ABCB1 C3435T基因多态性与成熟B细胞淋巴瘤患儿大剂量甲氨蝶呤血药浓度和不良反应的相关性研究

Correlations of ABCB1 C3435T genetic polymorphism with serum concentrations and adverse reactions of high-dose methotrexate in children with mature B-cell lymphoma

目的探讨成熟B细胞淋巴瘤患儿ABCB1 C3435T(CC型、CT型和TT型)基因多态性与大剂量甲氨蝶呤(HD-MTX)化疗后血药浓度和药品不良反应(ADR)的相关性。方法回顾性收集本院2019年10月1日至2022年10月1日收治的行HD-MTX化疗且检测ABCB1 C3435T基因型并测定MTX血药浓度的成熟B细胞淋巴瘤患儿的病历资料,分析基因多态性与MTX血药浓度和ADR的关系。结果共收集66例患者,其中男52例,女14例,平均年龄(7.46±3.09)岁(1.9~15.0岁)。HD-MTX化疗后常见ADR为中性粒细胞减少(98.48%)、贫血(89.39%)、血小板减少(77.27%)和黏膜损伤(53.03%)等。ABCB1 C3435T TT型比CC型的MTX 44 h血药浓度更高(P<0.05)。CT和TT型比CC型的黏膜损伤、呕吐和肝损伤发生率更高(P<0.05)。结论ABCB1 C3435T基因多态性与成熟B细胞淋巴瘤患儿HD-MTX血药浓度水平及ADR(黏膜损伤、呕吐和肝损伤)可能有关。

Objective To investigate the correlations between polymorphisms of ABCB1 C3435T genes(CC,CT and TT),blood drug concentrations and adverse drug reactions(ADR)during high-dose methotrexate(HD-MTX)chemotherapy in children with mature B-cell lymphoma.Methods The medical data of children with mature B-cell lymphoma who had received HD-MTX chemotherapy and had had their MTX concentrations after administration determined and polymorphisms of ABCB1 C3435T detected was retrospectively collected from Oct,2019 to Oct,2022.The relationships between ABCB1 C3435T gene polymorphisms,MTX plasma concentrations and ADR were analyzed.Results A total of 66 patients,including 52 males and 14 females with an average age of 7.46±3.09 years(1.9~15.0 years),were enrolled.The most common ADR associated with HD-MTX were neutropenia(98.48%),anemia(89.39%),thrombocytopenia(77.27%)and mucosal injury(53.03%).The MTX 44 h blood concentration of the ABCB1 C3435T TT type was higher than that of the CC type(P<0.05).Compared with the ABCB1 C3435T CC type,CT and TT types had higher incidence of mucosal injury,vomiting and liver function damage(P<0.05).Conclusion ABCB1 C3435T gene polymorphisms may be associated with serum levels of HD-MTX and adverse reactions(mucosal injury,vomiting and liver function damage)in children with mature B-cell lymphoma.