2015 年第 1 期 第 13 卷

大剂量甲氨蝶呤治疗成人急性淋巴细胞白血病的药物代谢研究

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关键词：急性淋巴细胞白血病甲氨蝶呤血药浓度延迟排泄

• 摘要：
• 【摘要】目的 研究大剂量甲氨蝶呤(HD-MTX)在成人急性淋巴细胞白血病（ALL）治疗中药物代谢及不同解救方案的价值。方法 分析2003～2010年收治的124例成人ALL患者共190例次HD-MTX治疗的临床和实验室资料。结果 ① 190例次ALL的MTX血药浓度达到＜0.1μmol/L的中位时间是72（48-342）小时，76例次(40%)发生延迟排泄；延迟排泄组的毒性反应明显增高（P＜0.05），其体重指数（BMI）和MTX第7日的血肌酐均明显高于正常排泄组(P=0.046；P＜0.001）。② 解救加用左旋门冬酰胺酶不优于单用亚叶酸钙（CF）(P=0.849)。③ 缩短MTX输注时间并提前CF解救时机没有改善MTX延迟排泄，但减轻血液学毒性。结论 BMI、血肌酐水平影响MTX的代谢。对于改善MTX排泄和毒性，适度缩短MTX输注时间和提前CF解救时机可能是可行的。
• Objective To investigate the plasma pharmacokinetics of high dose methotrexate (HD-MTX) in the treatment of adult acute lymphoblastic leukemia (ALL) and the factors affecting MTX elimination, and evaluate the roles of various rescue schemes. Method Clinical and laboratory data from 124 adult ALL patients treated with HD-MTX in our hospital from 2003 to 2010 were retrospectively analyzed. Result ① The time to blood concertation of MTX less than 0.1μmol/L was 72 (48-342) hours. Of 190 case-times, delayed MTX eliminations were seen in 76 case-times (40%). More MTX toxicities were observed in delayed group (P＜0.05). Body mass index (BMI) and serum creatinine on MTX day 7 in delayed group were higher than those in normal group（P=0.046 and P＜0.001, respectively）. ② Calcium leucovorin (CF) + L-asparaginase rescue was not superior to CF alone (P=0.849). ③ Shortening infusion time of HD-MTX and early CF rescue did not decrease the proportion of delayed MTX elimination, but reduced hematologic toxicity. Conclusion BMI and serum creatinine impact MTX elimination. Moderate shortening infusion time for HD-MTX and early CF rescue are probably feasible to get adequate MTX elimination and less toxicity.