About CLL
Chronic lymphocytic leukaemia (CLL) is a type of lymphoma, even though it has the word leukaemia in its name. The World Health Organisation (WHO) classifies it as a subtype of lymphoma because it is a cancer of B-cell lymphocytes, which are blood cells.
CLL occurs due to changes in our DNA inside our cells. DNA makes up genes and genes control how our cells function. In CLL, there are often many different genetic changes which can vary from person to person.
Some of the most affected genes in CLL are:
- tumour protein 53 (TP53)
- ataxia telangiectasia mutated (ATM)
- neurogenic locus notch homolog protein 1 (NOTCH1)
- splicing factor 3B subunit 1 (SF3B1).
Different gene mutations carry different risks. Some mutations mean the disease is harder to treat or more aggressive. Some mutations mean the disease is likely to have a poorer prognosis.
The genetic changes in CLL means that the bone marrow produces too many abnormal white blood cells. In CLL, abnormal white cells mainly occupy the bone marrow and bloodstream. However, if abnormal white cells mainly accumulate in the lymph nodes, doctors diagnose this as small lymphocytic lymphoma (SLL). This means that CLL and SLL are viewed as the same disease and are treated in the same way. When this webpage refers to CLL, it is inclusive of SLL.
Usually, lymphocytes help protect against infection. However, in CLL, the abnormal white blood cells called lymphocytes do not work properly. These cells crowd the bone marrow, leaving less room to make healthy blood cells which include red cells, white blood cells, and platelets. The abnormal lymphocytes can build up in organs including the lymph nodes (glands), liver, spleen, and other parts of the body and cause problems.
Who gets CLL?
- 2400 Australians are diagnosed each year.
- 84% of people diagnosed are over 60 years of age.
- 71 years is the average age at diagnosis.
Causes of CLL
In most cases, there is no specific cause of CLL. Nevertheless, there are some risk factors that increase your likelihood of developing CLL. Such as:
- age – more common in older people
- gender – more common in men than women
- ethnicity – more common in people of European origin
- family history – people who have a parent, sibling or child with CLL
- exposure to high-risk chemicals like pesticides, benzene and heavy solvents.
Symptoms of CLL
Many people do not have any symptoms when they are diagnosed with CLL. Often, it is discovered during a routine blood test, which may show a high number of lymphocytes. This increase in lymphocytes is called lymphocytosis.
Common symptoms of CLL can include:
- tiredness
- weakness
- dizziness
- weight loss
- fevers
- infections
- night sweats
- easy bruising
- swollen lymph nodes
- abdominal discomfort/swelling.
Enlarged spleen
An enlarged spleen is a symptom of CLL. The spleen sits in the upper left part of your abdomen (stomach), near your rib cage. It acts like a sponge for blood cells. It also stores and makes blood cells. However, if your spleen starts making too many blood cells, it may swell up. When your spleen swells or becomes enlarged, doctors call it splenomegaly.
Symptoms of splenomegaly are:
- feeling of fullness in your abdomen
- discomfort or pain in the left upper side of your abdomen
- feeling full quickly when eating.
Swollen lymph nodes
If the CLL has spread to your lymph nodes, they may swell into small hard lumps. Swollen lymph nodes may appear in your armpits, on either side of your neck, and/or in your groin. They’re usually painless. The lymph nodes in your chest and abdomen can swell too, but scans are needed to see them. Swollen lymph nodes are called lymphadenopathy.
Diagnosis of CLL
CLL is diagnosed with a number of tests which include:
- medical history and physical exam
- blood tests – full blood count (FBC), kidney and liver function, electrolytes
- genetic tests.
It is possible that CLL will be picked up on a routine blood test that you might have for another reason.
Your treatment team will also look at how far the disease has spread.
Test for disease spread include:
- bone marrow biopsy
- lymph node biopsy
- computed tomography (CT) scan
- positron emission tomography (PET) scan
- ultrasound.
You can read more about these tests in the CLL booklet
Staging CLL
Staging CLL helps your haematologist prescribe the right treatment for your disease. There are two staging systems for CLL. In Australia the Binet system is typically used. This divides CLL into three stages, as shown in the illustration.
To stage your disease, your haematologist will look at:
- the number of red blood cells and platelets in your blood
- how many areas of swollen lymph nodes you have.
| Stage | Symptoms |
|---|---|
| Stage A/0 | Unlikely to have symptoms but you may feel a swollen lymph node in your neck, armpit or groin. |
| Stage B/I-III | You may feel tired, with low energy. |
| Stage C/III-IV | You will likely feel tired due to the low red blood cells. You could get nose bleeds, bruising or heavy periods. You could get frequent colds, lose weight without trying and have night sweats. |
Prognosis of CLL
A prognosis is an estimate made by your haematologist about the likely course and outcome of your disease. While there is currently no cure for CLL, available treatments are very effective at managing the condition. Your haematologist will explain your stage and prognosis, taking into account several factors, including:
- your lymphocyte count and how long it takes to double
- which chromosomes or genes are affected
- your stage of CLL
- your overall health
- your age.
Your prognosis might change for example, if your CLL comes back after treatment or changes to a different type of cancer.
Genetic changes can be an indicator of prognosis and treatment response. Some genetic changes cause a poorer prognosis, make treatment less effective, and increase the risk of disease progression.
Transformed CLL – Richter’s syndrome
Richter’s syndrome, also called Richter’s transformation, is a rare complication of CLL. In particular, it happens when CLL transforms into a more aggressive form of non-Hodgkin lymphoma (NHL) called diffuse large B-cell lymphoma (DLBCL) or into Hodgkin lymphoma (HL). This can affect up to 7% of people with CLL.
Prolymphocytic leukaemia
Prolymphocytic leukaemia is a rare complication of CLL. It can occur in up to 2% of people with CLL. It is aggressive, has a poorer prognosis, and can be difficult to treat.
Treatment of CLL
For many people with CLL, no treatment is required, and the disease has minimal impact on quality of life. When treatment is recommended, it is often very effective at managing CLL, allowing people to live long and healthy lives.
Treatment for CLL is based on:
- your stage of CLL at diagnosis
- whether you have symptoms of CLL
- your blood count
- your genetic changes
- whether your lymph nodes or spleen are larger than normal
- your age and general health
- your wishes.
Furthermore, your treatment plan could include one or more of the following:
- watch and wait (active observation) with regular checkups but no treatment
- supportive care to control symptoms of CLL like thrombocytopenia
- targeted therapy, immunotherapy or chemotherapy
- involvement in a clinical trial
- stem cell transplant.
Click on the treatment types below to learn more.
Many people with CLL do not need to start treatment due to minimal blood count changes and no symptoms. This approach is watch and wait. In other words, it involves regular check-ups and monitoring by your haematologist and/or general practitioner (GP). Studies show that watch and wait offers no disadvantages compared to early treatment for low-risk CLL. Furthermore, in some cases, CLL can be managed with this approach for years before it progresses.
Many people with CLL on watch and wait feel like they should be doing something. There are some actions people can take:
- Learn as much as you can about your CLL.
- Know the signs and symptoms that may mean your CLL has progressed.
- Join a CLL support group.
- Keep up-to-date with immunisations (avoid live vaccines). Plan a vaccination schedule with your treatment team (CLL is an immune compromising disease).
- Attend all appointments and have blood tests as recommended by your haematologist.
- Include regular moderate exercise or movement.
- Incorporate regular screening for other cancers (second cancers are more common in people with CLL).
- Eat well – find out some tips in our Eating Well booklet.
Supportive care prevents and treats symptoms and side effects. It includes emotional and social support too. The goal is to improve symptoms of your CLL, but it doesn’t treat the disease itself. People with stage B and C (intermediate-high risk) CLL may have supportive care alongside treatment.
Get more information on these webpages:
Cancer growth inhibitors
Cancer growth inhibitors are a type of targeted therapy. They block signals to cancer cells to stop them from growing or surviving.
CLL can be treated with different cancer growth inhibitors:
B-cell leukaemia/lymphoma-2 (BCL2) inhibitors
- BCL2 is a type of protein that some cancer cells make.
- BCL2 inhibitors block the BCL2 protein, and the cancer cells die.
- BCL2 inhibitors are taken as a tablet.
- Venetoclax is an example of a BCL2 inhibitor.
Bruton’s tyrosine kinase inhibitors (BTKi’s)
- Bruton’s tyrosine kinase (BTK) protein is essential to the growth of B-cells.
- BTKi’s block the B-cell receptor (BCR) on cancer cells.
- Cancer cells die when the receptor is blocked.
- BTKi’s are taken as a tablet.
- Ibrutinib, acalabrutinib, zanubrutinib are examples of BTKi’s.
Monoclonal antibodies
Monoclonal antibodies attach to a specific target on a cancer cell and stop it from growing. Additionally, they can also slow down cancer cell growth. These treatments can also be called immunotherapy or targeted therapy. In CLL, specific monoclonal anti-CD20 antibodies, such as rituximab or obinutuzumab, are prescribed. These work by binding to the CD20 protein on the surface of B-cells causing the cell to die.
Chemotherapy is used less often to treat CLL. However, depending on your type of CLL and genetic mutations, chemotherapy might be the best treatment option. In many cases, chemotherapy is often given in combination with immunotherapy.
Common treatment combinations
Venetoclax and Obinutuzumab
- Combination treatment with venetoclax, a BCL-2 inhibitor and obinutuzumab, a monoclonal anti-CD20 antibody.
- Doctors introduce treatment slowly due to the risk of tumour lysis syndrome.
- You will take venetoclax continuously.
- You will be given obinutuzumab over 1 – 2 days, every four weeks.
- You need frequent blood test monitoring when you start this treatment.
Fludarabine, Cyclophosphamide and Rituximab (FCR)
- Combination treatment with two chemo drugs, fludarabine and cyclophosphamide, and a monoclonal anti-CD20 antibody, rituximab.
- You will have this treatment intravenously over three days, every four weeks.
Bendamustine and Rituximab
- Combination treatment with one chemo drug, bendamustine, and a monoclonal anti-CD20 antibody, rituximab.
- You will have this treatment intravenously over two days, every four weeks.
Treatment side effects can vary. Read more about the general chemotherapy side effects.
Monitoring CLL
Monitoring CLL after you have commenced treatment includes regular checkups, blood tests and sometimes imaging scans. This can help catch any early symptoms of worsening disease. After a period of remission however, your CLL may relapse or transform. This news can be difficult to hear, and your treatment team will discuss your options with you. It’s important to seek support from those closest to you.
Living with CLL
How CLL affects your everyday life will depend on many factors. It could be that you are returning to or managing work, your emotional health or managing fatigue. There are some helpful resources and information to guide you – Living well with blood cancer. The Online Blood Cancer Support Service has information and resources on cancer related fatigue, transition to the new normal, emotional resilience and more.
Caring for someone with CLL
We have a range of information and resources that may help when you are caring for someone with chronic lymphocytic leukaemia (CLL).
References
- Chronic lymphocytic leukaemia | eviQ
- iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL | Blood | American Society of Hematology
- Leukaemia | Causes, Symptoms & Treatments | Cancer Council
- ON DEMAND: Evolving CLL Care – Optimising Frontline Therapy
- Prognostic significance of ATM mutations in chronic lymphocytic leukemia: A meta-analysis – ScienceDirect
- Signs and Symptoms of CLL | American Cancer Society
- Staging chronic lymphocytic leukaemia (CLL) | Cancer Research UK
- Table 1 WHO Classification of Haematolymphoid Tumours, 5th edition: B-cell lymphoid proliferations and lymphomas.
- What Causes CLL? | American Cancer Society
