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Leukaemia, acute lymphoblastic Content Supplied by NHS Choices
Introduction

Acute lymphoblastic leukaemia is a type of cancer that affects the white blood cells. It progresses rapidly and aggressively and requires immediate treatment. Both adults and children can be affected.

Acute lymphoblastic leukaemia is very rare, with around 650 people diagnosed with the condition each year in the UK. Half of all cases diagnosed are in adults and half in children.

Although rare, acute lymphoblastic leukaemia is the most common type of childhood leukaemia. About 85% of the cases that affect children occur in those younger than 15 (mostly between the ages of two and five). It tends to be more common in males than females.

Acute lymphoblastic leukaemia is different to other types of leukaemia, including acute myeloid leukaemia, chronic lymphocytic leukaemia and chronic myeloid leukaemia.

This page covers:

What happens in acute lymphoblastic leukaemia

Symptoms

When to get medical advice

Causes

Treatment

Complications

Outlook

What happens in acute lymphoblastic leukaemia

All of the blood cells in the body are produced by bone marrow, a spongy material found inside bones.

Bone marrow produces specialised cells called stem cells, which have the ability to develop into three important types of blood cells:

  • red blood cells - which carry oxygen around the body
  • white blood cells - which help fight infection
  • platelets - which help stop bleeding

Normally, bone marrow doesn't release stem cells into the blood until they are fully developed blood cells. But in acute lymphoblastic leukaemia, large numbers of white blood cells are released before they are ready. These are known as blast cells.

As the number of blast cells increases, the number of red blood cells and platelet cells decreases. This causes the symptoms of anaemia, such as tiredness, breathlessness and an increased risk of excessive bleeding.

Also, blast cells are less effective than mature white blood cells at fighting bacteria and viruses, making you more vulnerable to infection.

Symptoms of acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia usually starts slowly before rapidly becoming severe as the number of immature white blood cells in your blood increases.

Most of the symptoms are caused by the lack of healthy blood cells in your blood supply. Symptoms include:

  • pale skin
  • feeling tired and breathless
  • repeated infections over a short space of time
  • unusual and frequent bleeding, such as bleeding gums or nosebleeds
  • high temperature (fever) of 38C (100.4F) or above
  • night sweats
  • bone and joint pain
  • easily bruised skin
  • swollen lymph nodes (glands)
  • abdominal pain - caused by a swollen liver or spleen
  • unexplained weight loss
  • a purple skin rash (purpura)

In some cases, the affected cells can spread from your bloodstream into your central nervous system. This can cause a series of neurological symptoms (related to the brain and nervous system), including:

  • headaches
  • seizures (fits)
  • vomiting
  • blurred vision
  • dizziness

When to get medical advice

If you or your child has some or even all of the symptoms listed above, it's still highly unlikely that acute leukaemia is the cause. However, see your GP as soon as possible because any condition that causes these symptoms needs prompt investigation and treatment.

Read more about diagnosing acute lymphoblastic leukaemia.

What causes acute lymphoblastic leukaemia

It is a genetic change (mutation) in the stem cells that causes immature white blood cells to be released into the bloodstream.

It's not clear what causes the DNA mutation to occur, but known risk factors include:

  • previous chemotherapy - if you've had chemotherapy to treat unrelated cancers in the past, your risk of developing acute lymphoblastic leukaemia is increased; the risk relates to certain types of chemotherapy medicine (etoposide, mitoxantrone, amsacrine and idarubicin), and how much treatment you had
  • smoking - smokers are much more likely to develop acute leukaemia than non-smokers, and studies have shown that parents who smoke in the home may increase the risk of leukaemia in their children
  • being very overweight (obese) - some studies have shown that people who are very overweight have a slightly higher risk of developing leukaemia than those who are a normal weight
  • genetic disorders - a small number of cases of childhood acute lymphoblastic leukaemia are thought to be related to genetic disorders, including Down's syndrome
  • having a weakened immune system - people with lowered immunity (as a result of having HIV or AIDS or taking immunosuppressants) have an increased risk of developing leukaemia

Cancer Research UK has more information about acute lymphoblastic leukaemia risks and causes.

Treating acute lymphoblastic leukaemia

As acute lymphoblastic leukaemia is an aggressive condition that develops rapidly, treatment usually begins a few days after diagnosis.

Treatment is usually carried out in the following stages:

  • induction - initially, treatment aims to kill the leukaemia cells in your bone marrow, restore the balance of cells in your blood and resolve any symptoms you may have
  • consolidation - aims to kill any remaining leukaemia cells in your central nervous system
  • maintenance - involves taking regular doses of chemotherapy tablets to prevent the leukaemia returning

Chemotherapy is the main treatment for acute lymphoblastic leukaemia. Other treatments you may need include antibiotics and blood transfusions. In some cases, a bone marrow transplant may also be needed to achieve a cure.

Read more about treating acute lymphoblastic leukaemia.

Complications of acute lymphoblastic leukaemia

If a cure for acute lymphoblastic leukaemia isn't possible, there's a risk that the lack of healthy blood cells can make the person:

  • extremely vulnerable to life-threatening infections (because of the lack of white blood cells)
  • prone to uncontrolled and serious bleeding (because of the lack of platelets)

These two complications, plus a number of others, are discussed further in complications of acute lymphoblastic leukaemia.

Outlook

The outlook for children with acute lymphoblastic leukaemia is usually good. Almost all children will achieve remission (a period of time where they're free from symptoms), and 85% will be completely cured.

The outlook for adults with acute lymphoblastic leukaemia is less promising. Around 40% of people aged between 25 and 64 will live for five years or more after receiving their diagnosis. In those aged 65 or over, around 15% will live for five years or more after being diagnosed.

Cancer Research UK has more detailed survival statistics for acute lymphoblastic leukaemia.



Diagnosis

The first step in diagnosing acute lymphoblastic leukaemia is to check for physical signs of the condition, such as swollen glands, and to take a blood sample.

If the blood sample contains a high number of abnormal white blood cells, it could be a sign of acute leukaemia. Your GP will refer you to a haematologist (a specialist in treating blood conditions).

Bone marrow biopsy

To confirm a diagnosis of acute leukaemia, the haematologist will take a small sample of your bone marrow to examine under a microscope.

The haematologist will use a local anaesthetic to numb the skin over a bone - usually the hip bone - before removing a sample of bone marrow with a needle. 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 and you shouldn't have to stay in hospital overnight.

The bone marrow will be checked for cancerous cells and, if found, the type of acute leukaemia will be determined at the same time.

Some people with acute leukaemia will need to have a bone marrow assessment to check for cancerous cells every three months for at least two years during maintenance treatment or after having a bone marrow transplant.

Further tests

A number of additional tests (described below) can be used to find out about the progress and extent of the leukaemia. They can also help guide treatment.

Cytogenetic testing

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

Immunophenotyping

Immunophenotyping is a test to help identify the exact type of acute lymphoblastic leukaemia. A sample of blood, bone marrow or another type of fluid is studied.

This testing is important as the treatment needed may be slightly different for each type.

Polymerase chain reaction (PCR)

A polymerase chain reaction (PCR) test can be carried out on a blood sample. PCR can help 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.

Lymph node biopsy

If you've been diagnosed with acute leukaemia, further biopsies may be carried out on any enlarged lymph nodes that you have. These will establish how far the leukaemia has spread.

CT scans

If you have acute leukaemia, a computerised tomography (CT) scan may be used to assess how far the leukaemia has spread and to check that your organs, such as your heart and lungs, are healthy.

Chest X-ray

You may have an X-ray so that the chest can be examined for any swollen lymph nodes.

Lumbar puncture

A lumbar puncture may be carried out if there's a risk that acute leukaemia has spread to your nervous system.

A needle is inserted into the lower part of your spine to extract a small sample of cerebrospinal fluid (the fluid that surrounds and protects your spine), which is tested for cancer cells.



Treatment

Acute lymphoblastic leukaemia is an aggressive condition that develops quickly, so treatment usually begins a few days after diagnosis.

Stages of treatment

Treatment for acute lymphoblastic leukaemia is usually carried out in three stages. They are:

  • induction - the aim of the initial stage of treatment is to kill the leukaemia cells in your bone marrow, restore the balance of cells in your blood and resolve any symptoms you may have
  • consolidation - this stage aims to kill any remaining leukaemia cells in your central nervous system
  • maintenance - the final stage involves taking regular doses of chemotherapy tablets to prevent the leukaemia returning

Induction

The induction stage of treatment is carried out in hospital or a specialist centre. This is because you'll probably need regular blood transfusions as your blood won't contain enough healthy blood cells.

You'll also be vulnerable to infection, so it's important you're in a sterile environment where your health can be carefully monitored and any infection that develops can be treated quickly. Antibiotics may also be prescribed to help prevent further infection.

Chemotherapy

You'll have chemotherapy to kill the leukaemia cells in your bone marrow. Although some medications may be given as pills, you'll need more than one medication given as an injection. To make things easier and avoid repeated injections, they can all be given through a flexible tube (a 'central line') that goes into a vein in your chest.

Some chemotherapy medication may also be directly administered into your cerebrospinal fluid to kill any leukaemia cells that may have spread to your nervous system and brain. The type of chemotherapy medication used is called methotrexate and it's given as an injection into your spine, in a similar way to a lumbar puncture.

After you've had the injection, you'll have to lie flat for a few hours with your head positioned slightly lower than your feet. You may have a headache or feel sick afterwards.

Methotrexate is also given intravenously (directly into a vein) in adults with acute lymphoblastic leukaemia after induction therapy and before consolidation.

Other common side effects following chemotherapy include:

The side effects should resolve once treatment has finished. Your hair will usually take between three to six months to grow back.

Steroid therapy

You may also be given corticosteroid injections or tablets to help improve the effectiveness of chemotherapy.

Imatinib

If you have a type of leukaemia known as Philadelphia chromosome-positive acute lymphoblastic leukaemia, you'll also be given a medicine called imatinib. Imatinib works by blocking the signals in the cancerous cells that cause them to grow and reproduce. This kills the cancerous cells.

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

  • nausea
  • vomiting
  • swelling in the face and lower legs
  • muscle cramps
  • rash
  • diarrhoea

Depending on how well you respond to treatment, the induction phase can last from two weeks to several months. In some cases, you or your child may be able to leave hospital and receive treatment on an outpatient basis if your symptoms improve.

Consolidation

Leukaemia can return if just one cancerous cell remains in your body. Therefore, the aim of consolidation treatment is to ensure that any remaining leukaemia cells are killed.

Treatment involves receiving regular injections of chemotherapy medication. This is usually done on an outpatient basis, which means you won't have to stay in hospital overnight. However, you may need some short stays in hospital if your symptoms suddenly get worse or you develop an infection.

The consolidation phase of treatment lasts several months.

Maintenance

The maintenance phase is designed to act as further insurance against the possibility of the leukaemia returning. It involves taking regular doses of chemotherapy tablets while having regular check-ups to monitor the effectiveness of your treatment.

The maintenance phase can often last for two years.

Other treatments

As well as chemotherapy and imatinib, other treatments are used in some circumstances. These are described below.

Dasatinib

Dasatinib is a new type of medication used to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia, when all other treatments have proved unsuccessful.

Dasatinib blocks a protein called tyrosine kinase that helps stimulate the growth of cancer cells.

Dasatinib can't cure acute leukaemia but it can slow its growth, helping to relieve symptoms and prolong life.

The National Institute for Health and Care Excellence (NICE) hasn't decided whether the NHS should provide treatment with dasatinib for people with acute lymphoblastic leukaemia. This means it will be at the discretion of your local clinical commissioning group (CCG) as to whether you'll be offered dasatinib.

Radiotherapy

Radiotherapy is where high doses of controlled radiation are used to kill cancerous cells. It's usually used to treat acute leukaemia in the following two situations:

  • to treat advanced cases of acute lymphoblastic leukaemia that have spread to the nervous system or brain
  • to prepare the body for a bone marrow transplant (see below)

Side effects include:

  • hair loss
  • nausea
  • fatigue

These side effects should pass after your course of radiotherapy has been completed. However, your skin may be very sensitive to the effects of light for several months after treatment has finished. If this is the case, avoid sunbathing or exposure to sources of artificial light, such as sunbeds, for several months.

Many younger children treated with radiotherapy will go on to have restricted physical growth during puberty.

A small number of people develop cataracts several years after having radiotherapy. Cataracts are cloudy patches in the lens (the transparent structure at the front of the eye) that can make your vision blurred or misty. Cataracts can usually be successfully treated using cataract surgery.

Stem cell and bone marrow transplants

A stem cell and bone marrow transplant is a possible alternative treatment option if you or your child don't respond to chemotherapy.

Transplantations are more successful if the donor has the same tissue type as you, so the ideal donor is usually a brother or sister.

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

This can put a big strain on the body so transplantations are usually only successful when they're carried out in children and young people, or older people in good health, and when there's a suitable donor, such as a brother or sister.

Recent research has shown that it's possible for people over the age of 40 to have a reduced intensity stem cell transplant. This is where lower than normal doses of chemotherapy and radiotherapy are used before the transplant, which places less strain on the body.



Complications

Being immunocompromised (having a weakened immune system) is a possible complication for some people with acute 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 acute leukaemia can weaken the immune system

This makes you more vulnerable to developing an infection, and any infection you do have is more likely to cause serious complications.

You may be advised to take regular doses of antibiotics to prevent infections occurring. You should report any possible symptoms of an infection immediately to your GP or care team because prompt treatment may be needed 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 known to have an infection, even if it's 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 lower.

It's important to go outside on a regular basis, both for exercise and for your wellbeing, but you should avoid visiting crowded places and using public transport during rush hour.

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

Bleeding

If you have acute leukaemia, you'll bleed and bruise more easily because of the low levels of platelets (clot-forming cells) in your blood.

Although major bleeding is uncommon, you need to be aware of the related symptoms that can occur in different parts of the body.

Bleeding can occur:

  • inside the skull (intracranial haemorrhage)
  • inside the lungs (pulmonary haemorrhage)
  • inside the stomach (gastrointestinal haemorrhage)

The symptoms of an intracranial haemorrhage include:

  • severe headache
  • stiff neck
  • vomiting
  • change in mental state, such as confusion

The most common symptoms of a pulmonary haemorrhage are:

  • coughing up blood from your nose and mouth
  • breathing difficulties
  • a bluish skin tone (cyanosis)

The two most common symptoms of a gastrointestinal haemorrhage are:

  • vomiting blood
  • passing stools (faeces) that are very dark or tar-like

All three types of haemorrhages should be regarded as medical emergencies. Dial 999 for an ambulance if you suspect that you or your child is experiencing a haemorrhage.

Infertility

Many of the treatments used to treat acute leukaemia can cause infertility. Infertility is often temporary, although in some cases it may be permanent.

People who are particularly at risk of becoming infertile are those who've received high doses of chemotherapy and radiotherapy in preparation for stem cell and bone marrow transplants.

It may be possible to guard against any risk of infertility before you begin your treatment. For example, men can store sperm samples. Similarly, women can have fertilised embryos stored, which can be put back into their womb following treatment.

Psychological effects of leukaemia

Being diagnosed with leukaemia can be very distressing, particularly if a cure is unlikely. At first, the news may be difficult to take in.

It can be particularly difficult if you don't currently have any leukaemia symptoms, but you know that it could present a serious problem later on. Having to wait many years to see how the leukaemia develops can be very stressful and can trigger feelings of anxiety and depression.

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

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

Macmillan Cancer Support is also an excellent resource. Its helpline number is 0808 808 00 00 and is open Monday to Friday, 9am to 8pm.

Further information

You can read more about all aspects of living and coping with cancer at the following links:



"I was put in an ambulance that night ... I was petrified"

When Hazel Phillips went to see her GP about an ear infection, she suspected something more serious was wrong because of her other symptoms. A blood test confirmed her worst fears: she had acute lymphoblastic leukaemia.

Many years later, she's now in a successful, enjoyable job. She sometimes has anxiety but tries to put the experience behind her.

"When I was 11 years old I remember having an ear infection that lasted about four weeks. I also remember feeling really tired and faint when I was running in the playground, and seeing lines around everyone.

"One evening I came home with a really bad rash on my ankles, which we thought might be German measles. I was also getting out of breath walking up stairs.

"My mum took me to the doctor after school one evening to talk about the ear infection. My GP asked me some questions, and I told her about the other things that had been happening. She looked at me and said, 'We need to take you to hospital'.

"I had to go straight to Canterbury hospital that night to have a blood test. About two hours after the test they said, 'You've got leukaemia and you need to go to the Royal Marsden Hospital'. I was put in an ambulance and taken to the Marsden that night. I was petrified.

"I was in hospital for three months. I had quite a lot of chemotherapy but was lucky - there weren't too many adverse effects and I responded well to it.

"Some of my friends came to see me in hospital, which I found difficult. A lot of the time I couldn't stand up straight because of the lumbar punctures I'd had, and I'd put on weight because of the steroids.

"I then had about six weeks out of hospital, followed by another two weeks of very intensive chemotherapy. For the next year I was on chemotherapy.

"I've been in remission ever since, but it's not until five years after the treatment that you're told, 'OK, you only need to come back once a year now'.

"For the first few months I wasn't allowed to be in contact with many people as my immune system was low and I could get infections really easily. But I had great support from my family, and the charity Make-A-Wish Foundation gave me a pony when it was all over, which was lovely.

"Afterwards, I was absolutely fine, but three years ago I started to feel the effects of it emotionally. I suffer from anxiety quite a lot and I'm having counselling at the moment.

"I'm now working as an assistant marketing manager. I recently got a promotion and I'm really enjoying it."

Case study provided by Cancer Research UK.



 
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