高剂量甲氨蝶呤排泄延迟解救措施的病例系列报告

Rescue measures of delayed high-dose methotrexate excretion:A case series report

背景目前国内外对高剂量甲氨蝶呤(MTX)排泄延迟是否应该使用血液透析解救还存在争议。目的研究高通量血液透析(HF-HD)对肿瘤患儿MTX清除的有效性。设计病例系列报告。方法纳入2016年1月至2021年6月在上海交通大学医学院附属上海儿童医学中心血液肿瘤科行MTX化疗后44 h血药浓度>10μmol·L-1的连续病例,其中仅使用亚叶酸钙(CF)解救的患儿为非HF-HD组,使用HF-HD+CF解救的患儿为HF-HD组。比较2组患儿的胃肠道、肝功能、肾功能和血液系统毒性等指标。主要结局指标肝、肾功能不良反应发生率。结果20例发生20例次MTX延迟排泄,非HF-HD组9例,HF-HD组11例,两组患儿美国卫生及公共服务部常见不良事件评价标准v 4.0项目比较,CF组和HF-HD组肌酐、尿酸、ALT、AST、黏膜炎、24 h MTX浓度、MTX浓度恢复正常所需的时间差异均无统计学意义,两组患儿血液系统不良反应发生率差异无统计学意义(P>0.05);AST、ALT、发热、黏膜炎、WBC、NE、Hb、PLT异常发生率两组差异无统计学意义。结论肾功能正常的肿瘤患儿通过CF解救可有效安全清除MTX,非必要不选择透析。

Background There is controversy at home and abroad as to whether delayed high-dose methotrexate(MTX)excretion should be rescued by hemodialysis.Objective To investigate the effectiveness of high-flux hemodialysis(HF-HD)on MTX clearance in children with tumors.Design Case series report.Methods A retrospective analysis was performed for consecutive cases with blood levels>10μmol·L-1 at 44 h after MTX chemotherapy at the Department of Hematology Oncology at Shanghai Children's Medical Center affiliated with Shanghai Jiao Tong University School of Medicine between January 2016 to June 2021.The children with calcium folinate(CF)alone were in the non-HF-HD group,and those with HF-HD+CF were in the HF-HD group.Gastrointestinal tracts,liver and kidney function as well as hematologic toxicity indicators were compared between the two groups.Main outcome measures The incidence of adverse reactions to liver and kidney function.Results There were 20 times delayed MTX excretion with 9 in the non-HF-HD group and 11 in the HF-HD group.According to Common Terminology Criteria for Adverse Events v4.0,there was no significant difference in creatinine,uric acid,ALT,AST,mucositis,24 h MTX concentration,and the time required for MTX concentration to return to normal between the CF group and the HF-HD group.There was no significant difference in the incidence of hematologic adverse events between the two groups,while the differences in incidences of abnormalities of AST,ALT,fever,mucositis,WBC,NE,Hb,and PLT were not statistically significant between the two groups.Conclusions If the kidney function is normal,CF rescue can be used for children with tumors to clear MTX effectively and safely,and dialysis is not recommended unless it is necessary.