[Influence of Methylenetetrahydrofolate Reductase C677T Polymorphism on High-Dose Methotrexate Toxicity in Pediatric Mature B-cell lymphoma Patients].

Q4 Medicine

中国实验血液学杂志 Pub Date : 2024-12-01 DOI:10.19746/j.cnki.issn.1009-2137.2024.06.015

Jia-Qian Xu, Juan Wang, Su-Ying Lu, Yan-Peng Wu, Lan-Ying Guo, Bo-Yu Shi, Fei-Fei Sun, Jun-Ting Huang, Jia Zhu, Zi-Jun Zhen, Xiao-Fei Sun, Yi-Zhuo Zhang

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Abstract

Objective: To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients.

Methods: Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m ² MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included, and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed.

Results: Among the 58 pediatric patients, the number of CC, CT, and TT genotypes for MTHFR C677T was 33, 19 and 6, respectively. A total of 101 courses of HD-MTX therapy were counted, of which plasma MTX level >0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses, ≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level >0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P <0.05). Compared with wild-type (CC genotype), patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression, manifested as anemia, leucopenia, neutropenia and thrombocytopenia. However, plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism.

Conclusion: The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma, but is related to grade III to IV hematological toxicity.

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[亚甲基四氢叶酸还原酶C677T多态性对儿童成熟b细胞淋巴瘤患者高剂量甲氨蝶呤毒性的影响]。

目的：探讨MTHFR C677T （rs1801133）基因多态性对小儿成熟b细胞淋巴瘤患者甲氨蝶呤（MTX）相关毒性的影响。方法：选取2014年8月至2021年12月中山大学肿瘤中心接受5 g/m 2 MTX （24 h静脉输注）治疗的18岁以下成熟b细胞淋巴瘤患者58例，监测并分析其高剂量MTX （HD-MTX）的毒性。结果：58例患儿中，MTHFR C677T的CC、CT、TT基因型分别为33例、19例、6例。共统计101个疗程的HD-MTX治疗，其中35个疗程注射MTX后48 h血浆MTX水平>0.2 μmol/L， 66个疗程≤0.2 μmol/L。组间比较显示，注射MTX后48 h血浆MTX水平>0.2 μmol/L增加口腔黏膜炎发生的风险（P MTHFR C677T基因多态性）。结论：成熟b细胞淋巴瘤患儿发生口腔黏膜炎的风险与血浆MTX浓度相关。MTHFR C677T基因多态性与成熟b细胞淋巴瘤患儿血浆MTX浓度无关，但与III至IV级血液学毒性有关。

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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