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Chronic lymphocytic leukaemia (CLL) is the most common form of adult leukaemia in the western world, and is characterised by the clonal proliferation and accumulation of CD5+ B cells in the blood, marrow, lymph nodes and spleen.1 An estimated 10,020 adults will be diagnosed with, and 4,660 will die of, CLL in the US in 2006.2 Along with its high incidence, the chronic nature of the disease and its relatively longer survival make it one of the most prevalent of all leukaemias.2
Most patients with CLL are asymptomatic at presentation and diagnosed incidentally when lymphocytosis is noted on a routine blood count. In up to 20–30% of patients, this may be the only sign of disease. However, as the disease progresses, generalised lymphadenopathy, splenomegaly and even hepatomegaly may become apparent on physical exam. As bone marrow infiltration increases, anaemia and thrombocytopenia can develop. Immune dysregulation contributes to hypogamma-globulinaemia and an increased risk of infection, as well as autoimmune haemolytic anaemia and thrombocytopenia.3
In approximately 5% of patients, CLL can undergo transformation to a more aggressive lymphoid neoplasm, most commonly a diffuse large B-cell lymphoma (Richter transformation)4 enlarging lymphadenopathy and increased lactate. Survival after transformation is short.Although the natural history of the disease can vary among individuals with survival times ranging from two to 20 years, the overall five-year relative survival rate for 1996–2002 from a recent Surveillance, Epidemiology, and End Results (SEER) analysis was 73.7%.2
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