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. 2022 Aug 1;44(4):527-534.
doi: 10.1097/FTD.0000000000000957.

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation

Intisar Al-Riyami  1 , Murtadha Al-Khabori  2 , Khalid Al Balushi  3 , Shoaib Al-Zadjali  4 , Mohammed Al-Rawahi  5 , David Dennison  2 , Mohammed Al-Hunaini  2 , Abdulhakeem Al-Rawas  6 , Mansour Al-Moundhri  1
Affiliations

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation

Intisar Al-Riyami et al. Ther Drug Monit. .

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.

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Conflict of interest statement

The authors declare no conflict of interest.

References

    1. McCune JS, Holmberg LA. Busulfan in hematopoietic stem cell transplant setting. Expert Opin Drug Metab Toxicol. 2009;5:957–969.
    1. Schiltmeyer B, Klingebiel T, Schwab M, et al. Population pharmacokinetics of oral busulfan in children. Cancer Chemother Pharmacol. 2003;52:209–216.
    1. Galaup A, Paci A. Pharmacology of dimethanesulfonate alkylating agents: busulfan and treosulfan. Expert Opin Drug Metab Toxicol. 2013;9:333–347.
    1. Ten Brink MH, van Bavel T, Swen JJ, et al. Effect of genetic variants GSTA1 and CYP39A1 and age on busulfan clearance in pediatric patients undergoing hematopoietic stem cell transplantation. Pharmacogenomics. 2013;14:1683–1690.
    1. Ansari M, Huezo-Diaz P, Rezgui MA, et al. Influence of glutathione S-transferase gene polymorphisms on busulfan pharmacokinetics and outcome of hematopoietic stem-cell transplantation in thalassemia pediatric patients. Bone Marrow Transpl. 2016;51:377–383.

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