Chronic and myeloid disorders
Chronic lymphocytic leukaemia
Overview
Indolent mature B-cell neoplasm, commonly found incidentally in older adults. Small lymphocytic lymphoma is the tissue-predominant counterpart.
- Most common leukaemia in the Western world; mainly older adults; very variable natural history1.
- Median age at diagnosis is about 60, with about twice as many men as women; much less common in Asian populations3.
- CLL versus SLL: the same disease. It is called CLL when the blood lymphocyte count is above 5 x 10^9/L, and SLL when disease is mainly in nodes3.
- Genetics: unlike most lymphoid cancers, translocations are rare. Common changes are deletion of 13q14 (the most frequent), trisomy 12, and deletions of 11q and 17p3.
- Monoclonal B lymphocytosis: small numbers of CLL-like cells in the blood of well people, below the CLL threshold; only about 1% a year progress to CLL3.
- Treatment is generally not curative, so is not started until symptoms develop1.
Assessment
B symptoms, recurrent infection, autoimmune haemolysis, bulky nodes/spleen and cytopenias. Examine node regions and organomegaly.
- Often asymptomatic early with insidious onset. Staging uses Rai or Binet systems; routine imaging is not recommended for initial staging1.
- Common ways it comes to light: an incidental lymphocytosis on a routine FBC, fatigue, recurrent infections, painless nodes, or an autoimmune cytopenia. Generalised lymphadenopathy and hepatosplenomegaly are present in about half of symptomatic patients2,3.
- Immune failure: low immunoglobulins (hypogammaglobulinaemia) are common and cause recurrent bacterial infections. Paradoxically, 10-15% develop autoimmune haemolytic anaemia or immune thrombocytopenia from antibodies made by normal B cells; pure red cell aplasia also occurs2,3.
- These immune complications are managed in their own right, whether or not the leukaemia itself needs treatment, and they do not raise the stage2.
Rai and Binet staging, based only on examination and FBC2.
| Risk | Rai | Binet |
|---|---|---|
| Low | 0: lymphocytosis only | A: fewer than 3 node areas, no anaemia or low platelets |
| Intermediate | I: plus nodes; II: plus spleen or liver | B: 3 or more node areas, no anaemia or low platelets |
| High | III: anaemia; IV: low platelets | C: anaemia or low platelets |
- Anaemia or thrombocytopenia from marrow failure (Rai III-IV, Binet C) marks the high-risk group that almost always needs treatment2.
Urgent features
Sepsis, severe autoimmune cytopenia, rapidly progressive nodes/spleen or possible Richter transformation with rapid growth/B symptoms requires prompt review.
- About 2-10% of CLL transforms to diffuse large B-cell lymphoma (Richter syndrome)1.
- Spotting Richter transformation: one node or the spleen grows rapidly out of step with the rest, often with new B symptoms. It carries a poor outlook3.
Diagnosis
Persistent clonal B lymphocytosis on flow cytometry; FBC/film and prognostic molecular testing guide management. Routine marrow biopsy is not always required.
- Diagnosis by peripheral blood flow cytometry showing clonal B lymphocytes; prognostic testing (e.g. IGHV, TP53, FISH) at diagnosis helps predict prognosis1.
- Film: many small, mature-looking lymphocytes with scanty cytoplasm, plus "smudge cells", fragile CLL cells crushed while the smear is made2,3.
- Immunophenotype: B-cell markers (CD19, CD20) together with CD5 and CD23, and weak surface immunoglobulin. Mantle cell lymphoma is the other CD5-positive B-cell tumour, so CD23 positivity and absence of cyclin D1 help separate them2,3.
- Adverse features: 17p or 11q deletion and unmutated immunoglobulin heavy-chain genes (IGHV) predict a more aggressive course2,3.
- Some patients have a small monoclonal protein band in the serum3.
Management
Observation for asymptomatic early disease. Treat symptomatic/progressive disease with targeted regimens based on genetics, comorbidity and local protocols; prevent and promptly manage infection.
- Chemoimmunotherapy and targeted therapy reduce symptoms and prolong survival; first-line regimens may include BTK inhibitors and BCL-2 inhibitors (venetoclax), with or without chemotherapy1.
References
- Merck Manual Professional: Chronic lymphocytic leukemia (CLL)
- Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. Chapter 110, Malignancies of lymphoid cells.
- Kumar V, Abbas AK, Aster JC, editors. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia: Elsevier Saunders; 2015. Chapter 13, Diseases of white blood cells, lymph nodes, spleen, and thymus.
Last updated from Sen’s notes on 22 October 2026.