甲氨蝶呤治疗急性淋巴细胞性白血病期间不良反应的特征及影响因素分析

Analysis of the Characteristics and Influencing Factors of Adverse Reactions in Patients with Acute Lymphoblastic Leukemia Treated by Methotrexate

目的探讨甲氨蝶呤治疗急性淋巴细胞性白血病(acute lymphocytic leukemia,ALL)期间不良反应的特征,并分析影响患儿不良反应发生风险的相关因素。方法以142例ALL患儿为研究对象,并进行前瞻性分析。患儿均接受大剂量甲氨蝶呤治疗,记录其治疗期间不良反应特征,并比较不同临床资料患儿不良反应发生情况,分析影响甲氨蝶呤治疗期间ALL不良反应发生的危险因素。结果患儿甲氨蝶呤治疗期间最常见的不良反应为骨髓抑制,发生率为52. 82%且以3~4级为主,其次为1~2级胃肠道反应,患儿不良反应均经对症治疗后于1~21 d内消失。非条件Logistic多因素回归分析结果示,年龄与甲氨蝶呤治疗期间感染率相关,性别与甲氨蝶呤治疗期间胃肠道反应及黏膜损伤相关,RFC1 A80G基因型与治疗期间骨髓抑制相关,差异有统计学意义(P <0. 05)。结论甲氨蝶呤治疗ALL期间不良反应以骨髓抑制、胃肠道反应为主,虽然经对症治疗后可好转,但仍应注重针对高危因素的早期甲酰四氢叶酸钙解救治疗,尽可能预防不良反应的发生。

Objective To discuss the characteristics of adverse reaction in patients with acute lymphoblastic leukemia( ALL) treated by methotrexate,and to analyze the risk factors of complications. Methods 142 patients with ALL were selected as the prospective research object. The patients were treated with high dose methotrexate,the adverse reactions during treatment were recorded,the adverse reactions were compared between different clinical data,and the risk factors of adverse reactions during treatment were analyzed. Results The most common adverse reactions during methotrexate therapy for children with ALL was arrest of bone marrow,with the incidence rate of 52. 82% and the 3 ~ 4 level,followed by 1 ~ 2 grade gastrointestinal reactions. The adverse reactions of children were disappeared within 1 ~ 21 d after symptomatic treatment. Non conditional Logistic regression analysis results showed that age was associated with methotrexate infection,sex was associated with gastrointestinal tract response and mucosal damage,and RFC1 A80 G genotype was associated with myelosuppression,the difference was statistically significant( P < 0. 05). Conclusion The main adverse reactions during treatment are bone marrow suppression and gastrointestinal reaction,although after symptomatic treatment can be improved,but still should pay attention to the rescue treatment of early calcium formyltetrahydrofolate to prevent adverse effects.