Overview
Definition
A clonal neoplastic disease of mature, immunologically incompetent B-lymphocytes, characterized by progressive accumulation of these cells in the blood, bone marrow, and lymphatic tissues.
Epidemiology
The most common leukemia in adults in Western countries. Median age at diagnosis is ~70 years.
Etiology & Risk Factors
- Acquired genetic abnormalities (deletions of 13q, 11q, 17p, trisomy 12) affecting B-cell apoptosis
Clinical Symptoms
- Often asymptomatic (incidentally found on routine blood tests showing lymphocytosis)
- Painless lymphadenopathy (cervical, supraclavicular, axillary)
- Constitutional B symptoms (fever, night sweats, weight loss)
- Hepatosplenomegaly
- Recurrent infections (hypogammaglobulinemia)
Clinical Approach
Diagnosis
- Absolute lymphocytosis (>= 5,000 monoclonal B-cells/mcL for at least 3 months)
- Peripheral blood smear showing characteristic 'smudge cells' (fragile lymphocytes ruptured during slide prep)
- Flow cytometry showing co-expression of B-cell markers (CD19, CD20, CD23) and CD5
Management
- Asymptomatic early-stage: Observation ('watch and wait')
- Symptomatic or progressive disease: Targeted therapies (BTK inhibitors like Ibrutinib/Acalabrutinib; BCL2 inhibitors like Venetoclax; monoclonal antibodies like Obinutuzumab)
Complications
- Autoimmune Hemolytic Anemia (AIHA) or immune thrombocytopenia (Evans syndrome)
- Severe, recurrent infections
- Transformation to aggressive diffuse large B-cell lymphoma (Richter's Transformation)