目的 探讨急性淋巴细胞白血病（acute lymphoblastic leukemia, ALL）患儿亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase, MTHFR）rs1801133及γ-谷氨酰水解酶（γ-glutamyl hydrolase, GGH）rs11545078基因多态性对大剂量氨甲蝶呤（methotrexate, MTX）治疗后MTX血药浓度（plasma concentration of MTX, C_MTX）及药物毒性反应的影响。 方法 选取2021年1月—2024年4月就诊于徐州医科大学附属徐州儿童医院的ALL患儿为研究对象，采用多重聚合酶链反应技术检测MTHFR rs1801133及GGH rs11545078基因型，采用酶放大免疫分析法测定C_MTX，其毒性反应按照不良事件通用术语标准5.0评级，分析MTHFR rs1801133及GGH rs11545078基因型与C_MTX及相关毒性反应的关系。 结果 低危组ALL患儿MTHFR rs1801133基因型与72 h C_MTX升高有相关性（P<0.05），中高危组MTHFR rs1801133基因型与48 h MTX C_MTX升高有相关性（P<0.05）。GGH rs11545078基因型与48 h C_MTX升高有相关性（P<0.05）。中高危组ALL患儿MTHFR rs1801133基因型与血红蛋白减少的发生有相关性（P<0.05），GGH rs11545078基因型与血小板减少的发生有相关性（P<0.05）。 结论 在用大剂量MTX治疗ALL时，可通过检测MTHFR rs1801133与GGH rs11545078基因型来预测C_MTX升高及毒性反应的发生，以便及时做出相关处理，提高安全性。

Objective To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). Methods Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. Results In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). Conclusions Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.