Hematology

Chronic Lymphocytic Leukemia

Monoclonal proliferation of mature CD5+CD23+ B lymphocytes; most common adult leukaemia in the West with variable indolent to progressive course.

Last reviewed 12 Jul 2026 - MedicoMedics editorial team

Bone marrow with mature B lymphocytes in CLL

Pathophysiology

B-cell receptor signalling drives clonal survival; genetic aberrations (del(17p)/TP53, del(11q), IGHV unmutated) predict worse prognosis.

Sources: iwCLL 2018 (Blood 2018;131:2745); NEJM Acalabrutinib 2020;383:432

Presentation

Often asymptomatic lymphocytosis; painless lymphadenopathy, splenomegaly, fatigue, autoimmune haemolytic anaemia, ITP; recurrent infections.

Diagnosis

Absolute B lymphocyte count >=5x10^9/L with characteristic immunophenotype (CD5+, CD19+, CD23+, kappa/lambda restricted). Smudge cells on peripheral smear.

Management

Watch-and-wait if asymptomatic. Treatment triggers (Rai/Binet advanced, cytopenia, bulky nodes): first-line BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) or venetoclax-obinutuzumab; consider TP53 testing.

Sample USMLE-style MCQs

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Question 1

A 68-year-old asymptomatic patient has ALC 32x10^9/L. Smear shows mature lymphocytes and smudge cells. Best next step?

Question 2

Which first-line option is preferred in del(17p) CLL?

Question 3

Which transformation to be aware of?

Question 4

Which staging system is used?

Question 5

Autoimmune complication of CLL?

References

Primary guidelines and peer-reviewed sources used for this entry. Reviewed 12 Jul 2026 by MedicoMedics editorial team.

Frequently asked

Smudge cells?

Fragile lymphocytes flattened during smear prep - suggestive of CLL.

Which mutation portends resistance to chemo?

TP53/del(17p) - prefer targeted agents.

Complication?

AIHA, ITP, Richter transformation to diffuse large B-cell lymphoma.

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