大剂量甲氨蝶呤在治疗急性淋巴细胞白血病中血药浓度监测的意义

Blood Concentration Monitoring of Methotrexate in the Chemotherapy of Patients with Acute Lymphoblastic Leukemia

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 evaluate the adverse reaction of high-dose methotrexate （MTX） on acute lymphoblastic leukemia and to assess meaning of blood concentration monitoring. Methods The types of adverse effects and blood concentration in 35 cases with acute lymphoblastic leukemia were observed. Results 24 h. 66 h. 72 h MTX blood drug concentration was （36.86 ± 7. 42）. （0.82 ± 0.59） and （0.09 ± 0. 04） μmol/L respectively. Gastrointestinal reaction, hepatic damage. stomatocace were the common adverse reaction of high-dose methotrexate. while the incidence rate of adverse reaction was higher when concentration of 48 h was 〉0. 25 μmol/L. Conclusion HDMTX individualized treatment under the instruction of blood concentration monitor supplies the necessary security to improve the treatment effect of ALL and reduce the adverse reaction. Methotrexate. adequate hydration and alkalization and calcium folinate administeration play an important role in high-dose methotrexate.