23rd July 2024

Chronic lymphocytic leukaemia

Background of CLL

CLL (known as small lymphocytic lymphoma, SLL, if the disease is predominantly in the lymph nodes) is an indolent lymphoproliferative disorder of mature monoclonal B-cells. CLL is the most common leukaemia in Western adults. Median age of diagnosis is 70 years with a male predominance.

There appears to be a genetic predisposition to CLL. No environmental risk factors have been identified.

Presentation and diagnosis of CLL

The majority of patients are asymptomatic at diagnosis, usually identified on a routine FBC.

If symptomatic, patients may present with lymphadenopathy, splenomegaly, hepatomegaly, signs of BM failure (as discussed in the section on AML) or with ‘B’ symptoms of lymphoma (fever, fatigue, weight loss, night sweats).

Cytopenias can also occur as a result of autoimmune haemolytic anaemia (AIHA; in ~10% of patients) and immune thrombocytopenia (ITP; in ~1-2%).

Diagnosis usually involves:

• Blood tests: FBC with absolute lymphocytosis (>5 x109/L); there may be anaemia or thrombocytopenia
• Blood film: lymphocytosis with ‘smudge’ or ‘smear’ cells
• Immunophenotyping with flow cytometry: positive for CD5, CD19, CD20, CD23, kappa or lambda immunoglobulin light chain

BM biopsy is usually not required.

Image Source: Wikimedia Commons (2014). Smear cells, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Chronic_lymphocytic_leukemia#/media/File:Smear_cells.jpg (Accessed: 16 January 2024).

Management and prognosis of CLL

CLL is staged using cell counts, lymphadenopathy and hepatosplenomegaly.

Early stage asymptomatic disease is managed with observation. Indications to initiate treatment include:

• Progressive bone marrow failure
• AIHA/ITP unresponsive to steroids
• Massive (≥6 cm below costal margin) or progressive splenomegaly
• Massive (≥10 cm) or progressive lymphadenopathy
• Progressive lymphocytosis with >50% increase in 2 months or doubling time <6 months
• Significant constitutional symptoms (weight loss ≥10% in 6 months, fevers >2 weeks without infection, night sweats without infection, significant fatigue)

If the decision is made to begin chemotherapy, factors such as age, performance status, comorbidities and severity of symptoms can be used to decide between a palliative approach, minimising toxicity, and an approach aiming for complete remission. Chemotherapy choice is guided by cytogenetic analysis.

If treatment is required, first-line chemotherapy can achieve 25-50% remission rates. However, there is a high risk of relapse, with most patients requiring further treatment after 2-3 years.