血液系统恶性肿瘤患儿甲氨蝶呤清除延迟危险因素的回顾性分析

doi:10.5246/jcps.2022.10.064

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (10): 746-754.DOI: 10.5246/jcps.2022.10.064

血液系统恶性肿瘤患儿甲氨蝶呤清除延迟危险因素的回顾性分析

李苗¹, 孔晓岩², 王淑梅³^,⁴^,⁵^,^*()

1. 首都医科大学附属北京世纪坛医院儿科, 北京 100038
2. 武警北京总队医院药剂科, 北京 100027
3. 首都医科大学附属北京世纪坛医院药剂科, 北京 100038
4. 临床合理用药评价北京市重点实验室, 北京100038
5. 临床合理用药评价国际合作联合实验室, 北京100038

收稿日期:2022-05-25 修回日期:2022-06-14 接受日期:2022-07-22 出版日期:2022-10-31 发布日期:2022-10-31
通讯作者: 王淑梅
作者简介:
+ Tel.: +86-10-63926368; Fax: +86-10-63926368; E-mail: wangshumei1980@126.com; wsm-pharm@ccmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81872926 and No. 81503135), Beijing Municipal Administration of Hospitals' Youth Programme (Grant No. QML20160703), Enhancement Funding of Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use (BZ0439), and Science and Technology Fund of Beijing Shijitan Hospital (Grant No. 2017-c01).

Risk factors for delayed methotrexate elimination in pediatric patients with hematological malignancies: a retrospective analysis

Miao Li¹, Xiaoyan Kong², Shumei Wang³^,⁴^,⁵^,^*()

1 Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
2 Department of Pharmacy, Armed police Beijing Corps Hospital, Beijing 100027, China
3 Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
4 Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing 100038, China
5 International Cooperation & Joint Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing 100038, China

Received:2022-05-25 Revised:2022-06-14 Accepted:2022-07-22 Online:2022-10-31 Published:2022-10-31
Contact: Shumei Wang

摘要/Abstract

摘要：

甲氨蝶呤延迟清除是接受大剂量甲氨蝶呤化疗患者的一个临床特别关注点。本文旨在回顾性分析与血液系统恶性肿瘤患儿甲氨蝶呤浓度和延迟清除相关的因素。根据甲氨蝶呤治疗后24或42小时血清甲氨蝶呤浓度, 将甲氨蝶呤化疗周期分为正常清除组或延迟清除组。通过χ²检验、Fisher's精确检验、Mann-Whitney检验或Spearman's相关性检验评价与甲氨蝶呤浓度和延迟清除相关的临床特征。采用广义估计方程校正同一名患者多个化疗周期的聚集效应和混淆因素。本研究共纳入43例患儿138个化疗周期进行评价。剂量、白细胞、血红蛋白和血尿素氮与24小时甲氨蝶呤血清浓度显著相关(P < 0.05)。未发现基线特征与42小时甲氨蝶呤血清浓度之间的显著相关性。在34个化疗周期(24.6%)中观察到甲氨蝶呤延迟清除, 剂量、白细胞、血红蛋白、血尿素氮和并发感染是甲氨蝶呤延迟清除的显著危险因素(P < 0.05)。本研究发现了与甲氨蝶呤浓度和消除相关的数个风险因素, 可用于识别甲氨蝶呤清除延迟高风险的患者, 但研究结果有待在进一步的大规模研究中证实。

关键词: 甲氨蝶呤, 延迟清除, 治疗药物监测

Abstract:

Delayed elimination of methotrexate (MTX) is a major clinical concern in patients receiving high-dose MTX (HD-MTX) therapy. In the present study, we aimed to retrospectively explore the factors associated with MTX concentrations and elimination delay in pediatric patients with hematological malignancies. Cycles of HD-MTX therapy were categorized into the normal elimination group and delayed elimination group according to the serum MTX concentrations at 24 (C₂₄) or 42 h (C₄₂) after the start of MTX therapy. Clinical characteristics associated with MTX concentrations and elimination delay were assessed by χ² test, Fisher’s exact test, Mann-Whitney test, or Spearman's correlation coefficient. Generalized Estimating Equations (GEE) were used to adjust for the clustering effects of multiple cycles in one patient and confounders. A total of 43 patients with 138 cycles of HD-MTX chemotherapy were included and evaluated in the current study. Dose, white blood cells (WBC), hemoglobin (HB), and blood urea nitrogen (BUN) were significantly correlated with MTX C₂₄ (all P < 0.05). No significant correlations were noticed between baseline characteristics and MTX C₄₂. Delayed MTX elimination was observed in 34 (24.6%) courses. Dose, WBC, HB, BUN, and concurrent infection were the significant risk factors for delayed MTX elimination (all P < 0.05). Our study identified several risk factors associated with MTX levels and elimination, which might be used to recognize patients with a high risk of delayed MTX elimination. However, the findings need to be confirmed in further large-scale studies.

Key words: Methotrexate, Elimination delay, Therapeutic drug monitoring

Supporting:

李苗, 孔晓岩, 王淑梅. 血液系统恶性肿瘤患儿甲氨蝶呤清除延迟危险因素的回顾性分析[J]. 中国药学(英文版), 2022, 31(10): 746-754.

Miao Li, Xiaoyan Kong, Shumei Wang. Risk factors for delayed methotrexate elimination in pediatric patients with hematological malignancies: a retrospective analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(10): 746-754.

图/表 5

Table 1. Baseline characteristics for 138 courses of HD-MTX in 43 patients.

Table 2. Correlations between baseline characteristics and serum MTX concentrations (unadjusted for clustering).

Table 3. Correlations between baseline characteristics and serum MTX concentrations by GEE analysis.

Figure 1. Correlation between serum MTX levels at 24 h (C24) and 42 h (C42) after the start of MTX infusion (A). Correlation between serum MTX C24 (B) and C42 (C) in the first and second cycles. Abbreviations: MTX, methotrexate; r, Spearman's correlation coefficient.

Table 4. Relations between baseline characteristics and delayed MTX elimination by GEE analysis.

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血液系统恶性肿瘤患儿甲氨蝶呤清除延迟危险因素的回顾性分析

Risk factors for delayed methotrexate elimination in pediatric patients with hematological malignancies: a retrospective analysis

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