Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m2/day (7.7%), 12 g/m2/day (35.4%), or 14 g/m2/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I-IV and 26.6% for grades II-IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies.

Children's Hospital Regina Margherita University of Turin Turin Italy

Children's Hospital University of Erlangen Erlangen Germany

Department for Children and Adolescents Division for Stem Cell Transplantation Immunology and Intensive Care Medicine Goethe University Frankfurt Germany

Department of Pediatric Hematology and Oncology Collegium Medicum UMK Torun Bydgoszcz Poland

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

Department of Pediatric Hematology Oncology and BMT University Hospital Muenster Muenster Germany

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

Department of Pediatric Hematology Oncology and Transplantology Medical University of Lublin Lublin Poland

Department of Pediatrics Hannover Medical School Hannover Germany

Department of Pediatrics Jena University Hospital Jena Germany

Depertment of Pediatrics 3 University Hospital of Essen Essen Germany

Great Ormond Street Hospital London UK

IRCCS Bambino Gesú Children's Hospital Sapienza University of Rome Rome Italy

medac GmbH Wedel Germany

Medical College University Children's Hospital in Cracow Jagiellonian University Cracow Poland

Sheffield Children's Hospital Sheffield UK

University Children's Hospital Heidelberg Heidelberg Germany

University Children's Hospital of Wuerzburg Wuerzburg Germany

University Hospital of Regensburg Regensburg Germany

University Medical Center Hamburg Eppendorf Hamburg Germany

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

Treosulfan vs busulfan conditioning for allogeneic bmt in children with nonmalignant disease: a randomized phase 2 trial

Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study

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EudraCT
2013–003604–39

ClinicalTrials.gov
NCT02333058