Definition and diagnosis of sporadic and familial chronic lymphocytic leukemia

This article describes the main defining criteria for chronic lymphocytic leukemia (CLL) and its differential diagnosis from closely related B-cell disorders. In addition to the morphology of circulating lymphocytes, the key diagnostic aid is the "CLL score" based on the typical immunophenotype of CLL as ascertained with five reagents: CD5, CD23, CD79b (or CD22), FMC7, and intensity of SmIg staining. The concepts of polyclonal and monoclonal B-cell lymphocytosis are defined with focus on the latter and its incidence in elderly individuals and its significant increase in healthy relatives from CLL families. The value of flow cytometry in the analysis of minimal residual disease after therapy also is discussed with a comparison with findings in bone marrow trephine biopsies. No candidate gene has been linked to the high incidence of CLL (?10%) seen in families of patients with this disease.