Pharmacogenetic Profiling of Allogeneic Stem Cell Transplantation Patients: An Exploratory Descriptive Study
Background/Objectives: Patients receiving allogeneic hematopoietic stem cell transplantation (alloHCT) for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are at high risk for severe disease and treatment-related complications and toxicities. Pharmacogenetic studies suggest that genetic variants can alter the response to several drugs critical to alloHCT outcomes, including tacrolimus and cyclophosphamide, potentially impacting toxicity and treatment outcomes. Methods: To assess the frequency of pharmacogenetic variants in AML/ALL patients undergoing alloHCT, we used a validated 11-gene pharmacogenetic panel in an exploratory descriptive study. We retrospectively genotyped 142 AML/ALL patients including two atypical chronic myeloid leukemia (aCML) patients, ≥18 years, who underwent alloHCT at our center between January 2020 and June 2024. Results obtained from 470 individuals in the Lifelines NEXT population cohort were used as controls. Results: Almost all patients carried at least one pharmacogenetic variant (97.2%), with a mean of 3.2 (standard deviation = 1.5) variants per patient. Variants known to influence tacrolimus metabolism (CYP3A4 and CYP3A5) were present in 26.8% of patients. Variants known to influence cyclophosphamide metabolism (CYP2B6, CYP2C9, CYP2C19) were present in 81.7% of patients. Variant frequencies did not significantly differ from controls. Conclusions: Actionable pharmacogenetic variants are highly prevalent in alloHCT-recipients. Future studies should investigate whether genotype-guided drug selection and dosing could improve outcomes in alloHCT recipients.