Correlation among poor prognostic indicators in B-cell chronic lymphocytic leukemia (B-CLL). A.W. Block1, P.K. Wallace2, K.C. Miller3, M.S. Czuczman3, A.A. Chanan-Khan3, S. Padmanabhan3. 1) Clinical Cytogenetics Laboratory, Roswell Park Cancer Institute, Buffalo, NY; 2) Laboratory of Flow Cytometry, Roswell Park Cancer Institute, Buffalo, NY; 3) Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.
B-CLL, the most common leukemia in adults, is a malignant disorder characterized by progressive accumulation of functionally incompetent B-lymphocytes. Clinical staging systems are of prognostic importance, but cannot predict outcome of individual patients in early clinical stages. Factors that are independent predictors of disease progression and outcome in B-CLL include genomic aberrations and somatic mutation status in the expressed immunoglobulin heavy chain variable region (IgVH). Using a FISH panel that identified specific numerical and structural abnormalities (+12, del(13q), del(11q), del(17p), 14q32 abn) and ZAP-70 (70-kD zeta-associated protein, a surrogate for mutation status) expression assessed by flow cytometry, we studied peripheral blood and bone marrow from 37 unselected B-CLL patients (pts) to investigate the concordance of high-risk markers in these pts. 20/37 (54.1%) pts (10 males, 10 females; median age 62, range 49-85 yrs) showed ZAP-70 expression in less than 20% of cells (mutated status), and were considered ZAP-70 negative. Genomic aberrations were detected in 12/20 (60%) pts with del(13q) in 9/12 (75%) pts. High risk (del 11q and 17p) features were seen in 3/12 (25%) abn cases. 17/37 (45.9%) pts (12 males, 5 females; median age 69, range 42-85 yrs) exhibited ZAP-70 expression in 20% of cells and were considered ZAP-70 positive (non-mutated status). Genomic aberrations were detected in 14/17 (82%) pts with high risk deletions observed in 5/14 (35.7%) abn cases. To develop risk-adapted strategies, prognostic factors are needed to allow the prediction of individual patient clinical course. In this study, poor risk patients were defined by advanced clinical stage, increased age, male predominance, non-mutated status and high risk cytogenetic aberrations.