Ml-03 reconsideration of treatment for elderly patients with primary central nerve system lymphomas

Abstract BACKGROUND The therapeutic response to high-dose methotrexate therapy (HD-MTX) for primary central nervous system lymphoma (PCNSL) varies. Polyglutamylation (PG) is a reversible protein modification, tumor cells show frequent occurrence of PG. Intracellularly polyglutamylated MTX is not subject to competitive inhibition by leucovorin (LV). Tumor cells with high PG levels are selectively killed, whereas normal cells with lower PG are rescued by LV. We previously reported that PG is a predictor of therapeutic response to HD-MTX in PCNSL. However, PG did not affect overall survival (OS) in the elderly unlike the young patients, suggesting that there are other significant predictors in the elderly. The aim of this study is to identify the prognostic factors in aged PCNSL. METHODS The prognostic factors were investigated in 48 patients (M/F=23/25) aged 65 and older undergoing HD-MTX in our institute with data of area under the concentration-time curve of MTX, AUCMTX (μmol/L/h). RESULTS The median OS of elderly PCNSL was 937days. In the AUCMTX high group (median 1706.3 or more, n=24) and the low group (median below, n=24), OS was significantly shortened in the high group compared with the low group (median 728 vs 1290days, p=0.032). Even in multivariate analysis, AUC was the only independent poor prognostic factor of OS (p=0.031). On the other hand, AUC was not a prognostic factor for OS in PCNSL younger than 65 years. AUCMTX of aged PCNSL was significantly higher compared with younger patients (p<0.01). These results suggested that PG may be a good prognostic factor of OS when AUCMTX is low. CONCLUSION In the aged PCNSL, OS was shortened when AUCMTX was high. With the results of the previous research, it is suggested that if PG levels is high in elderly PCNSL, the OS prolongation can be expected if the MTX dose is reduced.