Mercaptopurine related toxicity in the child patients with acute lymphoblastic leukemia and its relationship with the thiopuine S-methyltransferase genetic polymorphisms
XIE Qian, XIAO Jian-wen, XIAN Ying, et al. Mercaptopurine related toxicity in the child patients with acute lymphoblastic leukemia and its relationship with the thiopuine S-methyltransferase genetic polymorphisms[J]. Journal of Chongqing Medical University, 2011,36(7):777-781.
XIE Qian, XIAO Jian-wen, XIAN Ying, et al. Mercaptopurine related toxicity in the child patients with acute lymphoblastic leukemia and its relationship with the thiopuine S-methyltransferase genetic polymorphisms[J]. Journal of Chongqing Medical University, 2011,36(7):777-781. DOI: 10.13406/j.cnki.cyxb.2011.07.016.
Objective:To observe the mercaptopurine related toxicity in the child patients with acute lymphoblastic leukemia(ALL)treated with CCLG-08 protocol
and to investigate the thiopurine S-methyltransferase(TPMT)gene polymorphisms in the patients and discuss its relationship with the mercaptopurine related toxicity.Methods:The occurances of leukocytopenia
hepatotoxicity and pancreatitis in the consolidation therapy stage and the maintenane therapy stage were observed.The polymorphisms of TPMT G238C
G460A
and A719G were determined by allele-specific PCR(ASPCR)
PCR-restriction fragment length polymorphism(PCR-RFLP)
and MALDI-TOF MS technique.Results:19.35%(n=24)of the ALL patients in the consolidation therapy stage and 13.83%(n=13)in the maintenane therapy stage experienced serious leukocytopenia.10.64%(n=10)of the patients experienced hepatotoxicity in the maintenane therapy stage.No different occurance rate of mercaptopurine related toxicity was found in the two groups of the maintenance therapy.The study didn’t find the relationship between the TPMT polymorphisms and the mercaptopurine related toxicity.Conclusion:Although considerable ratio of the mercaptopurine related toxicity occured
the consolidation therapy and the maintenance therapy of CCLG-08 protocol were safely experienced by the ALL patients in this study.The mutation rate of TPMT gene G238C
G460A
and A719G is 0.67% in Han ethnic patients with ALL in Chongqing area.No relationship between TPMT G238C
G460A
and A719G genetic polymorphisms and the mercaptopurine related leukocytopenia and hepatotoxicity were found in the study.GroupⅠof maintenance therapy(take mercaptopurine 4 weeks continuously)was not lead to more or severe leukocytopenia and hepatotoxicity compared with groupⅡ of maintenance therapy(take mercaptopurine 3 weeks continuously and withdrawal 1 week).