巯基嘌呤甲基转移酶基因多态性与急性淋巴细胞白血病6-巯基嘌呤化疗不良反应关系的Meta分析

目的:探讨巯基嘌呤甲基转移酶(thiopurine methyltransferase,TPMT)基因多态性与急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL) 6-巯基嘌呤(6-mercaptopurine,6-MP)化疗时不良反应的关系?方法:检索ALL不同TPMT基因多态性患者6-MP化疗不良反应的人数为效应指标的相关文献,选择符合入选标准的文献,应用Stata11.0软件对研究结果进行异质性检验和效应值合并,并进行敏感性分析和偏倚评估?结果:纳入TPMT基因多态性与ALL不良反应的文献共5篇,共计病例426例?白细胞减少与TPMT基因多态性关系固定效应模型OR = 4.55,95% CI:1.92~10.80;肝脏损害与TPMT基因多态性关系固定效应模型OR = 2.63,95% CI:1.40~4.93?结论:TPMT基因多态性与6-MP治疗所引起的白细胞减少?肝脏损害等不良反应显著相关,更可靠的结论尚需大样本进行进一步研究?

Thiopurine methyltransferase polymorphisms and thiopurine toxicity in treatment of acute lymphoblastic leukemia

Objective:To investigate the relationship between thiopurine methyltransferase (TPMT) polymorphisms and thiopurine-induced adverse drug reactions (ADRs) in 6-macraptopurine(6-MP)of acute lymphoblastic leukemia (ALL). Methods:Eligible articles that compared the frequency of TPMT polymorphisms among thiopurine-tolerant and intolerant ALL patients were included. Statistical analysis was performed with STATA 11.0. Sub-analysis/sensitivity analysis and bias evaluation were also performed. Results:Five studies that investigated a total of 426 participants met our inclusion criteria. The incidence of TPMT gene mutation was increased 4.55-fold (95% CI:1.92-10.80,P = 0.001) and 2.63-fold (95% CI:1.40-4.93,P < 0.003),respectively,in ALL patients with bone marrow toxicity (BMT) and thiopurine-induced hepatotoxicity,compared with controls. Conclusion:This meta-analysis suggests that the TPMT polymorphisms are associated with BMT and hepatotoxicity. We need father investigation based upen big sample to draw more realiable conclusions