维族、汉族急性淋巴细胞白血病患儿甲氨蝶呤不良反应探讨

Adverse effects of methotrexate in the treatment of acute lymphoblastic leukemia in Uyghur and Han children

摘要:

目的：通过对维吾尔族及汉族急性淋巴细胞白血病（ALL）患儿甲氨蝶呤（MTX）血药浓度监测结果的分析，为MTX不良反应的发生提供判断依据。方法：根据24 h MTX血药浓度监测结果，将28例（汉族 15 例，维吾尔族 13 例）接受大剂量MTX化疗的ALL患儿分为>10 μmol/L与≤10 μmol/L组；根据48 h MTX血药浓度监测结果分为>1.0 μmol/L与≤1.0 μmol/L组。采用酶放大免疫测定法对行MTX治疗的所有患儿给药后24 h及48 h血药浓度进行检测并观察不良反应发生情况。结果：不良反应发生率在不同24 h MTX血药浓度组间差异无统计学意义(P>0.05)；48 h MTX血药浓度>1.0 μmol/L组的消化道反应及黏膜损害发生率高于血药浓度≤1.0 μmol/L组 (P0.05)；汉族患儿24 h及48 h MTX血药浓度均高于维吾尔族(P<0.05)；除消化道反应外，汉族患儿肝功能异常、黏膜损害及骨髓抑制的发生率高于维吾尔族患儿 (P<0.05)。结论：24 h MTX血药浓度不能预测不良反应的发生，48 h MTX血药浓度对不良反应的发生有一定预测价值；24 h、48 h MTX血药浓度及不良反应发生率在维吾尔族及汉族间存在差异；MTX血药浓度监测结果可能对及时调整MTX用量，从而达到MTX个体化治疗具有重要意义。

Abstract:

OBJECTIVE: To study blood concentrations of methotrexate (MTX) in Uyghur and Han children with acute lymphoblastic leukemia (ALL), and to provide criteria for judging the incidence of adverse effects of MTX. METHODS: Twenty-eight children with ALL (15 Han children and 13 Uyghur children), who received high-dose MTX chemotherapy, were divided into >10 μmol/L and ≤10 μmol/L groups according to 24-hour blood concentration of MTX, and divided into >1.0 μmol/L and ≤1.0 μmol/L groups according to 48-hour blood concentration of MTX. Enzyme multiplied immunoassay was used to measure blood concentrations of MTX in the MTX-treated children at 24 and 48 hours after MTX administration, and the adverse effects were observed. RESULTS: There was no significant difference in the incidence of adverse effects between the >10 μmol/L and ≤10 μmol/L groups (P>0.05). The >1.0 μmol/L group showed higher incidences of gastrointestinal reactions and mucosal injuries than the ≤1.0 μmol/L group (P0.05). Compared with Uyghur children, Han children showed higher 24- and 48-hour blood concentrations of MTX (P<0.05) and higher incidence of abnormal liver function, mucosal injuries, and bone marrow suppression (P<0.05). CONCLUSIONS: The 24-hour blood concentration of MTX cannot be used to predict the incidence of adverse effects in MTX chemotherapy, but 48-hour blood concentration of MTX is helpful in this regard. There are significant differences in 24- and 48-hour blood concentrations of MTX and the incidence of adverse effects between Uyghur and the Han children with ALL who receive MTX chemotherapy. Monitoring of blood MTX concentration maybe significant for timely adjustment of MTX dosage and individualized MTX chemotherapy.