胸苷酸合成酶基因多态性对甲氨喋呤治疗急性淋巴细胞白血病患儿不良反应的影响

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。

Influence of thymidylate synthase gene polymorphisms on high-dose methotrexaterelated toxicities in childhood acute lymphoblastic leukemia

Objective To investigate the influence of thymidylate synthase (TS) gene polymorphisms on highdose methotrexate (HD-MTX)-related toxicities in childhood acute lymphoblastic leukemia (ALL). Methods A total of 73 children who were diagnosed with ALL between March 2011 and March 2013 were included into this study. Genomic DNAs were extracted from their peripheral blood. And then the genotypes of TS 5''-UTR were determined by direct DNA sequencing after PCR. The toxicity response of 73 patients receiving HD-MTX chemotherapy were observed and recorded, and plasma MTX concentrations at 42-48 hours after chemotherapy were measured. Results The main HDMTX- related toxicities of 73 patients receiving HD-MTX chemotherapy were neutropenia, decreased hemoglobin level, thrombocytopenia, liver toxicity, mucosal damage, and gastrointestinal reactions. There were no significant differences in the incidence rate of HD-MTX-related toxicities between children with different TS 5''-UTR genotypes after chemotherapy (P>0.05). TS 5''-UTR genotype was not significantly correlated with plasma MTX concentrations at 42-48 hours after chemotherapy (P>0.05). Conclusions TS gene polymorphisms have no influence on the incidence of HDMTX- related toxicities in childhood ALL.