TY - CHAP M1 - Book, Section TI - Chronic Lymphocytic Leukemia A1 - Byrd, John C. A1 - Kittai, Adam S. A1 - Awan, Farrukh T. A2 - Kaushansky, Kenneth A2 - Prchal, Josef T. A2 - Burns, Linda J. A2 - Lichtman, Marshall A. A2 - Levi, Marcel A2 - Linch, David C. PY - 2021 T2 - Williams Hematology, 10e AB - SUMMARYChronic lymphocytic leukemia (CLL) is a malignancy of small B cells characterized by progressive lymphocytosis, lymphadenopathy, splenomegaly, and cytopenias. The progressive accumulation of leukemic B cells is a consequence of the constitutive B-cell receptor activation, defective apoptosis, and inappropriate survival signals derived from the microenvironment. The median age of onset of CLL is 70 years and it is very uncommon in younger adults and rare in children. It has a relatively high coincidence in family members. The disease is characterized by a monoclonal B-cell lymphocytosis, and replacement of marrow with neoplastic B lymphocytes, which may result in anemia and thrombocytopenia, superficial and deep lymphadenopathy, and splenomegaly. The monoclonal B cells are characteristically positive for CD19, dim CD20, and dim surface immunoglobulin, and are negative for CD10, CD79b, and FMC7 by flow cytometry. Progressive disease results in dysregulation of the cellular and humoral components of the effector immune system and hypogammaglobulinemia with a resultant increase in the incidence of infectious complications, which constitutes the leading cause of morbidity and mortality in this disease. Autoimmune hemolytic anemia and or autoimmune thrombocytopenia occur in a significant minority of patients. Monoclonal B-cell lymphocytosis is often a precursor of CLL. The former is defined as the presence of a monoclonal population of B lymphocytes in the blood at a level less than 5 × 109 monoclonal B cells/L and an absence of other signs of CLL. Approximately 1% of such individuals per year have progression to CLL. Significant therapeutic advances for CLL have been realized, especially with the development of well-tolerated targeted small molecules directed at inhibiting B-cell receptor signaling, antiapoptotic networks, and microenvironmental protection. Although not curative, these therapies are replacing older chemotherapy approaches in many situations, with significant improvements in patient outcomes. Challenges for the future of CLL management include responding to development of resistance to these agents, survivorship issues that arise from them, the propensity to Richter transformation, a more aggressive B-cell malignancy, and disease-related immune suppression that contributes to morbidity and mortality of this disease. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - hemonc.mhmedical.com/content.aspx?aid=1178750621 ER -