Prospective clinical trials indicate that certain genetic abnormalities are associated with adverse outcomes in response to standard chemo(immuno)therapy regimens. Molecular cytogenetics (FISH) for del(13q), del(11q), del(17p), add(12) in peripheral blood lymphocytesД¬onventional karyotyping in peripheral blood lymphocytes (with specific stimulation) Serum chemistry, serum immunoglobulin, and direct antiglobulin test When clinically indicated (unclear cytopenia) Immunophenotyping of peripheral blood lymphocytes A significant proportion of circulating prolymphocytes (в‰Ґ10%) seems to indicate a more aggressive form of CLL (with NOTCH1 or genetic TP53 aberrations). Finding в‰Ґ55% prolymphocytes would favor a diagnosis of prolymphocytic leukemia however, this diagnosis remains difficult and is solely based on morphological criteria, because no reliable immunological or genetic marker has been identified. A small percentage of larger or atypical cells or prolymphocytes can be found admixed with morphologically typical CLL cells. Gumprecht nuclear shadows, or smudge cells, found as cellular debris, are additional morphologic features commonly associated with CLL. The leukemia cells found in the blood smear are characteristically small, mature lymphocytes with a narrow border of cytoplasm and a dense nucleus lacking discernable nucleoli and partially aggregated chromatin.

The clonality of these B lymphocytes needs to be confirmed by demonstrating immunoglobulin light chain restriction using flow cytometry. The diagnosis of CLL requires the presence of в‰Ґ5 Г— 10 9/L B lymphocytes in the peripheral blood, sustained for at least 3 months.

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