Acute lymphoblastic leukemia

About acute lymphoblastic leukemia

Leukemia is cancer of the white blood cells. Acute leukemia means the condition progresses rapidly and aggressively and requires immediate treatment.

Acute leukemia is classified according to the type of white blood cells affected by cancer. There are 2 main types:

lymphocytes, which are mostly used to fight viral infections.
neutrophils, which perform several functions, such as fighting bacterial infections, defending the body against parasites and preventing the spread of tissue damage.

These pages focus on acute lymphoblastic leukemia, which is cancer of the lymphocytes. The following other types of leukemia are covered elsewhere:

chronic lymphocytic leukemia
chronic myeloid leukemia
acute myeloid leukemia

Warning signs of acute leukemia

Symptoms of acute lymphoblastic leukemia usually begin slowly before rapidly getting severe as the number of immature white blood cells in your blood increases. Symptoms include:

pale skin
tiredness
breathlessness
having repeated infections over a short space of time
unusual and frequent bleeding

Read more about the symptoms of acute lymphoblastic leukemia.

What happens in acute leukemia?

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

Bone marrow produces specialized 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.

The bone marrow usually produces stem cells which are allowed to fully develop before being released into the blood. But in acute leukemia, bone marrow starts releasing large numbers of immature white blood cells known as blast cells.

As the number of blast cells increases there is a drop in the number of red blood cells and platelet cells. This drop causes the symptoms of anemia, such as tiredness, and increases the 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.

Despite being uncommon overall, acute lymphoblastic leukemia is the most common type of cancer to affect children.

The cause or causes of acute leukemia are uncertain, but known risk factors include:

exposure to high levels of radiation
exposure to benzene, a chemical used in manufacturing that is also found in cigarettes.

Read more information about the causes of acute lymphoblastic leukemia.

Symptoms of acute lymphoblastic leukemia

Symptoms of acute lymphoblastic leukemia usually begin slowly before rapidly getting severe as the number of blast cells (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 of acute lymphoblastic leukemia include:

pale skin
feeling tired and breathless
having repeated infections over a short space of time
unusual and frequent bleeding, such as bleeding gums or nose bleeds
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 of acute lymphoblastic leukemia, 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 seek medical advice

If you or your child has some or even all of these symptoms, it is still highly unlikely that acute leukemia is the cause.

However, see your GP as soon as possible because any condition that causes these symptoms needs to be promptly investigated and treated.

Causes of acute lymphoblastic leukemia

Acute lymphoblastic leukemia is caused by a DNA mutation in the stem cells causing too many white blood cells to be produced.

The white blood cells are also released from the bone marrow before they are mature and able to fight infection like fully developed 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 leukemia.

It is not known exactly what causes this DNA mutation to occur, but there are a few factors which may increase the risk of developing acute lymphoblastic leukemia.

Risk factors

Genetic disorders

A small number of childhood acute lymphoblastic leukemia cases are thought to be caused by related genetic disorders. For example, rates of leukemia tend to be higher in children with Down’s syndrome.

Radiation exposure

Exposure to very high levels of radiation, either before birth or afterwards, is a known risk factor. However, it would require a significant level of radiation, such as the amount released during the nuclear reactor accident at Chernobyl.

Due to the potential risk of radiation to unborn babies, medical techniques and equipment that use radiation, such as X-rays, are rarely used on pregnant women.

Most cases of childhood leukemia occur in children with no history of genetic disorders or exposure to radiation.

Possible environmental factors

Experts have also carried out extensive research to determine whether the following environmental factors could be a trigger for leukemia:

living near a nuclear power station
living near a power line
living near a building or facility that releases electromagnetic radiation, such as a mobile phone mast

At the moment there is no evidence to confirm that any of these environmental factors increase the risk of developing leukemia.

Benzene

Exposure to the chemical benzene is a known risk factor for adult acute leukemia. Benzene is found in petrol and is also used in the rubber industry. However, there are strict controls to protect people from prolonged exposure.

Benzene is also found in cigarettes, which could explain why smokers are three times more likely to develop acute leukemia than non-smokers. People who have had chemotherapy and radiotherapy to treat earlier, unrelated cancers also have an increased risk of developing acute leukemia.

Other risk factors

There is some evidence to show an increased risk of acute lymphoblastic leukemia in people who:

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

Diagnosing acute lymphoblastic leukemia

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

A high number of abnormal white blood cells in the blood sample could indicate the presence of acute leukemia and you will then be referred to a hematologist (a specialist in treating blood conditions).

Bone marrow biopsy

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

The hematologist will use a local anesthetic to numb the skin over a bone – usually the hip bone – and then use a needle to remove a sample of bone marrow. You may experience some pain once the anesthetic wears off and some bruising and discomfort for a few days afterwards. The procedure takes around 15 minutes to complete, 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 leukemia will be determined at the same time.

Further tests

There are various additional tests that can be used to help reveal more information about the progress and extent of the leukemia. They can also provide an insight into how the leukemia should be treated. These tests are described below.

Cytogenetic testing

Cytogenetic testing involves identifying the genetic make-up of the cancerous cells. There are specific genetic variations that can occur during leukemia, 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 leukemia. 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 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.

Lymph node biopsy

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

CT scans

If you have acute leukemia, a computerized tomography scan (CT scan) may be used to check that your organs, such as your heart and lungs, are healthy.

Chest X-ray

An X-ray may be performed to examine the chest for any swollen lymph nodes.

Lumbar puncture

If it is felt that there is a risk that acute leukemia has spread to your nervous system, a lumbar puncture may be carried out.

A lumbar puncture is a test where a needle is used under local anesthetic to extract a sample of cerebrospinal fluid (fluid that surrounds and protects your spine) from your back. The fluid is tested to determine whether the leukemia has reached your nervous system.

Treating acute lymphoblastic leukemia

Treatment for acute lymphoblastic leukemia usually begins a few days after diagnosis as it’s an aggressive condition that develops rapidly.

Stages of treatment

Treatment for acute lymphoblastic leukemia is carried out in stages:

induction – the aim of the initial stage of treatment is to kill the leukemia 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 leukemia cells in your central nervous system.
maintenance – the final stage involves taking regular doses of chemotherapy tablets to prevent the leukemia returning.

Maintenance only seems to be effective in treating acute lymphoblastic leukemia; it’s not usually used in the treatment of acute myeloid leukemia.

Induction

The induction stage of treatment is carried out in hospital or in a specialist center. This is because you will probably need to have regular blood transfusions as it’s likely that your blood will not contain enough healthy blood cells.

You will also be vulnerable to infection, so it is important that you are in a sterile environment where your health can be carefully monitored and any infection that you have can be promptly treated. You may also be prescribed antibiotics to help prevent further infection.

Chemotherapy

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

Some chemotherapy medication may also be directly administered into your cerebrospinal fluid to kill any leukemia cells that may have spread to your nervous system. This is given using a needle that is placed into your spine, in a similar way to a lumbar puncture.

Side effects that occur following chemotherapy are common. They can include:

nausea
vomiting
diarrhea
loss of appetite
mouth ulcers
tiredness
skin rashes
infertility
hair loss

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 leukemia known as Philadelphia chromosome-positive acute lymphoblastic leukemia, you will 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
diarrhea

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

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

Treatment involves receiving regular injections of chemotherapy medication. This is usually done on an outpatient basis, which means you will not have to stay in hospital overnight. However, you may require some short stays in hospital if your symptoms suddenly get worse or if 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 leukemia returning. It involves taking regular doses of chemotherapy tablets while undergoing regular check-ups to monitor how effective your treatment is proving.

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 leukemia, when all other treatments have proved unsuccessful.

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

Dasatinib cannot cure acute leukemia, but it can slow its growth, helping to relieve symptoms and prolong life.

Radiotherapy

Radiotherapy involves using high doses of controlled radiation to kill cancerous cells. There are two main reasons why radiotherapy is usually used to treat acute leukaemia:

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

Side effects of both types of radiotherapy include:

hair loss
nausea
fatigue

The side effects should pass once your course of radiotherapy has been completed. However, your skin may be very sensitive to the effects of light for several months after the 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 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 surgery.

Bone marrow and stem cell transplants

If you or your child do not respond to chemotherapy, a possible alternative treatment option is bone marrow or stem cell transplantation.

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 are carried out in children and young people, or older people who are in good health, and when there is a suitable donor, such as a brother or sister.

Read about bone marrow transplantation for more information.

Complications of acute lymphoblastic leukemia

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

There are 2 reasons for this:

the lack of healthy white blood cells means that your immune system is less able to fight infection.
many of the medicines used to treat acute leukemia can weaken the immune system.

This means that 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
diarrhea
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 lower.

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 containing activated particles of viruses of 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

Bleeding

If you have acute leukemia, you will bleed and bruise more easily due to the low levels of platelets (clot-forming cells) in your blood. Bleeding may also be excessive when it does occur.

Bleeding can occur:

inside the skull (intracranial hemorrhage)
inside the lungs (pulmonary hemorrhage)
inside the stomach (gastrointestinal hemorrhage)

The symptoms of an intracranial hemorrhage include:

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

The most common symptoms of a pulmonary hemorrhage are:

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

The 2 most common symptoms of a gastrointestinal hemorrhage are:

vomiting blood
passing stools (feces) that are very dark or tar-like.

All 3 types of hemorrhages should be regarded as medical emergencies. Phone 911 to request an ambulance if you suspect that you or your child is experiencing a hemorrhage.

Infertility

Many of the treatments that are used to treat acute leukemia 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 have received high doses of chemotherapy and radiotherapy in preparation for bone marrow or stem cell transplantation.

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

Psychological effects of leukemia

Receiving a diagnosis of leukemia 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 leukemia 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 leukemia develops can be immensely stressful and can trigger feelings of stress, anxiety and depression.

If you have been diagnosed with leukemia, talking to a counsellor or psychiatrist (a doctor who specializes 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 leukemia. Your GP or multidisciplinary team may be able to provide you with details of local support groups.