PB1918: HIGH BAX/BCL-2 RATIO IS ASSOCIATED WITH GOOD PROGNOSIS AND BETTER SURVIVAL IN PATIENTS WITH B CELL CHRONIC LYMPHOCYTIC LEUKEMIA

Abstract

Topic: 5. Chronic lymphocytic leukemia and related disorders - Biology & Translational Research Background: Chronic lymphocytic leukemia (CLL) is a clinically heterogenous disease characterized by the accumulation of mature appearing lymphocytes in the blood, marrow, lymph nodes and spleen. There is considerable heterogeneity in CLL in terms of cellular biology, molecular genetics and prognosis. Bcl-2 family of antiapoptotic (Bcl-2, Bcl-xl, Mcl-1) and proapoptotic (Bax, Bak, BAD) proteins are critical regulators of apoptosis in CLL and its deregulated function is involved in the pathogenesis and progression of CLL. Aims: Determination of Bax/Bcl-2 ratio as a predictive tool to recognize CLL patients’ outcome and prognosis to decide the time and type of therapy. Methods: This prospective study was carried out on 100 patients with newly diagnosed CLL. Bax and Bcl-2 expression in peripheral blood were measured by flow-cytometry. The association of Bax/Bcl-2 ratio with CLL laboratory markers, Rai stage, overall survival (OS) and progression-free survival (PFS) at 18 months was investigated. The sensitivity and specificity of Bax/Bcl-2 in predicting survival was evaluated. Results: The best cut-off value of Bax/Bcl-2 ratio to predict the survival, detected by receiver operating characteristic (ROC) curve, was 1.2 with 80 % sensitivity and 60.86 % specificity. A ratio of ≤1.20 was detected in 78 % of patients and was associated with worse prognosis. A lower Bax/Bcl-2 ratio was associated with higher modified Rai stage at time of diagnosis and a significantly shorter both OS (64.1 % versus 90.9 %, p < 0.026) and PFS (66.7 % versus 90.9 %, p < 0.031) at 18 months. In multivariate analysis, Bax/Bcl-2 ≤ 1.2 was an independent prognostic factor for overall survival, (p = 0.025) Summary/Conclusion: Lower Bax/Bcl-2 ratios were associated with worse prognosis as evidenced by lower OS and PFS in CLL patients. It was also associated with markers of high tumor burden and unfavorable prognostic markers. Recognition of patients with low Bax/Bcl-2 ratio would make them good candidates for the novel Bcl-2 inhibitory targeted chemotherapy to avoid resistance to the traditional therapy.Keywords: B-CLL, Chronic lymphocytic leukemia, Bax, BCL2