PHENOTYPIC PROFILE AND CHANGE IN CEREBROSPINAL FLUID EBV-DNA BURDEN DURING THERAPY AS PROGNOSTIC FACTORS IN AIDS-RELATED PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA.

Abstract

103 Background: Infection by Epstein-Barr virus (EBV) occurs in almost all AIDS-related Primary Central Nervous System Lymphomas (PCNSL) and the detection of EBV-DNA in cerebrospinal fluid (CSF) is a tumor marker for a non-invasive diagnostic approach. No data have been reported on the value of PCNSL immunophenotypic characterization and of EBV-DNA burden in CSF for monitoring response to treatment. Methods: During a 2-year period 8 consecutive HIV patients with biopsy-proven PCNSL received a multimodal therapeutic scheme with high dose intravenous methotrexate, oral procarbazine, and intrathecal methotrexate followed by whole-brain radiotherapy to 30 Gy. All cases were monoclonal B-cell expansion and were investigated for protein expression of the BCL-6 proto-oncogene and the EBV-encoded LMP-1 antigen. A semiquantitative estimation of EBV-DNA was performed by PCR (detection limit: 1000 EBV/ml) at baseline and during CT follow-up. Results: CD4+, histology, BCL-6 and LMP-1 expression, viral load in CSF, response to therapy are in table.No caption available. Responder patients were BCL-6+/LMP-1− with mean value of EBV-DNA load of 4.85 log10 copies/ml at baseline and 3.50 log10 copies/ml after therapy (difference between means 1.35 log10;p=0.022). Progressed patients were BCL-6−/LMP-1+ with mean value of 3.43 and 4.53 log10/ml, respectively (difference between means 1.10:p=0.031). Stable patients were BCL-6+/LMP-1+ or BCL-6−/LMP-1+ with mean values of 4.10 and 4.43 log10/ml respectively (difference between means 0.33;p=0.60). Median survival was 243 days in patients with a viral load reduction and 121 days in those whitout reduction. The 6 months probability of survival was 0.67 and 0.20 respectively (p at Mantel-Cox=0.048). Conclusions: The results of the study suggest a prognostic value of the phenotypic profile and of the change in EBV-DNA burden in CSF of patients with AIDS-PCNSL. Phenotypic characterization and monitoring of EBV-DNA burden may serve to identify subgroups of AIDS-related PCNSL with different clinical evolution and could represent a useful tool for predicting response in treated patients and to segregate AIDS-related PCNSL into different biologic and prognostic categories.