title: The influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in children with non-Hodgkin malignant lymphoma.
abstract: BACKGROUND
  We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL).
  
  
  METHODS
  In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms.
  
  
  RESULTS
  Carriers of at least one MTHFR 677T allele had significantly higher MTX area under the time-concentration curve levels at third MTX cycle (P = 0.003). These patients were also at higher odds of leucopoenia (P = 0.006) or thrombocytopenia (P = 0.041) and had higher number of different HD-MTX-related toxicity (P = 0.035) compared to patients with wild-type genotype.
  
  
  CONCLUSIONS
  Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTX-related toxicity in children with NHL.
authors.affiliation: Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Erculj
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Barbara Faganel
authors.initials: BF
authors.lastname: Kotnik
authors.affiliation: Centre for Medical Genetics, University Children's Hospital, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Marusa
authors.initials: M
authors.lastname: Debeljak
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Jazbec
authors.affiliation: Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Vita
authors.initials: V
authors.lastname: Dolzan
keywords: childhood; folate pathway; high-dose methotrexate; non-Hodgkin lymphoma; polymorphism; toxicity