6-巯基嘌呤代谢产物监测与急性淋巴细胞白血病患儿的药品不良反应  

Monitoring of 6-mercaptopurine metabolites and drug adverse reactions in children with acute lymphoblastic leukemia

作　　者：郭佳 周彦生 田运娇[1] 李培岭[1] 马岩岩 赵东菊[1] Guo Jia;Zhou Yan-sheng;Tian Yun-jiao;Li Pei-ling;Ma Yan-yan;Zhao Dong-ju(Department of Pediatrics,The First Affiliated Hospital of Xinxiang Medical College,Xinxiang 453100,China;Department of Infection Control,The First Affiliated Hospital of Xinxiang Medical College,Xinxiang 453100,China)

机构地区：[1]新乡医学院第一附属医院儿科,新乡453100 [2]新乡医学院第一附属医院感控管理部,新乡453100

出　　处：《中国药物应用与监测》2025年第2期305-310,共6页Chinese Journal of Drug Application and Monitoring

基　　金：河南省医学科技攻关计划项目(LHGJ20220615)。

摘　　要：目的分析急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患儿应用6-巯基嘌呤(6-mercaptopurine,6-MP)的药品不良反应(ADR),探讨6-MP代谢产物浓度与ADR的关系。方法采用回顾性研究方法,选取新乡医学院第一附属医院2019年4月至2024年2月接受维持治疗且发生ADR的ALL患儿共76例,用液相色谱-串联质谱法(liquid chromatography-tandem mass spectrometry,LC-MS/MS)检测患儿采集血液中6-MP代谢产物的浓度,结合患儿的不良反应分析6-MP代谢产物浓度与ADR的关系。结果76例ALL患儿中,低危组占比最高(48.68%),高危组占比最低(18.42%);大多数患儿接受CCLC-2018方案治疗(92.11%),仅少数采用CCCG-2015方案(7.89%)。其中,男患儿数量(50例,65.79%)多于女患儿数量(26例,34.21%)(χ^(2)=7.613,P<0.05)。76例ALL患儿中,1~6岁的患儿数量(53例,69.74%)多于7~14岁患儿数量(23例,30.26%)。76例患儿均完成至少3周的口服药物治疗,患儿的连续用药天数在2个疗程或以上共65例(85.53%);连续用药天数在1个疗程的患儿仅有11例(14.47%)。在用药剂量方面,服用50 mg·m^(-2)巯嘌呤片联合20 mg·m^(-2)甲氨蝶呤片的患儿共有42例(55.26%);而服用65 mg·m^(-2)巯嘌呤片联合20 mg·m^(-2)甲氨蝶呤片的患儿共有34例(44.74%)。52例(68.42%)因ADR或血象波动(如白细胞<2.0×10^(9)/L)曾短暂停药(≤3 d),后恢复用药;24例(31.58%)患儿出现细胞毒性而减少用药量。在服用6-MP治疗期间,ALL患儿发生的148例次ADR中,Ⅰ级不良反应77例次(52.03%),Ⅱ级不良反应45例次(30.41%),Ⅲ级不良反应22例次(14.86%),Ⅳ级不良反应4例次(2.70%)。ADR中以血液系统疾病(35.81%)及皮肤反应(24.32%)为主,通过血常规、肝肾功能等检查诊断22例(28.95%)发生骨髓抑制,13例(17.11%)出现肝功能损害,2例(2.63%)肾脏排泄功能减弱。测定6-MP代谢产物6-硫鸟嘌呤核苷酸(6-thioguanine nucleotides,6-TGNs)和6-甲基巯基嘌呤(6-methylmercaptopurine,6-MMP)浓度后发现,发生�Objective To analyze the adverse drug reactions(ADRs)of 6-mercaptopurine(6-MP)in children with acute lymphoblastic leukemia(ALL)and to explore the relationship between the concentration of 6-MP metabolites and ADRs.Methods A total of 76 children who received maintenance treatment for ALL and developed ADRs in the First Affiliated Hospital of Xinxiang Medical College from April 2019 to February 2024 were selected using a retrospective study method. The concentration of 6-MP metabolites in the blood collected from the children was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationship between the concentration of 6-MP metabolites and ADRs was analyzed by assessing the adverse reactions of the children. Results Among the 76 children with ALL, the low-risk group accounted for the highest proportion (48.68%) and the high-risk group accounted for the lowest proportion (18.42%). Most children were treated with the CCLC-2018 regimen (92.11%), and only a few were treated with the CCCG- 2015 regimen (7.89%). Among them, the number of male children (50 cases, 65.79%) was greater than that of female children (26 cases, 34.21%) (χ^(2)=7.613, P<0.05). Among 76 children with ALL, the number of children aged 1 to 6 years (53 cases, 69.74%) was greater than that of children aged 7 to 14 years (23 cases, 30.26%). All 76 children completed at least 3 weeks of oral drug treatment, and 65 children (85.53%) received continuous medication for 2 or more courses;only 11 children (14.47%) received continuous medication for 1 course. In terms of dosage, 42 patients (55.26%) took 50 mg·m^(-2) mercaptopurine tablets combined with 20 mg·m^(-2) methotrexate tablets. There were 34 cases (44.74%) who took 65 mg·m^(-2) mercaptopurine tablets combined with 20 mg·m^(-2) methotrexate tablets. 52 cases (68.42%) stopped the drug briefly ( ≤ 3 days) due to ADR or blood pattern fluctuation (such as white blood cells <2.0×10^(9)/L), and then resumed the drug. 24 cases (31.58%) of pediatric patients reduced their d

关 键 词：6-巯基嘌呤 急性淋巴细胞白血病 液相色谱-串联质谱法 巯嘌呤代谢 药品不良反应 

分 类 号：R733.71[医药卫生—肿瘤]