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Leukaemia, chronic myeloid

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Leukaemia, chronic myeloid


 


Leukaemia, chronic myeloidLeukaemia, chronic myeloidLeukaemia, chronic myeloidLeukaemia, chronic myeloidLeukaemia, chronic myeloid

Introduction 

Leukaemia is cancer of the white blood cells. Chronic leukaemia means the condition progresses slowly over many years.

Chronic leukaemia is classified according to the type of white blood cells that are affected by cancer. There are two main types:


lymphocytes – mostly used to fight viral infections

myeloid cells – which perform a number of different functions, such as fighting bacterial infections, defending the body against parasites and preventing the spread of tissue damage


These pages focus on chronic myeloid leukaemia, which is a cancer of the myeloid cells. The following other types of leukaemia are covered elsewhere:


chronic lymphocytic leukaemia

acute myeloid leukaemia

acute lymphoblastic leukaemia


What happens in chronic leukaemia

Your bone marrow produces stem cells. These are unique cells because they have the ability to develop into three important types of blood cell:


red blood cells – which carry oxygen around the body

white blood cells – which help fight infection

platelets – which help stop bleeding


In leukaemia, a genetic mutation in the the stem cells causes a huge over-production of white blood cells and corresponding drop in red blood cells and platelets.

It's this lack of red blood cells which causes symptoms of anaemia, such as tiredness, and the lack of platelets that increases the risk of excessive bleeding.

Warning signs of chronic myeloid leukaemia

In its early stages, chronic myeloid leukaemia usually causes no noticeable symptoms. As the condition develops, symptoms include:


tiredness 

weight loss 

night sweats

a feeling of bloating

bruising 

bone pain 


 

 How common is chronic myeloid leukaemia? 

Chronic myeloid leukaemia is quite a rare type of cancer. Around 8,600 people are diagnosed with leukaemia every year in the UK. In 2011, around 680 people in the UK were diagnosed with chronic myeloid leukaemia.

Chronic myeloid leukaemia can affect people of any age, but it is more common in people aged 40-60. There is no evidence that it runs in families.

Outlook

The outlook for chronic myeloid leukaemia depends to a large extent on how well a person responds to medication.

Most patients (60-65%) do well on imatinib tablets, which are taken every day for life.

For those who don't do well on imatinib, more than half respond to one of the alternative drugs. Nilotinib is recommended by the National Institute for Health and Care Excellence (NICE) for patients with chronic myeloid leukaemia who are not responding to, or can't tolerate imantinib.

Those who fail these drugs or cannot tolerate them may be offered a bone marrow transplant, if this is a suitable treatment.

If the condition is diagnosed early (the chronic phase), the outlook is excellent, with almost 90% of people living at least five years after diagnosis.

 

 Symptoms of chronic myeloid leukaemia  

In its early stages, chronic myeloid leukaemia usually causes no noticeable symptoms and it is often diagnosed during tests for a different condition.

When symptoms do develop, they are similar to those of many other illnesses and can include:


tiredness

frequent infections

unexplained weight loss

a feeling of bloating

less commonly, swollen lymph nodes – glands found in the neck and under your arms, which are usually painless


Chronic myeloid leukaemia can also cause swelling in your spleen (an organ that helps to filter impurities from your blood). This can cause a lump to appear on the left side of your abdomen, which may be painful when touched. A swollen spleen can also put pressure on your stomach, causing a lack of appetite and indigestion.

The symptoms of chronic myeloid leukaemia in its advanced stage will be much more noticeable and troublesome. They include:


severe fatigue

bone pain

night sweats

fever

easily bruised skin




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Causes of chronic myeloid leukaemia 

Chronic myeloid leukaemia is caused by a DNA mutation in the stem cells which produce white blood cells.

The change in the DNA causes the stem cells to produce more white blood cells than are needed.

They are also released from the bone marrow before they are mature and able to fight infection like healthy 'adult' white blood cells.

As the number of immature cells increases, the number of healthy red blood cells and platelets fall, and it's this fall which causes many of the symptoms of chronic leukaemia.

Philadelphia chromosome

Although the cause of chronic myeloid leukaemia is genetic, it is not inherited as it is an acquired genetic abnormality.

Most people with the condition have an abnormal chromosome, where a section of DNA from one chromosome has been swapped with a section from another.

This is called the Philadelphia chromosome and it makes the cell produce a protein that encourages the leukaemic cells to resist normal cell death and grow and multiply far more quickly than usual.

Possible triggers for chronic leukaemia

What triggers the development of chronic leukaemia and causes the initial mutation in stem cells is unknown. The one proven risk factor is exposure to radiation.

However, radiation is only a significant risk if the levels are extremely high, such as those recorded after an atomic bomb explodes, or those released after a nuclear reactor accident, such as the one at Chernobyl.

Benzene

There is limited evidence that prolonged exposure to the chemical benzene leads to an increased risk of chronic myeloid leukaemia. Benzene is found in petrol and is also used in the rubber industry, but in the UK there are strict controls to protect people from prolonged exposure.

Benzene is also found in cigarettes. However, it is thought that smoking is more of a risk factor in acute leukaemia than it is in chronic leukaemia.

Occupational risks

A number of occupations have been linked to an increased risk of chronic leukaemia, possibly due to exposure to certain substances such as pesticides or chemicals.

These occupations include:


all types of agricultural workers

people who are involved with rubber or plastic manufacture

tailors and dressmakers

cleaners

builder’s labourer


Other risk factors

There is some evidence to show an increased risk of chronic leukaemia in people who:


are obese

have a weakened immune system – due to HIV or AIDS or taking immunosuppressants after an organ transplant

have inflammatory bowel disease – such as ulcerative colitis or Crohn's disease


 

Diagnosing chronic myeloid leukaemia 

Chronic myeloid leukaemia is often first detected when a routine blood test is carried out to diagnose another, unrelated, condition.

A blood test that reveals abnormally high levels of white blood cells could be a sign of chronic leukaemia. If you have a blood test with abnormal results, you will be referred to a haematologist (a specialist in treating blood conditions) for further testing.

Bone marrow biopsy

To confirm a diagnosis of chronic leukaemia, the haematologist will take a small sample of your bone marrow to examine under a microscope. This procedure is known as a bone marrow biopsy. A bone marrow biopsy is usually carried out under a local anaesthetic.

The haematologist will numb an area of skin at the back of your hip bone, before using a needle to remove the bone marrow sample. You may experience some pain once the anaesthetic wears off and some bruising and discomfort for a few days afterwards. The procedure takes around 15 minutes to complete and you should not have to stay in hospital overnight.

The bone marrow sample will be checked to see if there are cancerous cells. If there are, the biopsy will also be able to help determine which type of chronic leukaemia is present.

Further tests

There are a number of additional tests that can be used to help reveal more information about the progress and extent of the leukaemia. These can also provide an insight into how the leukaemia should be treated. These are outlined below.

Cytogenetic testing

Cytogenetic testing involves identifying the genetic make-up of the cancerous cells. There are a number of specific genetic variations that can occur during leukaemia and knowing what these variations are can have an important impact on treatment.

For example, 90% of people with chronic myeloid leukaemia have the Philadelphia chromosome. People who have this chromosome are known to respond well to a medicine called imatinib.

Polymerase chain reaction (PCR)

A polymerase chain reaction (PCR) test can be done on a blood sample. This is an important test to diagnose and monitor the response to treatment.

The blood test is repeated every three months for at least two years after starting treatment, then less often once remission is achieved.

Imaging tests

In some cases, the hospital may want to perform some imaging tests to help rule out other conditions or confirm a diagnosis. This may be either:


an X-ray – usually to examine your chest

an ultrasound scan – usually to examine your spleen and liver


 

Treating chronic myeloid leukaemia 

Imatinib tablets are usually given as soon as you have been diagnosed with chronic myeloid leukaemia, to slow its progression. These tablets are taken every day for life, and most patients do really well on them.

The aim of treatment is to achieve the following:


by three months, correct the blood count

by 12 months, clear the bone marrow of cells containing the Philadelphia chromosome (see Causes page for information on this)

by 18 months, get to a stage where the leukaemia can only be detected by a very sensitive molecular test (molecular remission)


Chemotherapy is usually offered if the cancer reaches an advanced stage.

These treatments are explained below.

Treating early-stage chronic myeloid leukaemia

Imatinib

A medicine called imatinib is the main treatment recommended for chronic myeloid leukaemia. It is usually given as soon as a diagnosis is made because the medicine is designed to slow the progression of the cancer and to prevent the condition reaching the accelerated or advanced phase.

Imatinib is a type of tyrosine kinase inhibitor. This means it blocks a protein called tyrosine kinase (tyrosine kinase helps to stimulate the growth of cancer cells). This reduces the production of abnormal white blood cells.

Imatinib is taken as a tablet. The side effects of imatinib are usually mild and should improve with time. They include:


nausea

vomiting

swelling in the face and lower legs

muscle cramps

rash

diarrhoea


Nilotinib

It is estimated that 10-40% of people who take imatinib become resistant to its effects, so an alternative treatment is required.

The National Institute for Health and Care Excellence (NICE) has recommended nilotinib for the treatment of chronic myeloid leukaemia that is resistant or intolerant to imantinib. In some cases, nilotinib is recommended as the first treatment.

Nilotinib works in a similar way to imatinib in that it blocks the effects of proteins that help stimulate the growth of cancer cells.

Side effects of nilotinib can include:


vomiting

abdominal pain

bone and joint pain

dry skin

loss of appetite

hair loss

insomnia

night sweats

dizziness

tingling or numbness


If the side effects become particularly troublesome, temporarily stopping the treatment usually helps to bring them under control. Treatment can then be resumed, possibly using a lower dose of medication.

Read about the complications of chronic myeloid leukaemia for more information and advice about being vulnerable to infection and bleeding.

Treating advanced chronic myeloid leukaemia

Chemotherapy

Once chronic myeloid leukaemia has progressed to a more advanced stage, chemotherapy is the next treatment.

Chemotherapy tablets are usually used first because they have fewer and milder side effects than chemotherapy injections. Side effects include:


tiredness

skin rash

increased vulnerability to infection


Chemotherapy can weaken your immune system, which helps protect you against infection. This is known as being immunocompromised.

See chronic leukaemia – complications for more information about this.

If your symptoms persist or get worse, chemotherapy injections (intravenous chemotherapy) will need to be used. Intravenous chemotherapy causes more side effects than chemotherapy tablets and they tend to be more severe.

Side effects include:


nausea

vomiting

tiredness

hair loss

infertility


These side effects should resolve after your treatment has finished, although there is a risk that infertility could be permanent.

Bone marrow and stem cell transplants

A bone marrow transplant can offer a cure for chronic leukaemia, although it is only suitable and necessary for some patients.

Before transplantation can take place, the person receiving the transplant has to have aggressive, high-dose chemotherapy and radiotherapy to destroy any cancerous cells in their body.

This can put enormous strain on the body and can cause significant side effects and potential complications. Transplantations have better outcomes if the donor has the same tissue type as the person who is receiving the donation. The best candidate to provide a donation is usually a brother or sister with the same tissue type.

Due to these issues, transplantations are usually only successful when they are carried out in children and young people, or older people in good health, and there is a suitable brother or sister who can provide a donation.

In most cases of chronic leukaemia, the potential risks of transplantation far outweigh any benefit. For example, the chances of an elderly person with advanced chronic leukaemia surviving a bone marrow transplant can be as low as one in five.

However, your specific circumstances may mean that the benefits of treatment outweigh the risks.

 



 


Clinical trials

In the UK, a number of clinical trials are underway that aim to find the best way to treat chronic leukaemia. Clinical trials are studies that use new and experimental techniques to see how well they work in treating and possibly curing chronic leukaemia.

However, you should be aware there is no guarantee the techniques being studied in the clinical trial will be more effective than current treatments.

Search clinical trials on chronic leukaemia

Your care team will be able to let you know whether there are any clinical trials available in your area, as well as explaining the benefits and risks involved.



Deciding against treatment

As many of the treatments described in this section have unpleasant side effects that can affect your quality of life, you may decide against having a particular type of treatment.

This is entirely your decision and your treatment team will respect any decision that you make. Pain relief and nursing care will be made available as and when you need it.

 

 

Complications of chronic myeloid leukaemia 

Being immunocompromised (having a weakened immune system) is a possible complication for some patients with chronic leukaemia.

There are two reasons for this:


the lack of healthy white blood cells means your immune system is less able to fight infection

many of the medicines used to treat chronic leukaemia can weaken the immune system


This means you are more vulnerable to developing an infection, and that any infection you have has an increased potential to cause serious complications.

You may be advised to take regular doses of antibiotics to prevent infections occurring. You should immediately report any possible symptoms of an infection to your GP or care team because prompt treatment may be required to prevent serious complications.

 

Symptoms of infection include:


high temperature (fever) of 38C (101.4F) or above

headache

aching muscles

diarrhoea

tiredness


Avoid contact with anyone who is known to have an infection, even if it is a type of infection that you were previously immune to, such as chickenpox or measles. This is because your previous immunity to these conditions will probably be suppressed (lowered).

While it is important to go outside on a regular basis, both for exercise and for your psychological wellbeing, avoid visiting crowded places and using public transport during rush hour.

Also ensure that all of your vaccinations are up-to-date. Your GP or care team will be able to advise you about this. You will be unable to have any vaccine that contains activated particles of viruses or bacteria, such as:


the mumps, measles and rubella (MMR) vaccine

the polio vaccine

the oral typhoid vaccine

the BCG vaccine (used to vaccinate against tuberculosis)

the yellow fever vaccine


 

Psychological effects of chronic leukaemia

Receiving a diagnosis of chronic leukaemia can be very distressing, particularly if it is unlikely that your condition can be cured. At first, the news may be difficult to take in.

The situation can be made worse if you are confronted with the knowledge that even though your leukaemia may not currently be causing any symptoms, it could be a serious problem in later life. Having to wait many years to see how the leukaemia develops can be immensely stressful and can trigger feelings of stress, anxiety and depression.

If you have been diagnosed with leukaemia, talking to a counsellor or psychiatrist (a doctor who specialises in treating mental health conditions) may help you to combat feelings of depression and anxiety. Antidepressants or medicines that help to reduce feelings of anxiety may also help you cope better with the condition.

You may find it useful to talk to other people who are living with leukaemia. Your GP or multidisciplinary team may be able to provide you with details of local support groups.

Another excellent resource is Macmillan Cancer Support. Their helpline number is 0808 808 00 00 FREE and is open Monday to Friday, 9am-8pm.  



 Leukaemiachronic myeloid