The influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in children with non-Hodgkin malignant lymphoma
We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in pediatric patients with T-cell non-Hodgkin lymphoma (NHL). In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms. 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 leukopenia (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. Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTX-related toxicity in children with NHL.