CAJ | 학술논문

目的：研究大剂量甲氨蝶呤（HD-MTX）治疗成人急性淋巴细胞白血病时的药物代谢作用及不同解救方案的价值。方法回顾性分析2003至2010年收治的124例成人患者（共190例次 HD-MTX 治疗）的临床和实验室资料。结果190例次患者的甲氨蝶呤血药浓度降至0.1μmol/L 以下的中位时间是72 h（48～342 h），76例次（40%）发生延迟排泄；延迟排泄组患者的不良反应显著增高（P＜0.05），其体质指数和甲氨蝶呤治疗第7日的血清肌酐水平均显著高于正常排泄组（分别为 P=0.046和 P＜0.001）。甲酰四氢叶酸钙联合左旋门冬酰胺酶解救不优于单用亚叶酸钙（P=0.849）。缩短甲氨蝶呤输注时间并提前亚叶酸钙的解救时机不能改善甲氨蝶呤的延迟排泄，但可减轻血液学不良反应。结论体质指数、血清肌酐水平影响甲氨蝶呤的代谢。适度缩短甲氨蝶呤输注时间和提前亚叶酸钙的解救时机或能改善甲氨蝶呤的排泄和不良反应。
목적：연구대제량갑안접령（HD-MTX）치료성인급성림파세포백혈병시적약물대사작용급불동해구방안적개치。방법회고성분석2003지2010년수치적124례성인환자（공190례차 HD-MTX 치료）적림상화실험실자료。결과190례차환자적갑안접령혈약농도강지0.1μmol/L 이하적중위시간시72 h（48～342 h），76례차（40%）발생연지배설；연지배설조환자적불량반응현저증고（P＜0.05），기체질지수화갑안접령치료제7일적혈청기항수평균현저고우정상배설조（분별위 P=0.046화 P＜0.001）。갑선사경협산개연합좌선문동선알매해구불우우단용아협산개（P=0.849）。축단갑안접령수주시간병제전아협산개적해구시궤불능개선갑안접령적연지배설，단가감경혈액학불량반응。결론체질지수、혈청기항수평영향갑안접령적대사。괄도축단갑안접령수주시간화제전아협산개적해구시궤혹능개선갑안접령적배설화불량반응。
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 to evaluate the roles of various rescue schemes. Method Clinical and laboratory data of 124 adult ALL patients treated with HD-MTX in our hospital from 2003 to 2010 were retrospectively analyzed. Result The median time for blood con-centration of MTX decreased to below 0.1 μmol/L was 72 (48~342) hours. Of 190 case-times, delayed MTX elimina-tions 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). The rescue regimen of calcium leucovorin (CF) + L-asparaginase was not superior to CF alone (P=0.849). Shortened infusion time of HD-MTX and early CF rescue did not decrease the proportion of de-layed MTX elimination, hematologic toxicities were reduced though. Conclusion BMI and serum creatinine impact MTX elimination. Moderately shortened infusion time for HD-MTX and early CF rescue are probably feasible to get adequate MTX elimination and less toxicity.