中国药物警戒 ›› 2019, Vol. 16 ›› Issue (1): 13-17.

• 基础与临床研究 • 上一篇    下一篇

大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病不良反应的临床分析

蒋志平, 彭骞, 何莉梅, 祝文兵, 吴攀   

  1. 湖南省儿童医院, 湖南 长沙 410007
  • 收稿日期:2018-12-14 修回日期:2019-02-18 出版日期:2019-01-20 发布日期:2019-02-18
  • 作者简介:蒋志平,男,本科,副主任药师,医院药学与药事管理。

Clinical Analysis of Adverse Drug Reactions of High-dose Methotrexate in Children with Acute Lymphoblastic Leukemia

JIANG Zhiping, PENG Qian, HE Limei, ZHU Wenbing, WU Pan   

  1. Hunan Children's Hospital, Hunan Changsha 410007, China
  • Received:2018-12-14 Revised:2019-02-18 Online:2019-01-20 Published:2019-02-18

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摘要： 目的 研究临床上采用大剂量甲氨蝶呤（HD-MTX）治疗儿童急性淋巴细胞白血病（ALL）期间出现的不良反应（ADR）,分析用药安全性及防范措施。方法 回顾性分析某院诊治的67例ALL患儿,观察记录HD-MTX治疗过程中出现的ADR,根据患儿MTX血药浓度检测结果和亚叶酸钙（CF）解救后的情况进行数据分析。结果 67例ALL患儿共接受264次HD-MTX治疗,不良反应多见于骨髓抑制、胃肠道反应、黏膜损伤、肝肾功能损害等,未出现严重的呕吐、腹泻、黏膜损伤、心肾功能损害（Ⅳ级）和死亡（Ⅴ级）病例。不同危险度分级的患儿在呕吐、黏膜损伤方面的ADR发生率存在显著差异（P <0.05）。不同危险度分级的患儿在化疗后44 h的MTX血药浓度>1.0μmol·L-1和68 h的MTX血药浓度>0.3μmol·L-1的发生率均无显著差异（P>0.05）。除血小板减少、心肌酶升高无显著差异（P >0.05）外,排泄延迟组与排泄正常组患儿的其他7项ADR发生率差异具有统计学意义（P <0.05）。结论 采用HD-MTX规范化治疗ALL患儿,提前采取预防和保护性的对症措施,参照MTX血药浓度监测结果定时定量采用CF解救,能够在一定范围内降低ADR发生,改善患儿生活质量。

关键词: 大剂量, 甲氨蝶呤, 儿童, 急性淋巴细胞白血病, 不良反应

Abstract: Objective To explore the clinical safety of high-dose methotrexate (HD-MTX) by analyzing its adverse drug reactions (ADRs) in the treatment of childhood acute lymphoblastic leukemia (ALL), and discuss the Methods to prevent those ADRs. Methods Retrospective research was performed in 67 cases of ALL children diagnosed and treated in certain hospital. ADRs were recorded during the treatment. data analysis was conducted in patients concerning the blood concentration of MTX before and after the rescue of formyl tetrahydrofolate (CF). Results A total of 264 chemotherapy sessions with HD-MTX were performed in 67 children with ALL. Adverse reactions mainly included bone marrow suppression, gastrointestinal reactions, mucosal damage, liver toxicity, cardiotoxicity, renal toxicity, etc. No children experienced adverse events such as severe emesis or diarrhea, severe mucosal damage, severe cardiotoxicity, severe infection (level IV) or death (level V) during the treatment period. After HD-MTX treatment, statistic significance (P <0.05) for the incidence of emesis and mucosal damage were detected among patients grouped by different hazard level. But there was no such significant difference (P >0.05) for the incidence of blood plasma concentration of methotrexate> 1.0 μmol·L-1 after HD-MTX treatment for 44 hours or blood plasma concentration of methotrexate> 0.3 μmol·L-1 after HD-MTX treatment for 68 hours. Apart from the thrombocytopenia and myocardial enzyme elevation (P >0.05), there is statistic significance for the incidence of other 7 types of ADRs between delayed excretion group and normal excretion group (P <0.05). Conclusion The incidence of adverse reactions could be reduced within a certain range by the use of standardized HD-MTX treatment of children with ALL, CF rescue for MTX-intoxicated children in reference to MTX serum concentration, and effective measures to prevent and diminish adverse reactions, which could improve the life quality of those children.

Key words: high dose, methotrexate, children, acute lymphoblastic leukemia, adverse drug reaction

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