title: MTHFR polymorphisms' influence on outcome and toxicity in acute lymphoblastic leukemia patients.
abstract: Recently the influence of polymorphisms of different genes involved in metabolism of chemoterapic agents have been studied especially in childhood acute lymphoblastic leukemia (ALL). We evaluated the influence of C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms on time to relapse and survival and on methotrexate (MTX) toxicity in 82 ALL adult patients. Relapse free survival and event free survival between homozygous wild-type and variant patients in both polymorphisms were not significantly different. However, we observed an association between 677TT variant and survival in a subset of ALL patients homogenously treated with MTX-based maintenance (p=0.02). In the same subgroup we confirmed the role of 677TT variant on toxicity during MTX treatment (p=0.003).
authors.affiliation: Hematology Department, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy. p.chiosolo@rm.unicatt.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Chiusolo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Reddiconto
authors.forename: Giuliana
authors.initials: G
authors.lastname: Farina
authors.forename: Alice
authors.initials: A
authors.lastname: Mannocci
authors.forename: Alessia
authors.initials: A
authors.lastname: Fiorini
authors.forename: Mariangela
authors.initials: M
authors.lastname: Palladino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Torre
authors.forename: Luana
authors.initials: L
authors.lastname: Fianchi
authors.forename: Federica
authors.initials: F
authors.lastname: Sorà
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leone
authors.forename: Simona
authors.initials: S
authors.lastname: Sica
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D012008:Recurrence; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate