Symptoms & diagnosis
Signs & symptoms
CLL usually develops very slowly and more than half of all patients do not have any symptoms in the early stages of the disease.
In 70-80% of cases, the disease is often found by ‘accident’ when a person has a routine blood test (full blood count) as part of a health check for something else. As the disease develops, the B-cells grow steadily and accumulate in the bone marrow, the blood and lymph nodes. The overproduction of abnormal B-cells means that the bone marrow may be unable to make enough healthy blood cells as it becomes overcrowded.
Over time CLL patients often develop symptoms as a result of lower than normal numbers of red blood cells (anaemia), white blood cells (neutropenia) and/or platelets (thrombocytopenia).
Some symptoms may occur before you’re diagnosed, others you may experience after diagnosis. It’s important to know that not everyone will experience the same symptoms.
The most common CLL symptoms may include:
- Feeling tired all the time (fatigue)
- Infections – these may be more frequent, persistent and/or more severe
- Swollen lymph nodes in the neck, armpits or groin
- Breathlessness, tiredness and headaches due to a lack of red blood cells (anaemia)
- Bruising and bleeding easily due to a lack of platelets in the blood (thrombocytopenia)
- Swollen abdomen caused by an enlarged spleen or lymph nodes
- Some abdominal discomfort or unable to eat large meals/ feeling full easily due to enlargement of the spleen
- A high temperature (fever)
- Severe sweating at night
- Weight loss
- Changes in appetite
Related resources
How is CLL diagnosed?
If CLL is suspected, you’ll have a set of tests to confirm the diagnosis.
The full blood count (FBC) is one of the key tests in the diagnostic process and is the first step. When a smear of blood is prepared in a laboratory and looked at through a microscope, CLL cells appear as small, dark purple or blue cells, some of which break easily when a microscope film is made – these abnormal cells are known as ‘smudge or smear cells’ and are a characteristic feature of CLL. A FBC alone and blood cell examination will not be enough to confirm a diagnosis and more specialist blood tests including immunophenotyping will also be needed. The following blood tests and procedures may be used to help confirm diagnosis as well as to enable your consultant to find out about your cancer’s stage and plan what treatment you are most likely to benefit from:
Blood tests
Full Blood Count (FBC) and blood cell examination (peripheral blood smear) – this measures the number and appearance of red cells, white cells and platelets in the blood. The normal parameters of a full blood count are as follows:
| Haemaglobin (Hb) for males | 130 - 180 |
| Haemaglobin (Hb) for females | 115 - 165 |
| Platelets | 150 - 450 |
| White Cell Count (WCC) | 4.00 - 11.00 |
| Neutrophils | 2.00 - 7.5 |
| Lymphocytes | 1.00 - 4.00 |
Immunophenotyping – this is one of the most important techniques for definitively diagnosing CLL. It involves the use of a machine called a flow cytometer. A flow cytometer emits lasers to detect the type of B-cell that is abnormal by identifying specific markers (prognostic markers) such as CD38 which is found on the outside of CLL cells and where high levels means that the disease is likely to progress quicker.
Cytogenetic testing
Blood or bone marrow samples may be tested to see if there are any changes in the genes of CLL- cells compared to normal B-cells. Fluorescent in situ hybridisation (FISH) is a very accurate and quick type of cytogenetic test using fluorescent dyes that attach to certain parts of chromosomes.
There are a number of different gene changes specific to CLL cells that can greatly affect the way CLL behaves and how the patient responds to treatment and FISH analysis should always be tested prior to a patient receiving treatment. The two most important genetic prognostic markers for CLL are:
- Chromosome 17 deletion 17p (del17p); 1 in 10 CLL patients test positive for del17p. In addition, more complicated tests to predict prognosis involve directly sequencing the DNA to look for mutations. The most important tests are to identify TP53 mutation or IgVH mutation in your blood.
- Del17p and/or TP53 mutations remain the most important adverse prognostic features predicting poorer treatment responses and survival in CLL and should indicate the need to have different therapy to that usually used to treat CLL.
Further testing is not routinely done at diagnosis and only done at a point where disease progression is identified to aid treatment decisions to choose the most appropriate treatment that will have the best response.
Additional tests
- Imaging Tests – ultrasound and CT (computed tomography) scanning enables your consultant to more accurately examine enlarged lymph nodes, liver and spleen before starting treatment.
- Lymph node biopsy – You may need a lymph node biopsy if your lymph nodes are swollen. A lymph node biopsy is a minor surgical procedure where a small sample is taken from a lymph node then studied under a microscope. This is usually done in a day and does not require a hospital stay.
- Bone marrow aspiration and biopsy – this test is not usually needed to diagnose CLL but may be important to give your consultant information about the extent of CLL cells in your bone marrow before you start any treatment. Also bone marrow tests may be performed after you have completed your treatment to see if the bone marrow disease has completely gone.
- Immunoglobulin (antibody) – this test is not used for diagnosis but helps your consultant to check if you have enough antibodies to fight infections and how your body, and more specifically your bone marrow, may respond to treatment.
- Direct Coombs Test – in CLL the immune system does not function normally. One consequence of this is that 10-20% of patients develop antibodies which destroy their own red blood cells- so called auto-immune haemolytic anaemia (AIHA).
- Beta-2 Microglobulin (β2M) and Lactate Dehydrogenase (LDH) – these simple blood tests provide further prognostic information.
Staging
Staging is a grading method used by consultants to describe the size of the cancer, where it is located and the extent at which the CLL is affecting the blood count and number and size of existing lymph nodes. Grading CLL helps your doctor predict how quickly the cancer may grow and spread, as well as to decide the best treatment for you and when it should be started.
There are two main systems used to stage CLL. Most doctors in the UK and Europe use the Binet system, whereas in the USA doctors more commonly use the Rai system.
Binet staging system
This is a three-step staging system (A to C) that is based on the number of groups of swollen lymph nodes and blood cell counts:
Stage A:
- No anaemia and a normal platelet count
- Fewer than three areas of lymph node enlargement
Stage B:
- No anaemia and a normal platelet count and
- Three or more areas of lymph node enlargement
Stage C:
- Anaemia and/or low platelet count
- Regardless of the number of areas of lymph node enlargement
*The lymphoid areas are the neck, the armpits, the groin, the spleen and the liver (involvement of both groins or both armpits count as one area).
Rai staging system
This is a five-step staging method (0 to IV) that classifies CLL into low (stage 0), intermediate (stages I and II) and high-risk (III- IV) stages:
Stage 0:
- Absolute lymphocytosis*
- No enlarged lymph nodes, spleen or liver
- No anaemia, or low platelets
Stage I:
- Absolute lymphocytosis*
- Enlarged lymph nodes
- No enlarged spleen or liver, anaemia, or low platelets
Stage II:
- Absolute lymphocytosis*
- Enlarged liver or enlarged spleen
- With or without enlarged lymph nodes
Stage III:
- Absolute lymphocytosis* and anaemia
- With or without enlarged lymph nodes, spleen or liver
Stage IV:
- Absolute lymphocytosis* and low platelet count
- With or without enlarged lymph nodes, spleen, liver or anaemia