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中国循证儿科杂志

中国循证儿科杂志 ›› 2024, Vol. 19 ›› Issue (6): 436-439.DOI: 10.3969/j.issn.1673-5501.2024.06.005

• 论著 • 上一篇    下一篇

联用别嘌醇改善儿童青少年淋巴母细胞淋巴瘤维持期巯嘌呤相关肝损害的病例系列报告

张楠楠1a,3，李英1b,3，孙豪2，段彦龙1a，黄爽1a，张梦1a，李楠1a，王晓玲1b，金玲1a   

  1. 1 国家儿童医学中心，首都医科大学附属北京儿童医院北京,100045；a儿童肿瘤中心，肿瘤内科，儿童血液病与肿瘤分子分型北京市重点实验室，儿童肿瘤国家临床重点专科，儿科重大疾病研究教育部重点实验室，b药学部；2 大连市妇女儿童医疗中心（集团）药学部大连,116000；3 共同第一作者
  • 收稿日期:2024-07-16 修回日期:2024-11-14 出版日期:2024-12-25 发布日期:2024-12-25
  • 通讯作者: 金玲；王晓玲

Combined allopurinol to improve mercaptopurine associated liver damage during maintenance of lymphoblastic lymphoma in children and adolescents: A case series report

ZHANG Nannan1a,3,LI Ying1b,SUN Hao2,DUAN Yanlong1a,HUANG Shuang1a,ZHANG Meng1a, LI Nan1a, WANG Xiaoling1b,JIN Ling1a   

  1. 1 Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, a.Medical Oncology Department, Pediatric Oncology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education;b. Department of Pharmacy;2 Department of Pharmacy, Dalian Women and Children's Medical Center (Group), Dalian 116000, China; 3 Co-first author
  • Received:2024-07-16 Revised:2024-11-14 Online:2024-12-25 Published:2024-12-25
  • Contact: JIN Ling; WANG Xiaoling

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摘要： 背景巯嘌呤（6-MP）为淋巴母细胞淋巴瘤（LBL）维持治疗期间的核心药物。作为6-MP中间代谢产物的6-甲基巯基嘌呤(6-MMPN)被认为与6-MP肝毒性密切相关。国外研究表明，联用别嘌醇可能减轻其肝毒性。 目的评估别嘌醇与减低剂量的6-MP联用在LBL患儿维持治疗期间能否减轻6-MP肝毒性。 设计病例系列报告。 方法回顾性总结首都医科大学附属北京儿童医院肿瘤内科2021年6月至2022年6月维持治疗期间合并肝功能损害的LBL患儿的年龄、性别、临床分期、肝功能、6-MP相关药物基因等指标，分析联用别嘌醇后肝功能变化、疾病状态及除肝损害外的其他不良反应。 主要结局指标肝功能、中性粒细胞绝对值（ANC）达标周数。 结果联合别嘌醇前，17例LBL患儿均存在肝功能异常,起始ALT波动在281.5（200.6~618.0）U·L-1，AST 118.8（88.2~185.8）U·L-1，联用别嘌醇后ALT 32.8（27.7~36.75）U·L-1，AST 31.8（23.7~36.8）U·L-1。联用别嘌醇后ALT和AST恢复正常时间分别为6（1,18）周和7（3,11）周。比较联用别嘌醇前后ALT、AST水平，差异均有统计学意义（P＜0.001）。联用别嘌醇前后ANC达标周数占总维持治疗期的比例分别为21.4%和34.2%，差异有统计学意义（P＜0.001），无患儿发生中性粒细胞缺乏性发热。 结论接受6-MP治疗的LBL患儿维持治疗期间联用别嘌醇可有效减轻其肝毒性，保证了6-MP的连续应用，其不良反应可控，安全有效。

关键词: 巯嘌呤, 别嘌醇, 肝毒性, 淋巴瘤, 淋巴母细胞性, 儿童

Abstract: BackgroundMercaptopurine (6-MP) is the core drug during the maintenance treatment of lymphoblastic lymphoma (LBL). 6-methylmercaptopurine (6-MMPN) is an intermediate metabolite of 6-MP, which is thought to be closely related to hepatotoxicity of 6-MP. Foreign studies have shown that the combination of allopurinol may reduce hepatotoxicity ObjectiveTo evaluate whether allopurinol combined with a reduced dose of 6-MP can alleviate the hepatotoxicity of 6-MP during maintenance therapy in children with LBL. DesignCase series report. MethodsAge, gender, clinical stage, liver function, and 6-MP related drug gene of LBL in children with liver function impairment during maintenance therapy from June 2021 to June 2022 in the Department of Oncology, Beijing Children's Hospital Affiliated to Capital Medical University were collected. The changes in liver function, disease status, and other adverse reactions other than liver damage after receiving allopurinol were analyzed retrospectively. Main outcome measures Liver function, the number of weeks that absolute value of neutrophil (ANC) reached standard. ResultsBefore receiving allopurinol, all 17 children had abnormal liver function tests (LFTs). The initial ALT fluctuation was 281.5（200.6-618.0）U·L-1, and AST 118.8（88.2-185.8）U·L-1. After allopurinol administration, ALT was 32.8（27.7-36.75）U·L-1, and AST was 31.8（23.7-36.8）U·L-1, and the time for ALT and AST to return to normal after allopurinol was 6(1,18) weeks and 7 (3,11)weeks, respectively. There was a significant difference in ALT and AST before and after the addition of allopurinol (P<0.01). The ratio of ANC compliance weeks to total maintenance treatment period before and after combination with allopurinol was 21.4% and 34.2%, respectively, with statistical significance (P< 0.001). No neutrophil deficiency fever occurred in the patients. ConclusionThe combination of allopurinol during maintenance treatment in children with LBL treated with 6-MP can effectively reduce their hepatotoxicity and ensure the continuous application of 6-MP. It is safe and effective with controlled adverse reactions.

Key words: 6-Mercaptopurine, Allopurinol, Hepatotoxicity, Lymphoma, Lymphoblastic, Children