Evaluating the Efficacy, Toxicity and Pharmacokinetic Profile of Oral Busulfan in Allogeneic Stem Cell Transplant Patients.

Ross Salvaris, Sam Salman, Sean O'Halloran, David Joyce, Navin Mathew, Julian Cooney, Matthew Wright, Paul Cannell, Duncan Purtill
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Abstract

Background: Oral busulfan and intravenous cyclophosphamide (Bu/Cy) are common myeloablative preparations used in allogeneic hematopoietic stem cell transplantation (HSCT). Herein, we investigated the safety of (Bu/Cy) administration during HSCT.

Methods: Patients administered Bu/Cy for allogeneic HSCT at Royal Perth Hospital and Fiona Stanley Hospital between 2007 and 2017 were reviewed for inclusion in the study. We performed busulfan pharmacokinetic (PK) testing for a subset of patients and allometric scaling modeling to assess the best method of busulfan dosing in patients at extremes of weight.

Results: Sixty-nine patients were included in the clinical outcome analysis. The median follow-up period was 32 months (range, 9-114 months). The three-year overall survival rate was 62% (95% confidence interval (CI), 51%-75%), and transplant-related mortality was 4% at 6 months (95% CI, 1-7%), with a low rate of sinusoidal obstruction syndrome of the liver being observed. In addition, relapse was 38% (95% CI, 30%-44%) at 3 years. The PK information of 15 patients receiving busulfan was available after oral dosing. The average per-dose busulfan exposure was 1,350 μmol.min/L (range, 878-1,717 μmol.min/L), and the within target range was 1,000-1,500 μmol.min/L in 73% of patients. Of the size measures investigated, ideal and adjusted body weight (ABW40) provided the best fit. No association was observed between busulfan exposure, toxicity, and relapse.

Conclusions: Overall, Bu/Cy administration appeared safe when dosed in relation to weight, showing a low early transplant-related mortality rate following adequate busulfan exposure in majority of the cases. Body size measures, such as ideal body weight or ABW40, are likely more suitable for use during busulfan dosing, particularly at high extremes of the body mass index classification.

Abstract Image

Abstract Image

评估异体干细胞移植患者口服布苏凡的疗效、毒性和药代动力学特征。
背景:口服丁硫凡和静脉注射环磷酰胺(Bu/Cy)是同种异体造血干细胞移植(HSCT)中常用的清髓制剂。在此,我们研究了HSCT期间(Bu/Cy)给药的安全性。方法:回顾2007年至2017年在皇家珀斯医院和菲奥娜斯坦利医院接受Bu/Cy治疗的同种异体造血干细胞移植患者。我们对一部分患者进行了busulan药代动力学(PK)测试,并进行了异速缩放模型,以评估在极端体重情况下患者给药busulan的最佳方法。结果:69例患者纳入临床结局分析。中位随访时间为32个月(范围9-114个月)。3年总生存率为62%(95%可信区间(CI), 51%-75%), 6个月时移植相关死亡率为4% (95% CI, 1-7%),观察到肝窦阻塞综合征发生率低。此外,3年复发率为38% (95% CI, 30%-44%)。15例患者口服给药后可获得丁硫凡的PK信息。平均每剂量暴露量为1350 μmol。min/L范围为878 ~ 1717 μmol.min/L,目标范围为1000 ~ 1500 μmol。73%的患者为min/L。在所调查的尺寸测量中,理想体重和调整体重(ABW40)最适合。未观察到布硫丹暴露、毒性和复发之间的关联。结论:总体而言,当剂量与体重相关时,Bu/Cy给药似乎是安全的,在大多数病例中,暴露于足够的丁硫丹后,早期移植相关死亡率较低。体型测量,如理想体重或ABW40,可能更适合在给药期间使用,特别是在身体质量指数分类的高极值时。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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