Retrospective evaluation and prediction of clearance and toxicity of high dose methotrexate in childhood acute lymphoblastic leukemia patients

To find the predictors of High Dose Methotrexate toxicities in childhood Acute Lymphoblastic Leukemia Patients. This study included 198 Childhood Acute Lymphoblastic Leukemia patients (303 infusions) who were treated with High Dose Methotrexate. Methotrexate levels at different time point were measured by modified enzyme multiplied immunoassay technique assay. The correlation between Methotrexate levels and toxicity was evaluated by Receiver Operating Characteristic curve. When the Methotrexate level at 42 h was lower than 0.76 µmol/L, the sensitivity for predicting thorough clearance at 66 h was 90.78%. When the Methotrexate level at 42 h was higher than1.5 µmol/L, the sensitivity for predicting delayed clearance was 82.17%. When the Methotrexate level at 66 h was higher than 0.5 µmol/L, the sensitivity for predicting Methotrexate toxicity was 89.09%. When the Methotrexate level at 66 h was lower than 0.1 µmol/L, the sensitivity for predicting Methotrexate nontoxicity was 92.73%. The Methotrexate level at 42 h could be predictor for delayed clearance. The Methotrexate level at 66 h could be predictor for toxicity.

本研究旨在探寻儿童急性淋巴细胞白血病（Acute Lymphoblastic Leukemia）患者大剂量甲氨蝶呤（High Dose Methotrexate）毒性反应的预测因子。本研究共纳入198例接受大剂量甲氨蝶呤治疗的儿童急性淋巴细胞白血病患者，共计303次给药输注。采用改良酶倍增免疫测定技术（modified enzyme multiplied immunoassay technique）检测不同时间点的甲氨蝶呤血药浓度。通过受试者工作特征曲线（Receiver Operating Characteristic curve）评估甲氨蝶呤血药浓度与毒性反应的相关性。当给药后42小时的甲氨蝶呤血药浓度低于0.76 μmol/L时，预测66小时达到完全清除的灵敏度为90.78%；当给药后42小时的甲氨蝶呤血药浓度高于1.5 μmol/L时，预测清除延迟的灵敏度为82.17%；当给药后66小时的甲氨蝶呤血药浓度高于0.5 μmol/L时，预测发生甲氨蝶呤毒性反应的灵敏度为89.09%；当给药后66小时的甲氨蝶呤血药浓度低于0.1 μmol/L时，预测未发生甲氨蝶呤毒性反应的灵敏度为92.73%。给药后42小时的甲氨蝶呤血药浓度可作为清除延迟的预测因子，给药后66小时的甲氨蝶呤血药浓度可作为毒性反应的预测因子。