Primary Central Nervous System Lymphoma (PCNSL) in Immunocompetent Patients: An Analysis of Prognostic Factors and Treatment Strategies

The incidence of primary CNS lymphoma in immunocompetent patients is increasing for unknown reasons. Survival estimates from academic centers show an improvement in overall survival (OS) while community epidemiological data estimate minimal difference in OS in the last thirty years. Age greater than 60, poor performance status, elevated initial LDH, high CSF protein and involvement of deep regions of the brain have been associated with worse survival. Optimal dosing strategies and delivery of chemotherapy as well as the role of radiation therapy (RT) have yet to be clearly defined given the limitations of treatment related toxicity in patients achieving remissions.

To characterize the PCNSL patient population treated at a single institution by studying prognostic factors and assessing OS according to treatment strategies.

45 cases of confirmed CNS Lymphoma diagnosed at Rush University Medical Center between January 2000 and November 2010 were studied. Demographic, clinical and treatment data were collected and reviewed. Hospital records and the Social Security Death Index were used to determine death dates. Survival data were compared based on treatment groups.

23 of the 45 cases met all inclusion criteria and had no evidence of previous systemic lymphoma or pre-morbid immunocompromised conditions (i.e. HIV). The age range at diagnosis was from 21 to 81 years old with a median age of 68. One patient had ocular involvement. Three patients had malignant cells in the CSF at diagnosis and 4 patients had multifocal tumors. Biopsies revealed one case of a cerebral T-cell lymphoma and 22 were diffuse large B-cell lymphoma (DLBCL). Elevated CSF protein above the mean (96.1 mg/dl) was associated with worse OS (p=0.02). Elevated LDH above the mean (227 U/L) was associated with worse OS (p= 0.039). Age, performance status and location of tumor within the brain (deep vs. superficial) did not correlate with survival patterns. Comparative survival analysis between treatment groups revealed no statistically significant difference (p=0.134). In addition to systemic chemotherapy, 15 patients received intrathecal chemotherapy

The description of PCNSL in immunocompetent patients outside of the clinical-trial setting is necessary to inform prospective trial designs. This study supports the use of LDH and CSF protein in determining prognosis and treatment strategy. This analysis of conventional treatment is ongoing. Collaboration on gathering descriptive data for PCNSL in immunocompetent patients should be pursued.

Gregory:Genentech:.