Chronic lymphocytic leukemia
Chronic lymphocytic leukemia is the most common adult leukemia, a clonal proliferation of mature B lymphocytes usually discovered as incidental lymphocytosis in older adults with smudge cells on smear. Diagnosis rests on absolute B-lymphocytosis with a characteristic flow cytometry immunophenotype, and asymptomatic early-stage disease is observed while symptomatic or progressive disease is treated with targeted agents such as ibrutinib and venetoclax.
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What this article covers
- Overview
Definition: chronic lymphocytic leukemia (CLL) is a clonal proliferation of small, mature-appearing B lymphocytes that accumulate in blood, marrow, and lymphoid tissue; the identical disease with…
- Epidemiology
Most common adult leukemia: CLL is the most common leukemia in adults, presenting almost exclusively after age 50 and essentially never in children.
- Risk factors
Older age: the dominant risk factor; incidence rises steadily with advancing age.
- Pathophysiology
Clonal B-cell accumulation: a single mature B-cell clone escapes apoptotic regulation and accumulates progressively in blood, marrow, lymph nodes, and spleen rather than proliferating rapidly.
- Clinical features
Asymptomatic lymphocytosis, the most common presentation: an elevated white cell count with marked lymphocyte predominance found incidentally on a routine CBC in an older adult with no symptoms.
- Differential diagnosis
Acute lymphoblastic leukemia: immature blasts, cytopenias, and constitutional symptoms, distinguished by blast morphology and a precursor (TdT+) immunophenotype rather than mature CD5+/CD23+ cells (acute lymphoblastic leukemia).
- Diagnosis
Establish the diagnosis with absolute B-lymphocytosis at or above 5,000/microL (5 x 10^9/L) sustained for at least 3 months, confirmed by flow cytometry showing the characteristic CLL…
- Management
Confirm stage and risk before deciding on treatment: obtain the Rai stage, FISH panel, and IGHV status at diagnosis, because treatment decisions are driven by symptoms and disease burden, not the absolute lymphocyte count alone.
- Complications
Richter transformation: transformation to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma, occurs in about 5% of patients and carries a poor prognosis; suspect it with rapidly…
- Prognosis
Rai stage predicts survival at diagnosis: median survival exceeds 150 months in stage 0, about 101 months in stage I, about 71 months in stage II, and falls to about 19 months in stage III-IV.
- Prevention
No primary prevention exists for CLL, since no modifiable risk factor has been established; prevention efforts target monitoring known clonal states and averting complications of established disease.
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