Diagnosis of CLL
The diagnosis of CLL requires an absolute lymphocytosis in the peripheral blood, composed of ≥5000 mature appearing lymphocytes/µL.1 Flow cytometry is essential for making the diagnosis of CLL and ruling out other morphologically similar appearing lymphoid malignancies. The typical immunophenotypic signature of CLL is CD5+, CD23+, FMC7-, with weak expression of surface immunoglobulin and CD20.5 A bone marrow biopsy is not required for the diagnosis of CLL; greater than 30% lymphocytes in the bone marrow is consistent with the diagnosis of CLL.
Most patients with CLL will have progressive, symptomatic disease that will require treatment. Once treatment is initiated, the natural history of CLL is initial response to therapy followed by multiple relapses, ultimately culminating in refractory disease and death, most often due to infection. Since no chemotherapy has been shown to be curative for patients with CLL,6 early treatment of asymptomatic patients is not warranted.Although recent advances in identifying molecular and cellular prognostic markers such as ZAP-70 expression,7 CD38 expression,8 mutational status of immunoglobulin heavy chain variable region (IgVH)9 and cytogenetics10 have helped to stratify patients on clinical trials, prospective studies are needed to validate these markers in the setting of modern therapy. Until these data are widely available, treatment guidelines are those provided by the National Cancer Institute (NCI) Working Group, which are based on the classic clinical staging systems of Rai and Binet.11,12