大剂量甲氨蝶呤治疗儿童白血病毒副作用临床研究

Clinical studies of the toxicity effect of high-dose methotrexate used in treating acute lymphocytic leukemia in children

目的:研究大剂量甲氨蝶呤(HDMTX)加四氢叶酸钙(CF)解救的方案治疗儿童白血病的临床毒副作用.方法:16例急性淋巴细胞白血病进行了40例次的HDMTX+CF的治疗,对用药前后患儿的临床表现、血尿常规、心电图、心肌酶谱、肝肾功能等和患儿的一般反应、皮肤粘膜损害、心脏毒性、肝肾损害、神经毒性、骨髓抑制等进行对照研究.结果:骨髓抑制发生率72.5%,持续时间3～13d;肝功能损害37.5%,但均较轻;恶心、呕吐30.0%;皮疹约5.0%;心电图异常和心肌酶谱异常为12.5%和17.5%;2例因严重不良反应死亡.结论:大剂量甲氨蝶呤加四氢叶酸钙治疗儿童白血病时,毒副作用较为常见,大多可耐受;个别可出现严重毒副作用,故应注意患儿个体差异,有条件的单位应监测血药浓度,防止出现严重的毒副作用,并根据血药浓度进行适当的四氢叶酸钙解救,避免过度解救而影响疗效.

Objective:To study the toxicity effect of high dose methotrexate(HDMTX)used in treating acute lymphoblastic leukemia(ALL)in children.Methods:16children with ALL received high dose methotrexate(3g/m 2 )treatment.The general situation of the pa-tients,skin lesion or rash,mucous membrane,heart function,renal and liver function,blood cell count and the hematopoietic activity in bone marrow before and after the treatment were observed and evaluated.Results:In all patients,72.5%have bone marrow depression which last from3to13days;37.5%of the patients showed abnormal liver function.30.0%of the patients had nausea and vomiting.Ab-normal electrocardiogram and myocardium zymogram account for12.5%and17.5%of the patients.5.0%of the patients had rashes.Two patients died of severe bone marrow suppression plus secondary infection and severe dermatitis exfoliativa respectively.Conclusions:HDMTX results in toxicity in ALL patients receiving this treatment,which include bone marrow suppression,abnormal liver function,GI symptoms and mucositis.A few vital cases of toxicity are found.However,leucovorin rescue plays a key role in preventing the toxicity and getting an optimal treatment effect.MTX level should be monitored closely to help decide the point to initiate leucovorin rescue.