The biology and treatment of chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the progressive accumulation of functionally incompetent, mature looking, monoclonal CD5+, CD23+ B lymphocytes in blood, bone marrow, lymph nodes and spleen/liver. CLL B cells express low levels of surface immunoglobulin (Ig)M, IgD (10% of those on normal B cells), CD21, CD22 and CD79b. Close to 99% of B-CLL lymphocytes in peripheral blood are in the G0 or early G1 phase of the cell cycle [1]. Defects in apoptosis have been associated with the accumulation of leukemic cells and disease progression, and presumably account for much of the chemotherapy-resistance of this disease. However recent data indicate that a relatively high proportion of cells are also dividing [2]. The diagnosis of B-CLL has usually been based on the classical criteria as outlined by the International Workshop on CLL (IWCLL) and the National Cancer Institute (NCI)-working group guidelines; however, current definitive criteria require an absolute blood lymphocytosis of >5 · 10/l consistent with the appearance of small mature looking lymphocytes, with an immunophenotype consistent with that described for B-CLL. The typical immunophenotype required for establishing the diagnosis is based on the identification of CD19+ B cells which also are CD5+, CD23+, FMC7-, and weak or negative for CD22/CD79b and surface Ig [3]. B-CLL is the most common adult leukemia in the Western world and accounts for about 40% of all leukemias in adults over the age of 65 years. The clinical course of B-CLL is heterogeneous. Some patients remain stable for a long time (even for the rest of their lives), without need of therapy, while others progress rapidly to a more advanced disease and die despite aggressive treatment.