Krzysztof Kalwak , 1 , Monika Mielcarek 1 , Katharine Patrick 2 , Jan Styczynski 3 , Peter Bader 4 , Selim Corbacioglu 5 , Birgit Burkhardt 6 , Karl Walter Sykora 7 , Katarzyna Drabko 8 , Jolanta Gozdzik 9 , Franca Fagioli 10 , Johann Greil 11 , Bernd Gruhn 12 , Rita Beier 13 , Franco Locatelli 14 , Ingo Müller 15 , Paul Gerhardt Schlegel 16 , Petr Sedlacek 17 , Klaus Daniel Stachel 18 , Claudia Hemmelmann 19 , Ann-Kristin Möller 19 , Joachim Baumgart 19 , Ajay Vora 20
20 March 2020
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.