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目的探讨不同胸苷酸合成酶(TS)基因型对急性淋巴细胞白血病(ALL)患儿经大剂量甲氨蝶呤(HD-MTX)治疗后不良反应的影响。方法选取2011年3月至2013年3月确诊的ALL患儿73例,提取其基因组DNA,PCR扩增后测序鉴定TS基因型。观察并记录所有ALL患儿经HD-MTX化疗后的不良反应,并监测化疗后42~48 h MTX血药浓度。结果 73例ALL患儿接受HD-MTX治疗后,其不良反应主要包括中性粒细胞减少、血红蛋白降低、血小板减少、肝脏毒性、黏膜损害和胃肠道反应,不同TS基因型患儿化疗后不良反应发生率比较差异均无统计学意义,各基因型与ALL患儿化疗后42~48 h MTX血药浓度的变化无关联。结论 TS基因多态性对ALL患儿HD-MTX化疗后不良反应的发生无影响。
Objective To investigate the effect of different genotypes of thymidylate synthase (TS) on the adverse reactions of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods Totally 73 children with ALL diagnosed from March 2011 to March 2013 were selected for genomic DNA extraction and TS genotypes were identified by PCR amplification and sequencing. All patients with ALL were observed and recorded adverse reactions after HD-MTX chemotherapy, and MTX plasma concentrations were monitored 42-48 h after chemotherapy. Results 73 cases of ALL children receiving HD-MTX treatment, the adverse reactions include neutropenia, decreased hemoglobin, thrombocytopenia, hepatotoxicity, mucosal damage and gastrointestinal reactions, different TS genotype in children with poor after chemotherapy There was no significant difference in the incidence of response between the two groups. There was no correlation between the genotypes and the changes of MTX plasma concentrations in 42-48 h after chemotherapy in ALL children. Conclusion TS gene polymorphism has no effect on the incidence of adverse reactions after HD-MTX chemotherapy in children with ALL.