PHARMACOGENETIC MARKERS IN PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA THERAPY.

Abstract

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Despite major advances in therapy, the treatment of ALL remains a significant challenge. Therapeutic protocols are based on the use of combinations of chemotherapeutic drugs. While such combinations increase treatment efficacy, they also complicate the assessment of toxicity. It should be noted that the variability in the occurrence of toxic responses to ALL therapy in children may be determined by the presence of gene variants that influence both the pharmacokinetics and pharmacodynamics of chemotherapeutic drugs. This review summarized and analyzed the most significant and well-studied pharmacogenetic markers to date associated with the toxicity and response to chemotherapeutic agents used in the treatment of pediatric ALL. In particular, pharmacogenetic markers for the following drugs were analyzed: anthracyclines (doxorubicin, daunorubicin), vincristine, glucocorticoids (prednisone, dexamethasone), L-asparaginase, methotrexate, alkylating agents (cyclophosphamide, ifosfamide), 6-mercaptopurine, cytarabine, and etoposide. At present, only a few genes, TPMT and NUDT15, have well-established clinical utility, whereas the clinical relevance of pharmacogenetic markers for other drugs used in pediatric ALL therapy remains under investigation. The review also highlights the main knowledge gaps in current research and outlines promising directions for future studies aimed at integrating pharmacogenetic testing into clinical practice for personalized treatment of ALL.