高剂量甲氨蝶呤的药代动力学反应的变化对于儿童急性淋巴细胞白血病（ALL）患者的预后和毒性管理至关重要。本系统综述旨在识别和评估与儿科 ALL 治疗巩固阶段甲氨蝶呤药代动力学参数显着相关的遗传多态性。使用系统评价首选报告项目（PRISMA）指南，我们系统地回顾了2013年至2023年的文献。使用的数据库是PubMed和Scopus。感兴趣的结果是研究设计、患者特征、样本量、采用的化疗方案、确定的药代动力学参数以及所涉及的遗传多态性。我们在定性综合中纳入了 31 篇文章，发现 SLCO1B1、ABCB1、ABCC2 和 MTHFR 基因似乎在 MTX 代谢和清除中发挥重要作用。其中，SLCO1B1 的变化对甲氨蝶呤清除率的影响最为显着且一致。这些相关变异可能有助于儿科 ALL 患者 HD-MTX 治疗的精确性和定制性。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

Variations in pharmacokinetic responses to high-dose methotrexate are essential for the prognosis and management of toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL) patients. This systematic review aimed to identify and evaluate genetic polymorphisms that are significantly associated with the pharmacokinetic parameters of methotrexate during the consolidation phase of pediatric ALL treatment. Using the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, we systematically reviewed the literature from 2013 to 2023. The databases used were PubMed and Scopus. The outcomes of interest are the study design, patient characteristics, sample size, chemotherapy protocol utilized, pharmacokinetic parameters identified, and genetic polymorphisms implicated. We included 31 articles in the qualitative synthesis and found that the SLCO1B1, ABCB1, ABCC2, and MTHFR genes appear to play significant roles in MTX metabolism and clearance. Among these, variations in SLCO1B1 have the most significant and consistent impact on methotrexate clearance. These implicated variants may contribute to the precision and tailoring of HD-MTX treatment in pediatric ALL patients.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.