Impact of treosulfan exposure on clinical outcome after allogeneic stem cell transplantation in children: A substudy of 2 phase 2 trials.

IF 3.1 3区医学 Q2 PHARMACOLOGY & PHARMACY

British journal of clinical pharmacology Pub Date : 2024-11-19 DOI:10.1111/bcp.16339

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

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引用次数: 0

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.

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硫丹暴露对儿童异基因干细胞移植后临床结果的影响：2项2期试验的子研究。

目的：异基因造血干细胞移植（allo-HSCT）是治疗各种儿科恶性和非恶性疾病的重要方法。异体造血干细胞移植前的调理治疗对成功移植至关重要。特罗硫安是一种细胞毒性原药，与用于调理治疗的传统烷化剂相比毒性较低，因此受到了广泛欢迎：方法：我们在一项汇集了两项多中心二期临床试验结果的子研究中，对儿童患者服用硫丹的药代动力学和药效学之间的关系进行了调查。共有83名患有恶性和非恶性疾病的儿童接受了以硫丹为基础的治疗。研究调查了硫丹暴露及其与临床结果的关系，包括存活率、移植物失败和移植物抗宿主疾病：结果：我们的研究结果表明，如果按照批准的产品信息进行用药，硫丹暴露量与主要临床结果或毒性之间没有明显关联（P值介于0.22和0.99之间）：结论：这些研究结果表明，在儿科allo-HSCT中，基于体表面积的标准化剂量是适当的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British journal of clinical pharmacology 医学-药学

CiteScore

6.30

自引率

8.80%

发文量

419

审稿时长

1 months

期刊介绍： Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.