Haematology & Oncology

Chronic Lymphocytic Leukaemia

A clonal accumulation of mature but functionally incompetent B lymphocytes that pile up slowly in blood, marrow and nodes rather than dividing rapidly, so most patients are asymptomatic for years and the disease is found incidentally on a routine blood count.

In a nutshell

CLL is an accumulation, not a proliferation, of mature but functionally incompetent B cells, so the disease is slow and often asymptomatic for years. Functional immune failure and, later, marrow crowding explain the infections and cytopenias that eventually develop, while del(17p)/TP53 status and IGHV mutation status determine prognosis and treatment choice.

Classic presentation

An older adult found incidentally to have a raised lymphocyte count on a routine blood test, sometimes with painless lymphadenopathy.

Key points

CLL cells look mature but function poorly, so infections occur despite a high total lymphocyte count.
Slow accumulation means marrow failure and organ infiltration are late features, which is why watch and wait is appropriate for early disease.
Diagnosis requires immunophenotyping (CD5, CD19, CD23 co-expression), not lymphocytosis on FBC alone.
del(17p)/TP53 mutation and IGHV mutation status are checked before treatment: TP53-aberrant disease responds poorly to chemotherapy and mandates a targeted agent (BTK inhibitor or venetoclax-based regimen), while unmutated IGHV predicts a shorter treatment-free interval.
Autoimmune haemolytic anaemia and immune thrombocytopenia are immune-mediated complications treated with immunosuppression, distinct from disease progression.
Richter's transformation to high-grade lymphoma should be suspected with a rapidly enlarging node or new B symptoms.

First-line investigation

FBC and blood film to identify sustained lymphocytosis with smudge cells, followed by immunophenotyping to confirm the clonal B-cell markers and prognostic testing (del(17p)/TP53, IGHV mutation status) before treatment decisions.

Management

Confirm and risk-stratify

Confirm the clonal B-cell phenotype and obtain current TP53/del(17p) and IGHV information before treatment selection.¹

Watch and wait when appropriate

Monitor asymptomatic disease with a documented review and safety-netting plan; the lymphocyte count alone is not a treatment indication.^1,2

Treat active disease

Use risk-, comorbidity- and interaction-adapted targeted therapy; NICE options include BTK-inhibitor and venetoclax-based regimens.^1,5,6,7,4

Prevent and treat complications

Address infection, vaccination, hypogammaglobulinaemia and autoimmune cytopenias through specialist and local protocols.^1,2,4

Do not miss transformation

Escalate rapidly enlarging nodes, abrupt B symptoms or a rapidly changing course for urgent tissue-based assessment.¹

Exam traps

Do not start treatment purely because the lymphocyte count is high: the decision to treat is based on symptoms and progression, not the count alone.
Smudge cells on a blood film are a strong clue toward CLL, reflecting the fragility of the clonal cells during film preparation.
A falling haemoglobin in a CLL patient is not always disease progression: check a direct antiglobulin test for autoimmune haemolysis, which is managed differently.
Chemoimmunotherapy (e.g. FCR) is no longer first-line for most patients now that targeted agents are available; it is reserved for the few unable to have a BTK inhibitor or venetoclax-based regimen.

Illustrations

Blood film in CLLPeripheral blood film showing small mature lymphocytes and characteristic smudge (smear) cells.Dr Graham Beards, Wikimedia Commons · CC-BY-SA-3.0

Accumulation versus proliferationDiagram contrasting the slow clonal accumulation of mature cells in CLL with the rapid proliferation of immature blasts in acute leukaemia.PassFinals · original

Flow cytometry immunophenotypeFlow cytometry plot illustrating co-expression of CD5, CD19 and CD23 on the clonal B-cell population.PassFinals · original

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.