Functional polymorphic variants of methionine metabolism influence neurotoxicity and survival in primary central nervous system lymphoma (PCNSL) treated with high-dose methotrexate

8579 Background: Methotrexate (MTX) is the most efficient chemotherapeutic drug in primary central nervous system lymphoma (PCNSL); it directly interferes with methionine metabolism. Patients and Methods: Eight functional polymorphic variants influencing methionine metabolism were investigated in 65 PCNSL patients and were analyzed for their impact on the occurrence of confluent CNS white matter changes (WMC) (Pearson’s Chi-square test and multinominal regression analysis) and for their influence on survival (univariate Log Rank and multivariate COX regression analyses). Results: Twenty/65 (31%) patients developed WMC, which was significantly predicted by the genotype of methylenetetrahydrofolate reductase c.1298A>C (p.E429A; patients with WMC, AA/AC/CC: 0.80/0.10/0.10; patients without WMC: 0.40/0.47/0.13; nominal logistic regression: χ2=11.54; p=0.003). In addition, the transcobalamin 2 variant c.776C>G (p.P259R) influenced the occurrence of WMC (patients with WMC: 0.20/0.45/0.35; patients without WMC: ...