中国实用儿科杂志

中国实用儿科杂志 ›› 2025, Vol. 40 ›› Issue (8): 700-704.DOI: 10.19538/j.ek2025080615

• 论著 • 上一篇    

大剂量甲氨蝶呤治疗儿童髓母细胞瘤排泄延迟的危险因素及预后分析

  

  1. 1.首都医科大学附属北京世纪坛医院儿科，北京  100038；2.首都医科大学附属北京儿童医院血液病中心，北京  100045
  • 出版日期:2025-08-06 发布日期:2025-09-15
  • 通讯作者: 王天有，电子信箱：wangtianyou@bch.com.cn
  • 基金资助:
    首都医科大学附属北京世纪坛医院青年基金（2023-q01）

Risk factors and prognostic analysis of delayed excretion of high-dose methotrexate in the treatment of pediatric　medulloblastoma

  1. Department of Pediatrics，Beijing Shijitan Hospital，Capital Medical University，Beijing  100038，China
  • Online:2025-08-06 Published:2025-09-15

摘要：

目的　大剂量甲氨蝶呤（high-dose methotrexate，HD-MTX）是治疗儿童髓母细胞瘤的常用化疗方案，研究旨在探讨导致甲氨蝶呤（MTX）排泄延迟的危险因素，并分析药物排泄延迟与患儿预后的关系。方法　回顾性分析2019年1月至2020年12月在首都医科大学附属北京世纪坛医院儿科接受 HD-MTX 治疗的髓母细胞瘤患儿，收集患儿的一般资料，包括性别、发病年龄、组织学分型、分子亚型、疾病分期，同时收集24 h 血药浓度C24和42 h 血药浓度 C42及血常规、肝肾功能指标。采用 Mann-Whitney 检验及 Kruskal-Wallis 检验分析血药浓度在不同临床特征方面的差异，采用 Logistic 回归模型进行药物排泄延迟的危险因素分析，应用 Cox 回归模型进行单因素和多因素生存分析。结果　共纳入髓母细胞瘤患儿41例，中位诊断年龄为2.9岁（0.6~13.6岁）。HD-MTX 化疗次数共167例次，发生排泄延迟31例次，发生率为18.6%，鞘内注射 MTX 133例次（80%）。C24在未行鞘内注射（P=0.017）和白细胞减少（P=0.044）的患儿中明显升高，C42在3岁以上（P=0.006）和存在脑脊液播散（P<0.001）的患儿中明显升高。排泄正常和排泄延迟患儿在不良反应方面差异无统计学意义。脑脊液播散是髓母细胞瘤患儿发生排泄延迟的独立危险因素（P=0.002，OR=4.864，95%CI 1.797~13.167），MTX 排泄延迟并非影响患儿预后的因素。结论　HD-MTX 治疗在髓母细胞瘤儿童中表现出良好的安全性。脑脊液播散是导致 MTX排泄延迟的危险因素，而排泄延迟未对患儿的预后产生显著影响。

关键词:

Abstract: Objective　High-dose methotrexate（HD-MTX）is a widely employed chemotherapy regimen for the treatment of medulloblastoma in pediatric patients.This study is aimed to investigate the risk factors associated with delayed methotrexate excretion and to evaluate the correlation between delayed excretion and the prognosis of the children. Methods　A 
retrospective analysis was conducted on children with medulloblastoma who received high-dose methotrexate（HD-MTX） treatment in the Department of Pediatrics of Beijing Shijitan Hospital，Capital Medical University between January 2019 and December 2020.Clinical data were collected，including gender，age at onset，histological type，molecular subtype，and disease stage.Additionally，24-hour（C24）and 42-hour（C42）blood drug concentrations，as well as blood routine and liver and kidney function indices，were recorded.The Mann-Whitney U test and Kruskal-Wallis H test were used to analyze the differences in blood drug concentrations across various clinical characteristics.Logistic regression analysis was employed to identify risk factors associated with delayed drug excretion. Furthermore，univariate and multivariate survival analyses were conducted using the Cox proportional hazards model. Results　A total of 41 children（24 boys，17 girls）with medulloblastoma were enrolled in this study，with a median age of 2.9 years（ranging from 0.6 to 13.6 years） at diagnosis.A total of 167 HD-MTX chemotherapy sessions were conducted，of which 31 sessions （18.6%）exhibited delayed excretion. Intrathecal MTX injection was performed in 133 sessions（80%）.C24 levels were significantly elevated in children who did not receive intrathecal injection（P=0.017）and those with leukopenia（P=0.044），and C42 levels were significantly elevated in children aged 3 years or older（P=0.006）and those with cerebrospinal fluid metastasis（P<0.001）.No statistically significant difference in adverse reactions was observed between children with normal excretion and those with delayed excretion. Cerebrospinal fluid metastasis was identified as an independent risk factor for delayed excretion in children with medulloblastoma（P=0.002，OR=4.864，95% CI 1.797 - 13.167）.Delayed MTX excretion was not a factor affecting the prognosis of children with medulloblastoma. Conclusion　The HD-MTX treatment exhibits favorable safety in pediatric patients with medulloblastoma. Cerebrospinal fluid metastasis is identified as a risk factor for delayed MTX excretion；however，the delayed excretion does not have a significant impact on the prognosis of the children.

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