大剂量甲氨蝶呤两种方案治疗小儿急性白血病的毒副作用观察

Observation of the side effects of high-dose methotrexate with two clinical treatments on acute lymphoblastic leukemia in children

目的研究大剂量甲氨蝶呤(HD-MTX,3g/m2)24小时持续静脉滴注,开始用药后第36小时予四氢叶酸钙(CF)解救治疗小儿急性淋巴细胞白血病(ALL)的安全性。方法26例患儿进行72例次的HD-MTX加CF治疗,将患儿随机分为A、B两组,A组采用方案Ⅰ(MTX总量3g/m2,于12小时内匀速持续静滴,开始用药36小时后用CF解救),B组采用方案Ⅱ(MTX总量3g/m2,于24小时内匀速持续静滴,开始用药36小时后用CF解救),配合水化、碱化、保肝等治疗。观察两组病人出现的毒副作用,以及是否因毒副作用而影响下一疗程的化疗。结果两种方案出现的毒副作用相同,以黏膜损害、骨髓抑制、肝功能损害为最常见,两组病人的毒副作用发生率差异无显著性,两种方案中均有极少数患者(A组1例占总数3.3%,B组2例占总数4.8%)因毒副作用而推迟下一疗程化疗,两组发生率差异无显著性。结论大剂量甲氨蝶呤加四氢叶酸钙治疗小儿急性白血病时,毒副作用较为常见,大多可耐受;通过充分的水化、碱化及合理的CF解救,可以保证方案Ⅱ获得与方案Ⅰ同样的安全性。

Objective To observed the safety of high-dose methotrexate（HD-MTX）3g/m^2 infused intravenously for 24 hours and calcim folinate （CF） followed for rescue at 36th hour in the treatment of the children with acute lymphoblastic leukemia （ALL） and the toxic side effects. Methods HD-MTX was infused for 24 hours in 72cases of children with ALL and followed by CF. 26 children with ALL were divided randomly into 2 groups with different treatment.（1）group A： HD-MTX3g/m^2 was infused for 12 hours and followed by CF for rescue at 36th hour; （2）greup B： HD-MTX3g/m^2 was infused for 24 hours and followed by CF for rescue at 36th hour. The treatments of Hydration,alkalify and protection of liver function were also applied in the two groups. The incidence rate of the side effects and the delay rate of postpone the following course of chemotherapy induced by the side effects were observed. Results There was no difference on the incidence rate of the side effects in two groups. The main adverse reaction appeared as the mucosal damage, bone marrow and abnormal liver function. 1 patient from group A （3.3%） and 2 patients from group B （4.8%） postponed their following course of chemotherapy because of the side effects, and there was no significant difference in delay rates in the two groups. Conclusions The side effects of HD-MTX with CF were very frequent and can be bear on acute lymphoblastic leukemia in children; Through adequate hydration and alkalify, correct CF rescue, the two treatments can ensure the same therapeutic safety.