急性白血病患儿大剂量甲氨蝶呤后合并过敏诱发重度骨髓抑制临床观察及文献复习

A Clinical Analysis and Literature Reviewed About Non-methotrexate Related Allergies Aggravate Serious Bone Marrow Suppression After High Dose Methotrexate in 4 Patients with Acute Lymphoblastic Leukemia

目的探讨急性淋巴细胞白血病(ALL)患儿应用大剂量甲氨蝶呤(HDMTX)后合并非MTX性过敏,导致重度骨髓抑制等并发症的临床特点、发生机制及相应处理措施。方法总结我院4例2011年至2014年参照2006年儿童急性淋巴细胞白血病诊疗建议(第三次修订草案)诊疗的ALL患儿,维持治疗期间应用HDMTX后合并非MTX过敏出现严重并发症病例的临床特点,并复习文献。结果 4例ALL患儿既往均多次应用HDMTX,化疗均顺利。此次应用HDMTX 72 h后血常规、肝功能、肾功能、血药浓度均正常,但过敏后均发生MTX血药浓度轻度增高、重度骨髓抑制、黏膜炎、感染或胃肠道出血,经对症支持后疗效良好。结论过敏因素增加MTX血药浓度,导致其体内代谢明显延迟,加重黏膜炎及延长骨髓抑制期,从而出现较严重的感染及出血并发症,但临床转归良好,不同于MTX过敏所致的持续高MTX血症患者。对儿童ALL应用HDMTX后应密切观察病情变化,定期监测血药浓度,及时加强对症支持治疗。

Objective To investigate the clinical features, pathological mechanisms and treatment of high dose methotrexate （HDMTX） related serious complications in 4 patients with acute lymphoblastic leukemia （ALL）, which happened after allergies induced by other factors. Methods Four patients with ALL treated with MTX in our hospital were summarized who occurred serious complications after allergies induced by other factors, and the related literatures were reviewed. Results All of 4 patients experienced HDMTX treatment smoothly many times before, this time they showed a normal MTX concentration at 72 hours, and all of them occurred allergy induced by other factor, and happened serious complications such as bone marrow suppression, peptic ulcer and mucositis, but the efficacy was good at the end. Conclusion Many factors are involved in the metabolism of MTX, allergies induced by other factors can extend the metabolism time of MTX, which results serious bone marrow suppression and mucositis, but had a good therapy efficacy. So we should closely observe the change of disease, monitoring the levels of serum MTX, and strengthen symptomatic and supportive treatment in the MTX treatment.