The influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in children with non-Hodgkin malignant lymphoma

叶酸代谢途径多态性对高剂量甲氨蝶呤相关毒性和儿童非霍奇金淋巴瘤生存率的影响

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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). PATIENTS AND 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.

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