大剂量甲氨蝶呤治疗小儿急性淋巴细胞白血病的血药浓度与不良反应相关性探讨

The Relationship between the Plasma Concentrations and Adverse Reactions of High Dose Methotrexate Used in the Treatment of Pediatric Acute Lymphoblastic Leukemia

关键词:  甲氨蝶呤  急性淋巴细胞白血病  血药浓度  不良反应

Key words:  methotrexate  acute lymphoblastic leukemia  plasma concentration  adverse reaction

摘要:

目的 探讨大剂量甲氨蝶呤(MTX)治疗儿童急性淋巴细胞白血病血药浓度与不良反应相关性，为临床合理用药提供依据。方法 采用荧光偏振免疫法测定72位患儿血药浓度，结合临床不良反应观察，采用χ²检验分析血药浓度与不良反应发生的关系。结果 血清MTX C_{24 h}≥40 μmol·L^-1的常见不良反应发生率与血清MTX C_{24 h}<40 μmol·L^-1相比有显著性差异(P<0.05)。血清MTX C_{48 h}≥1.0 μmol·L^-1的不良反应发生率与血清MTX C_{48 h}<1.0 μmol·L^-1相比有极显著性差异(P<0.01)。结论 MTX不良反应的发生率直接取决于MTX血药浓度的高低和持续时间的长短。

Abstract:

OBJECTIVE To investigate the relationship between the plasma concentration and adverse reactions of high dose methotrexate (MTX) used in the treatment of pediatric acute lymphoblastic leukemia. METHODS The concentration of MTX in plasma samples of 72 patients were measured by a flurorescence polarization immunoassay, which were analyzed combined with the clinical manifestions by Chi-square test. RESULTS When the MTX C_{24 h}≥40 μmol·L^-1, the incidence rates of adverse reaction were higher than those of MTX C_{24 h}<40 μmol·L^-1(P<0.05). When the MTX C_{48 h}≥1.0 μmol·L^-1, the incidence rates of adverse reaction were higher than those of MTX C_{48 h}<1.0 μmol·L^-1(P<0.01). CONCLUSION The incidence rates and the severity of adverse reactions of high dose MTX were ralated directly with the level and the persistence time of the plasma concentration.