大剂量甲氨蝶呤治疗毒副作用系统分析

Adverse effects of high-dose methotrexate therapy

摘要:

目的 总结大剂量甲氨蝶呤（HDMTX）治疗的毒副作用，为优化HDMTX治疗提供理论基础。方法 回顾性分析601例次接受HDMTX治疗的120例急性淋巴细胞白血病或非霍奇金淋巴瘤患儿临床资料，按照WHO抗癌药物毒副作用分级标准对各系统毒副作用进行分析。结果 HDMTX治疗后骨髓抑制几乎出现在所有患儿，以粒细胞减少最为多见（93.3%）。最常见的消化系统毒副作用是谷丙转氨酶升高（60.4%）；泌尿系统最常见的毒副作用是蛋白尿（9.2%）；皮肤症状发生率最高的为皮肤红斑（7.2%）；神经系统毒副作用如痛觉过敏、肢体麻木或头痛仅观察到7例次。HDMTX的严重毒副作用仅见于血液系统和消化系统。与MTX3 g/m²组比较，5 g/m² HDMTX组的24 h MTX血药浓度较高（P < 0.05），血红蛋白及血小板降低、口腔黏膜炎、蛋白尿和皮肤症状等毒副作用的发生率也较高（P < 0.05）。结论 HDMTX治疗后严重毒副作用主要发生在血液系统和消化系统，骨髓抑制、口腔黏膜炎、蛋白尿、皮肤症状等毒副作用的发生均有一定的剂量依赖性。

Abstract:

Objective To investigate the adverse effects of high-dose methotrexate (HDMTX) therapy, and to provide a theoretical basis for optimizing clinical treatment. Methods A retrospective analysis was performed for the clinical data of 120 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma who underwent 601 times of HDMTX therapy. The adverse effects of various systems were analyzed according to the WHO criteria for the classifcation of adverse effects of anticancer drugs. Results Almost all the children experienced bone marrow suppression, and 93.3% had granulocytopenia. The most common adverse effects in the digestive system and urinary system were elevated glutamic-pyruvic transaminase (60.4%) and proteinuria (9.2%) respectively. For skin symptoms, skin erythema had the highest incidence rate (7.2%). The adverse effects in the nervous system (hyperpathia, numbness of extremities, or headache) were only observed in 7 cases. Serious adverse effects were only seen in the blood system and digestive system. Compared with the 3 g/m² methotrexate (MTX) group, the 5 g/m² HDMTX group had a signifcantly higher 24-hour plasma MTX concentration, signifcant reductions in hemoglobin and platelet count, and signifcantly higher incidence rates of oral mucositis, proteinuria, and skin symptoms (P < 0.05). Conclusions Serious adverse effects of HDMTX therapy mainly involve the blood system and digestive system, and the adverse effects such as bone marrow suppression, oral mucositis, proteinuria, and skin symptoms occur in a dose-dependent manner.