Chronic Myeloid Leukaemia

Because CML develops slowly, it is difficult to detect in its early stages. Sometimes it is discovered only when a blood test is done for another reason.

The symptoms of CML are often vague and non-specific and are caused by the increased number of abnormal white blood cells in the bone marrow and the reduced number of normal blood cells:

  • a feeling of fullness or a tender lump on the left side of the abdomen. This is because, in CML, the spleen can become enlarged. The spleen is an organ which lies just below the ribs on the left side of the abdomen. It filters the blood and removes worn-out red blood cells. The swelling of the spleen may also cause pressure on the stomach, which can lead to indigestion and poor appetite
  • some people feel tired and look pale, due to a lack of red blood cells (anaemia)
  • due to a lower number of platelets in the blood some people may notice that they bleed or bruise more easily. As well as bruising more easily than normal, a special type of bruising can be seen. This consists of small blood-like spots usually seen on the legs or in the mouth and is called petechiae. Women may find that their periods become very much heavier. However, these symptoms and signs are rare
  • some people may notice a generalised itching.

If you have any of the above symptoms, it is important to see your doctor, but remember, they are common to many illnesses other than chronic myeloid leukaemia.

Phases of CML

Chronic myeloid leukaemia is a blood and bone marrow disease that develops slowly. It has three phases. The phase is determined by the number of blast cells in the blood and bone marrow and the severity of symptoms.

The chronic phase

Most people are diagnosed when the CML is in the chronic phase. At this time CML progresses very slowly and is often stable for long periods. It is sometimes called the ‘stable phase’. There may be few symptoms and most people find they can lead a normal life. It is rare to need to go into hospital. Treatment can be given as an outpatient and usually does not cause many side effects. You will have regular appointments to check your condition and to have your blood tested. Although it varies from person to person this phase lasts on average about 4–5 years but can be longer.

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

The accelerated phase

After some time, the leukaemia may gradually move into an accelerated phase, during which the disease is developing more quickly. In this phase there are 6–30% blast cells in the blood and bone marrow. Sometimes this change may be picked up from your blood tests, in which blast cells can be seen, or from symptoms you may have. These may include feeling very tired (due to anaemia), infections, bruising or bleeding. If you notice any of these symptoms, let your doctor know straight away. The treatment for the accelerated phase is often more intensive than in the stable phase and you may need to spend some time in hospital as an in-patient.

The blast phase

After some time in the accelerated phase, usually months, the leukaemia ‘transforms’ into a ‘blast phase’, which is more like an acute leukaemia. In this phase much of the bone marrow has been replaced by many very immature (blast) cells. In this phase there are more than 30% blast cells in the blood and bone marrow.

In some people chronic myeloid leukaemia changes quickly from the chronic phase to the blast phase without going through the accelerated phase. If tiredness, a high temperature and an enlarged spleen occur during the blast phase this is known as blast crisis.

Rarely, CML develops into a condition called myelofibrosis. This means that the bone marrow cannot make red cells, white cells or platelets because it is replaced by scar tissue (fibrosis).

Relapsed chronic myeloid leukaemia

A relapse is when the number of blast cells increases after a period of remission. Remission is when the number of blast cells in the blood and bone marrow goes back to normal following treatment.

Complete remission means that all of the blood and bone marrow tests are normal. A molecular remission is when the Philadelphia chromosome cannot be found even by a very sensitive test called PCR.

How it is diagnosed?

Usually you will begin by seeing your family doctor (GP) who will examine you and take a blood test. If the results of the test are found to be abnormal your GP will refer you to hospital for specialist advice and treatment. In CML the blood test will generally show a high number of white blood cells.

The doctor at the hospital will take your full medical history before doing a full physical examination and a blood test which checks the number and stage of development of all the different types of blood cell.

If the blood test shows that leukaemia cells are present, your doctor will want to take a sample of your bone marrow. This is to confirm the diagnosis so that the best treatment can be planned.

  • Bone marrow sample
  • Philadelphia chromosome

Bone marrow sample

A small sample of bone marrow is taken from the back of the hip bone (pelvis) or occasionally the breast bone (sternum). It is looked at under the 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 normally taken under a local anaesthetic. You are given a small injection to numb the area and a needle is passed through the skin into the bone. A small sample of the bone marrow is then drawn into a syringe for examination under a microscope.

 

The test can be done on the ward or in the outpatients department. The whole procedure lasts about 15–20 minutes. It may be painful, but this only lasts a short time as the marrow is drawn into the syringe. You may be offered a sedative to reduce any pain or discomfort during the test.

Sometimes a small core of marrow is needed (a trephine biopsy) and this procedure takes a few minutes longer. You may feel bruised after the test and have an ache for a few days. This can be eased with mild painkillers.

The sample of bone marrow is examined to find out if the Philadelphia chromosome is present. This information helps the doctors to make decisions about treatment. It can take about a week to get the results of a bone marrow biopsy.

Philadelphia chromosome

Most people with CML have a genetic abnormality known as a Philadelphia chromosome which can be detected by laboratory tests. Every cell in the body has a nucleus that contains chromosomes. Chromosomes are long structures made up of DNA. DNA determines how the cell looks and acts. The Philadelphia chromosome develops when part of chromosome 9 (the ABL gene) wrongly attaches to chromosome 22 (the BCR gene) during cell division. This creates a new gene, known as BCR-ABL which produces a specific new protein. The protein causes the production of an enzyme called tyrosine kinase, which leads to the chronic phase of CML by stimulating the production of abnormal blood cells by the bone marrow.

The Philadelphia chromosome is not inherited and cannot be passed on to your children.

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