Impact of treosulfan exposure on clinical outcome after allogeneic stem cell transplantation in children: A substudy of 2 phase 2 trials
Year: 2024
Type: article
Abstract: AIMS: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a vital treatment for various paediatric malignant and nonmalignant diseases. The conditioning treatment before allo-HSCT is crucial for successful engraftment. Treosulfan, a cytotoxic prodrug, has gained popularity due to its lower toxicity compared to traditional alkylating agents used for conditioning treatment. METHODS: We investigated the relationship between pharmacokinetics and pharmacodynamics of treosulfan in paediatric patients, in a substudy pooling from 2 multicentre phase 2 clinical trials. A total of 83 children with malignant and nonmalignant diseases received treosulfan-based conditioning. Treosulfan exposure and its relationship with clinical outcomes, including survival, graft failure and graft-vs.-host disease, were investigated. RESULTS: Our findings reveal no significant association between treosulfan exposure and the key clinical outcomes or toxicity (P-values between .22 and .99), if the dosing is based on the approved product information. CONCLUSION: These findings suggest that treosulfan exposure after standardized body surface area-based dosing is appropriate in paediatric allo-HSCT.
DOI: 10.1111/bcp.16339
Authors: Krzysztof Kalwak, Ajay Vora, Peter Bader, Birgit Burkhardt, Selim Corbacioglu, Katarzyna Drabko, Jolanta Gozdzik, Johann Greil, Bernd Gruhn, Katharine Patrick, Ansgar Schulz, Petr Sedlacek, Jan Styczynski, Monika Mielcarek‐Siedziuk, Franco Locatelli, Dirk Reinhardt, Paul‐Gerhardt Schlegel, Joachim Baumgart, Jochen Kehne, Xieran Li, Rita Beier
Institutions: University of Wrocław, Wroclaw Medical University, Great Ormond Street Hospital, Goethe University Frankfurt, University Hospital Münster, University of Regensburg, Medical University of Lublin, Jagiellonian University, Heidelberg University, University Hospital Heidelberg, Jena University Hospital, Sheffield Children's NHS Foundation Trust, University Hospital Ulm, University Hospital in Motol, Nicolaus Copernicus University, Bambino Gesù Children's Hospital, Essen University Hospital, Universitätsklinikum Würzburg, Medac (Germany), Medizinische Hochschule Hannover
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4404549552