Chronic Lymphocytic Leukaemia
Pathophysiology
CLL is a malignancy of monoclonal B lymphocytes. These B cells look mature in appearance, but functionally are immature.
Epidemiology
CLL is a disease of the elderly, with a median age of diagnosis of 72. It is the most common type of leukaemia in western countries. 1
Clinical Presentation
CLL is often picked up incidentally when an FBC is done for other purposes. Patients are often asymptomatic.
If they are symptomatic, features relate to B lymphocytes accumulating in lymph nodes, the spleen and the liver, causing lymphadenopathy, splenomegaly, hepatomegaly. Other signs and symptoms relate low haemoglobin and platelet production, and reduced white blood cell function. These low counts occur because too much space in the marrow is occupied with the malignant B lymphocytes and because B cells can produce antibodies against red blood cells and platelets (autoimmune haemolytic anaemia and secondary Immune thrombocytopenic purpura).
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Low Haemoglobin - symptoms of anaemia such as fatigue, pallor
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Low Platelet count - petechiae, gum bleeding, epistaxis, easy bruising
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Poor functioning white blood cells - increased susceptibility/recurrent infections
B symptoms such as weight loss, night sweats and fever are also presenting features.
Investigations
Staging
The Binet Staging system is used in CLL and is based on the degree of Haemoglobin and platelet cytopenia, and lymphadenopathy.
Stage A: Hb>10, Platelets >100 x 10^9, <3 lymph node areas involved
Stage B: Hb>10, Platelets >100 x 10^9, 3 or more lymph node areas involved
Stage C: Hb<10, Platelets <100 x 10^9 or both
Management
In early stage disease, a Wait and Watch approach is recommended. This includes regular monitoring of full blood count.
Chemotherapy is started if the patient has:
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active symptomatic disease - B symptoms, massive lymphadenopathy
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progressive increase in lymphocyte count
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progressive marrow failure (worsening cytopenias)
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autoimmune haemolytic anaemia or thrombocytopenia not responsive to steroid therapy
Stem cell transplantation is the only curative option.
Antibiotic and antifungal prophylaxis may be necessary as these patient's white cells are poo quality and therefore they are susceptible to life-threatening infections.
Complications
Richter's transformation: this is when the B cells rapidly transform into a high grade B cell lymphoma (most commonly diffuse large B cell lymphoma). It occurs in 5-10% of CLL patients. In these cases, further chemotherapy and occasionally stem cell transplantation is used as treatment. 1,2
Autoimmune haemolytic anaemia and Immune thrombocytopenic purpura: Antibodies produced by the B cells against red blood cells and platelets. This can be managed with steroids.1
Hyperviscosity Syndrome: This is a group of symptoms that occur as a result of very high white cell counts, which make the blood very thick. This can affect the blood vessels supplying the eye, resulting in retinopathy. It can cause neurological symptoms such as headaches and seizures due to reduced blood flow to the brain.1,3
References
1. Tidy C. CLL Leukemia [Internet]. Patient UK. 2017 [cited 10 March 2020]. Available from: https://patient.info/doctor/chronic-lymphocytic-leukaemia-pro
2. Parikh S, Kay N, Shanafelt T. How we treat Richter syndrome. Blood. 2014;123(11):1647-1657.
3. Gertz M. Acute hyperviscosity: syndromes and management. Blood. 2018;132(13):1379-1385.