ArticleFrontiers in pharmacology2024
Novel genomic variants influencing methotrexate delayed clearance in pediatric patients with acute lymphoblastic leukemia.
Article in Frontiers in pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Phenotype-Specific Pharmacogenetic Patterns of Methotrexate Neurotoxicity in Pediatric Acute Lymphoblastic Leukemia.Journal of clinical medicine · 2026Article
- The role of pharmacogenetics in the therapy regimen of acute lymphoblastic leukemia in children: recent discoveries and future perspectives.Pharmacological reports : PR · 2026Review
- Population Pharmacokinetics and Covariate Analysis of Methotrexate in Pediatric Acute Lymphoblastic Leukemia.Drug design, development and therapy · 2025Article
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Authors and funding
12 authors.
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Abstract
Background: Methotrexate (MTX) is the primary drug used in the treatment of pediatric acute lymphoblastic leukemia (ALL). However, some patients exhibit delayed clearance of high-dose (HD) MTX, which induces severe nephrotoxicity, mucositis, hepatotoxicity, and neurotoxicity. We sought to identify relevant variants associated with delayed clearance of HD-MTX in pediatric patients with ALL. Methods: Whole-exome sequencing of germline DNA was performed in 51 Korean pediatric patients with ALL. A total of 341 HD-MTX infusion data points from 51 patients were analyzed. MTX levels and laboratory measurements reflecting toxicity outcomes were obtained. Correlations between peak serum MTX levels at 24 h and toxicity outcomes were assessed. Analyses were performed to identify variants affecting delayed MTX clearance. Results: The 24 h MTX level strongly correlated with the subsequent creatinine (Cr) level. Moreover, rs2229866 in Conclusion: This is the first whole-exome sequencing-based analysis of delayed MTX clearance in pediatric patients with ALL.
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