.2 years (range, 0.3-9.1). 3-year overall survival was 0.71 (BU, 95% confidence interval [0.64-0.77]) and 0.72 (TREO, [0.63-0.79]) and 3-year event-free survival was 0.60 (BU, [0.53-0.67]) and 0.55 (TREO, [0.46-0.63]). The 3-year cumulative incidence of relapse (BU, 0.31 [0.25-0.38]; TREO, 0.36 [0.27-0.44]); and nonrelapse mortality (BU, 0.08 [0.05-0.13]; TREO, 0.09 [0.05-0.15]) were comparable. One case of fatal veno-occlusive disease occurred in each group. No significant differences in acute and chronic graft-versus-host disease (GVHD) or 3-year GVHD-free and relapse-free survival (BU, 0.48 [0.41-0.55]; TREO, 0.45 [0.37-0.54]) were recorded. Outcomes for patients in first and second CR were similar irrespective of the regimen. In conclusion, BU/THIO/FLU or TREO/THIO/FLU regimens can be an alternative to TBI for patients with ALL aged >4 years with contraindications or lack of access to TBI. 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 Geneva Switzerland

Department Cell Therapy and Allogeneic Stem Cell Transplant Karolinska University Hospital Stockholm Sweden

Department of Paediatric Oncology University Hospital Leuven Leuven Belgium

Department of Pediatric Hematology and Oncology IRCCS Ospedale Pediatrico Bambino Gesù Catholic University of the Sacred Heart Rome Italy

Department of Pediatric Hematology and Oncology National Institute of Children's Diseases Comenius University Bratislava Slovakia

Department of Pediatric Hematology and Oncology Oslo University Hospital Oslo Norway

Department of Pediatric Hematology and Oncology St Anna Children's Hospital Medical University of Vienna Vienna Austria

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

Department of Pediatric Hematology Oncology and Bone Marrow Transplantation Wroclaw Medical University Wroclaw Poland

Department of Pediatric Hematology Oncology and Stem Cell Transplantation University Children's Hospital Regensburg Regensburg Germany

Department of Pediatrics and Adolescent Medicine Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Division for Hematology and Oncology Department of Pediatrics Zagreb University Hospital Center Zagreb Croatia

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

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

Division of Pediatric Hematology and Oncology Hospital Universitari Vall d'Hebron Barcelona Spain

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

Division of Pediatric Stem Cell Therapy Department of Pediatric Oncology Hematology and Clinical Immunology Medical Faculty Heinrich Heine University Duesseldorf Germany

Hospital de Pediatría Prof Dr Juan P Garrahan 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 National Institute of Hematology and Infectious Diseases Central Hospital of Southern Pest Budapest Hungary

Pediatric Hematopoietic Stem Cell Unit Fondazione IRCCS San Gerardo dei Tintori Monza Italy

Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands

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

School of Medicine and Surgery University of Milano Bicocca Monza Italy

St Anna Children's Cancer Research Institute Vienna Austria

Stem Cell Transplant Unit Agia Sofia Children's Hospital Athens Greece

The Children's Hospital at Westmead Sidney NSW Australia

University of Helsinki and the Hospital for Children and Adolescents University of Helsinki Helsinki Finland

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ClinicalTrials.gov
NCT01949129