Chronic lymphocytic leukemia: ESMO minimum clinical recommendations for diagnosis, treatment and follow-up.

The diagnosis of CLL is established by a sustained increase of peripheral CD5+ B-lymphocytes (‡5 · 10 cells/l) not explained by other clinical disorders and a predominance of small, morphologically mature lymphocytes in the blood smear. The composite immunophenotype CD5+, CD19+, CD20+ (low), CD23+, sIg low, CD79b low, FMC7– allows most cases of CLL to be distinguished from other CD5+ B-cell lymphoma. For prognostic and therapeutic reasons, every effort should be made for adequate differential diagnosis to exclude mantle cell lymphoma, splenic marginal zone lymphoma etc. by applying morphology, immunophenotyping and FISH and/or molecular biology for detection of t(11;14) translocation. In cases with isolated rapid tumor growth, biopsy should be performed to exclude Richter’s syndrome. The following examinations are recommended prior to treatment initiation [III, B]: history and physical examination, including a careful palpation of all lymph node areas; complete and differential blood count; serum chemistry, including lactate dehydrogenase (LDH), bilirubin, serum immunoglobulin; Coombs’ test; chest X-ray; and infectious disease status, especially viral hepatitis, CMV. The following additional examinations prior to treatment are desirable [III, C]: bone marrow biopsy is not needed for diagnosis, but is recommended prior to initiating therapy in cases with cytopenia. Because the detection of cytogenetic abnormalities by FISH has apparent prognostic and predictive value, this examination should be performed prior to therapy. Newer prognostic parameters, such as the expression of CD38, ZAP70 and the immunoglobulin mutational status (IgVH mutation), may predict the time to progression from an early stage to advanced disease, but should not be used for a treatment indication in CLL. CT scans are recommended only in clinical trials to assume the treatment response [III, C].