Pharmacogenomics in allogeneic hematopoietic stem cell transplantation: Implications on supportive therapies and conditioning regimens

Allogeneic HSCT mortality has declined substantially largely due to improvements in managing post-transplant complications, including graft versus host disease (GVHD), infections, and treatment-related toxicities [1,2]. Nonetheless, non-relapse mortality at one year remains ∼10% and quality of life (QOL) is significantly impaired in those experiencing post-HSCT complications [1,2]. Personalized approaches to pharmacotherapy management during and post-HSCT may improve such outcomes.

Pharmacogenomics (PGx) is the study of the impact of inherited genetic differences on drug pharmacokinetics (PK), pharmacodynamics (PD), and/or response [3]. Approximately 90–95% of patients carry at least one clinically actionable genotype affecting drug response [4]. PGx results can help guide drug and dose selection for dozens of medications commonly used to manage cancer- and treatment-related symptoms including anxiety/depression, nausea, and pain, which are commonly experienced throughout HSCT. The U.S. Food and Drug Administration (FDA) developed the Table of Pharmacogenetic Associations, which lists drug-gene interactions for which data support therapeutic management recommendations [5]. The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes peer-reviewed, evidence-based clinical guidelines on how to translate PGx results into actionable prescribing decisions [6]. Phenotypes of drug-metabolizing enzymes are categorized into 5 groups based on the combined function of alleles: ultrarapid metabolizer (UM), rapid metabolizer (RM), normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM) [7]. For allogeneic HSCT, specimens for PGx testing should be collected prior to HSCT to avoid contamination of the donor's DNA (Fig. 1). This review summarizes clinical applications of PGx in allogeneic HSCT, with a focus on antifungals, immunosuppressants, and supportive care management (Table 1). Further, we highlight emerging evidence for use of PGx in conditioning regimens. Hematologists can utilize this information to reduce adverse drug events, optimize treatment outcomes, and improve patient QOL post-HSCT.

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