Pharmacogenomic Study of Adverse Reactions in Children with Acute Lymphoblastic Leukemia after High-dose Chemotherapy with Methotrexate
نویسندگان
1 Pediatric Hematology and Oncoloy Department, Northwest Women's and Chil-dren's Hospital, Xi'an, 710000, China
2 Department of Pediatric Medicine, Baoji Maternal and Child Health Hospital, Baoji, 721006, China
3 Neonatal Intensive Care Department, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, 710000, China
doi
10.22034/ircmj.2025.463456.1246چکیده
Background and Objectives: Methotrexate (MTX) is essential for treating Acute Lymphoblastic Leukemia (ALL), but few studies have explored the gene polymorphisms affecting drug metabolism in children with ALL. This research aims to examine these adverse reactions and related genetic variations. Methods: Bone marrow samples were collected from 375 children with ALL before chemotherapy. Polymerase Chain Reaction (PCR) was used to determine the mutation of drug genes, and the occurrence of adverse reactions after chemotherapy was collected. Results: The incidence of bone marrow suppression was 88.00%, gastrointestinal reaction was 16.00% and liver damage was 14.00%. The gene mutations of adenosine triphosphate (ATP) binding cassette subfamily B member 1 (ABCB1) and AT-rich interaction domain-containing protein 5B (ARID5B) were related to bone marrow suppression in children. The mutations genes of ABCB1, ARID5B and ATP binding cassette subfamily G member 2 (ABCG2) were associated with delayed excretion in children. Mutations genes of solute carrier family 19 (folate transporter), member 1 (SLC19A1), ABCB1 and Retinoblastoma 1 (RB1) were associated with gastrointestinal reactions. Mutations genes of ABCB2 and 5,10-methylenetetrahydrofolate reductase (MTHFR) were concerned with liver damage. Conclusion: Individualized treatment strategies may reduce adverse reactions and provide guidance for optimizing the treatment of children with ALL.
