Influence of MTHFR C677T and A1298C polymorphisms on the survival of pediatric patients with non-Hodgkin lymphoma

Objective: We investigated the influence of methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms on the survival of pediatric non-Hodgkin lymphoma (NHL) cases in south China treated with the modified Berlin-Frankfurt-Munster 95 protocol. Methods: We reviewed the medical records of 374 patients newly diagnosed at our center between 2014 and 2020. A subgroup of 158 patients was genotyped based on polymorphisms C677T and A1298C. Results: Overall, there were 283 male (75.7%) and 91 female patients (24.3%); the median age was 9 years (range, 1–18 years). The tumor types included Burkitt lymphoma (BL; n = 180), lymphoblastic lymphoma (LBL; n = 95), anaplastic large cell lymphoma (ALCL; n = 64), and diffuse large B cell lymphoma (DLBCL; n = 35). At diagnosis, 327 patients (87.4%) had advanced-stage disease; 159 (42.5%) and 152 patients (40.6%) were stratified into the intermediate- and high-risk group, respectively. Seventy (18.7%) and 36 cases (9.6%) had bone marrow and central nervous system (CNS) involvement, respectively. The median follow-up time was 28.5 months (range, 1–76 months); complete remission rate, estimated 5-year event-free survival, and 5-year overall survival rate was 86.1%, 74.2%, and 85.7%, respectively. The C677T variant allele was correlated with favorable survival in BL/DLBCL, while ALCL, CNS involvement, advanced stage, and intermediate/high risk were associated with poor survival in NHL. Conclusion: Analysis of the C677T polymorphism could be used for survival prediction and potential risk stratification for further treatment protocols for Chinese pediatric NHL. Further larger studies are needed to verify the clinical value of the C677T polymorphism.