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目的:对大剂量甲氨蝶呤(high-dose methotrexate,HD-MTX)治疗儿童急性淋巴细胞白血病(acute lymphoblastic leukemi,ALL)进行血药浓度监测,探讨用药后48,72 h的血药浓度变化、排泄延迟与临床毒副反应的相关性。方法:收集37例急性淋巴细胞白血病住院患儿病例,共进行HD-MTX治疗188例次,采用酶放大免疫法(EMIT)测定甲氨蝶呤(methotraxate,MTX)给药后48,72 h的血药浓度,根据血药浓度测定结果调整四氢叶酸钙(CF)解救剂量,同时观察不良反应。结果:B细胞系急性淋巴细胞白血病患儿(B-ALL),48 h血药浓度1.16μmol·L-1以上组与以下组相比,黏膜损害、胃肠道反应、肾功能损害发生率较高,差异有显著性;72 h血药浓度0.22μmol·L-1以上组与以下组相比,胃肠道反应、肾功能损害、呼吸道反应发生率较高,差异有显著性。T细胞系急性淋巴细胞白血病患儿(T-ALL),48 h血药浓度1.16μmol·L-1以上组与以下组相比,肾功能损害、呼吸道反应发生率较高,差异有显著性。结论:血药浓度与不良反应有相关性,MTX血药浓度监测可较好地指导ALL患儿的临床治疗。
OBJECTIVE: To monitor the plasma concentrations of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL) and to explore the changes of plasma concentrations 48 and 72 h after treatment , Excretion delay and clinical toxicity. Methods: Thirty-seven children hospitalized with acute lymphoblastic leukemia were enrolled. A total of 188 cases of HD-MTX were treated with enzyme-linked immunosorbent assay (EMIT). The levels of methotrexate (MTX) Blood concentration, according to the determination of plasma concentration adjusted leucovorin (CF) rescue dose, and observed adverse reactions. Results: Compared with the following groups, the incidence of mucosal injury, gastrointestinal reaction and renal dysfunction were significantly higher in children with B lymphocytic leukemia (B-ALL) than in those with B-ALL at 48 h and 1.48 μmol·L-1 for 48 h High, the difference was significant; 72 h plasma concentration of 0.22μmol·L-1 above group compared with the following group, gastrointestinal reactions, renal dysfunction, respiratory tract infection was higher, the difference was significant. T-ALL children with acute lymphoblastic leukemia (T-ALL), 48 h plasma concentration of 1.16μmol·L-1 above group compared with the following groups, the higher the incidence of renal damage, respiratory reactions, the difference was significant. Conclusion: There is a correlation between serum concentration and adverse reactions. MTX blood concentration monitoring can better guide the clinical treatment of children with ALL.