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目的研究大剂量甲氨蝶呤(high-dose methotrexate,HD-MTX)在急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)治疗中的应用,了解血药浓度监测的意义。方法对35例ALL患者应用HD-MTX治疗186例次,观察和总结不良反应发生情况,并分别于给药后24 h、66 h、72 h测定MTX的血药浓度,在血药浓度和不良反应监测指导下解救治疗。结果 24 h、66 h、72 h MTX的血药浓度分别为(36.86±7.42)μmol/L、(0.25±0.09)μmol/L、(0.09±0.04)μmol/L。胃肠道反应、肝功能损害、口腔溃疡、骨髓抑制是HD-MTX治疗过程中常见的不良反应。MTX在体内排泄个体差异大,根据血药浓度测定结果调整甲酰四氢叶酸钙(calcium folinate,CF)剂量及时机,安全性高,疗效满意。结论 HD-MTX治疗应强调剂量个体化,血药浓度的监测为提高ALL的疗效,降低药物治疗的不良反应,提供必要保障。
Objective To study the application of high-dose methotrexate (HD-MTX) in the treatment of acute lymphoblastic leukemia (ALL) and to understand the significance of monitoring blood concentration. Methods HD-MTX was used to treat 186 ALL patients in 35 ALL patients. The adverse reactions were observed and summarized. The plasma concentrations of MTX were measured at 24 h, 66 h and 72 h after administration. Response monitoring and guidance under the rescue treatment. Results The plasma concentrations of MTX at 24 h, 66 h and 72 h were (36.86 ± 7.42) μmol / L, (0.25 ± 0.09) μmol / L and (0.09 ± 0.04) μmol / L, respectively. Gastrointestinal reactions, impaired liver function, oral ulcers, and myelosuppression are common side effects of HD-MTX therapy. MTX excretion in the individual differences in individuals, according to blood concentration measurement results to adjust the dosage of calcium folinate (CF) and timing, high safety, satisfactory results. Conclusions HD-MTX therapy should emphasize dose individuation. The monitoring of blood concentration should provide the necessary protection to improve the curative effect of ALL and reduce the adverse reactions of drug treatment.