Evidence-based Evaluation of Thiopurine Methyltransferase Genetic Testing in Guiding the Individualized Treatment of Childhood Acute Lymphoblastic Leukemia with 6-Mercaptopurine in China

OBJECTIVE To systematically review the association between 6-mercaptopurine(6-MP) treatment of acute lymphoblastic leukemia(ALL) related bone marrow suppression and thiopurine methyltransferase(TPMT) gene polymorphism in Asian children and evaluate the economy of TPMT genetic testing in Chinese ALL children. METHODS Evidence-based medicine method was used to collect the randomized control trials or observational studies about the relationship between 6-MP treatment of ALL related bone marrow suppression and TPMT gene polymorphism in Asian children by meta analysis, and cost-effectiveness analysis of 2 kinds of initial dose regimen of 6-MP for ALL children in China were performed with decision tree model. RESULTS Finally a total of 6 literatures involving 577 Asian children with ALL were included. The results of meta-analysis showed the following:the TPMT polymorphisms were relevant to myelotoxicityOR=5.61, 95%CI (2.05, 15.34), P=0.000 8. In the fundamental data analysis, aimed to the above 2 kinds of treatment, the incremental cost-effectiveness ratio was 10 403.83 when the incidence of severe myelosuppression was taken as the effective index. Sensitivity analysis showed that the results were stable. CONCLUSION This meta-analysis suggest that the TPMT polymorphisms of Asian children with ALL are significantly associated with myelosuppression. In China, the initial dose of 6-MP adjusted by TPMT gene detection in ALL children is not superior to the standard dose.