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Chronic Lymphocytic Leukemia (CLL)

  • Chronic Lymphocytic Leukemia (CLL) is the most common type of leukemia, typically manifesting in the elderly, and following an indolent course. CLL cells are phenotypically most similar to mature B-cells and are essentially identical to cells of Small Lymphocytic Lymphoma (SLL), a Non-Hodgkins Lymphoma. The major distinguishing feature of these two diseases is solely their anatomic sites of involvement, with CLL manifesting more prominently in the peripheral blood and the bone marrow.
  • The etiopathogenesis of CLL is poorly understood but the cells most closely resemble mature B-cells. However, CLL cells are essentially non-functional with low expression of surface immunoglobulin. In recent years it has become clear that there is more to CLL than a simple neoplastic pathogenesis and it is suspected that patients with CLL harbor nuanced immune defects which support and promote the growth of CLL cells.
  • The neoplastic cells of CLL are largely found in the peripheral blood and bone marrow, although significant involvement of lymph nodes, spleen, and liver usually occur. CLL cells in the blood are characterized by their small, mature phenotype, with scant cytoplasm, and dense nuclei. Because the cells tend to be somewhat fragile, they often break apart on peripheral blood smears, manifesting as characteristic "smudge cells".
Clinical Features
  • CLL is often detected incidentally in routine blood work as an unexplained lymphocytosis. However, when symptomology does manifest, patients may complain of new onset fatigue, waxing-waning painless lymphadenopathy, hepatomegaly, or splenomegaly. In some patients, extensive bone marrow involvement of CLL cells may yield a myelophthisic anemia or in turn a pancytopenia.
  • Consistent with the notion that CLL pathogenesis is in part due to immune derangements, patients with CLL often display increased infection susceptibility, with infections beings the usual cause of death. Additionally, patients display a predilection to develop autoantibodies to platelets and red blood cells, yielding idiopathic thrombocytopenic purpura or autoimmune hemolytic anemia.
  • CLL represents an indolent tumor with a long, chronic course that patients can live with for years. Because of the tumor's indolence the classic teaching goes that CLL should be treated only when patients are symptomatic, either from excessive lymphadenopathy/splenomegaly, or excessive bone marrow infiltration.