Salvaris Ross, Salman Sam, O'Halloran Sean, Joyce David, Mathew Navin, Cooney Julian, Wright Matthew, Cannell Paul, Purtill Duncan
Department of Haematology, Fiona Stanley Hospital, Western Australia, Australia.
Medical School, University of Western Australia, Western Australia, Australia.
Blood Cell Ther. 2022 Apr 22;5(2):61-68. doi: 10.31547/bct-2021-019. eCollection 2022 May 25.
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.
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.
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.
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.
口服白消安和静脉注射环磷酰胺（Bu/Cy）是异基因造血干细胞移植（HSCT）中常用的清髓性预处理方案。在此，我们研究了HSCT期间给予（Bu/Cy）的安全性。
回顾性分析2007年至2017年期间在皇家珀斯医院和菲奥娜·斯坦利医院接受Bu/Cy进行异基因HSCT的患者，以纳入本研究。我们对一部分患者进行了白消安药代动力学（PK）检测，并进行了异速生长比例模型分析，以评估体重极端患者白消安给药的最佳方法。
69例患者纳入临床结局分析。中位随访期为32个月（范围9 - 114个月）。三年总生存率为62%（95%置信区间（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较低。此外，3年时复发率为38%（95% CI，30% - 44%）。15例接受白消安口服给药患者的PK信息可用。每剂白消安平均暴露量为1350μmol·min/L（范围878 - 1717μmol·min/L），73%的患者在目标范围内（1000 - 1500μmol·min/L）。在所研究的体型测量指标中，理想体重和调整体重（ABW40）拟合最佳。未观察到白消安暴露、毒性和复发之间的关联。
总体而言，根据体重给药时，Bu/Cy给药似乎是安全的，在大多数情况下，白消安充分暴露后早期移植相关死亡率较低。体型测量指标，如理想体重或ABW40，可能更适合在白消安给药期间使用，特别是在体重指数分类的极端情况下。
