Pharmacogenetic Determinants of Methotrexate-Induced Toxicities in Pediatric Acute Lymphoblastic Leukemia: A Systematic Review

Abstract Methotrexate (MTX) is a crucial chemotherapy drug often associated with various adverse effects. Predicting the frequency and severity of these side effects poses a challenge, as they can vary significantly among individuals. This study aims to examine previous research that identifies genetic differences linked to MTX-induced toxicities. We conducted a systematic review using PubMed and Scopus. The principal findings of this study encompass the study design, patient demographics, sample size, chemotherapy regimens employed, pharmacokinetic variables identified, genetic polymorphisms, and the genetic associations of MTX-induced toxicities in children with acute lymphoblastic leukemia. The qualitative synthesis included 15 publications, which indicated that the SLCO1B1, ABCB1, ABCC2, and MTHFR genes significantly influence the metabolism and elimination of MTX. Variants in the SLCO1B1 gene have a pronounced and consistent impact on the rate at which MTX is cleared from the body. A strong correlation was observed between blood MTX levels and the associated toxicity experienced by patients. Understanding the relationship between genetic variants may facilitate the tailoring of MTX dosing to individual patients' well-being, enhancing both accuracy and effectiveness in health care.