论文部分内容阅读
目的预测肌酐三磷酸焦磷酸酶(ITPA)活性与6-巯基嘌呤(6-MP)维持治疗儿童急性淋巴细胞白血病(ALL)不良反应发生。方法选取于2002年3月至2012年9月就诊,采用6-MP和甲氨蝶呤维持治疗的54例ALL患儿作为研究对象。回顾性分析患儿ITPA浓度与治疗期间白细胞减少和肝毒性等不良反应发生,检测患儿ITPA以及6-巯嘌呤基转移酶等位基因突变体(TPMT)的基因型。结果 54例患儿的ITPA活性在2.2-343μmol/(h.gHb)之间。18例为ITPA 94C>A突变杂合子,2例为纯合子。6-MP不良反应发生率为70.4%,其中白细胞减少发生率为35.8%,肝毒性发生率为58.2%。有肝毒性患儿的ITPA活性低于无肝毒性患儿,差异有统计学意义(P=0.01)。20例ITPA活性<126μmol/(h.gHb)患儿中有10例(50.0%)因肝毒性而不得不降低6-MP治疗浓度者,而34例ITPA活性≥126μmol/(h.gHb)患儿中无一降低治疗浓度,差异有统计学意义(P=0.01);ITPA活性<126μmol/(h.gHb)患儿的6-MP治疗浓度低于ITPA活性≥126μmol/(h.gHb)的患儿,差异有统计学意义(P=0.01)。结论 ALL患儿维持治疗期ITPA活性与6-MP不良反应发生有关。
Objective To predict the adverse reactions of creatinine triphosphate pyrophosphatase (ITPA) activity and 6-mercaptopurine (6-MP) maintenance treatment of childhood acute lymphoblastic leukemia (ALL). Methods From March 2002 to September 2012, 54 children with ALL who were treated with 6-MP and methotrexate were enrolled in this study. A retrospective analysis of children with ITPA concentration and treatment of leukopenia and hepatotoxicity and other adverse reactions, detection of children with ITPA and 6-mercaptopurine transferase allele mutant (TPMT) genotype. Results The ITPA activity of 54 children was between 2.2-343μmol / (h.gHb). 18 cases were ITPA 94C> A mutant heterozygotes and 2 cases were homozygotes. The incidence of 6-MP adverse reactions was 70.4%, including leukopenia 35.8% and hepatotoxicity 58.2%. The ITPA activity of children with hepatotoxicity was lower than that of children without hepatotoxicity, the difference was statistically significant (P = 0.01). Of the 20 patients with ITPA activity <126 μmol / (h.gHb), 10 (50.0%) had to lower their 6-MP concentrations due to hepatotoxicity, while 34 patients with ITPA activity ≥126 μmol / (h.gHb) The concentration of 6-MP in children with ITPA activity <126μmol / (h.gHb) was lower than that of children with ITPA activity ≥126μmol / (h.gHb) Children, the difference was statistically significant (P = 0.01). Conclusion The ITPA activity in maintenance treatment of ALL children is related to the occurrence of 6-MP adverse reactions.