Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation
Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation
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DOI：
10.1016/j.bbmt.2007.09.015
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Boelens, Jaap J.
中科院分区：
文献类型：
--
作者：
Bartelink, Imke H.;Bredius, Robbert G. M.;Boelens, Jaap J.
由于在儿童中布苏凡（Bu）的个体内和个体间的可变性、生物利用度和药代动力学，在没有治疗药物监测（TDM）的情况下口服布苏凡被认为与更高的移植物失败率和更高的毒性（例如，静脉闭塞性疾病[VOD]）有关。本研究比较了两组患者造血干细胞移植（HSCT）的结果：1)30例患者接受基于TDM的每日一次静脉注射（i.v）剂量靶向布苏芬（BUdtIV）骨髓消融治疗，2)30例患者接受目前的非靶向口服布苏芬（BLTPO）治疗。患者接受3小时的Bu输注，首次剂量为120mg /m(2)（年龄>= 1岁）或80mg /m(2)（< 1岁），或BUPO 1mg /kg，每日4次。两种治疗方案均持续4天。曲线下目标面积（AUC）定义为17,500 μ g*h/1。与BUPO相比，BUdtIV具有更高的无事件生存率（EFS）和生存率(EFS: 30%对83%，P
Because of intra- and interindividual variability, bioavailability, and pharmacokinetics of busulfan (Bu) in children, oral busulfan without therapeutic drug monitoring (TDM) is assumed to be associated with higher graft failure rates as well as higher toxicity (eg, veno-occlusive disease [VOD]). This study compares the outcome of hematopoietic stem cell transplantation (HSCT) of 2 groups: 1) 30 patients who received myeloablation with once-daily intravenous (i.v.) dose-targeted busulfan (BUdtIV) based on TDM and 2) 30 patients who received the current practice of untargeted oral busulfan (BLTPO). Patients received a 3-hour infusion of Bu at a first dose of 120 mg/m(2) (age >= 1 year) or 80 mg/m(2) (< 1 year), or BUPO 1 mg/kg 4 times daily. Both regimens were continued for 4 days. The target area under the curve (AUC) was defined as 17,500 mu g*h/1. BUdtIV resulted in higher event-free survival (EFS) and survival rates compared to BUPO (EFS: 30% versus 83 %, P