title: Methylenetetrahydrofolate reductase gene haplotypes affect toxicity during maintenance therapy for childhood acute lymphoblastic leukemia in Japanese patients.
abstract: Abstract The aim of this study was to investigate the influence of daily 6-mercaptopurine (6-MP) and low-dose weekly methotrexate (MTX) combination treatment and methylenetetrahydrofolate reductase (MTHFR) haplotypes on toxicity during maintenance therapy in Japanese childhood acute lymphoblastic leukemia (ALL). We retrospectively analyzed the MTHFR C677T and A1298C polymorphisms and influence of haplotypes on toxicity in 73 patients. Patients with the MTHFR 677TT and 677CT + 1298AC were associated with severe liver toxicity (p = 0.014, odds ratio [OR] = 3.82, 95% confidence interval [CI] = 1.27-11.46) and more rapid onset of liver toxicity (p = 0.010). Patients with MTHFR 677TT and 677CT + 1298AC were associated with lower frequency of 6-MP and MTX dose reduction due to leukopenia (p < 0.05). No difference was observed in average drug doses in the MTHFR genotypes. In conclusion, the MTHFR C677T and A1298C haplotypes might be useful for monitoring adverse effects in childhood ALL maintenance therapy in Japanese patients.
authors.affiliation: Department of Clinical Pharmacy, Center for Clinical Pharmacy and Sciences, School of Pharmacy, Kitasato University , Tokyo , Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.forename: Hisaya
authors.initials: H
authors.lastname: Nakadate
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kondoh
authors.forename: Kozue
authors.initials: K
authors.lastname: Nakamura
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Koh
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Takako
authors.initials: T
authors.lastname: Komiyama
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007564:Japan; D060046:Maintenance Chemotherapy / Q000009:adverse effects*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics; D000097630:Inosine Triphosphatase
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008780:Methyltransferases; D011755:Pyrophosphatases; C022745:thiopurine methyltransferase; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase