儿童急性淋巴细胞白血病患者接受大剂量甲氨蝶呤治疗后的神经毒性的种族特异性预测因素。
Ethnic-specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high-dose methotrexate.
机构信息
Section of Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Houston, Texas, USA.
出版信息
Cancer. 2023 Apr 15;129(8):1287-1294. doi: 10.1002/cncr.34646. Epub 2023 Jan 24.
BACKGROUND
High-dose methotrexate (HD-MTX; 5000 mg/m ) is an important component of curative therapy in many treatment regimens for high-risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose-limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD-MTX in an ethnically diverse population of patients with ALL.
METHODS
The authors retrospectively reviewed the medical records of patients who were diagnosed with ALL and treated with HD-MTX at Texas Children's Cancer Center (2010-2017). Methotrexate neurotoxicity was defined as a neurologic episode (e.g., seizures or stroke-like symptoms) occurring within 21 days of HD-MTX that resulted in methotrexate treatment modifications. Mixed effects multivariable logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between clinical factors and neurotoxicity.
RESULTS
Overall, 351 patients (58.1% Latino) who received 1183 HD-MTX infusions were evaluated. Thirty-five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, the authors observed that serum creatinine elevations ≥50% of baseline were associated with a three-fold increased odds (OR, 3.32; 95% CI, 0.98-11.21; p = .05) for neurotoxicity compared with creatinine elevation <25%. Notably, predictors of neurotoxicity differed by ethnicity. Specifically, Latino children experienced a nearly six-fold increase in neurotoxicity odds (OR, 5.80; 95% CI, 1.39-24.17; p = .02) with serum creatinine elevation ≥50% compared with creatinine elevation <25%.
CONCLUSIONS
The current findings indicate that serum creatinine elevations ≥50% may be associated with an increased risk for neurotoxicity among Latino children with ALL and may identify potential candidates for therapeutic or supportive care interventions.
背景
大剂量甲氨蝶呤（HD-MTX；5000mg/m2）是许多高危儿童急性淋巴细胞白血病（ALL）治疗方案中重要的治疗组成部分。然而，甲氨蝶呤治疗可能导致剂量限制的神经毒性，这可能会不成比例地影响拉丁裔儿童。本研究评估了在具有 ALL 的种族多样化患者人群中，HD-MTX 后发生神经毒性的危险因素。
方法
作者回顾性审查了在德克萨斯儿童癌症中心（2010-2017 年）诊断为 ALL 并接受 HD-MTX 治疗的患者的病历。甲氨蝶呤神经毒性定义为在接受 HD-MTX 后 21 天内发生的导致甲氨蝶呤治疗修改的神经事件（例如，癫痫发作或类似中风的症状）。使用混合效应多变量逻辑回归来估计临床因素与神经毒性之间关联的优势比（OR）和相应的 95%置信区间（CI）。
结果
总体而言，评估了 351 名患者（58.1%为拉丁裔），共接受了 1183 次 HD-MTX 输注。35 名患者（10%）出现神经毒性，其中 71%为拉丁裔。在调整临床危险因素后，作者观察到血清肌酐升高≥50%基线与神经毒性的三倍以上几率（OR，3.32；95%CI，0.98-11.21；p=0.05）相关与肌酐升高<25%相比。值得注意的是，神经毒性的预测因素因种族而异。具体而言，与肌酐升高<25%相比，血清肌酐升高≥50%的拉丁裔儿童发生神经毒性的几率增加近六倍（OR，5.80；95%CI，1.39-24.17；p=0.02）。
结论
目前的研究结果表明，血清肌酐升高≥50%可能与 ALL 拉丁裔儿童的神经毒性风险增加有关，并可能确定潜在的治疗或支持性护理干预的候选者。
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