Optimal conditioning prior to allogeneic hematopoietic stem cell transplantation for children with non-malignant diseases is subject of ongoing research. This prospective, randomized, phase 2 trial compared safety and efficacy of busulfan with treosulfan based preparative regimens. Children with non-malignant diseases received fludarabine and either intravenous (IV) busulfan (4.8 to 3.2 mg/kg/day) or IV treosulfan (10, 12, or 14 g/m2/day). Thiotepa administration (2 × 5 mg/kg) was at the investigator's discretion. Primary endpoint was freedom from transplantation (treatment)-related mortality (freedom from TRM), defined as death between Days -7 and +100. Overall, 101 patients (busulfan 50, treosulfan 51) with at least 12 months follow-up were analyzed. Freedom from TRM was 90.0% (95% CI: 78.2%, 96.7%) after busulfan and 100.0% (95% CI: 93.0%, 100.0%) after treosulfan. Secondary outcomes (transplantation-related mortality [12.0% versus 3.9%]) and overall survival (88.0% versus 96.1%) favored treosulfan. Graft failure was more common after treosulfan (n = 11), than after busulfan (n = 2) while all patients were rescued by second procedures except one busulfan patient. CTCAE Grade III adverse events were similar in both groups. This study confirmed treosulfan to be an excellent alternative to busulfan and can be safely used for conditioning treatment in children with non-malignant disease.

Charité University Hospital Berlin Germany

Children's Hospital Antonio Cao Cagliari Italy

Children's Hospital Bambino Gesú Rome Italy

Children's Hospital Regina Margherita Turin Italy

Children's Hospital S Maria della Misericordia Perugia Italy

Children's Hospital San Matteo Pavia Italy

Department of Pediatric Hematology and Oncology University Hospital Collegium Medicum UMK Bydgoszcz Poland

Department of Pediatric Hematology Oncology and BMT Wroclaw Medical University Wroclaw Poland

Department of Pediatrics Jena University Hospital Jena Germany

Department of Pediatrics University Medical Center Ulm Ulm Germany

Hannover Medical School Ped Haematology and Oncology Hannover Germany

Jagiellonian University Medical College Center of Transplantation University Children's Hospital in Cracow Cracow Poland

medac GmbH Wedel Germany

Pediatric Hematology Oncology Azienda Ospedaliera Universitaria Integrata Verona Italy

University Hospital Essen Germany

University Hospital Frankfurt Frankfurt Main Germany

University Hospital Heidelberg Germany

University Hospital Monza Italy

University Hospital Motol Prague Czech Republic

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