This information is about chronic lymphocytic leukaemia (CLL), a type of low-grade non-Hodgkin lymphoma.
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This information is about chronic lymphocytic leukaemia (CLL), which is a type of low-grade non-Hodgkin lymphoma. It aims to answer the questions people ask about CLL and about the form of CLL known as ‘small lymphocytic lymphoma’ or SLL:
- What is chronic lymphocytic leukaemia (CLL)? (page 1)
- Who gets CLL and why? (page 2)
- How does CLL affect the body? (page 2)
- What are the symptoms of CLL? (page 3)
- What are the tests for CLL? (page 3)
- What are the ‘stages’ of CLL? (page 4)
- What can I expect to happen if I have CLL? (page 4)
- How is CLL treated? (page 5)
- What happens after finishing a course of treatment? (page 12)
- Living with CLL (page 12).
What is chronic lymphocytic leukaemia (CLL)?
Chronic lymphocytic leukaemia (CLL) is a type of blood cancer that develops from blood cells called lymphocytes. It is called a ‘leukaemia’ because the cancerous lymphocytes (or ‘CLL cells’) are found in the blood and in the bone marrow. It is described as ‘chronic’ because it lasts for a long time.
Technically speaking, CLL is actually a type of low-grade non-Hodgkin lymphoma and in some people the CLL cells are not found in the blood in large numbers, but rather they are found mainly in lymph nodes. This is then called small lymphocytic lymphoma or SLL because the abnormal lymphocytes are small in size and found in the lymph nodes rather than the blood. CLL and SLL are two forms of the same illness and they are treated in the same way.
If you have SLL, the information here will therefore apply to your illness too. Both forms will be described together as ‘CLL’ unless there is something different about the SLL form that is important to highlight.
Who gets CLL and why?
Over 3,000 people in the UK are diagnosed with CLL each year – it is the commonest type of leukaemia in adults. It has been estimated that there are around 30,000 people living with CLL in the UK.
CLL can affect adults of any age but it is more common in older people. The average age for developing CLL is 72 and only 1 in 10 people are under the age of 55 when they are diagnosed. It is more common in men.
Although it has been noticed that people with CLL are more likely than other people to have a family member with CLL or with another type of lymphoma, it is not an ‘inherited’ disease. Most people who have a relative with CLL will never develop it themselves.
It is not known what causes CLL. You can’t catch it from, or pass it on to, someone else. Nothing you have done will have caused the CLL to develop.
How does CLL affect the body?
CLL is different from most other types of lymphoma because it usually affects mainly the blood and bone marrow.
CLL cells can also collect in lymph nodes, in the spleen and in the liver. When the CLL cells are mainly present in the lymph nodes or the spleen, the CLL is called ‘small lymphocytic lymphoma’ or SLL.
If CLL cells collect in the bone marrow in large numbers they can stop the bone marrow from making enough healthy blood cells. This can cause:
- a lack of red blood cells (anaemia), which can lead to tiredness, weakness or breathlessness
- low numbers of platelets (thrombocytopenia), which can cause unexplained bruising or bleeding
- low numbers of infection-fighting white blood cells called neutrophils (neutropenia), which can mean you have frequent or persistent infections.
CLL also stops the immune system from working properly, so that it:
- doesn’t react against bacteria and viruses as well as it should, making you more likely to have infections
- can start to react against your body’s own blood cells – this is called ‘autoimmunity’ and it may cause:
- a type of anaemia called autoimmune haemolytic anaemia (AIHA) if the red blood cells are attacked
- a bleeding condition called immune thrombocytopenic purpura (ITP) if platelets are attacked.
Your body can also sometimes react to the CLL by releasing chemicals that cause tiredness, weight loss and sweating.
It is these effects that CLL has on the body that cause the symptoms of CLL.
What are the symptoms of CLL?
In more than three-quarters of people with CLL the illness is discovered quite by chance, for example when a blood test is done to check for something else.
Many people have no symptoms at all.
As the cancerous cells build up in the body, some people will start to notice symptoms such as:
- tiredness and a feeling of being generally weak or unwell
- swelling of lymph nodes, often causing lumps in more than one place (such as in the neck, armpits or groin)
- swelling and tenderness in the upper left-hand side of the abdomen and sometimes symptoms of indigestion or of feeling full after eating only small amounts of food (if the spleen is swollen)
- repeated infections
- a tendency to bruise or bleed easily
- night sweats
- weight loss.
What are the tests for CLL?
CLL is suspected when blood tests show that there are large numbers of lymphocytes in the blood. CLL is diagnosed by looking at these abnormal lymphocytes under the microscope and by testing the proteins on the surface of the lymphocytes.
The SLL form is diagnosed by taking a biopsy from a lymph node and finding these same abnormal lymphocytes.
Your examination and test results will be used by your medical team to give your CLL a ‘stage’.
We have more information about tests for lymphoma, which you can read on our website at www.lymphomas.org.uk. You can also print this information at home or ask our helpline to send you copies – email firstname.lastname@example.org or ring 0808 808 5555.
What are the ‘stages’ of CLL?
Knowing the stage of a lymphoma helps doctors decide when and how to treat you. Most doctors in the UK use a system called the Binet staging system to stage CLL. This system is based on how many groups of lymph nodes are swollen and your blood cell counts:
- Stage A – fewer than three groups of swollen lymph nodes can be felt by your doctor
- Stage B – three or more groups of swollen lymph nodes can be felt by your doctor
- Stage C – there are reduced numbers of red blood cells and/or platelets in your blood (however many swollen lymph nodes there are)
You might hear doctors talk about another staging system called the ‘Rai staging system’. This has five stages (0 to IV) and is more commonly used in the USA.
What can I expect to happen if I have CLL?
In many people, CLL will be very slow-growing. If you have this type of CLL, you will probably go for long periods of time without needing any treatment – often for several years.
Other people have a faster-growing form of CLL. If this applies to you, you are likely to need courses of treatment more frequently.
There are certain things about your CLL that will give your doctor an idea of how quickly it will grow and how long it is likely to be before you need treatment. These are called ‘prognostic factors’ and include:
- your age, general health and any other illnesses you have
- the stage of your CLL
- the number of lymphocytes in your blood
- how quickly the numbers of lymphocytes in your blood are increasing
- whether your blood tests show low numbers of red blood cells and platelets
- whether you have particularly swollen lymph nodes
- what changes have happened to the genes and chromosomes of the abnormal lymphocytes.
The medical team will take all these factors into account when your treatment is planned.
In a few people (about 1 in 10 people) the CLL can start to change over time and grow more quickly. This kind of change is called ‘transformation’. CLL can transform into:
- another type of leukaemia called B-cell prolymphocytic leukaemia
- a faster-growing type of lymphoma – usually diffuse large B-cell lymphoma (or, less commonly, Hodgkin lymphoma).
When CLL changes into a diffuse large B-cell lymphoma, this is called Richter syndrome.
Symptoms that might suggest that CLL has transformed are:
- feeling much more unwell, sometimes with fevers, sweating and weight loss
- sudden swelling of lymph nodes
- abdominal pain and/or tenderness due to swelling of the spleen.
Further tests (such as a lymph node biopsy and more blood tests) would be needed to work out whether your CLL has transformed. If it has, you would be treated with the treatments that are normally given for these faster-growing lymphomas.
We have more information on transformation.
We have more information about transformation, which you can read on our website at www.lymphomas.org.uk. You can also print this information at home or, if you prefer, our helpline can send you a copy – email email@example.com or ring 0808 808 5555.
Before you read more about CLL and its treatments, you might find this overview of CLL by Dr George Follows helpful. It was filmed in Cambridge in June 2014 at a CLL Support Association meeting.
Video courtesy of CLL Support Association
How is CLL treated?
If the CLL isn’t causing troublesome symptoms and the blood counts are not causing concern, you will not need any treatment at first. This approach is called ‘active monitoring’ or ‘watch and wait’.
Treatment is usually only started if the CLL becomes active – for example if it begins to cause:
- severe symptoms such as fevers, sweating, fatigue or weight loss
- rapidly rising numbers of lymphocytes in your blood
- very enlarged lymph nodes, spleen or liver
- low blood counts due to bone marrow failure.
Treatments for CLL aim to:
- reduce the numbers of CLL cells in your blood, lymph nodes, spleen and bone marrow
- relieve your symptoms.
If the CLL is refractory (meaning that it doesn’t respond well when it is treated) or if it relapses (meaning that it becomes active again later on), you can be given another course of treatment, which may be a different type of therapy.
People with CLL usually have several courses of treatment over a period of many years, with periods of watch and wait between them.
Watch and wait
Until your CLL becomes active you will not have treatment, but you will have check-ups every 3–12 months at your GP surgery or in the hospital outpatient clinic. At these check-ups your doctor will:
- ask how you are feeling and about any symptoms you have
- examine you
- do blood tests.
The doctors will be able to tell from these check-ups if you need treatment for your CLL.
Although you won’t have any treatment for the CLL itself while you are on watch and wait, you will have treatment for low blood counts if these are caused by autoimmunity (see later section on Supportive treatments).
We have more information on watch and wait.
We have more information about watch and wait, which you can read on our website at www.lymphomas.org.uk. You can also print this information at home or, if you prefer, our helpline can send you a copy – email firstname.lastname@example.org or ring 0808 808 5555.
The chemotherapy drugs that are used most commonly to treat CLL are:
- is a gentle form of treatment that has fewer side effects than other forms of chemotherapy
- is especially suitable for people with a milder form of CLL
- can be given again if the CLL comes back
- might be given in combination with an antibody therapy
- is given as tablets, usually for 7 days every month for 6–12 months.
Fludarabine and cyclophosphamide:
- are usually given together as FC, and usually also with the antibody rituximab in a combination called FCR
- can only be given to people who are medically fit enough for this stronger type of treatment; in particular, their kidneys have to be working relatively well because fludarabine cannot be given to anyone with severe kidney problems
- are given either as tablets for 5 days or intravenously (into a vein) for 3 days, once a month, for up to six cycles; the rituximab is given intravenously.
- can be given to people who cannot have fludarabine
- can be given if a course of chlorambucil hasn’t controlled the CLL
- is given with the antibody rituximab in a combination called R-bendamustine
- is given intravenously on the first 2 days of each cycle; this is repeated every month for up to six cycles.
Note: after you have had treatment with fludarabine or bendamustine you must be given specially prepared ‘irradiated blood’ if you need to have blood transfusions in future. This is so that you don’t develop a rare but serious complication of blood transfusion called ‘transfusion-associated graft-versus-host disease’.
We have more information about chemotherapy for lymphoma and its side effects and about irradiated blood, which you can read on our website at www.lymphomas.org.uk. You can also print this information at home or, if you prefer, our helpline can send you copies – email email@example.com or ring 0808 808 5555.
Antibodies used to treat CLL now include:
- is given with chemotherapy in FCR, R-bendamustine or R-chlorambucil
- is given intravenously over several hours on the first day of each treatment – the first dose may be split over 2 days if the number of lymphocytes in the blood is above a certain level.
Alemtuzumab (MabCampath® or Campath):
- works well for people whose CLL is mainly in the blood and bone marrow
- can be given to people whose CLL hasn’t responded to treatments containing fludarabine (eg FCR)
- is a good treatment for people whose CLL is ‘difficult to treat’ with chemotherapy because their CLL cells show certain genetic changes in cytogenetic tests (you might hear these called ‘deletion 17p’ or ‘p53 mutation’)
- can be given together with high doses of steroids to people whose CLL shows genetic changes that make it difficult to treat and who also have large lymph nodes
- is given three times a week for up to 3–4 months – either intravenously or subcutaneously (injected just under the skin).
- can be given to people who have CLL that hasn’t responded to or can’t be treated with fludarabine or alemtuzumab
- can be combined with chemotherapy drugs such as chlorambucil
- is awaiting approval for funding in England and Wales from the National Institute for Health and Clinical Excellence (NICE) as an initial treatment for people who can’t have fludarabine, bendamustine or alemtuzumab (given with chlorambucil).
Obinutuzumab (Gazyvaro®, previously called GA101):
- can be given with chlorambucil to older people with CLL who might not be able to have more intensive treatments
- is awaiting approval for funding in England and Wales from NICE as an initial treatment for people with CLL who cannot have fludarabine or bendamustine (given with chlorambucil).
We have more information about antibody therapy and its side effects, which you can read on our website at www.lymphomas.org.uk. You can also print this information at home or, if you prefer, our helpline can send you copies – email firstname.lastname@example.org or ring 0808 808 5555.
In CLL, steroids are given:
- to treat low blood counts caused by autoimmunity
- before starting chemotherapy, to treat low blood counts caused by bone marrow failure (where there are large numbers of CLL cells in the bone marrow)
- alone, or with rituximab, in people who cannot have chemotherapy
- instead of (or as well as) alemtuzumab in people who haven’t responded well to standard chemotherapy.
We have more information on steroids and on their possible side effects.
We have more information about steroids, which you can read on our website at www.lymphomas.org.uk. You can also print this information at home or, if you prefer, our helpline can send you a copy – email email@example.com or ring 0808 808 5555.
Radiotherapy is not often used to treat CLL. It might be used to treat:
- early-stage SLL where there is just one area with swollen lymph nodes – radiotherapy has the potential to cure this form of the illness if it has been diagnosed and treated at such an early stage
- large lymph nodes in people with CLL who can’t have chemotherapy or antibody therapy or who haven’t responded to these treatments.
We have more information about radiotherapy and its side effects, which you can read on our website at www.lymphomas.org.uk. You can also print this information at home or, if you prefer, our helpline can send you a copy – email firstname.lastname@example.org or ring 0808 808 5555.
Splenectomy or splenic radiotherapy
A few people with CLL need to have their spleen removed if autoimmune complications of CLL (AIHA or ITP) are causing severe symptoms and haven’t responded to other treatments such as steroids or rituximab. This operation is called a ‘splenectomy’. A splenectomy is rarely needed to treat the CLL itself.
Occasionally, frailer patients may benefit more from splenic radiotherapy than splenectomy or chemotherapy.
We have more information on splenectomy and the precautions you need to take if you have had this operation.
We have more information about splenectomy and on the precautions you need to take if you have had this operation on our website (www.lymphomas.org.uk). You can print this information at home or, if you prefer, our helpline can send you a copy – email email@example.com or ring 0808 808 5555.
Allogeneic stem cell transplantation
An allogeneic stem cell transplant is the only treatment given for CLL that is aiming to cure the disease (apart from radiotherapy in early-stage SLL).
An allogeneic stem cell transplant is a challenging and risky treatment. Usually only relatively young, fit people whose CLL has a high risk of getting worse would be offered this treatment (for example people with a p53 deletion or people who do not respond well to FCR treatment).
The transplant is more likely to be successful if the CLL is in a good remission after a course of chemotherapy.
We have more information on allogeneic stem cell transplantation.
We have more information about allogeneic stem cell transplantation, which you can read on our website at www.lymphomas.org.uk. You can also print this information at home or, if you prefer, our helpline can send you a copy – email firstname.lastname@example.org or ring 0808 808 5555.
Newer ‘targeted’ treatments
There are several new treatments that are currently being tested as treatments for CLL. These work by targeting and interfering with important biological processes in the CLL cells – stopping them from multiplying or killing them.
As with any new treatment, they have been tested first in people with relapsed or refractory CLL, but some may one day be used as initial treatments for CLL. Some are only available in the UK in the setting of a clinical trial.
These drugs are often suitable for older or less fit people with CLL, in whom standard chemotherapy might be too intensive. Another advantage is that they can often be taken in tablet or capsule form.
Ibrutinib, idelalisib and ABT-199 are newer drugs that are showing particular promise.
- has been used to treat people whose CLL has come back
- seems to work better than the standard treatments in people with genetic changes in their CLL cells that make the CLL difficult to treat using other treatments.
Idelalisib (Zydelig®, previously known as CAL-101 and GS-1101):
- has been used to treat CLL that has relapsed
- reduces the size of large lymph nodes quickly
- has shown promising results when given together with rituximab.
- has shown promising results in people with difficult-to-treat CLL.
Many of the new treatments are also being tested in combination with other, more established treatments – for example in combination with antibody therapy.
The following video is a Q&A session on clinical trials with Dr George Follows.
Video courtesy of CLL Support Association
There is more information on newer drugs and on clinical trials on our website at www.lymphomas.org.uk. We also produce a booklet about clinical trials. You can print this information at home or, if you prefer, our helpline can send you copies – email email@example.com or ring 0808 808 5555.
‘Supportive treatments’ are treatments that help with the symptoms of CLL or with the side effects of the drug treatments you are having for the CLL. Examples of supportive treatments that you may need are:
- antibiotics and antiviral drugs to prevent or treat infections
- immunoglobulin replacement therapy – a transfusion of general immune antibodies prepared from blood donations (not to be confused with antibodies such as rituximab which are used as a specific treatment to target the CLL itself); immunoglobulin replacement therapy is given if your blood antibody levels are low and you have had a serious infection or repeated infections
- red blood cell transfusions and/or platelet transfusions – given if your blood counts fall because of bone marrow failure
- drug treatments for AIHA and/or ITP – steroids are usually given initially but there are several other drugs that can be given for these autoimmune complications.
There is more information on steroids and on transfusion of blood products on our website at www.lymphomas.org.uk. You can also print this information at home or ask our helpline to send you a copy – email firstname.lastname@example.org or ring 0808 808 5555.
What happens after finishing a course of treatment?
Most people will go back to a watch and wait approach after a course of treatment.
As an alternative to going back to watch and wait, some people who go into a good remission might be considered for an allogeneic stem cell transplant.
At some stage the disease is likely to flare up again and further treatment will be needed. What treatment is given next will depend on:
- how quickly your CLL has come back
- what treatment you had before
- how well your CLL responded to the earlier treatment.
The same treatment can often be given again.
Because no treatment works quite as well or for as long the second time around, sooner or later you will probably need different and possibly stronger treatments. Or you might be offered one of the newer targeted treatments.
The latest developments in treatment for relapsed CLL were discussed at the European Hematology Association conference in Milan in 2014. Dr Peter Hillmen summarised the latest research in this interview.
Video courtesy of Leeds Teaching Hospital
In some other low-grade non-Hodgkin lymphomas it has been found that giving additional drug treatment after the main course of treatment is finished makes remissions last longer. This is called ‘maintenance treatment’.
Maintenance treatment is still at an experimental stage in CLL. Drugs that are being investigated as maintenance treatments for CLL in clinical trials include rituximab, alemtuzumab, ofatumumab, lenalidomide, ibrutinib and idelalisib.
All these drugs have side effects, such as an increased likelihood of developing serious infections. This means that the risks and benefits of maintenance treatments will be carefully assessed in these research studies. Current national guidelines do not recommend the use of maintenance treatments for CLL.
Living with CLL
CLL is an illness that most people live with for many years. You might find our information on living with lymphoma on our website and in our booklet Living with lymphoma helpful. These cover the more everyday aspects of living with a chronic condition like CLL, such as how to cope with tiredness and other symptoms, your feelings and relationships, diet and exercise and other practical things like managing medical appointments, financial matters, travel and vaccinations.
You could approach the CLL Support Association for help and support. Other organisations that offer further information and support for people with lymphoma can be found on our page of Useful organisations.
Our information about living with lymphoma on our website can be printed off at home or you can ask the helpline to send it to you. If you would like a copy of Living with lymphoma, please ring the helpline on 0808 808 5555 or email email@example.com.
You could approach the CLL Support Association (www.cllsupport.org.uk) for help and support. On their website you can watch interviews with experts in the field of CLL, including two very helpful presentations by Dr George Follows (‘An overview of CLL’ and ‘New treatments for CLL’) that were filmed at their June 2014 conference. The website also hosts a film interview with Cambridge CLL and Lymphoma Nurse Specialist, Gwyneth Stafford about managing CLL symptoms.
Please ring our helpline on 0808 808 5555 if you would like details of other organisations that offer information or support for people with CLL.
The following are a few of the sources we used to prepare this information. The full list of sources is available on request. Please contact us by email (firstname.lastname@example.org) or by ringing 01296 619409 if you would like a copy.
Brown JR, Porter DL, O’Brien SM. Novel treatments for chronic lymphocytic leukemia and moving forward. American Society of Clinical Oncology Education Book, 2014. 34: e317–e325.
Ghia P, Hallek M. Management of chronic lymphocytic leukemia. Haematologica, 2014. 99: 965–972.
Marcus R, Sweetenham JW, Williams ME (editors). Lymphoma: Pathology, Diagnosis and Management. 2nd edition. 2014. Cambridge University Press, Cambridge.
Oscier D, et al., on behalf of the British Committee for Standards in Haematology. Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia. British Journal of Haematology, 2012. 159: 541–564.
Hallek M. Chronic lymphocytic leukemia for the clinician. Annals of Oncology, 2011. 22 (Suppl 4): iv54–iv56.
With thanks to Dr George Follows, Consultant Haematologist and Clinical Lead for Lymphoma, CLL and clinical trials, Addenbrookes NHS Trust Hospital, Cambridge for reviewing this information.
We would also like to thank the members of our reader panel who gave their time to review this information.
Content last reviewed: November 2014
Next planned review: November 2017
If you would like a printed copy of any of our lymphoma information, complete our information order form and we will post it to you free of charge (UK, Channel Islands and Republic of Ireland only). If you live outside the UK, we recommend that you contact the lymphoma patient and carer organisation in your country as treatments and healthcare systems vary overseas.