Chronic Lymphocytic Leukaemia (CLL)


Treatment is not offered to chronic lymphocytic leukaemia (CLL) patients unless there is evidence of advanced or progressive disease. Patients with stable early stage CLL can be managed by regular simple review and often do not require treatment either at all, or for many years. Monitoring can often be done through the CLL Outreach (postal) clinic.

CLL is one of the chronic lymphoproliferative disorders, characterised by a progressive accumulation of functionally incompetent lymphocytes, which are monoclonal in origin. Early stage CLL is:

  • a low grade B-lymphoproliferative disorder
  • the most common type of adult leukaemia
  • mainly found in those aged over 50 years (median 65 years)

Early stage disease:

  • has a low risk of disease progression in the next 5 years.
  • a median survival of over 12 years
  • does not require treatment unless there is evidence of advanced or progressive disease
  • usually progresses slowly with increasing lymphocytosis, bone marrow involvement with cytopenias, lymphadenopathy, hepatomegaly and splenomegaly

Other complications of CLL include:

  • autoimmune haemolytic anaemia
  • immune thrombocytopenia
  • hypogammaglobulinaemia with recurrent respiratory tract infections
  • herpes zoster
  • transformation to high grade disease


Signs and Symptoms

Suspect an early stage chronic lymphocytic leukaemia if:

  • Full Blood Count (FBC) shows persistent lymphocytosis only i.e. the lymphocyte count is more than 5x 109/L and haemoglobin and platelets are normal
  • The patient is otherwise well

History and Examination

Examine for lymphadenopathy, hepatomegaly, and splenomegaly.

Differential Diagnoses

If there is a persistent lymphocytosis (more than 3 months), consider referral for immunophenotyping (surface markers) of peripheral blood lymphocytes according to the Lymphocytosis Pathway.

Ask about fever, weight loss (e.g. more than 10% in 6 months) and night sweats.


Review centres around

  • FBC
    • The absolute white blood count is less important than the development of any cytopenias, night sweats, or weight loss.
    • Rise of white blood cells: The absolute lymphocyte count can rise to more than 400 x 109/L and is not a reason alone to start treatment.
  • Ask about a history of infections, weight loss, fatigue, night sweats, enlarged lymph nodes
  • Check weight and examine for lymphadenopathy and hepatosplenomegaly
  • Screen for other malignancies:
    • Patients with CLL have an increased risk of other malignancies. Non-melanoma skin cancers can progress rapidly
    • Consider age-appropriate screening for breast, prostate, and colon cancer
    • Offer smoking cessation advice
  • Educate about presenting early if there is any infection or shingles


Patients should be seen by a haematologist and specialist nurse at diagnosis who can discuss topics such as prognosis, immunisation and immunoglobulin replacement, monitoring, current treatment approaches, concerns about family members being affected, practical issues such as insurance, quality of life impact. The word 'leukaemia' can generate significant anxiety which needs to be explored sensitively. These and other issues may require discussion on several occasions.

For more information see the Macmillan website.

Regular monitoring can be undertaken without hospital outpatient visits, which is generally more convenient for patients. This can be undertaken through blood tests at the GP surgery and concomitant return to the haematology department of a simple questionnaire. This also allows a route for rapid formal review if needed. Monitoring is usually 4 monthly for the first year, then 6 monthly to yearly if stable or slow, asymptomatic progression. This will be offered to most patients diagnosed through the haematology service.

Patients should be offered vaccination against Str. Pneumoniae (conjugate vaccine), H. Influenzae type B at diagnosis and annual vaccination against seasonal influenza and novel strains. Live vaccines such as polio, H. Zoster and yellow fever should be avoided.


Referral Criteria

If the patient is not being monitored through the haematology service request haematologist assessment if:

  • significant symptoms (e.g. night sweats, significant weight loss, extreme fatigue), after excluding other causes such as infection.
  • Disfiguring, uncomfortable or rapidly enlarging lymphadenopathy or hepatosplenomegaly.
  • blood tests show cytopenias
  • lymphocyte count doubles in less than 6 months or rises by more than 50% in less than 2 months

Urgent or written advice is available.

Referral Instructions

e-Referral Service Selection

  • Specialty: Haematology
  • Clinic Type: Not otherwise specified
  • Service: DRSS-Eastern-Haematology-Devon CCG- 15N

Referral Forms

DRSS Referral Form

Supporting Information

Pathway Group

This guideline has been signed off by NEW Devon CCG.

Publication date: July 2016


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