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.
Costea
Irina
I
Research Center of the CHU Sainte-Justine, Montréal, Québec, Canada.
Moghrabi
Albert
A
Laverdiere
Caroline
C
Graziani
Alexandru
A
Krajinovic
Maja
M
D002648:Child; D018572:Disease-Free Survival; D005492:Folic Acid / Q000235:genetics / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000627:therapeutic use* / Q000633:toxicity; D006402:Hematologic Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008727:Methotrexate / Q000627:therapeutic use* / Q000633:toxicity; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*
D005493:Folic Acid Antagonists; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate