造血干细胞移植中马利兰血药浓度监测及其临床意义

Clinical significance of monitoring Busulfan concentration in haemopoietic stem cell transplantation

目的:利用高效液相色谱法监测造血干细胞移植(HSCT)预处理中静脉马利兰(BU)的血药浓度,观察BU血药浓度与移植疗效之间的关系。方法:我科42例患者HSCT中预处理方案采用静脉剂型BU,对其中12例患者[肝静脉闭塞病(HVOD)、可疑HVOD和移植后出现复发]和1例慢性移植物抗宿主病(cGVHD)进行BU血药浓度监测。BU第一剂静脉用药前及用药后1、2、4、6h抽取血标本,计算BU浓度时间曲线下面积(AUC)。结果:1例cGVHD,AUC值为695.89μmol/min;2例HVOD,AUC值为770.56μmol/min和788.22μmol/min,2例均复发;2例可疑HVOD,AUC值为1 411.02μmol/min和1 564.9μmol/min;10例(23%)复发,其BU浓度较低,AUC平均值为827.36(685.82～1109.53)μmol/min。结论:预处理方案中应用静脉BU,其浓度是安全的。9例复发患者BU血药浓度低于治疗窗浓度。

Objective：To monitor the concentration of intravenous busulfan undergoing hematopoietic stem cell transplantation conditioning with HPLC assay and observe its clinical significance. Method：Among 42 patients with intravenous busulfan as conditioning regimen,13 patients were monitored the concentration of intravenous busulfan.One patient had chronic GVHD,other patients had HVOD,doubtful HVOD,or disease relapse.Plasma samples were collected every 0,1,2,4,6 h during the first dose busulfan intravenous injection.Plasma busulfan concentration was expressed as the area under the concentration-time curve（AUC）. Result：In one case of chronic GVHD,AUC was 695.89 μmol/min.HVOD occurred in 2 patients who both relapsed.AUC was 770.56 μmol/min and 788.22 μmol/min separately in these two patients,Doubtful HVOD occurred in 2 patients whose AUC were 1 411.02 μmol/min and 1 564.9 μmol/min separately.disease relapse were found in ten cases（23%）whose AUC was lower[average 827.36（685.82-1 109.53）μmol/min]. Conclusion：Intravenous busulfan as conditioning regimen in the patients undergoing hematopoietic stem cell transplantation was safety.Nine patients with disease relapse had low concentration plasma busulfan.