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.
题目: MTHFR C677T基因多态性对儿童成熟B细胞淋巴瘤患者大剂量甲氨蝶呤治疗相关毒性的影响.
目的: 探讨 MTHFR C677T（rs1801133）基因多态性对成熟B细胞淋巴瘤患儿甲氨蝶呤（MTX）相关毒性的影响。.
方法: 纳入2014年8月至2021年12月在中山大学肿瘤防治中心接受MTX 5 g/m 2（24 h静脉滴注）治疗的58例中国18岁以下成熟B细胞淋巴瘤中危及高危的患儿，监测并分析患儿的毒副反应。.
结果: 58例患儿中， MTHFR C677T野生型33例，杂合型19例，纯合型6例。共统计了101个疗程，其中35个疗程观察到MTX输注后48 h血药浓度>0.2 μmol/L，66个疗程≤0.2 μmol/L。组间比较发现，输注后48 h血浆MTX水平>0.2 μmol/L可增加发生口腔黏膜炎的风险（P <0.05）。相比野生型患儿，突变型（杂合型+纯合型）患儿更容易发生骨髓抑制，表现为贫血、白细胞减少、中性粒细胞减少和血小板减少。48 h血浆MTX水平与 MTHFR C677T基因多态性无关。.
结论: 成熟B细胞淋巴瘤患儿口腔黏膜炎发生风险与血浆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，与III-IV级血液学毒性相关。.
Keywords: mature B-cell lymphoma; children; methotrexate; toxicity; polymorphism.