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Chronic Myeloid Leukaemia

CML

Leukaemia is a cancer of cells in the bone marrow (the cells which develop into blood cells). 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.

What is normal blood made up of?

  • 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.

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.

Stem cells

Stem cells are primitive (immature) cells. There are two main types in the bone marrow - myeloid and lymphoid 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 bacteria, viruses, etc.
T lymphocytes 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.

The main types of leukaemia are:

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

What is chronic myeloid 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.

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

Who gets chronic myeloid leukaemia?

CML is the rarest of the four main types of leukaemia. The average age at diagnosis is 50 years. It is very rare in children. It is more common in men than in women.

What causes chronic myeloid leukaemia?

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.

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.
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 'blast' (immature) white blood cells. In this phase there are 6-30% blast cells in the blood and bone marrow.

  • Anaemia.
  • Blood clotting problems.
  • Serious infections.

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 gets 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.

How is chronic myeloid leukaemia diagnosed?

A blood test
A blood test typically shows changes in the number and pattern of white blood cells. This suggests the diagnosis of CML.
A bone marrow sample
Cell and genetic tests
Detailed tests are done on the abnormal cells obtained from the bone marrow sample or blood test. 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'.

Various other tests

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

What is the treatment for chronic myeloid leukaemia?

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.

Imatinib (Glivec®) 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.

A stem cell transplant (SCT) - sometimes called a bone marrow transplant - is sometimes an option in younger patients with CML. This may be curative.

Treatment for transformation and blast phases

Treatment is usually with more intensive chemotherapy than is given for the chronic phase.

What is the outlook (prognosis)?

Overall, the outlook 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.


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