Al-Riyami Intisar, Al-Khabori Murtadha, Al Balushi Khalid, Al-Zadjali Shoaib, Al-Rawahi Mohammed, Dennison David, Al-Hunaini Mohammed, Al-Rawas Abdulhakeem, Al-Moundhri Mansour
Clinical Pharmacy, Pharmacy Department, Sultan Qaboos University Hospital, Muscat, Oman.
Department of Hematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Ther Drug Monit. 2022 Aug 1;44(4):527-534. doi: 10.1097/FTD.0000000000000957.
Busulfan (Bu) is an alkylating drug used in many preparative regimens before hematopoietic stem cell transplantation (HSCT). It is conjugated in the liver mainly by glutathione S-transferase isoenzyme A1-1 ( GSTA1 ). Genetic polymorphisms in these isoenzymes may affect the pharmacokinetics of Bu and the clinical outcomes of HSCT. This study aimed to assess the impact of glutathione S-transferase ( GST ) genetic polymorphisms on the clearance of Bu and the clinical outcomes of patients undergoing HSCT.
This single-center retrospective study included patients who received IV Bu before HSCT at Sultan Qaboos University Hospital (SQUH), Oman from January 2003 to October 2016. Genotyping for polymorphisms was performed for GSTM1 , GSTT1 , GSTA1 , and GSTP1 . Each GST polymorphism was analyzed for its impact on Bu clearance and HSCT outcomes.
A total of 135 patients were included. The mean Bu clearance was 3.7 ± 0.98 mL/min/kg. Patients with GSTA1 A-513G heterozygosity (AG) were found to have a higher incidence of graft loss ( P = 0.006). Homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft versus host disease ( P = 0.04). Double non-null GSTM1 and GSTT1 and non-null GSTM1 increased the risk of mortality ( P = 0.034 and 0.021, respectively).
GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.
白消安（Bu）是一种烷化剂药物，用于造血干细胞移植（HSCT）前的多种预处理方案。它主要在肝脏中通过谷胱甘肽S-转移酶同工酶A1-1（GSTA1）进行共轭。这些同工酶的基因多态性可能会影响白消安的药代动力学以及HSCT的临床结局。本研究旨在评估谷胱甘肽S-转移酶（GST）基因多态性对白消安清除率及接受HSCT患者临床结局的影响。
这项单中心回顾性研究纳入了2003年1月至2016年10月在阿曼苏丹卡布斯大学医院（SQUH）接受HSCT前静脉注射白消安的患者。对GSTM1、GSTT1、GSTA1和GSTP1进行基因多态性基因分型。分析每种GST多态性对白消安清除率和HSCT结局的影响。
共纳入135例患者。白消安的平均清除率为3.7±0.98 mL/（min·kg）。发现GSTA1 A-513G杂合子（AG）患者的移植物丢失发生率较高（P = 0.006）。GSTM1和GSTT1纯合双缺失与急性移植物抗宿主病的发生率较高相关（P = 0.04）。GSTM1和GSTT1双非缺失以及GSTM1非缺失增加了死亡风险（分别为P = 0.034和0.021）。
HSCT前的GST基因分型可能预测HSCT结局。这项初步回顾性研究的结果需要在更大规模的前瞻性研究中得到证实。
