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What is leukaemia

Leukaemia is a cancer of the white blood cells. White blood cells are produced by the bone marrow. The four main types of leukaemia are acute myeloblastic (AML), acute lymphoblastic (ALL), chronic lymphocytic (CLL) and chronic myeloid (CML). Each disease has its own characteristics and treatment. CancerBACUP has sections on all these types of leukaemia.

Classification of AML

There are several classification systems that break AML down into various sub-types. The most commonly used system in the UK is the French-American-British (FAB) system. FAB classification of acute myeloid leukaemia

• M0 Acute myeloid leukaemia with minimal evidence of myeloid differentiation
• M1 Acute myeloblastic leukaemia without maturation
• M2 Acute myeloblastic leukaemia with maturation
• M3 Acute promyelocytic leukaemia (APL)
• M4 Acute myelomonocytic leukaemia
• M5 Acute monocytic/monoblastic leukaemia
• M6 Acute erythroleukaemia
• M7 Acute megakaryoblastic leukaemia

These terms describe the exact type of cell that is being overproduced and the stage of development (maturation) of the leukaemia cells. The blood and bone marrow samples will be checked by haematologists and pathologists to find out which type of leukaemia it is. They will look to see exactly which type of cell has become leukaemic and at which stage of their development. The cells may also be tested with antibodies for specific proteins on their surface. This process is known as immunohistiotyping. The genetic make-up of the leukaemia cells will also be examined, as the different types are associated with particular genetic changes. Knowing the exact type of leukaemia, from the results of the cytogenetics tests, helps the doctors to know which treatment is likely to be most effective in treating the leukaemia.

The bone marrow

Bone marrow is a spongy material that fills the bones and produces the cells (called stem cells) which develop into the three different types of blood cells:

• Red blood cells which carry oxygen to all cells in the body
• White blood cells which are essential for fighting infection
• Platelets which help the blood to clot and so control bleeding

All these cells normally stay inside the bone marrow until they are mature enough to circulate in the blood and perform their functions properly.

White blood cells

The bone marrow produces two main types of white blood cell: myeloid cells (including neutrophils) and lymphocytes. These cells work together to fight infection. As the neutrophils and some lymphocytes only live for a few days, the bone marrow is constantly making new cells to replace the old ones in the blood. When they are mature enough to leave the bone marrow, the white blood cells are released into the blood and circulate around the body in the bloodstream.

What is acute myeloblastic leukaemia (AML)?

Acute myeloid leukaemia is a rare type of cancer, affecting approximately 2,000 adults and 50 children per year in the UK. Leukaemia is a cancer of the white blood cells. Acute myeloid leukaemia is an overproduction of immature myeloid white blood cells. The immature cells are sometimes referred to as blast cells. Normally, white blood cells repair and reproduce themselves in an orderly and controlled way. In leukaemia, however, the process gets out of control and the cells continue to divide, but do not mature. These immature dividing cells fill up the bone marrow and prevent it from making healthy blood cells. As the leukaemia cells do not mature, they cannot work properly, which leads to an increased risk of infection. As the bone marrow cannot make enough healthy red blood cells and platelets, symptoms such as anaemia and bruising also occur. Acute myeloid leukaemia can affect adults of all ages, but is more common in older age groups. It is rare in people under 20.

Causes of acute myeloblastic leukaemia

The exact causes of acute myeloid leukaemia are unknown. Research into possible causes is going on all the time. In very rare cases, leukaemia may occur after exposure to chemicals such as benzene and other solvents used in industry. Large doses of radiation and some drugs used to treat other cancers may also rarely cause leukaemia, many years after people have received them. People exposed to high levels of radiation due to atomic bomb explosions or nuclear industry accidents are more likely to develop leukaemia than people who have not been exposed to radiation. People with certain blood disorders (such as myelodysplastic syndrome) or some genetic disorders, including Down's syndrome, are known to have a higher risk of developing leukaemia. Acute myeloid leukaemia, like other cancers, is not infectious and cannot be passed on to other people. It is not caused by an inherited faulty gene that can be passed on from one generation to the next.

What are the symptoms of AML?

The main symptoms of acute myeloid leukaemia are caused by the increased number of immature white cells (blast cells) in the bone marrow, which reduces the production of normal blood cells. The main signs and symptoms are:

• Anaemia (a lack of red blood cells), which can cause people to look pale, feel very tired and sometimes breathless at the slightest effort.
• Feeling generally unwell and run down - this may be caused by anaemia or repeated infections.
• Repeated infections - for example, a sore throat or sore mouth caused by a lack of white blood cells.
• Aching joints and bones - bones may be affected by leukaemia cells.

Unusual bleeding caused by a reduction in the number of platelets. This may include bruising (bruises may appear without any apparent injury), bleeding gums, frequent nosebleeds, and heavy periods in women. As well as bruising more easily than normal, a particular type of bruising can be seen. This consists of small blood-like spots called petechiae, usually seen on the legs or in the mouth. Rarely, areas of the skin or gums may be affected by the leukaemia cells. The affected areas can appear sore and take a long time to heal. Occasionally, a person will have none of these symptoms and the leukaemia is discovered during a routine blood test. The symptoms of acute myeloid leukaemia may appear within a few weeks and people often feel very ill quite quickly. Treatment needs to be given as quickly as possible. If you have any of the above symptoms you should have them checked by your doctor - but remember, they are common to many illnesses other than leukaemia.

How is it diagnosed?

Usually it begins by seeing the family doctor (GP), who will do an examine and take a blood test. If the results of the test are abnormal in any way, the GP will refer the patient to hospital for advice and treatment from a doctor who specialises in the treatment of blood problems (known as a haematologist).

At the hospital

Most people with AML are referred for treatment at a specialist heamatology unit where a group of specialist doctors work together. This is known as a multidisciplinary team and includes one or more haematologists, a medical oncologist (chemotherapy specialist) and a clinical oncologist (radiotherapy specialist). The team will also include specialist nurses, social workers, dietitians and physiotherapists. The doctor at the hospital will take the full medical history before doing a physical examination and a more specific blood test, which checks the numbers of all the different types of blood cell. If the blood test shows that leukaemia cells are present, the doctor will want to take a sample of bone marrow. This is the most important test for finding out if the patient has leukaemia, and gives information that the doctors need to plan the best treatment.

Bone marrow sample/biopsy

A sample of bone marrow is taken from the back of the hipbone (pelvis) or, less commonly, the breastbone (sternum). It is looked at under a microscope by a pathologist to see if it contains any abnormal white blood cells. The pathologist will be able to tell which type of leukaemia it is by identifying the type of abnormal white cell. The bone marrow sample is taken under a local anaesthetic (except for infants who are given a general anaesthetic). A small injection is given to numb the area and a needle is passed gently through the skin into the bone. A small sample of the marrow is drawn out into a syringe for examination under the microscope. The test can be done on the ward or in the outpatients department. The whole procedure takes about 15 minutes. It may be uncomfortable but it only lasts a short time as the marrow is drawn into the syringe. Some hospitals give a short-acting sedative which makes the patient feel drowsy or sleepy while the biopsy is taken. Sometimes a small core of marrow is needed (a trephine biopsy). This procedure takes a few minutes longer. A special type of needle is passed through the skin to the bone marrow. The needle has a tip that can cut out a sample of the bone marrow. The doctor may ask to have further tests, which may include a chest x-ray to check that the lungs and heart are healthy.

Cytogenetics

Within each cell of the body are chromosomes which are made up of genes. The genes control all activities of the cell. In myeloid leukaemia there are often changes in the structure of the chromosomes within the leukaemic cells, but not the normal cells of the body. The tests on the blood and bone marrow sample will include a chromosome analysis to look for any particular changes in the chromosomes. These tests, known as cytogenetic tests, can help to decide on the best treatment and predict how well the leukaemia may respond to that treatment.