Description

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

Epidemiology

Incidence

• CLL represents the most common form of leukemia in adults in the United States (2021 incidence of 21,050).
• Second leading cause of death among adults with leukemia in the United States after acute myeloid leukemia
• CLL primarily affects elderly individuals, with median age of diagnosis being 70 years.
• Predominant sex: male > female (1.6:1); higher among Caucasians

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.
• Genetic mutations leading to disrupted function and prolonged survival of affected lymphocytes are suspected but are not well known. The BCL2 proto-oncogene (suppressor of apoptosis or programmed cell death) is overexpressed in CLL.

Genetics
Familial cases are rare. CLL does 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 (1).

Risk Factors

Uncertain; possible chronic immune stimulation is suspected; monoclonal B-cell lymphocytosis: 1% risk progression to CLL

Commonly Associated Conditions

• Immune system dysregulation is common.
• Autoimmune hemolytic anemia (AIHA)
• Immune thrombocytopenia purpura (ITP)
• Pure red cell aplasia (PRCA)