Folate cycle gene variants and chemotherapy toxicity in pediatric patients with acute lymphoblastic leukemia.

The gene polymorphisms of the methotrexate (MTX) action pathway influence event-free survival (EFS) in children with acute lymphoblastic leukemia (ALL). Here we assessed whether the gene variants associated with lower EFS also correlate with lower rates of episodes of toxicity. Homozygous individuals for cyclin D1 (CCND1) A870 allele and carriers of at least one methylenetetrahydrofolate reductase (MTHFR) T677 variant had a significantly lower frequency of weeks with high-grade hematologic and liver toxicity during consolidation and maintenance treatment, as based on the analysis of 186 pediatric ALL patients. This finding may have importance for MTX dose adjustment.