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ISRN Oncology  2013 

New Insights into Biology, Prognostic Factors, and Current Therapeutic Strategies in Chronic Lymphocytic Leukemia

DOI: 10.1155/2013/740615

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Abstract:

Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation and accumulation of mature B lymphocytes. CLL cells show an antiapoptotic profile, suggesting the important role of apoptosis inhibition in the disease development. However, there is some population of proliferating CLL cells, which may also play a role in progression of the disease. There are several newer, biological prognostic factors in CLL. Currently, cytogenetic abnormalities with different prognostic values seem to be the most biologically relevant. During the last decades, the treatment of CLL has been significantly changed. Different strategies such as monotherapy with chlorambucil and purine nucleoside analogues (PNA) used alone or in combination with cyclophosphamide have been introduced. Most recently, immunochemotherapy with anti-CD20 monoclonal antibody, rituximab, combined with fludarabine and cyclophosphamide, became a gold standard of first-line treatment in eligible CLL patients. Currently, new treatment strategies including new monoclonal antibodies, bendamustine, lenalidomide, or inhibitors of several cell signaling pathways are under clinical studies in resistant/relapsed CLL patients. Moreover, allogeneic stem cell transplantation has to be considered, especially in younger high risk patients, for example, those who are resistant to PNA or those with 17p deletion. In this paper, we present the most important recent advances in CLL biology and treatment. 1. Introduction Chronic lymphocytic leukemia (CLL), the most common lymphoid malignancy in the Western world, is characterized by clonal proliferation and accumulation of mature B lymphocytes. CLL is a disease of the adults, with median age at diagnosis ranging between 67 and 72 years [1]. Recent data indicate that approximately 6% of the normal elderly population develops a monoclonal B-cell lymphocytosis (MBL), which can transform into CLL in 1%-2% of cases. Cytogenetically and immunophenotypically MBL cells correspond to leukemic cells in CLL. Typical immunophenotype of the CLL cell is the presence of the B-cell surface antigens CD19, CD22, and CD23 with coexpression of T-cell lineage antigen, CD5, and expression of CD20 and CD79b lower than that observed in normal B cells [2, 3]. Recently, a significant progress has been made in elucidating the biology and improving treatment for CLL. This progress led to the identification of a subset of CLL patient with an early relapse of the disease and high risk of shorter survival, who may potentially benefit from a more aggressive upfront therapy. 2. Biology

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