Leucémie myéloïde chronique

What is chronic myeloid leukaemia?

Chronic myeloid leukaemia (CML) is sometimes called chronic myelogenous leukaemia, chronic granulocytic leukaemia, or chronic myelocytic leukaemia.

CML develops due to a problem with a stem cell in the bone marrow, which becomes abnormal. The abnormal stem cell multiplies and the cells that are made from the abnormal stem cells mature and develop into near-normal white cells - mainly neutrophils, basophils and eosinophils (collectively called granulocytes). Large numbers of these cells are made in the bone marrow and spill into the bloodstream.

(In contrast, in aiguë myeloid leukaemia (AML) the abnormal cells that are made in large quantities are immature abnormal blast cells. This is quite a different disease to CML.)

Typically, CML develops and progresses slowly - over months or years, even without treatment.

CML is the rarest of the four main types of leukaemia. There are around 750 cases in the UK each year. It occurs mainly in adults and becomes more common with increasing age. The average age at diagnosis is 50 years. It is very rare in children. It is more common in men than in women.

A leukaemia is thought to start first from one abnormal cell. What seems to happen is that certain vital genes, which control how the cell divides, multiplies and dies, are damaged or altered. This makes the cell abnormal. If the abnormal cell survives it may multiply, produce many abnormal cells and develop into a leukaemia. In the case of CML, it is a blood stem cell which is first damaged and affected.

In most cases of CML, the reason why a stem cell becomes abnormal is not known. Research has shown that exposure to electromagnetic fields and living near high-voltage electricity cables do not increase your risk of developing CML. There are certain 'risk factors' which increase the chance that leukaemia will develop but these only account for a small number of cases. Risk factors known for CML are high-dose radiation (for example, previous radiotherapy for another condition) and exposure to the chemical benzene.

CML is not an inherited condition and does not run in families.

Typically, CML runs a course of three phases:

An initial chronic phase

This phase usually lasts a number of years (often five years or more). During this phase the disease progresses very slowly. You may remain stable, with little or no change in the severity of the disease for long periods. Many people in this phase have no symptoms, or only minor symptoms. CML may be first diagnosed by chance in this phase when a blood test is taken for another reason.

The average length of time for this phase is 4-5 years. However, in some people this phase can last for more than 20 years.

In the chronic phase there are 5% or fewer blast cells in the blood and bone marrow.

A transformation phase (also known as the accelerated phase)

In time, the disease process tends to speed up and change. In this phase, the number of abnormal cells in the bone marrow and bloodstream builds up. Many of the abnormal cells are immature (blast) white blood cells. In this phase there are 6-30% blast cells in the blood and bone marrow. As many abnormal cells build up in the bone marrow it is difficult for normal cells in the bone marrow to survive and make enough normal blood cells. Therefore, the main problems and symptoms which tend to 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 white blood cells and blast cells 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.

Other symptoms may include mild pain on the left side of the tummy (abdomen), caused by a swollen spleen (the spleen may enlarge with abnormal cells), sweats and weight loss.

The transformation phase typically lasts 6-24 months before passing into the third blast phase. Sometimes the chronic phase goes directly into the blast phase with no intermediate transformation phase.

A third blast phase

In this phase the condition rapidly becomes worse and behaves like an acute leukaemia. Many immature blast cells develop and fill much of the bone marrow and cause worsening of symptoms described above. Many blast cells spill out into the bloodstream and the blast cell count in blood tests is high. In this phase there are more than 30% blast cells in the blood and bone marrow.

Very rarely, CML develops into a condition called myelofibrosis. This means that the bone marrow can no longer make red cells, white cells or platelets because it is replaced by scar tissue (fibrosis).

Un test sanguin

Une test sanguin typically shows changes in the number and pattern of white blood cells. This suggests the diagnosis of CML. A bone marrow sample is then usually done to confirm the diagnosis. In the accelerated and blast phase, the number of blast cells seen in the blood sample (the blast cell count) also increases.

A bone marrow sample

For this test a needle is inserted into the pelvic bone (or sometimes the breastbone (sternum)). Local anaesthetic is used to numb the area. A small amount of marrow is removed using a syringe. 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.

Cell and genetic tests

Detailed tests are done on the abnormal cells obtained from the bone marrow sample or blood test. The chromosomes within the cells are checked for certain changes. Chromosomes are the parts in the cell which contain DNA - the genetic makeup of the cell.

In most cases of CML the abnormal cells contain a change in chromosome 22. This changed chromosome is shortened and is called the 'Philadelphia chromosome'. An abnormal gene called BCR-ABL is made on the abnormal chromosome 22. This gene is likely to be responsible for the abnormal cancerous behaviour of each abnormal cell. (These chromosome changes only occur in the leukaemia cells, not the normal body cells.) Some rarer subtypes of CML do not have the Philadelphia chromosome. See separate leaflet called Genetic Testing for more details.

Various other tests

Une radiographie thoracique, blood tests and other tests may be done to assess your general well-being.

Treatment for the initial chronic phase

The aim of treatment is to control the disease process, to ease any symptoms and to prevent (or delay) the progression into the further two stages.

You may be advised to have one or more of the following treatments:

• Imatinib tablets. This medicine is known as a tyrosine kinase inhibitor. The chemical tyrosine kinase is made by the abnormal gene BCR-ABL on the Philadelphia chromosome described above. This is thought to be responsible for the abnormal growth and behaviour of the abnormal cells. Imatinib works by blocking the effect of tyrosine kinase.

• Interferon alfa. This medicine has been shown to help the immune system to combat leukaemia cells. Interferon alfa is sometimes given, although now imatinib is given much more often.

• Chemotherapy tablets. Chemotherapy is a treatment which uses anti-cancer medicines to kill cancer cells, or to stop them from multiplying. See separate leaflet called Chemotherapy for more details. Another medicine called arabinoside is also sometimes used to treat CML.

• A stem cell transplant (SCT) - sometimes called a bone marrow transplant - is sometimes an option in younger patients with CML. This may be curative. See separate leaflet called Stem Cell Transplant for more details.

Treatment for transformation and blast phases

Treatment is usually with more intensive chemotherapy than is given for the chronic phase. This usually means a combination of chemotherapy medicines given directly into a vein (intravenous chemotherapy). Imatinib tablets may also be used.

Traitement de soutien

Other treatments include antibiotics or antifungal medicines if infection occurs and blood and platelet transfusions to improve low levels of red blood cells and/or platelets.

Overall, the outlook (prognosis) is reasonably good. Treatment in most cases is not curative but treatment often keeps the disease under control for a number of years. A successful SCT in people who have this treatment is the only means of a permanent cure.

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. As mentioned above, there are some newer medicines 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.