ALL患儿HD-MTX血药浓度对疗效及不良反应的影响

Influence of HD-MTX blood concentration on the efficacy and adverse reactions in children with ALL

目的监测大剂量甲氨蝶呤(HD-MTX)在治疗儿童急性淋巴细胞白血病(ALL)过程中的血药浓度,分析给药剂量、性别、民族对血药浓度、排泄延迟的影响及不良反应发生情况。方法采用回顾性分析方法,收集2015年1月至2017年6月在我院接受HD-MTX化疗的57例患儿(共计246例次)化疗期间的基本资料、实验室检查结果、MTX血药浓度,以及化疗后发生的不良反应。结果 5 g/m^2组24、36 h的血药浓度高于3 g/m^2组、4 g/m^2组(P <0.05),三个剂量组的48 h MTX血药浓度比较差异无统计学意义(P> 0.05);回族儿童与汉族儿童比较,3 g/m^2组36 h MTX血药浓度差异有统计学意义(P <0.01),其余组别差异均无统计学意义(P> 0.05);不同性别患儿各时间点血药浓度比较差异均无统计学意义(P> 0.05);不同给药剂量、性别、民族组的药物排泄延迟发生率比较差异均无统计学意义(P> 0.05);不良反应以骨髓抑制(45.8%)、黏膜损伤(19.0%)、肝功能损害(17.1%)较多见。结论 HD-MTX治疗ALL患儿安全有效,但患儿个体间血药浓度差异较大。因此,应监测患儿(尤其是对药物排泄延迟的患儿)的MTX血药浓度,积极采取有效治疗措施,减少不良反应的发生,保证ALL患儿化疗的安全性。

Objective To monitor the blood concentration of high-dose methotrexate（HD-MTX） in children with acute lymphoblastic leukemia（ALL） ,and analyze the effect of dosage, gender and nationality on blood concentration and excretion delay of MTX and the occurrence of adverse reactions. Methods Totally 57 ALL children who received HD-MTX chemotherapy（246 times） in our hospital from January 2015 to June 2017 were selected. The basic data,laboratory results,MTX blood concentration and adverse reactions after chemotherapy were analyzed. Results The blood concentration of MTX after 24 h and 36 h in 5 g/m^2 group were higher than those in 3 g/m^2 group and 4 g/ m^2 group（P 〈 0. 05 ）, but there was no significant difference in the serum concentration after 48 h among the three groups（P 〉0. 05）. There was no significant difference in the serum MTX concentration of children between Hui nationality and Han nationality（P 〉 0. 05 ）, except the concentration after 36 h in 3 g/m^2 group（P 〈 0. 01 ） ; there was no significant difference in blood concentration of MTX at different time points between the children with different gender （ P 〉 0. 05 ） ; there was no significant difference in the incidence of excretion delay of MTX between different dosage groups, gender groups or nationality groups （P 〉 0. 05 ）. The main adverse reactions included myelosuppression （45.8%） ,mucosal injury（ 19.0% ） and liver function damage（ 17. 1% ）. Conclusion HD-MTX is safe and effective in the treatment of ALL children,but the blood concentration of MTX has the characteristics of individual differences. Therefore, we should pay close attention to monitoring the blood concentration of MTX,especially for children with de- layed drug excretion, and take effective measures to reduce the occurrence of adverse reactions and ensure the safety of chemotherapy for ALL children.