title: Effects of methylenetetrahydrofolate reductase gene polymorphisms on toxicities during consolidation therapy in pediatric acute lymphoblastic leukemia in a Chinese population.
abstract: This study aimed to investigate whether there was a correlation between the genotype or haplotype of the methylenetetrahydrofolate reductase gene (MTHFR) and toxicities during consolidation therapy or plasma methotrexate (MTX) levels at 48 h after the first dose of MTX infusion. We retrospectively genotyped 181 children with newly diagnosed acute lymphoblastic leukemia (ALL) who were treated with the Chinese Children's Leukemia Group protocol. In standard- and medium-risk treatment branches, the 677T carriers (CT + TT) had a higher risk of developing thrombocytopenia when compared with carriers of the CC genotype (odds ratio [OR] 5.21, 95% confidence interval [CI] 1.18-23.01, p = 0.017). The 1298AC/CC genotypes were associated with a decrease in skin toxicity, as compared with the common AA genotype (p = 0.037). An estimation of haplotype frequencies showed that there was no 677T-1298C haplotype in the population. A lower frequency of anemia (OR 0.44, 95% CI 0.21-0.90, p = 0.025) and lower MTX level (p = 0.044) were observed in patients with the 677C-1298C haplotype than in those without. High plasma MTX level was correlated with anemia (p = 0.011) and neutropenia (p = 0.044). In the high-risk group, the polymorphisms or plasma MTX levels were not correlated with any toxicity. Taken together, our data demonstrate that genotyping of MTHFR and measurement of plasma MTX levels might be useful to optimize MTX therapy.
authors.affiliation: Hematological Center, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, China.
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Liu
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.forename: Wei-Jing
authors.initials: WJ
authors.lastname: Li
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009503:Neutropenia / Q000139:chemically induced; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D012189:Retrospective Studies; D012871:Skin Diseases / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D015122:Mercaptopurine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate