ACUTE MYELOID LEUKAEMIA

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Treatment

Treatment for acute myeloid leukaemia

The aim of treatment for acute myeloid leukaemia (AML) is to destroy the leukaemia cells and allow the bone marrow to work normally again. When there is no sign of the leukaemia and the
marrow is working normally this is called remission. For many people with AML the remission lasts indefinitely and the person is said to be cured.

Types of treatment
AML trials
Second opinion
Giving your consent
Benefits and disadvantages of treatment

Types of treatment

Chemotherapy is the main treatment used. Research has shown that certain types of chemotherapy drugs can be very effective in treating AML. These drugs are usually given in combination. Most people with acute myeloid leukaemia go into remission after chemotherapy, and many people are cured.

In some situations high-dose chemotherapy and a stem cell or bone marrow transplant are used to improve the chances of curing the leukaemia.

People who have a type of AML called acute promyelocytic leukaemia (APL) are usually treated with a drug called ATRA (All Trans-Retinoic Acid). It is a specialised form of vitamin A and is also known as tretinoin (Vesanoid®).

ATRA is given for up to three months alongside chemotherapy treatment. It makes the leukaemia cells mature (differentiate), and so can reduce leukaemia symptoms very quickly.

Your doctor will plan your treatment by taking into account a number of factors, including your age, general health, and the type of abnormal genes that are present in the leukaemia cells.

AML trials

Most people who are under 60 with AML will be asked if they would like to take part in the AML-15 trial. This trial is comparing the effectiveness of the current treatments used for AML. People aged 60 and over may be invited to take part in this trial if they are fit enough for intensive chemotherapy.

There is also a trial designed for people over 60 with AML: the AML-16 trial. It is comparing the effectiveness of a number of different treatments for AML and uses slightly less intensive treatment.

Other trials are also underway looking into the use of newer drugs to treat AML. Your doctor may ask you to take part in one of these trials. You will be given written information about any trial in which you are invited to take part.

See the clinical trials booklet for more information about acute myeloid leukaemia trials.

If you have any questions about your treatment, don't be afraid to ask your doctor or nurse.
It is often useful to make a list of questions for your doctor and to take a relative or close friend with you. The fill-in form on the last page may help.

Second opinion

Some people find it reassuring to have another medical opinion to help them decide about their treatment. Most doctors would normally be pleased to refer you to another specialist for this.
However, a second opinion can sometimes take time to arrange. As treatment for AML should usually be started as soon as possible there may not be time to arrange this for you.

If you would like a second opinion, it is a good idea to discuss this with your specialist when you first see them.

Giving your consent

Before you have treatment a doctor will explain its aims to you. Medical treatment can't be given to someone without their permission, so you will usually be asked to sign a form giving permission (consent) for the hospital staff to give you treatment. Before signing this, you should have been given full information about:

the type and extent of the treatment you are advised to have
the advantages and disadvantages of the treatment
any other treatments that may be available
any significant risks or side effects of the treatment.

If you don't understand what you have been told, ask for things to be explained again. Treatments for leukaemia can be complex, so it is not unusual for people to need to go over things more than once.

There may be written information about your treatment, which you can take away and read in your own time. It often helps to have a friend or relative with you when the treatment is explained. They can help you to remember what has been said. You may also find it useful to write down a list of questions you want to ask before seeing the doctor.

You are also free to choose not to have treatment. It is important that you understand what may happen if you do not have treatment. The medical staff will need to record your decision in your
medical notes.

The staff will be able explain what support may be available if this is your choice.

Benefits and disadvantages of treatment

The possible benefits of treatment vary depending on each individual situation.

Most people under 60 with AML are offered intensive chemotherapy. For many people this will cure the leukaemia, but it involves spending periods of time in hospital and can cause side effects. Most of these side effects are temporary and can usually be controlled with medicines. However some, such as effects on fertility, may be permanent for some people.

Some people over the age of 60 will have intensive chemotherapy to try to cure the leukaemia. However, not everyone will be fit enough to undergo intensive treatment. Also, some people may not want to have it. Instead they may have lower doses of chemotherapy to control the leukaemia cells in the bone marrow rather than to try to get rid of them completely. This treatment can often be given as an outpatient so less time is spent in hospital. The chances of the disease going into remission are lower with this type of treatment.

If the leukaemia is at an advanced stage and treatment to control it is no longer helpful, or if you choose not to have treatment, you can still be given supportive (palliative) care, with medicines
and transfusions to help to control symptoms.

Your haematologist is the best person to discuss your situation with. In some hospitals, specialist nurses are available to talk over all the possible benefits and side effects of treatment.

Chemotherapy for acute myeloid leukaemia

What is chemotherapy?
How chemotherapy is given
Induction chemotherapy
Consolidation chemotherapy
High-dose treatment
Low-dose treatment
Central lines
PICC lines
Supportive care
Possible side effects

What is chemotherapy?

Chemotherapy is the use of anti-cancer (cytotoxic) drugs to destroy the leukaemia cells. It works by disrupting the way leukaemia cells grow and divide. As the drugs circulate in the blood they can reach leukaemia cells all over the body.

The main aim of treatment for acute myeloid leukaemia is to try to cure it. The first step is to achieve a remission. This means that the abnormal, immature cells, or blasts, can no longer be
detected in your blood or bone marrow, and normal bone marrow has developed again.

When you are in remission there may still be a small number of abnormal cells in your body, even though doctors can no longer detect any signs of the leukaemia, so you will need to have further chemotherapy to reduce the risk of the leukaemia coming back.

The doctors will monitor you closely to see how well your leukaemia is responding to the chemotherapy. They will plan what further treatment is necessary depending on how the leukaemia responds.

Our booklet on chemotherapy discusses the treatment and its side effects in more detail. Factsheets about individual drugs and their particular side effects is also available.

How chemotherapy is given

The chemotherapy drugs are usually given by drip or injection through a thin, flexible plastic tube. The tube is inserted under the skin and into a vein near the collarbone (central line or Hickman® line), or passed through a vein in the arm (PICC line). Your doctor or nurse will explain more about this to you, and there is more information in this booklet.

Chemotherapy is usually given as several sessions (cycles) of treatment. Each session lasts for 5- 10 days and is followed by a rest period of three to four weeks. This rest period allows your body to recover from the side effects of the treatment. Most people have four or five cycles of chemotherapy. The complete course of treatment can last about six months.

Induction chemotherapy

The first cycles of chemotherapy are called induction chemotherapy. Most people have two cycles of induction chemotherapy. You may be able to go home between treatments if you are well
enough.

The most commonly used induction chemotherapy drugs are cytarabine (Ara-C), daunorubicin, etoposide (Etopophos®, Vepesid®), fludarabine (Fludara®) and idarubicin (Zavedos®).

Currently two national trials (AML-15 and AML-16) are being carried out. One of the things the trials are trying to find out is whether giving a monoclonal antibody called gemtuzumab,
(Mylotarg®) with chemotherapy is better than chemotherapy alone. See newer treatments for information about gemtuzumab.

If the induction chemotherapy does not destroy all of the leukaemia cells, you will be given further cycles of chemotherapy aimed at getting the leukaemia into remission.

Consolidation chemotherapy

If there is no sign of the leukaemia in your bone marrow after induction chemotherapy, you will be given further cycles of chemotherapy to reduce the risk of the leukaemia coming back. This is
known as consolidation treatment. The most commonly used drugs for consolidation chemotherapy are cytarabine, etoposide, daunorubicin and mitoxantrone.

High-dose treatment

For some people, high-dose chemotherapy with a stem cell or bone marrow transplant may be helpful. The doctor will consider whether chemotherapy alone is likely to cure the leukaemia.

If there is a high risk that your leukaemia will come back after chemotherapy, your doctor may suggest that you have high-dose chemotherapy, or chemotherapy with radiotherapy, followed by a transplant. The transplant may be carried out using either your own, or a donor's, stem cells or bone marrow.

Low-dose treatment

This may be the best option for people who are not fit enough to have intensive chemotherapy and for people who choose not to have intensive treatment. It is aimed at controlling the number of leukaemia cells in the bone marrow but gives a lower chance of remission. The chemotherapy drugs may be given by mouth or by injection under the skin (subcutaneous). It can often be given on an outpatient basis.

One part of the AML-16 trial is looking at ways to improve the effectiveness of low-dose treatment by adding other newer types of drugs to the most commonly-used drug cytarabine (Ara-C). See newer treatments for more information.

Central lines

To make it easier to give the chemotherapy drugs, and to avoid having to have frequent injections, a plastic tube (called a central line or Hickman® line) can be put into a vein in the chest. The line is put in under a general or local anaesthetic and, apart from a stiff shoulder, which you may have for a couple of days, should be completely painless.

Once it is in place, the central line is either stitched or taped firmly to your chest to prevent it from being pulled out of the vein. Drugs are given through the tube directly into your bloodstream. The line can stay in for many months. The nurses will show you how to care for it to prevent blockages or infection. Blood can be taken from the line for testing and blood transfusions can also be given through it.

PICC lines

Sometimes a PICC (peripherally inserted central catheter) line can be used instead of a central line. A thin tube is inserted into a vein in the crook of your arm. This can stay in place for several
months.

Supportive care

During your treatment you will also have supportive care. This treats the symptoms that are caused by a lack of normal blood cells and often involves having transfusions of red blood cells
and platelets from time to time.

See the factsheets on blood transfusions and platelet transfusions for further information.

Possible side effects

Lowered resistance to infection

While the chemotherapy drugs are acting on the leukaemia cells in your body, they also reduce the number of normal cells in your blood for a while. When white blood cells are in short supply, you are more likely to get an infection. During chemotherapy your blood will be tested regularly. You will probably be given tablets or other medicines to reduce the risk of certain types of infection.

If you get an infection, you will be treated for it straight away. Most infections are caused by bacteria, fungi or viruses already present in your own body, or in the environment. These do not
normally cause infection, but when your immunity is low they are more likely to cause a problem.

It is best to avoid coming into contact with people who may have an infection. You may also be advised to be careful about what you eat, in order to guard against the risk of infection from raw, undercooked or contaminated food. The hospital will give you information on how to prepare foods and which foods to avoid.

If your temperature goes above 37.5C (100F) or you suddenly feel unwell, even with a normal temperature, contact your doctor or nurse at the hospital straight away.

Anaemia

If the level of red blood cells in your blood is low you may become very tired and lethargic. You may also become breathless. These are all symptoms of anaemia - a lack of red blood cells in the blood.

Anaemia can be treated by blood transfusions.

Increased risk of bruising and bleeding

Platelets help your blood to clot. When you have leukaemia, the number of platelets in your blood is lower than normal, and chemotherapy may temporarily reduce the numbers even more. This means that you may bruise very easily, and may bleed heavily from even minor cuts and grazes.

You may need to have a transfusion of platelets before your chemotherapy begins, and at times during your treatment, to increase the number of platelets.

If you develop any unexplained bruising or bleeding, contact the hospital immediately.

Tiredness (fatigue)

This is a very common side effect of chemotherapy. The fatigue may be caused by anaemia, but may also be due to chemotherapy, even if your blood count is normal. You may be especially
aware of this when you are at home between cycles of chemotherapy, and for a few months after the treatment has finished.

Changes to the way that your heart works

Some of the drugs used to treat acute myeloid leukaemia may affect the heart muscle. The doses of the chemotherapy drugs are carefully monitored, and heart tests may be done from time to time to check your heart function.

Sore mouth

Some chemotherapy drugs can make your mouth sore and cause mouth ulcers. Regular mouthwashes are important and the nurses will show you how to use these properly. If you don't feel like eating during treatment, you could try replacing some meals with nutritious drinks or a soft diet. A nurse or dietitian at the hospital can give you advice about how to eat well during your
chemotherapy if your mouth is sore.

Feeling sick

Some of the drugs used to treat acute myeloid leukaemia may make you feel sick and may sometimes cause vomiting. There are now very effective anti-sickness drugs (anti-emetics) to prevent or greatly reduce nausea and vomiting. Your doctor will prescribe these for you. If you still feel sick, despite the anti-emetics, let your doctor or nurse know so that they can change them for
other drugs, which may be more effective.

Hair loss

Hair loss is another common side effect of these drugs. This can be very upsetting. If your hair falls out it should start to grow back over a period of 3-6 months once the treatment ends. There are many ways of covering up, including, wigs, hats or scarves. You may be entitled to a free wig from the NHS and your doctor or one of the nurses on the ward can arrange for a wig specialist to visit you.

Chemotherapy affects different people in different ways. Some find they are able to lead a fairly normal life during their treatment, but many find they become very tired and have to take things
much more slowly. Do as much as you feel like and try not to overdo it.

Although they may be hard to deal with at the time, most of these side effects will disappear once your treatment is over.

Stem cell and bone marrow transplants for AML

Chemotherapy treatments reduce the production of blood cells by the bone marrow. The rest periods between courses of chemotherapy allow your bone marrow to recover. However, there is a limit to how much chemotherapy you can have without it causing permanent damage to your bone marrow.

Bone marrow and stem cell transplants are a way of allowing much higher doses of chemotherapy to be given, to improve the chances of completely curing the leukaemia. They are not suitable
treatments for everyone with acute myeloid leukaemia. If your doctor thinks that a transplant is necessary or possible for you, they will discuss it with you in detail.

Having a transplant
Autologous transplants
Allogeneic transplants

Having a transplant

Very high doses of chemotherapy, with or without radiotherapy, are given, which destroy all the cells in your bone marrow. Soon afterwards, stem cells (the immature blood cells which develop into red cells, white cells and platelets) are given back into your blood through your central or PICC line. These cells make their way into the bone marrow and start to make healthy blood cells.

The stem cells may be your own (taken before your high dose treatment), or donated by someone else (usually a brother or sister). The new stem cells take a few weeks to settle in your bone
marrow and produce the blood cells that you need. During this time you will have very low immunity. You will probably need to stay in hospital and be nursed in isolation. This is done to
reduce your risk from infection until your white blood cell count has recovered.

Stem cell transplants use stem cells which are taken from the blood. This is collected through a small tube (cannula) which is put into a vein. The stem cells are then removed, and the blood is
then returned through another cannula.

For a bone marrow transplant, some of the bone marrow is taken from the bones under general anaesthetic. The bone marrow contains stem cells.

Stem cell and bone marrow transplants carry some risk, and are generally carried out in major cancer treatment hospitals, so you may have to be treated at a hospital some distance from your
home.

Autologous transplants

Autologous transplants use your own stem cells. They are collected from your blood while you are free of any signs of leukaemia (in remission).

To collect the stem cells from the blood, you will be given daily injections of a growth factor - a protein that stimulates the bone marrow to produce lots of stem cells. These 'spill over' into the
blood and can then be collected. This growth factor will be given immediately following a course of chemotherapy, which is the time when it is most effective.

Allogeneic transplants

This type of transplant uses stem cells or bone marrow donated by someone else. Usually, you can only have this type of transplant if you have a brother or sister whose bone marrow is a close match to your own.

Sometimes it is possible to use an unrelated donor for a stem cell transplant if tests have shown that their white blood cells are a good match with yours. This type of transplant is called a MUD
(Matched Unrelated Donor) transplant.

We have a booklet on stem cell and bone marrow transplants which describes these treatments in detail.

Radiotherapy for acute myeloid leukaemia

Radiotherapy treats cancer by using high-energy rays to destroy the cancer cells, while doing as little harm as possible to normal cells.

If you need a bone marrow or stem cell transplant you may have a type of radiotherapy called total body irradiation, or TBI. Radiotherapy is given to the whole body to destroy the bone marrowcells. This is described in our booklet on stem cell and bone marrow transplants.

ATRA (All Trans-Retinoic Acid)

ATRA is given alongside chemotherapy to people with a type of acute myeloid leukaemia called acute promyelocytic leukaemia (APL). It works by making the leukaemia cells mature.

ATRA is also known as tretinoin (Vesanoid®). It is based on the natural substance vitamin A and is not a chemotherapy drug. However, it does have some side effects, which can include:

headaches
dry skin and mouth
feeling sick (nausea)
bone pain
dry eyes.

ATRA in pregnancy

It is important not to become pregnant while taking ATRA. ATRA shouldn't be given to women who are under 12 weeks pregnant as this can cause damage to the baby.

After 12 weeks it can be given safely. Usually it's given without chemotherapy as this is safer for the baby and still effective.

Newer treatments for AML

The following treatments are not licensed for use in the UK for acute myeloid leukaemia and so are not generally available outside of research trials. If you take part in a clinical trial you may be
offered one or more of these drugs as part of your treatment.

Clofarabine (Evoltra®)
Gemtuzumab
CEP701
Tipifarnib (Zarnestra®)
Arsenic trioxide (ATO, Trisenox®)

Clofarabine (Evoltra®)

Clofarabine is very similar to another drug commonly used to treat people with AML called fludarabine. It is thought that as clofarabine has fewer side effects than fludarabine it may be more
suitable for older people who are less able to have intensive chemotherapy.

Clofarabine is given by infusion and is only available for AML as part of research trials. Some people taking part in the AML-16 trial will be given clofarabine.

Gemtuzumab

Gemtuzumab also known as Mylotarg® is given as a drip into a vein (intravenously).

Gemtuzumab is a treatment made up of a combination of an antibody and a chemotherapy drug. The antibody attaches itself to a protein (CD33) found on the surface of leukaemia cells. In this
way the antibody carries the chemotherapy directly to the leukaemia cells. Because CD33 is found mainly on leukaemia cells, it is hoped this drug will target the chemotherapy against leukaemia cells while causing less damage to healthy cells.

This drug is not licensed in the UK and so is not generally available outside of research trials. Some people taking part in the research trials AML-15 and AML-16, will be given gemtuzumab as part of their treatment.

CEP701

CEP701 is an experimental new treatment designed to act against cells that have a change called a FLT3 mutation. It is a liquid that is drunk and can be taken as an outpatient.

About 1 in 3 people diagnosed with AML have a FLT3 mutation (change) in the leukaemia cells. This mutation can increase their risk of the leukaemia coming back in the future. It is hoped that by giving CEP701 between courses of chemotherapy this risk can be reduced.

Some people taking part in the AML-15 trial who have the FLT3 mutation will be offered CEP701.

Tipifarnib (Zarnestra®)

Tipifarnib is designed to block the messages that tell cells to grow, from reaching leukaemia cells. It is a tablet you swallow.

Tipifarnib belongs to a group of drugs called farnesyl transferase inhibitors (FTIs). Farnesyl transferase is a special protein that stimulates acute myeloid leukaemia cells to grow. FTI's block
this protein. It has fewer side effects than the high-dose chemotherapy usually used to treat AML, because it is a targeted therapy. Doctors therefore hope that when it is given with lower doses of chemotherapy it will improve the effectiveness of treatment for older people who aren't able to have intensive chemotherapy.

Some people taking part in the AML-16 trial will be given tipifarnib along with their chemotherapy treatment.

Arsenic trioxide (ATO, Trisenox®)

Arsenic trioxide is licensed to treat people who have acute promyelocytic leukaemia (APL) that has come back after treatment, or has not gone into remission with treatment. This drug is made from the poison arsenic, but is given at low, safe doses.

Although it is licensed to treat APL we don't yet know how well it might work for other types of AML. Some people taking part in the AML-16 trial will be given arsenic trioxide along with their chemotherapy treatment. Arsenic trioxide is given as a drip into a vein (intravenously). It may be given as an outpatient.

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