Novel genomic variants influencing methotrexate delayed clearance in pediatric patients with acute lymphoblastic leukemia.

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

SUBMITTER: Choi JY 

PROVIDER: S-EPMC11603417 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature