Factors Influencing the Response to High Dose Methotrexate-based Vincristine and Procarbazine Combination Chemotherapy for Primary Central Nervous System Lymphoma

The authors investigated objective response rate to high dose methotrexate (HDMTX)-based combination chemotherapy in primary central nervous system lymphoma (PCNSL), and sought to identify factors that influence response to HDMTX-based combination therapy. Prospective observational analysis was performed on 52 PCNSL patients. All patients received HDMTX (3.5 g/m(2)) and vincristine (1.4 mg/m(2)/day) for one day during weeks 1, 3, 5, 7, and 9, and procarbazine (100 mg/m(2)/day) for one week during weeks 1, 5, and 9. Forty-one patients (78.8%) achieved complete or partial remission. Higher objective response rates were observed for patients with: 1) age < 60 yr; 2) Eastern Cooperative Oncology Group (ECOG) performance score of < 2; 3) low risk status as defined by the International Extranodal Lymphoma Study Group; 4) p53 positivity; 5) XBP-1 negativity; 6) MUM-1 negativity; and 7) homogenous gadolinium enhancement in MR images. Multivariate analysis showed that ECOG performance score of < 2, low risk, negativity for XBP-1, homogenous gadolinium enhancement by MRI, and response to chemotherapy were associated with longer overall survival. In particular, it is interesting to note that patients with a PCNSL that is homogeneously enhanced by gadolinium have a higher objective response rate, and a longer progression-free survival and overall survival.