大剂量甲氨蝶呤治疗儿童ALL的血药浓度监测及其临床意义

目的分析儿童急性淋巴细胞白血病（ALL）采用大剂量甲氨蝶呤（MTX）化疗时的血药浓度监测结果，探讨其对于甲酰四氢叶酸钙（CF）个体化解救的临床意义。方法140例ALL患儿按照ALL危险度分组，标危组接受3．0g·m^-2 MTX治疗，高危组接受5．0g·m^-2 MTX治疗。采用高效液相色谱法测定MTX给药后固定时间点（24、44、68h）的血药浓度，根据血药浓度结果调整CF解救方案，同时观察不良反应。结果标危组24、44、68hMTX血药浓度分别为29．80±15．07、0．47±0．41、0．09±0．07μmol·L^-1，高危组24、44、68hMTX血药浓度分别为57．17±16．65、1．22±1．86、0．53±0．54μmol·L^-1，MTX血药浓度有显著的个体差异；不同剂量组CF解救剂量有显著差异；高危组中MTX排泄延迟的发生率较高（28／99）；所有病例无不可逆的严重不良反应发生。结论大剂量MTX化疗时的血药浓度监测是非常必要的，对于CF解救的个体化具有十分重要的临床意义。

Therapeutic drug monitoring of methotrexate in the high-dose chemotherapy of pediatric acute lymphoblastic leukemia

Aim To summarize the stage achievement of Therapeutic drug monitoring of high-dose methotrexate in pediatric acute lymphoblastic leukemia and assessing the clinical significance. Methods 140 acute lymphoblastic leukemia children were grouped accord- ing to the risk factor ,the low-risk group received MTX 3.0 g · m^ -2 and the high-risk group received MTX 5.0 g· m^ -2 . The MTX concentration in serum at 24 ,44 and 68h were detected by high performance liquid chromatography （HPLC）. Then adjust the dosage of CF according to MTX concentration and observe the adverse effects of MTX in patientsResults The concentration of MTX at 24,44 and 66 h of low-risk group were 29.80 ± 15.07,0.47 ±0.41,0.09 ±0.07 μmol· L^-1 and the concentration of MTX at 24,44 and 66h of high- risk group were 57.17 ± 16.65,1.22 ±1.86,0.53 ±0.54 μmol· L^-1 ,respectively. The concentration of MTX is varied in two group, especially 68h and it is varied individually in the same group. None serious adverse effects was observed in All patients. Conclusion It＇ s necessary to monitor the concentration of MTX when the patients received high-does MTX intravenously in order to give different formulas for different children.