不同剂量甲氨蝶呤与小儿急性白血病毒副反应的相关性分析

目的:探讨小儿急性白血病使用不同剂量甲氨蝶呤(MTX)的毒副反应,指导制定个体化治疗方案。方法:收集因患有急性白血病住院治疗的患儿237例,根据使用甲氨蝶呤的不同剂量分为2组。低危组:甲氨蝶呤的给药剂量为3 g·m^-2,共153例。高危组:甲氨蝶呤的给药剂量为5 g·m^-2,共84例。首次使用甲氨蝶呤36 h后使用四氢叶酸钙(CF)解救,监测24 h、48 h血药浓度,48 h后若>1 μmol·L^-1,则加大剂量继续解救,直至达到安全浓度(<0.1 mmol·L^-1);若48 h后<1 μmol·L^-1,则继续常规解救。对比分析2组24 h、48 h血药浓度;毒副反应的发生率。结果:2组患儿在24 h后血药浓度有差异,高危组明显高于低危组,差异具有统计学意义(P< 0.05)。2组患儿在48 h后血药浓度的差异不具有统计学意义(P> 0.05)。甲氨蝶呤化疗的毒副反应主要表现为消化道反应、肝肾功能损害等。2组的各毒副反应发生率不存在差异(P> 0.05)。结论:大剂量的甲氨蝶呤治疗小儿急性白血病24 h、48 h后血药浓度达到较高水平,经四氢叶酸钙解救后均有不同程度地下降,给药剂量大可降低解救的效果。治疗过程中会出现各类毒副反应,给药剂量较大更易导致消化道反应毒副反应的出现。

Correlation analysis of doses and toxic and side effects of methotrexate in children with acute leukemia

OBJECTIVE To investigate toxicity of methotrexate (MTX) at different doses in children with acute leukemia,guide the development of individualized treatment plan.METHODS A total of 237 children with acute leukemia were enrolled from January 2013 to January 2014,and divided into two groups by different doses of methotrexate:low-risk group,methotrexate 3 g·m^-2 for 153 cases; high-risk group,methotrexate 5 g·m^-2 for 84 cases.Leucovorin was administered for rescue 36 h after first dose of methotrexate,blood concentration was determined 24 h and 48 h later,if blood concentration at 48 h > 1 μmol ·L^-1,rescue dose would be increased till safe concentration was reached (<0.1 mmol·L^-1); if blood concentration at 48 h <1 μmol·L^-1,routine rescue was continued.Plasma concentrations,toxic and side effects were comparatively analyzed at 24 h and 48 h.RESULTS Two groups of children had varied blood concentrations 24 h later,high-risk group had significantly higher concentration than low-risk group (P< 0.05).Differences in plasma concentrations in two groups were not statistically significant (P> 0.05) 48 h later.Methotrexate toxicity was mainly displayed as gastrointestinal reactions,liver and kidney dysfunctions.Two groups had no difference in toxic and side effects (P> 0.05).CONCLUSION High dose methotrexate in children with acute leukemia can results in higher plasma concentrations 24 and 48 hours later,which will decline to varied extents after leucovorin rescue,but large dose will reduce rescue effect.During therapeutic course,various types of toxic and side effects appear,but large doses cause gastrointestinal reactions more easily.