NUDT15基因野生型、突变型ALL患儿维持治疗期间口服6-巯基嘌呤的耐受性对比观察

Comparison of oral 6-mercaptopurine tolerance during maintenance therapy between children with NUDT15 gene wild-type and mutant ALL

目的比较NUDT15基因rs116855232位点野生型、突变型急性淋巴细胞白血病(ALL)儿童维持期治疗期间口服6-巯基嘌呤(6-MP)耐受性。方法32例ALL患儿根据NUDT15基因rs116855232位点有无突变分为分为野生组(24例)和突变组(8例),比较两组维持期治疗期间6-MP的剂量、血象、粒细胞缺乏频率、使用短效重组人粒细胞集落刺激因子频率、感染频率、肝功能水平及患儿预后。结果与野生组比较,突变组6-MP每日用量少(P<0.05);与野生组比较,突变组白细胞、血小板水平降低(P均<0.05);与野生组比较,突变组粒细胞缺乏频率、使用短效重组人粒细胞集落刺激因子频率高(P均<0.05);两组感染频率比较,P均>0.05。与野生组比较,突变组ALT、AFU水平降低(P均<0.05);两组患儿原发病均处于完全缓解状态。结论与野生型相比,NUDT15基因rs116855232位点突变降低了ALL儿童患者巯嘌呤耐受性,6-MP用量减少,白细胞及血小板下降,增加了骨髓抑制风险,但感染风险并未升高,肝功能异常风险下降,原发病控制未受影响。

Objective To compare oral 6-mercaptopurine(6-MP)tolerance during maintenance therapy between children with wild-type and mutant acute lymphoblastic leukemia(ALL)at rs116855232 of NUDT15 gene.Methods Thirty-two children with ALL were divided into the wild-type group(24 cases)and mutant group(8 cases)according to the presence or absence of mutation at rs116855232 of NUDT15 gene.The doses of 6-MP,blood count,frequency of agranulocytosis during maintenance treatment,frequency of usage of short-acting recombinant human granulocyte colony-stimulating factor,frequency of infection,level of liver function,and prognosis of children were compared between the two groups.Results Compared with the wild-type group,the daily dosage of 6-MP in the mutant group was less(P<0.05).Compared with the wild-type group,the levels of leukocytes and platelets in the mutant group decreased(both P<0.05).Compared with the wild-type group,the frequencies of agranulocytosis and usage of short-acting recombinant human granulocyte colony-stimulating factor in the mutant group increased(both P<0.05).No significant difference was found in the infection frequency between the two groups(P>0.05).Compared with the wild-type group,the levels of ALT and AFU in the mutant group decreased(both P<0.05).The primary disease of children in the two groups was in complete remission.Conclusions Compared with the wild-type,the rs116855232 mutation in the NUDT15 gene reduces mercaptopurine tolerance in children with ALL,reduces the dosage of 6-MP,decreases white blood cells and platelets,and increases the risk of myelosuppression,but does not increase the risk of infection.The risk of abnormal liver function decreases,and the primary disease control is not affected.