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ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
( By JASCAP )

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Treatment for ALL

Treatment Overview

The aim of treatment for ALL 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. With treatment, 8 out of 10 adults with ALL (80%) will go into remission. For some, this lasts indefinitely and the person is said to be cured.

Multidisciplinary team approach

Your treatment will be planned by a team of doctors and other staff at your hospital, known as a multidisciplinary team. The team normally includes:

  • one or more haematologists who diagnose the leukaemia in collaboration with specialist laboratory scientists
  • a clinical oncologist (a doctor who specialises in radiotherapy and chemotherapy)
  • specialist nurses who give information and support.

Other staff are available to help if necessary, such as social workers, dietitians, counsellors and psychologists and physiotherapists.

When they are planning your treatment, they will consider a number of factors, including:

  • the type of ALL you have
  • any chromosomal abnormalities within the leukaemia cells
  • your age and general health.

In the UK, treatment for ALL is given according to guidelines which have been agreed by specialists and are based on the results of trials and research. You may be asked to take part in a trial of a new and possibly better treatment.

Chemotherapy (drug treatment) is the main type of treatment given for ALL. The chemotherapy is carried in the bloodstream to nearly all parts of the body, but does not reach the brain and spinal cord.

The brain and spinal cord are known as the central nervous system (CNS). Additional treatment is needed to prevent the leukaemia affecting the CNS; this is known as CNS directed therapy. It involves giving chemotherapy into the fluid around the brain and spinal cord, which may be combined with radiotherapy to the brain. In men, the chemotherapy does not reach the testes, so they may also be given radiotherapy to the testes.

Giving your consent

Before you have any treatment, your doctor will explain its aims. They will usually ask you to sign a form saying that you give your permission (consent) for the hospital staff to give you the treatment. No medical treatment can be given without your consent, and before you are asked to sign the form 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 possible treatments that may be available
  • any significant risks or side effects of the treatment.

If you don't understand what you have been told, let the staff know straight away so that they can explain again. Treatments for leukaemia can be complex, so it is common for people to need further explanations.

It is often a good idea to have a friend or relative with you when the treatment is explained, to help you remember the discussion more fully.

You may also find it useful to write down a list of questions before you go to your appointment.

Patients may feel that the hospital staff are too busy to answer their questions, but it's important for you to be aware of how the treatment is likely to affect you. The staff should be willing to make time for you to ask questions.

You can always ask for more time to decide about the treatment if you feel that you can't make a decision when it's first explained to you.

You are also free to choose not to have the treatment. It's important that you understand what will happen if you don't have treatment. The medical staff will need to record your decision in your medical notes. They can also explain what support may be available if this is your choice.

The benefits and disadvantages of treatment

Many people are frightened by the idea of cancer treatment because of the side effects that can occur. Some people ask what will happen if they do not have treatment.

Although many of the treatments can cause side effects, these can often be controlled or reduced with medicines. Treatment can be given for different reasons and the aims and possible benefits will vary depending upon the individual situation.

If the aim of your treatment is to achieve a remission and cure for your leukaemia, deciding whether to have the treatment may not be difficult.

However, if the treatment is being given just to control the leukaemia for a time, it may be more difficult to decide whether to go ahead. Making decisions about treatment in these circumstances is always difficult, and you may need to discuss this issue in detail with your doctor. If you choose not to have treatment, you can still be given supportive (palliative) care, with medicines to control any symptoms.

If you want to stop your treatment, it's important to tell a doctor or the nurse in charge. They can discuss your decision with you and offer you the best advice. They will also make a record of your decision in your medical notes.

Second opinion

Your multidisciplinary team will use national treatment guidelines to decide on the most suitable treatment for you. Even so, you may want to have another medical opinion. Your specialist or GP may be willing to refer you to another specialist for a second opinion, if you feel it will be helpful. However, getting a second opinion can take some time to arrange. Treatment for ALL usually needs to be started as soon as possible so there may not be enough time to arrange a second opinion.

If you do go for a second opinion, it may be a good idea to take a friend or relative with you, and have a list of questions ready so that you can make sure your concerns are covered during the discussion.

Chemotherapy for ALL

Chemotherapy uses anti-cancer (cytotoxic) drugs to destroy the leukaemia cells. These work by disrupting the production of the leukaemia cells.

Chemotherapy drugs circulate all over the body in the bloodstream. However, the chemotherapy drugs can't get into the fluid around the brain and spinal cord (cerebrospinal fluid – CSF), so they need to be injected directly into the fluid through a lumbar puncture. This is done even if leukaemia cells can't be detected in the CSF, as research has shown that there will almost always be some leukaemia cells in the CSF which need to be destroyed.

For people who have just been diagnosed with ALL it's important to start treatment quickly. Treatment is divided into three different phases:

Induction

This is the initial intensive phase of treatment, aimed at destroying as many leukaemia cells as possible. It usually achieves a remission of the disease. Common chemotherapy drugs which may be used in this phase include:

  • vincristine
  • daunorubicin or doxorubicin
  • methotrexate
  • crisantapase (asparaginase)
  • mercaptopurine
  • cyclophosphamide

Steroids are also given as part of the treatment. You may also have a drug called allopurinol which helps to protect the kidneys against damage caused by the increase in uric acid (a waste chemical produced when the leukaemia cells are destroyed).

Some people who have the Philadelphia chromosome may be given a drug called imatinib (Glivec®).

The induction phase of treatment normally lasts 3–8 weeks. As this is a very intense phase, you'll need to stay in hospital for about four weeks. This is because you're likely to need antibiotics and drips (infusions) of red blood cells and platelets.

Intensification (consolidation)

After the induction phase, more chemotherapy is given to increase the chance of destroying any remaining leukemia cells that cannot be seen in the blood or bone marrow. Drugs used during consolidation may include:

  • Cytaribine
  • Etoposide
  • Tioguanine (thioguanine)

as well as some of the same drugs used during induction.

The consolidation phase of the treatment usually lasts for several months.

Continuing therapy (maintenance)

This treatment reduces the risk of the leukaemia coming back at a later stage after treatment has finished. It's a less intensive course of chemotherapy. Common drugs used are mercaptopurine and methotrexate, which are given as tablets, and vincristine, which is given by injection. Steroids are usually continued in short courses.

This phase may last for a couple of years and is usually given as an outpatient. You don't usually need to be admitted to hospital unless you develop problems such as an infection.

Throughout these three phases of your treatment you'll have regular blood tests and lumbar punctures to check for leukaemia cells. Your doctor will check the results of these and will make changes to your treatment if needed. Instead of standard-dose maintenance chemotherapy, some people will have highdose chemotherapy with a stem cell transplant. This may be given to increase the chances of a cure. It may also reduce the possibility of a relapse if someone has risk factors which make it more likely for the ALL to come back.

The high-dose treatment may include radiotherapy to the whole body (known as total body irradiation or TBI) and high doses of a chemotherapy drug such as etoposide or busalfan.

If you have standard continuing chemotherapy, your complete chemotherapy course is likely to last for at least two years. If you have high-dose chemotherapy after the induction and intensification phases, the treatment time may be shorter and may finish in less than a year.

How the chemotherapy is given

The main induction and intensification treatments consist of a combination of three or four drugs given by injection into a vein (intravenously), and some drugs which are given as tablets.

Central lines

To make having chemotherapy easier and to prevent you from having frequent injections, a plastic tube (called a central line) can be put into a vein in your chest. The tube is put in under a general or local anaesthetic. Usually a small cut (incision) is made in the skin over your chest, and a narrow flexible plastic tube is placed under your skin and into a large vein in your neck. The other end of the tube stays outside your body and has a screw cap at the end. The tube can be used to give drugs, fluids, stem cells or bone marrow, and also to collect blood samples.

You may feel sore and uncomfortable for a couple of days after the line has been put in, but it should then be painless. It can stay in for as long as it's needed, which may be more than two years. The nurses will show you how to look after it to prevent blockages or infections.


Figure: A central line

PICC lines and implantable ports

Instead of a central line, a PICC line (peripherally inserted central venous catheter) or an implantable port may be used. A PICC line is a long, thin tube put into a vein in the crook of the arm. An implantable port is a thin, soft plastic tube that is put into a vein in the chest and has an opening (port) just under the skin of the chest or arm.

Your doctor or chemotherapy nurse will explain the procedure to you. You will be given a local anaesthetic before the line is put in.

Intrathecal chemotherapy

As is done by injection into a vein, chemotherapy for ALL is often given directly into the fluid around the brain and spinal cord (cerebrospinal fluid). Giving chemotherapy in this way is known as intrathecal chemotherapy. This is done using a similar procedure to the lumbar puncture. After giving a local anaesthetic, the doctor gently puts a needle into the fluid in the spine, a small amount of fluid is drawn off and the drugs are injected. The drugs will help to destroy any leukaemia cells in the fluid.

Supportive care

During your treatment you will also need treatment for the symptoms that have been caused by a lack of normal blood cells due to the leukaemia itself and the chemotherapy.

Drips (transfusions) of red blood cells and platelets are usually needed to replace the normal blood cells. Antibiotics may also be needed to prevent and treat any infections. These can also be given through your central line.

Side effects of chemotherapy

Risk of bruising and bleeding

Platelets help blood to clot. With 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 develop blood spots or rashes on the skin (called petichiae), bruise very easily, have nosebleeds or bleed more heavily from even minor cuts and grazes.

You may need to have a drip (transfusion) of platelets before your chemotherapy begins, and at times during your treatment, to replace the missing platelets. We can send you a fact sheet about platelet transfusions.

If you develop any unexplained bruising or bleeding, such as nosebleeds, blood spots, rashes on the skin or bleeding gums contact the hospital immediately.

Low 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 the white cells are low (known as neutropenia), you are more likely to get an infection.

During chemotherapy your blood will be tested regularly. You'll probably be given tablets or other medicines to reduce the risk of infection. If you get an infection, you'll be given medicines to treat it. Most infections are caused by bacteria or viruses already in your own body. These do not normally cause infection, but when your immunity is low they are more likely to cause a
problem.

It's best to avoid coming into contact with someone who may have an infection. You may also be advised to be careful about what you eat, 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 38°C (100.4°F) or you suddenly feel ill, even with a normal temperature, contact your doctor or the hospital straight away.

You may be given injections of a drug called G-CSF (granulocyte-colony stimulating factor). This is a type of protein that stimulates the bone marrow to produce more white blood cells. The injections are given under the skin (subcutaneously).

Anaemia

If the level of red blood cells (haemoglobin) 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 haemoglobin in the blood.

Anaemia can be treated very successfully by blood transfusions. You should quickly feel more energetic after a transfusion and the breathlessness will be eased. We can send you a fact sheet about blood transfusions.

Tiredness (fatigue)

This is a common effect of chemotherapy. The fatigue may be due to anaemia, but may also occur as a result of chemotherapy, even if your blood count is normal. You may be especially aware of this when you're at home between courses of chemotherapy and for a few months after the treatment.

Feeling sick

Some of the drugs used to treat ALL may make you feel sick (nausea) and may sometimes cause vomiting. There are very effective anti-sickness drugs (antiemetics) to prevent or greatly reduce nausea and vomiting, which your doctor can prescribe for you. Let them know if the anti-emetics are not controlling your nausea as they can prescribe different ones.

Sore mouth

Some chemotherapy drugs can make your mouth sore and cause mouth ulcers. Regular mouthwashes are important and your nurse 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.

Effects on the heart

Some of the drugs used to treat ALL may affect the heart muscle. The doses of the chemotherapy drugs are very carefully monitored, and heart tests (such as cardiac echograms) may be done from time to time to check your heart.

Hair loss

Unfortunately, hair loss is another common side effect of these drugs. If your hair falls out, you can cover your head by wearing wigs, hats or scarves. Most patients are entitled to a free wig from the NHS. Your doctor or one of the nurses on the ward can usually arrange for a wig specialist to visit you.

If your hair falls out, it will grow back over a period of 3–6 months when the treatment ends.

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

Coping with chemotherapy

Chemotherapy affects different people in different ways. Many people find that there are times during their treatment when they feel very unwell and tired and have to take things much more slowly. Do as much as you feel like and rest whenever you need to.

Contraception

It is not advisable to become pregnant or father a child while taking any of the chemotherapy drugs used to treat ALL, as they may harm the developing baby. It's important to use effective contraception during your treatment and for a few months afterwards. You can discuss this with your doctor or nurse.

Condoms should be used during sex for the first 48 hours after chemotherapy in order to protect your partner from any of the drug that may be present in semen or vaginal fluid.

Radiotherapy for ALL

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

Radiotherapy may be given to the head as part of CNS directed therapy. In some men it may also be given to the testes.

The course of treatment is given in the hospital radiotherapy department, usually in 8–10 sessions from Monday–Friday over two weeks, with a rest at the weekend. Your doctor will discuss your treatment with you in detail beforehand.

If you need to have high-dose treatment with stem cell support you may have a special form of radiotherapy called total body irradiation, or TBI. Radiotherapy is given to the whole body to destroy the bone marrow cells.

Planning your Radiotherapy treatment

Planning is a very important part of radiotherapy and may take a few visits. Careful planning makes sure that the radiotherapy is as effective as possible. It ensures the radiotherapy rays are aimed precisely at the cancer and cause the least possible damage to the surrounding healthy tissues.

The treatment is planned by your clinical oncologist, a physicist and sometimes by a senior radiographer. You may have your first treatment on the same day as your planning session, but usually it's necessary to wait a number of days while the team (physicist, oncologist or radiographer) prepare the final details.

The first step is to make sure that you lie in exactly the same position for each treatment. On your first few visits to the radiotherapy department you'll lie under a large machine called a simulator, which takes x-rays of the area to be treated. Sometimes a CT scanner may be used for the same purpose.

For cranial radiotherapy you may be fitted with a special clear plastic mask which is moulded to the exact size of your head and neck. This can be attached to the treatment couch and makes sure that your head stays in the correct position. Marks are made on the mask to show the treatment area.

If you're not wearing a mask for treatment, marks will be drawn on your skin. This helps the radiographer, who operates the machine and gives you your treatment, to position you accurately and to show where the rays are to be aimed.

These marks must stay visible throughout your treatment but they can be washed off once your treatment is over. Sometimes, you may have tiny permanent marks (like tattoos) on your skin. These will only be made with your permission. At the beginning of your radiotherapy you'll get instructions on how to look after your skin in the area being treated.

Before each session of radiotherapy the radiographer will position you carefully on the couch and make sure that you are comfortable. During your treatment, which only takes a few minutes, you'll be left alone in the room but you can talk by intercom to the radiographer, who will watch you from the next room. Radiotherapy is not painful but you have to lie still for a few minutes during the treatment.

Side effects of Radiotherapy Treatment

Radiotherapy can cause general side effects such as feeling sick (nausea) and tiredness. When radiotherapy is given to the head it can cause specific side effects such as severe tiredness and drowsiness (somnolence), which usually appear a couple of weeks after your treatment starts and may last for a few weeks.

Hair loss

If you have radiotherapy to the head or to the testes, the hair in these areas will fall out. This is only temporary and it will usually grow back once your treatment is over, but it may not be as thick as it was before.

Feeling sick

Nausea can usually be effectively treated by anti-sickness drugs (anti-emetics), which your doctor can prescribe. If you don't feel like eating, you can replace meals with nutritious high-calorie drinks. These are available from most chemists and can also be prescribed by your GP.

Tiredness

As radiotherapy can make you tired, try to get as much rest as you can.

All these side effects should disappear gradually once your treatment is over, but let your doctor know if they continue.

Radiotherapy does not make you radioactive and it is perfectly safe for you to be with other people, including children, throughout your treatment.

Our booklet on Radiotherapy gives more details about the treatment.

High-dose treatment with stem cell support for ALL

A stem cell transplant allows you to have much higher doses of chemotherapy than usual and may help to improve the chances of curing the leukaemia, or prolonging a remission.

Stem cells are blood cells in the very earliest stage of development in the bone marrow. They develop into the different types of blood cell.

High-dose treatment with stem cell support involves having very high doses of chemotherapy and sometimes radiotherapy over a few days. This destroys the bone marrow cells. After the treatment, stem cells, usually from either a sibling or unrelated donor, are given to you by a drip (infusion). These stem cells find their way to the bone marrow where they start producing new blood cells. This type of transplant is known as an allogeneic stem cell transplant.

Stem cell transplants may benefit a number of people with ALL. They are used to improve the chances of curing it or prolonging a remission, but may not be suitable for everyone. High-dose treatment is usually used after initial chemotherapy treatment.

If your specialist thinks that a stem cell transplant is necessary or a possible treatment option for you, they will discuss it with you in detail.

Other drugs

There are other drugs which can be used as part of the treatment for ALL. These are:

Dasatinib (Sprycel®)

Dasatinib is used in adults with Philadelphia chromosome positive ALL that is resistant to previous treatment, including imatinib. Like imatinib, dasatinib also works by blocking (inhibiting) the signals within the leukaemia cells that make them become abnormal and continue to divide. This makes the cells die.

While this drug is licensed for use in ALL, it hasn't been approved for use by NICE (National Institute for Health and Clinical Excellence) in England and Wales and so it is not generally available.

Nelarabine (Atriance®)

Nelarabine is a chemotherapy drug that is used to treat some types of ALL which have been resistant to treatment or come back after treatment. In Scotland, this drug has been approved for use before a stem cell transplant, but it is not generally available in the rest of the UK.

Rituximab (Mabthera®)

Rituximiab is a drug which is being tested to see if helps in the treatment of some types of ALL.

It belongs to a group of drugs known as monoclonal antibodies which work by recognising a particular protein on the surface of leukaemia cells. By locking onto these proteins, it is able to destroy the leukaemia cells. Research into the use of rituximab in ALL is still ongoing and it's not yet generally available.

Steroid therapy for ALL

Steroids are often given with chemotherapy to help destroy the leukaemia cells.

Prednisolone or dexamethasone are two commonly used steroids for ALL.

Side effects of steroid therapy

Steroids for ALL are generally given only for a few days a month and so usually have few side effects. They are given as tablets. The side effects you may notice are a bigger appetite, feeling more energetic and difficulty sleeping.

If you take steroids for some time, you may have some other temporary side effects. These can include water retention, high blood pressure, indigestion and a slightly increased risk of getting infections.

You may also have an increased level of sugar in the blood. If this happens, your doctor will prescribe drugs which will need to be taken daily to bring your blood sugar level back to normal. You may have to do a simple daily test to check for sugar in your urine. Your nurses will show you how to do this.

It is unusual for people with acute lymphoblastic leukaemia to have to take steroids for a long time, but if you do you may notice that you put on weight.

It is important to remember that all these side effects are temporary and will gradually disappear as the steroid dose is reduced. You should carry a card with you, or wear a Medicalert, stating that you are taking steroids.

Imatinib (Glivec®) for ALL

Imatinib is a drug known as a tyrosine kinase inhibitor or signal transduction inhibitor which may be used as part of the treatment for people with Philadelphia chromosome positive ALL. Imatinib is taken by mouth as capsules.

It works by blocking (inhibiting) signals within the leukaemia cells that make them become abnormal and continue to grow and divide. Inhibiting the signals makes the cells die.

Imatinib may make you feel a bit sick, and sometimes causes diarrhoea. It may also cause leg aches and cramps, rashes, and swelling of the face, especially around thes eyes. The side effects are usually mild and treatable.

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