Treosulfan-fludarabine-thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies

Kalwak K, Mielcarek M, Patrick K, Styczynski J, Bader P, Corbacioglu S, Burkhardt B, Sykora KW, Drabko K, Gozdzik J, Fagioli F, Greil J, Gruhn B, Beier R, Locatelli F, Mueller I, Schlegel PG, Sedlacek P, Stachel D, Hemmelmann C, Moeller AK, Baumgart J, Vora A (2020)

Publication Type: Journal article

Publication year: 2020

Journal

DOI: 10.1038/s41409-020-0869-6

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.

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Involved external institutions

Universitätsklinikum Regensburg Germany (DE) Universitätsklinikum Münster Germany (DE) Universitätsklinikum Würzburg Germany (DE) Nicolaus Copernicus University (NCU) / Uniwersytet Mikołaja Kopernika w Toruniu (UMK) Poland (PL) Great Ormond Street Hospital (GOSH) United Kingdom (GB) Motol University Hospital / Fakultní nemocnice v Motole Czech Republic (CZ) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Università degli studi "La Sapienza" Italy (IT) Medical University of Lublin / Uniwersytet Medyczny w Lublinie Poland (PL) Medac GmbH Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Sheffield Children's NHS Foundation Trust United Kingdom (GB) Universitätsklinikum Jena Germany (DE) Jagiellonian University / Uniwersytet Jagielloński (UJ) Poland (PL) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) University of Turin / Università degli Studi di Torino (UNITO) Italy (IT) Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Essen Germany (DE)

How to cite

APA:

Kalwak, K., Mielcarek, M., Patrick, K., Styczynski, J., Bader, P., Corbacioglu, S.,... Vora, A. (2020). Treosulfan-fludarabine-thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies. Bone Marrow Transplantation. https://doi.org/10.1038/s41409-020-0869-6

MLA:

Kalwak, Krzysztof, et al. "Treosulfan-fludarabine-thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies." Bone Marrow Transplantation (2020).

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