Leukemia, Chronic Lymphocytic

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  • Chronic lymphocytic leukemia (CLL) is a monoclonal disorder characterized by a progressive accumulation of mature but functionally incompetent lymphocytes.
  • CLL should be distinguished from prolymphocytic leukemia (PLL); based on percentage of prolymphocytes, the disease may be regarded as CLL (<10% prolymphocytes), PLL (>55% prolymphocytes), or CLL/PLL (>10% and <55% prolymphocytes).
  • Small lymphocytic lymphoma is a lymphoma variant of CLL.
  • System(s) affected: hematologic, lymphatic, immunologic


  • CLL represents the most common form of leukemia in adults in the United States with an estimated 18,960 new cases diagnosed in 2016 (1)[A].
  • In 2016, an estimated 4,660 adults in the United States died from CLL, which makes it the second leading cause of death among adults with leukemia in the United States after acute myeloid leukemia (1)[A].
  • Predominant age: CLL primarily affects elderly individuals, median age of diagnosis being 70 years. Incidence continues to rise in those age >55 years.
  • Predominant sex: male > female (1.7:1)
  • The incidence is higher among Caucasians than among African Americans.

Etiology and Pathophysiology

  • The cell of origin in CLL is a clonal B cell arrested in the B-cell differentiation pathway, intermediate between pre–B cells and mature B cells. In the peripheral blood, these cells resemble mature lymphocytes and typically show B-cell surface antigens: CD19, CD20, CD21, and CD23. In addition, they express CD5 (usually found on T cells).
  • The Bcl2 proto-oncogene is overexpressed in B-CLL. Bcl2 is a known suppressor of apoptosis (programmed cell death), resulting in extremely long life of the affected lymphocytes.
    • Genetic mutations leading to disrupted function and prolonged survival of affected lymphocytes are suspected but unknown.

CLL is an acquired disorder, and reports of truly familial cases are exceedingly rare. CLL has been shown, however, to occur at higher frequency among first-degree relatives of patients with the disease, and several somatic gene mutations have been identified at significantly higher rates among CLL patients.

Risk Factors

  • As in the case of most malignancies, the exact cause of CLL is uncertain.
  • Possible chronic immune stimulation is suspected but is still being evaluated.
  • Monoclonal B-cell lymphocytosis: 1% risk progression to CLL

General Prevention


Commonly Associated Conditions

  • Immune system dysregulation is common.
  • Conditions that may accompany CLL:
    • Autoimmune hemolytic anemia (AIHA)
    • Immune thrombocytopenia purpura (ITP)
    • Pure red cell aplasia (PRCA)

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