| 摘要: |
| [摘要]目的：根据急性淋巴细胞白血病（ALL）患儿在不同时间点的甲氨蝶呤（MTX）血药浓度，预测大剂量甲氨蝶呤（HDMTX）的清除和毒性。方法：采集接受HDMTX治疗的198例急性淋巴细胞白血病患儿（累积303例次输液）不同时间点血样，通过改良酶放大免疫法测定不同时间点MTX水平。通过接受者工作特征（ROC）曲线对MTX水平与毒性的相关性进行评价。另选取22例患儿进行模型验证，预测其准确度和特异性。结果：42 h MTX水平用于预测延迟清除的最佳浓度上限为1.50 μmol/L，灵敏度为82.17%；用于预测安全阈值的最佳浓度上限为0.76 μmol/L，灵敏度为90.78%。66 h MTX水平用于预测毒性的最佳浓度上限为0.50 μmol/L，灵敏度为89.09%；用于预测无毒性的最佳浓度上限为0.10 μmol/L，灵敏度为92.73%。22例进行模型验证的患儿中，42 h MTX水平用于预测延迟清除的准确度为80.60%；用于预测安全阈值的准确度为85.78%，特异性为91.50%。66 h MTX水平用于预测毒性的准确度为89.18%；用于预测无毒性的准确度为87.24%，特异性为92.20%。结论：输液后66 h内各时间点MTX水平可被准确测量，42 h MTX水平可用于延迟清除的预测，66 h MTX水平可用于毒性预测。 |
| 关键词: 儿童 急性淋巴细胞白血病 大剂量甲氨蝶呤 毒性 亚叶酸钙解救 |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2022.05.002 |
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| 基金项目:大连市医学科学研究计划项目,编号WSJ/KJC-01-JL-01。 |
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| Clearance and Toxicity Prediction of High-Dose Methotrexate in Children with Acute Lymphoblastic Leukemia |
| Liu Yang, Li Lujuan, Li Zhong |
| (Dalian Women and Children’s Medical Center (Group), Liaoning Dalian 116012, China) |
| Abstract: |
| [Abstract] Objective: To predict the clearance and toxicity of high-dose methotrexate (HDMTX) based on serum concentration of methotrexate (MTX) at different time points in children with acute lymphoblastic leukemia (ALL). Methods: Blood samples were collected from 198 children with acute lymphoblastic leukemia treated with HDMTX (303 infusions) at different time points. MTX levels at different time points were determined by modified enzyme amplification immunoassay. Correlation between MTX levels and toxicity was evaluated by receiver operating characteristic (ROC) curve. The clinical data of another 22 children were extracted to verify the accuracy and specificity of the prediction model. Results: The upper limit of the optimal concentration of 42 h MTX level for predicting delayed clearance was 1.50 μmol/L, with a sensitivity of 82.17%; the upper limit of the optimal concentration for predicting the safety threshold was 0.76 μmol/L, with a sensitivity of 90.78%. The upper limit of the optimal concentration of 66 h MTX level for predicting delayed clearance was 0.50 μmol/L, with a sensitivity of 89.09%; the upper limit of the optimal concentration for predicting non-toxicity was 0.10 μmol/L, with a sensitivity of 92.73%. The accuracy of 42 h MTX level in predicting delayed clearance was 80.60% in 22 children with model validation. The accuracy of predicting the safety threshold was 85.78% and the specificity was 91.50%. The accuracy of 66 h MTX level in predicting toxicity was 89.18%. The accuracy and specificity for predicting non-toxicity were respectively 87.24% and 92.20%. Conclusion: MTX levels can be accurately measured at various time points up to 66 h post-infusion, with 42 h MTX level being used for prediction of delayed clearance and 66 h MTX level being used for prediction of toxicity. |
| Key words: children acute lymphoblastic leukemia high-dose methotrexate toxicity leucovorin rescue |
