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The influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in children with non-Hodgkin malignant lymphoma |
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| Authors: | Nina Erculj Barbara Faganel Kotnik Marusa Debeljak Janez Jazbec Vita Dolzan |
| Institution: | 1. Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia;2. Department of Hematology and Oncology, University Children’s Hospital, University Medical Centre, Ljubljana, Slovenia;3. Centre for Medical Genetics, University Children’s Hospital, University Medical Centre, Ljubljana, Slovenia |
| Abstract: | BackgroundWe 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).Patients and methodsIn total, 30 NHL patients were genotyped for selected folate pathway polymorphisms.ResultsCarriers 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.ConclusionsOur results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTX-related toxicity in children with NHL. |
| Keywords: | childhood non-Hodgkin lymphoma folate pathway polymorphism high-dose methotrexate toxicity |