Influence of plasma methotrexate level and MTHFR genotype in Korean paediatric patients with acute lymphoblastic leukaemia. (3rd July 2020)

• Record Type: Journal Article
• Authors: Chae, Hyojin; Kim, Myungshin; Choi, Sun Hee; Kim, Seong-koo; Lee, Jae-Wook; Chung, Nack-Gyun; Cho, Bin; Kim, Yonggoo
• Is Part Of: Journal of chemotherapy. Volume 32:Number 5(2020)
• Page Start: 251
• Page End: 259
• Publication Date: 2020-07-03
• Subjects: Methotrexate -- MTHFR -- Korean pediatric patients -- Acute lymphoblastic leukemia -- Toxicity -- Polymorphism; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; 615.58
• DOI: 10.1080/1120009X.2020.1764280
• Languages: English
• ISSNs: 1120-009X

Abstract

Abstract : Whether plasma MTX concentrations and MTHFR C677T and A1298C polymorphisms could be used as a predictor of occurrence of MTX-related toxicities in Korean paediatric patients with acute lymphoblastic leukaemia (ALL) were assessed. HD-MTX related toxicities, MTHFR polymorphisms and MTX plasma concentrations following 337 HD-MTX cycles to 117 children with ALL on maintenance therapy were analyzed. A significantly higher frequency of hyperbilirubinemia ( P = 0.0443) and renal toxicity ( P = 0.0107) were associated with high MTX concentrations by Fisher's exact test. Moreover, high MTX concentrations at 24 h, 48, and 72 h were significantly associated with increased frequency of vomiting ( P < 0.05) and hyperbilirubinemia ( P < 0.05) by Mann-Whitney U test. There was a significantly higher frequency of mucositis in patients with the MTHFR 677 TT genotype ( P = 0.0273) and a significantly higher frequency of MTX dose reduction in patients with the 677 TT genotype ( P = 0.0217), compared to the CC/CT genotype. Independently, plasma MTX concentrations and MTHFR C677T genotype could be useful markers for tailoring MTX dosing and monitoring adverse effects in childhood ALL HD-MTX therapy in Korean patients.