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Chronic Lymphocytic Leukaemia

Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia (CLL) is a condition where you build up many abnormal white blood cells (lymphocytes). It occurs mainly in people aged over 60 years. It typically develops very slowly and symptoms such as anaemia, bleeding problems or infections may not occur for years after the disease starts. Treatment, when needed, aims to reduce the number of abnormal lymphocytes.

Leukaemia is a cancer of cells in the bone marrow (the cells which develop into blood cells). Cancer is a disease of the cells in the body. There are many types of cancer which arise from different types of cell. What all cancers have in common is that the cancer cells are abnormal and do not respond to normal control mechanisms. Large numbers of cancer cells build up because they multiply 'out of control', or because they live much longer than normal cells, or both.

With leukaemia, the cancerous cells made in the bone marrow spill out into the bloodstream. There are several types of leukaemia. Most types arise from cells which normally develop into white blood cells. (The word leukaemia comes from a Greek word which means 'white blood'.) If you develop leukaemia it is important to know exactly what type it is. This is because the outlook (prognosis) and treatments vary for the different types. Before discussing the different types of leukaemia it may help to know some basics about normal blood cells and how they are made.

  • Blood cells, which can be seen under a microscope, make up about 40% of the blood's volume. Blood cells are divided into three main types:
    • Red cells (erythrocytes). These make blood a red colour. One drop of blood contains about five million red cells. Red cells contain a chemical called haemoglobin. This binds to oxygen and takes oxygen from the lungs to all parts of the body.
    • White cells (leukocytes). There are different types of white cells which are called neutrophils (polymorphs), lymphocytes, eosinophils, monocytes and basophils. They are part of the immune system. Their main role is to defend the body against infection.
    • Platelets. These are tiny and help the blood to clot if we cut ourselves.
  • Plasma is the liquid part of blood and makes up about 60% of the blood's volume. Plasma is mainly made from water but contains many different proteins and other chemicals, such as hormones, antibodies, enzymes, glucose, fat particles, salts, etc.

When blood spills from your body (or a blood sample is taken into a plain glass tube) the cells and certain plasma proteins clump together to form a clot. The remaining clear fluid is called serum.

Bone marrow

Blood cells are made in the bone marrow by 'stem' cells. The bone marrow is the soft 'spongy' material in the centre of bones. The large flat bones, such as the pelvis and breastbone (sternum), contain the most bone marrow. To make blood cells constantly you need a healthy bone marrow and nutrients from your diet, including iron and certain vitamins.

Stem cells

Stem cells are primitive (immature) cells. There are two main types in the bone marrow - myeloid and lymphoid stem cells. These derive from even more primitive common 'pluripotent' stem cells. Stem cells constantly divide and produce new cells. Some new cells remain as stem cells and others go through a series of maturing stages ('precursor' or 'blast' cells) before forming into mature blood cells. Mature blood cells are released from the bone marrow into the bloodstream.

  • Lymphocyte white blood cells develop from lymphoid stem cells. There are three types of mature lymphocytes:
    • B lymphocytes make antibodies which attack infecting germs such as bacteria, viruses, etc.
    • T lymphocytes, which help the B lymphocytes to make antibodies.
    • Natural killer cells, which also help to protect against infection.

All the other different blood cells (red blood cells, platelets, neutrophils, basophils, eosinophils and monocytes) develop from myeloid stem cells.

Blood production

You make millions of blood cells every day. Each type of cell has an expected lifespan. For example, red blood cells normally last about 120 days. Some white blood cells last just hours or days - some last longer. Every day millions of blood cells die and are broken down at the end of their lifespan. There is normally a fine balance between the number of blood cells that you make and the number that die and are broken down. Various factors help to maintain this balance. For example, certain hormones in the bloodstream and chemicals in the bone marrow, called 'growth factors', help to regulate the number of blood cells that are made.

The main types are:

  • Acute lymphoblastic leukaemia (ALL).
  • Chronic lymphocytic leukaemia (CLL).
  • Acute myeloid leukaemia (AML).
  • Chronic myeloid leukaemia (CML).

There are various 'subtypes' of each of these. In addition there are some other rare types of leukaemia.

The word:

  • 'Acute' means the disease develops and progresses quite quickly.
  • 'Chronic' means persistent or ongoing. When talking about leukaemia, chronic also means that the disease develops and progresses slowly (even without treatment).
  • 'Lymphoblastic' and 'lymphocytic' mean that an abnormal cancerous cell is a cell that originated from a lymphoid stem cell.
  • 'Myeloid' means that an abnormal cancerous cell is a cell that originated from a myeloid stem cell.

The rest of this leaflet is only about CLL. There are other separate leaflets called Leukaemia - A General Overview, Childhood LeukaemiasAcute Lymphoblastic Leukaemia, Acute Myeloid Leukaemia and Chronic Myeloid Leukaemia.

Chronic lymphocytic leukaemia (CLL) is a condition where you have many abnormal B lymphocyte white blood cells. The lymphocytes look normal under a microscope, but are abnormal as they do not function properly. The main reason for the build-up of the abnormal lymphocytes is because they live too long - they do not die after the usual lifespan of a lymphocyte. (This is different to the acute types of leukaemias where the cells rapidly multiply 'out of control'. In CLL the abnormal lymphocytes are not thought to multiply faster than normal lymphocytes.) Typically, CLL progresses very slowly - over months or years, even without treatment.

CLL is the most common type of leukaemia. It occurs in around 2,750 people each year in the UK. Most cases occur in people over the age of 60 years. It is rare under the age of 40 years. It is more common in males. In about 1 in 10 cases it is familial (runs in families).

A leukaemia is thought to first start from one abnormal cell. What seems to happen is that certain vital genes which control how cells divide, multiply and die, are damaged or altered. This makes the cell abnormal. If the abnormal cell survives it may multiply and develop into a leukaemia. However, it is not known what causes the damage which leads to abnormal lymphocytes developing into CLL.

At first, in many cases, there are no symptoms. The condition is often first diagnosed by chance when a blood test is taken for another reason. Nearly half of people with CLL have no symptoms when they are diagnosed with this condition. Over months or years, a large number of abnormal lymphocyte white blood cells may gradually build up in the bloodstream without causing any problems.

In time, the abnormal lymphocytes may fill much of the bone marrow. Because of this, it is difficult for normal cells in the bone marrow to survive and make enough normal blood cells. Therefore, the main problems which may eventually develop include:

  • Anaemia. This occurs as the number of red blood cells in the bloodstream goes down. This can cause tiredness, breathlessness and other symptoms. You may also look pale.
  • Blood clotting problems. This is due to low numbers of platelets in the bloodstream. This can cause easy bruising, bleeding from the gums and other bleeding-related problems.
  • Serious infections. The abnormal lymphocytes do not protect against infection. If there is a reduced number of normal white blood cells, which usually combat infection, there is a risk of serious infections developing.

The abnormal lymphocytes may also build up in lymph glands and in the spleen. With CLL it is also common to develop swollen glands in various parts of the body, particularly in the neck and armpits, and develop an enlarged spleen. Other common symptoms include: persistent high temperature (fever), night sweats and weight loss.

Some people with CLL also have an associated autoimmune disease

Lymphocytes normally make antibodies to attack bacteria, viruses, and other 'germs'. In people with autoimmune diseases, the immune system also makes antibodies against part or parts of the body. About 1 in 8 people with CLL make antibodies against red blood cells and/or platelets. This can destroy red cells and platelets. This can lead to anaemia and bleeding problems, or make anaemia and bleeding problems worse if the CLL is already causing these problems.

Transformation of CLL

In about 1 in 6 cases, the CLL changes at some point (transforms) to a more 'acute' form of leukaemia. This then progresses more rapidly and responds less well to treatment. If this occurs, symptoms may rapidly become worse.

A blood test

A blood test typically shows a large number of lymphocyte white blood cells. These look normal under the microscope so further tests are needed to confirm the diagnosis.

Cell typing (immunophenotyping)

Detailed tests are done on the lymphocytes obtained from the blood test (or bone marrow sample). These help to confirm the diagnosis of CLL and to rule out other rarer related disorders. Some more detailed tests of the genes in the lymphocytes are being developed. These will help to subdivide CLL into different categories. This may help to predict which cases will develop into the more severe type of disease, and help to guide decisions about treatment. See separate leaflet called Genetic Testing for more details.

A bone marrow sample

This test is not always necessary to diagnose CLL. It may be done to confirm the diagnosis and rule out other conditions. For this test, a small amount of bone marrow is removed by inserting a needle into the pelvic bone or, sometimes, the breastbone (sternum). Local anaesthetic is used to numb the area. Sometimes a small core of marrow will also be taken (a trephine biopsy). The samples are put under the microscope to look for abnormal cells, and tested in other ways. See separate leaflet called Bone Marrow Biopsy and Aspiration for more details.

Various other tests

A chest X-ray, blood tests and other tests may be done to assess your general well-being.

Staging chronic lymphocytic leukaemia

The severity of CLL is commonly assessed by the following staging system:

  • Stage A - there are fewer than three areas in the body with swollen lymph glands.
  • Stage B - there are three or more areas in the body with swollen lymph glands.
  • Stage C - there is a low number of red cells (anaemia), a low number of platelets, or both.

Treatment for stage A (early stage)

Many people with stage A CLL do not need any treatment. This is because many people with stage A disease do not have any symptoms, and it often causes little harm. In many cases of stage A disease, the disease progresses slowly and never needs treatment. For people in stage A CLL, the risks of treatment often outweigh the benefits of treatment. Treatment may be started if symptoms develop, or when blood tests show that the disease is progressing more rapidly. Your specialist will advise on the pros and cons of treatment and on when it should be started.

However, it is important to have regular checks to detect if the CLL has progressed to stage B or C when treatment is then commonly advised.

Treatment for stages B and C (later stages)

The aim of treatment is to kill the abnormal cells. This then allows the bone marrow to function normally again and to produce normal blood cells. The main treatment is chemotherapy. Other forms of treatment are sometimes used.

  • Chemotherapy is a treatment which uses anti-cancer medicines to kill cancer (leukaemia) cells, or to stop them from multiplying. See separate leaflet called Chemotherapy with Cytotoxic Medicines for more details. For CLL, the chemotherapy is usually taken as tablets which you take each day. Sometimes chemotherapy medicines are given by injection.
  • Monoclonal antibodies are a fairly new treatment which is sometimes used to treat CLL - for example, products called alemtuzumab and rituximab. Monoclonal antibodies are small proteins and are different to normal chemotherapy. They work by attaching to the abnormal lymphocyte white blood cells, which destroys them without harming other cells. Monoclonal antibodies may be used in addition to chemotherapy.
  • Radiotherapy may be used to reduce the size of enlarged lymph glands or spleen.
  • Steroid tablets are sometimes added to the treatment. They may help the chemotherapy medicines to work better. Steroids also help to control autoimmune complications which occur in some cases (described above).

The treatments described above do not cure CLL. The above treatments aim to keep you in remission - that is, to keep you with very low levels of abnormal lymphocytes, which enables your bone marrow to function normally.

A stem cell transplant

A stem cell transplant (SCT) - sometimes called bone marrow transplant - is sometimes used, especially in younger patients with progressing disease. It involves intense chemotherapy. A successful SCT can cure CLL, as the lymphocytes made by the transplanted stem cells will be normal. See separate leaflet called Stem Cell Transplant for more details.

Supportive treatment

If needed, other treatments include antibiotics or antifungal medicines if infection occurs, and blood and platelet transfusions to improve low levels of red blood cells or platelets.

Overall, the outlook is reasonably good. Most patients are able to enjoy a good quality of life for many years, with little or no treatment. Although CLL is not a condition that can usually be cured, many cases are in stage A where the condition is not usually serious, and treatment is not usually needed. Treatment for stages B and C often puts the disease into remission. Your specialist will be able to give a more accurate prognosis for your particular circumstances.

Also, you have to bear in mind that most people with CLL are over the age of 60 years. CLL tends to be a slowly progressing disease which can last for years. Many people with CLL die of other unrelated conditions which affect older people.

The treatment of cancer and leukaemia is a developing area of medicine. New treatments continue to be developed and the information on outlook above is very general. There are some newer drugs that have been introduced in the last few years that show promise to improve the outlook. The specialist who knows your case can give more accurate information about the outlook for your particular situation.

Further help & information

Leukaemia Cancer Society

118 Myddleton Rd, London, N22 8NQ

Tel: 020 8374 4821

Leukaemia CARE

One Birch Court, Blackpole East, Worcester, WR3 8SG

Tel: (24-hr Careline) 08088 010 444, (Office) 01905 755977


39-40 Eagle Street, London, WC1R 4TH

Tel: (Support Line) 0808 2080 888, (Office) 020 7504 2200

Cancer Research UK

Angel Building, 407 St John Street, London, EC1V 4AD

Tel: (Nurse team) 0808 800 4040, (Switchboard) 020 7242 0200

Macmillan Cancer Support

89 Albert Embankment, London, SE1 7UQ

Tel: (Support Line) 0808 808 00 00

Further reading & references

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but makes no warranty as to its accuracy. Consult a doctor or other healthcare professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Tim Kenny
Current Version:
Dr Colin Tidy
Peer Reviewer:
Dr John Cox
Document ID:
4879 (v44)
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