淋巴系恶性肿瘤患者大剂量甲氨蝶呤化疗后不良反应预测模型的研究

目的 探究大剂量甲氨蝶呤化疗后淋巴系恶性肿瘤患者不良反应的影响因素，并构建其预测模型，为甲氨蝶呤个体化用药提供依据。方法 收集2014年6月—2016年12月新疆医科大学第一附属医院儿科及血液病中心收住的180例淋巴系恶性肿瘤患者，记录患者相关信息，先进行单因素分析，再采用非条件Logistic回归分析确定影响因素，建立不良反应预测模型，并用受试者工作特征曲线（ROC）对模型进行检验。结果 经Logistic回归分析显示，肝功能损伤影响因素包括年龄（OR=3.280）、化疗前24 h水化量（OR=2.045）、化疗前谷丙转氨酶（ALT）（OR=5.120）、化疗前谷草转氨酶（AST）（OR=12.962），预测方程：a=-1.479+1.188（年龄）+0.715（化疗前24 h水化量）+1.633（化疗前ALT）+2.562（化疗前AST），ROC曲线下AUC为0.774；骨髓抑制影响因素包括体表面积（OR=0.497）、化疗前白细胞（WBC）（OR=2.416）、化疗前碱性磷酸酶（ALP）（OR=10.248），MTX给药剂量强度（OR=0.593），预测方程：a=1.695-0.700（体表面积）+0.882（化疗前WBC）+2.327（化疗前ALP）-0.522（MTX剂量强度），ROC曲线下AUC为0.762；黏膜损伤影响因素包括MTHFR A1298C（OR=4.147）、疗程≥3次（OR=0.375），预测方程：a=-0.356+1.422（MTHFR A1298C）+0.641（x3）-0.982（x4），ROC曲线下AUC为0.765；胃肠道反应影响因素包括MTHFR A1298C（OR=11.060），预测方程：a=-1.773+2.403（MTHFR A1298C），ROC曲线下AUC为0.808。结论 临床应用大剂量甲氨蝶呤时，应多加关注患者的年龄、体表面积、疗程数、MTX剂量强度、水化量、MTHFR A1298C、化疗前肝功能或血常规等影响因素，以降低药物不良反应的发生率。

Preliminary Study on Prediction Model of Adverse Reactions in Patients with Lymphatic Tumors After Chemotherapy with High Dose Methotrexat

OBJECTIVE To investigate the influencing factors of adverse reactions in patients with lymphatic tumors after high-dose methotrexate (HD-MTX) chemotherapy, and to establish a prediction model of adverse reactions, to provide evidence for personalized medicine of methotrexate. METHODS Clinical cases of 180 patients with lymphatic cancer were collected from June 2014 to December 2016 in pediatric and hematology center of the First Affiliated Hospital of Xinjiang Medical University, the data was analyzed by unconditional univariate and multivariate Logistic regression, and the test of the model were assessed by the area under the ROC curve. RESULTS Logistic regression analysis showed that, the influencing factors of hepatic impair include age (OR=3.280), 24 h volume hydration before chemotherapy (OR=2.045), alanine aminotransferase (ALT, OR=5.120) and aspartate transaminase (AST, OR=12.962) before chemotherapy, predictive equation:a=-1.479+1.188(age)+0.715(24 h volume hydration before chemotherapy)+1.633(ALT before chemotherapy)+2.562(AST before chemotherapy), the ROC (AUC)=0.774;The influencing factors of myelosuppression include boby surface area (OR=0.497), the number of white blood cell (WBC) before chemotherapy (OR=2.416), alkaline phosphatase before chemotherapy (ALP, OR=10.248) and dosage of methotrexate (OR=0.593), predictive equation:a=1.695-0.700(boby surface area)+0.882(WBC before chemotherapy)+2.327(ALP before chemotherapy)-0.522(dosage of methotrexate), the ROC (AUC)=0.762;The influencing factors of mucositis include MTHFR A1298C (OR=4.147), more than three courses of HD-MTX (OR=0.375), predictive equation:a=-0.356+1.422(MTHFR A1298C)+0.641(x3)-0.982(x4), the ROC (AUC)=0.765;The influencing factors of gastrointestinal reaction include MTHFR A1298C (OR=11.060), predictive equation:a=-1.773+2.403(MTHFR A1298C), the ROC (AUC)=0.808. CONCLUSION When use HD-MTX in clinic, the medical staff shall pay more attention to the factors that age, body surface area, the number of courses, dosage of methotrexate, volume hydration, MTHFR A1298C, liver function or blood routine before chemotherapy, and to prevent the occurrence of adverse events.