Treosulfan–fludarabine–thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies
Krzysztof Kałwak, Monika Mielcarek‐Siedziuk, Katharine Patrick, Jan Styczyński, Peter Bader, Selim Corbacioglu, Birgit Burkhardt, Karl W. Sykora, Katarzyna Drabko, Jolanta Goździk, Franca Fagioli, Johann Greil, Bernd Gruhn, Rita Beier, Franco Locatelli, Ingo Müller, Paul G. Schlegel, Petr Sedláček, Klaus Daniel Stachel, Claudia Hemmelmann, Ann-Kristin Möller, Joachim Baumgart, Ajay Vora
Abstract
Abstract 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/m 2 /day (7.7%), 12 g/m 2 /day (35.4%), or 14 g/m 2 /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.