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Treatment overview
The treatment of CML depends on the phase of the illness. Your doctor will discuss the possible treatment options with you and the benefits and disadvantages of each.
Chronic phase
In the chronic phase, the aim of treatment is to control symptoms and keep you feeling well for many years, possibly for a normal lifespan.
People are usually treated with a tablet called imatinib (Glivec®). Most people manage well on this treatment and only have mild side effects.
Imatinib is one of a group of newer ‘targeted’ drugs called tyrosine kinase inhibitors, which have greatly improved the outlook for people with CML over the last decade. Many people have been taking imatinib for 10 years or more without any problems from their leukaemia.
Other tyrosine kinase inhibitors, such as dasatinib (Sprycel®) and nilotinib (Tasigna®), can be used if imatinib doesn’t work or for people who can’t take it due to problems with side effects.
Stem cell transplants (sometimes called bone marrow transplants) may be used for people who have CML that hasn’t responded to tyrosine kinase inhibitor treatment.
Accelerated phase
Imatinib can be used in the accelerated phase, but only if it hasn’t been used in the chronic phase. If imatinib isn’t used, treatment is usually a combination of chemotherapy drugs, given by injection into a vein (intravenously). High-dose treatment with a stem cell transplant may also be used for some people.
Blast phase
In the blast phase the aim of treatment is to reduce symptoms and try to put the leukaemia back into a second chronic phase. Imatinib may be used, as long as it hasn’t been given before. Blast phase CML is like an acute leukaemia, so combinations of chemotherapy drugs used to treat acute leukaemia are often given. If the leukaemia responds well to chemotherapy, the doctors may recommend high- dose chemotherapy treatment with a stem cell transplant.
Supportive treatments
Sometimes people have a very high number of white cells in their blood when they are diagnosed with CML. The cells can clog-up blood vessels and cause physical problems. Doctors may treat this by removing the excess cells from the blood using a machine called a cell separator. This process is called leukapheresis.
How your treatment is planned
Haematologists follow national guidelines for treating CML. Your treatment will be based on these guidelines but tailored to your particular situation.
In most hospitals a team of specialists will decide on the treatment that’s best for you. This multidisciplinary team (MDT) may include:
Other staff will be available to help you if necessary, such as:
The MDT will plan your treatment by considering a number of factors, including the stage of the leukaemia and your general health.
You may be invited to take part in a clinical trial of a new treatment for CML.
If you have any questions about your treatment, don’t be afraid to ask your doctor or nurse. It often helps to make a list of questions and to take a close friend or relative with you. They can remind you of questions you want to ask, and afterwards help you remember what the doctor said.
Giving your consent
Before you have any treatment, your doctor will explain its aims to you. 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 be given full information about:
If you don’t understand what you have been told, let the staff know straight away so that they can explain again. Some cancer treatments are complex, so it’s not unusual for people to need repeated explanations.
You can always ask for more time to decide about the treatment if you feel that you can’t make a decision when it is first explained to you.
You’re also free to choose not to have the treatment. The staff can explain what may happen if you don’t have it. It’s essential to tell a doctor or the nurse in charge if you choose not to have treatment, so that they can record your decision in your medical notes. You don’t have to give a reason, but it can be helpful to let the staff know your concerns so that they can give you the best advice.
The benefits and disadvantages of treatment
Sometimes people are frightened at the idea of having treatment for leukaemia because of the possible side effects. Although some of the treatments can cause side effects, these can usually be controlled or reduced with medicines.
If you’ve been offered treatment in the chronic phase, which aims to control the leukaemia for a long time and has few side effects, deciding whether to accept the treatment may not be difficult. However, if you are in the blast phase, and have been offered more intensive treatment, which may cause more side effects and has a lower chance of controlling the leukaemia, 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 in detail with your doctor whether you wish to have treatment. If you choose not to have treatment, you can still be given supportive (palliative) care to help relieve any symptoms.
Second opinion
Your MDT will use national treatment guidelines to decide on the most suitable treatment for you. Even so, you may want to have another medical opinion. If you feel it will be helpful, your specialist or GP will be willing to refer you to another specialist for a second opinion. If you decide to 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 prepared, so that you can make sure your concerns are covered during the discussion.
Imatinib (Glivec®) for chronic myeloid leukaemia
Imatinib is the main treatment for CML. It’s a type of treatment called a tyrosine kinase inhibitor.
It works by blocking (inhibiting) signals within the leukaemia cells that make them grow and divide. Blocking the signals makes the cells die.
The National Institute for Health and Clinical Excellence (NICE) has recommended imatinib as the first treatment to be considered in the chronic phase of CML. Imatinib can also be used in the accelerated or blast crisis phases of CML, as long as it hasn’t been used before.
Imatinib comes as a tablet. You take the tablet every day for as long as it’s working to control the leukaemia.
Side effects of Imatinib
The side effects are usually mild and treatable. They may be more noticeable in the first four weeks of treatment and then begin to settle after this.
Side effects generally go away when treatment is stopped, so if you have severe side effects your doctor may ask you to stop taking imatinib for a few days. After a short break, you may be able to start taking it again without having the same problems. Occasionally some people need to stop taking imatinib altogether because their side effects are too severe.
Always let your doctor know if you notice any new side effects or if your side effects get worse. Side effects of Imatinib may include:
Feeling sick (nausea) and indigestion: This is usually mild. It can be reduced by taking the tablet with a large glass of water after a main meal. If you continue to have problems with nausea, your doctor may prescribe anti-sickness medicine for you.
Diarrhoea: This can usually be controlled with anti-diarrhoeal medicine. It’s important to drink plenty of fluids if you have diarrhoea. Let your doctor know if it’s severe.
Loss of appetite: A dietitian or specialist nurse at your hospital can give advice and tips on boosting appetite, coping with eating difficulties and maintaining weight.
Headaches: Let your haematologist know if you are having headaches. They can advise you on what painkillers to take.
Muscle cramps, bone and joint pains: You may get cramps or pain in your hands, the calves of your legs and in your feet. Sometimes these lessen after a few weeks. Your haematologist can advise on what types of painkillers may help. They may also prescribe quinine, calcium or magnesium supplements to help if cramps are severe.
Build up of fluid in the tissues (oedema): This is fairly common. You may notice swelling around your eyes, especially in the morning. You may also notice swelling in other areas such as your ankles. Cutting down on the amount of salt in your diet can help. Your doctor may prescribe tablets to make you pass more urine (diuretics). It’s important to contact your doctor straight away if you gain a lot of weight quickly or if you feel breathless as this can be a sign of a more serious fluid build up.
Eye changes: Your eyes may produce more tears than normal, making them watery. Some people have painful eyes or blurred vision.
Skin changes: Imatinib can cause a skin rash. Usually it’s mild but sometimes it can be more severe. If the rash is itchy or your skin feels dry, antihistamine tablets and skin lotion may help. Speak to your doctor if you have a rash or other skin changes as they may prescribe additional treatments.
Some people notice changes in the colour (pigment) of their skin, with some areas becoming lighter or not tanning so well. This may be more noticeable if you have darker skin. Your skin may also become more sensitive to sunlight. It can help to use a sunscreen or cover up in the sun if you are affected.
Effects on your blood cells: Imatinib can lower the numbers of healthy blood cells that are being made in your bone marrow. This is more common if you start taking it when the CML is in accelerated or blast phase. You’ll have regular blood tests while you are taking imatinib to monitor the levels of your blood cells. If your blood cell numbers are low this can cause:
Lowered resistance to infection: if your white blood cell numbers are low. Contact your doctor or the hospital straight away if your temperature goes above 38°C (100.5°F) or you suddenly feel unwell (even with a normal temperature).
Bruising or bleeding: if your platelet (cells which help the blood to clot) numbers are low. Let your doctor know if you have any unexplained bruising or bleeding.
Anaemia: (too few red blood cells) You may feel tired and breathless. You may need to have a transfusion of blood if the number of red cells in your blood is too low.
If your blood cell numbers fall too low your doctor may stop your treatment for a few days to let them recover, or you may be prescribed injections of substances called growth factors. Growth factors work by boosting the numbers of white blood cells (G- CSF) or red blood cells (erythropoietin) your bone marrow can make.
Contraception and fertility while on Imatinib
Imatinib is quite a new drug so there isn’t a lot of experience of women becoming pregnant or men fathering children while taking it. But there is a slightly increased risk of damage to the developing baby if imatinib is taken during pregnancy. So, it’s strongly recommended that you use contraception while taking it.
If you are taking imatinib and wish to father a child or become pregnant it’s important to discuss this with your haematologist. He can discuss your treatment options with you.
Taking other medicines while on Imatinib
Some medicines can be affected by, or interact with, how imatinib works. This includes herbal medicines such as St John’s Wort and some commonly used painkillers such as paracetamol. So, it’s important to always check with your doctor before taking any medicines.
Monitoring response to treatment with Imatinib (Glivec®)
When you first start your treatment, you’ll need to go to the clinic every week or so. This is so that your doctors can keep a close eye on how you are responding and check for any side effects.
As time goes on you won’t need to go to the clinic as often and eventually you may only need a check-up about every three months.
At your follow ups your doctor will ask about your general health and if you’ve had any new symptoms or side effects from treatment. You’ll usually have blood taken to count the numbers of blood cells in your blood (called a full blood count or FBC) and for a PCR blood test. From time to time you may also have a bone marrow sample taken. Your doctor can tell you how often this might be necessary.
The results of the tests help your doctors to judge how well your leukaemia is responding to imatinib so that they can tailor your treatment.
Remission
The aim of your treatment is to put the CML into remission. Remission means that you don’t have any symptoms from CML. and that there aren’t any signs of leukaemia in your blood and bone marrow tests.
There are different levels of remission that can be measured in CML, and these depend on the sensitivity of the tests that are used:
Haematological remission
This is the first level of remission. It means that no leukaemia cells can be seen in a full blood count sample and there are normal numbers of white blood cells and platelets. If your spleen was larger than normal when you were first diagnosed, this should also have gone back to its normal size.
Most people get a haematological remission within three months of starting imatinib.
Cytogenetic remission
This is the next level of remission. It means there is no sign of the Philadelphia chromosome in your blood or bone marrow sample.
A bone marrow sample contains about 20 cells for your doctor to examine. When you are first diagnosed all of these cells will have the Philadelphia chromosome (Ph+). As your treatment begins to work the number of Ph+ cells in your bone marrow will decrease. This is called a cytogenetic response.
When the bone marrow sample contains no Ph+ cells this is called a cytogenetic remission.
It takes longer (sometimes several months) to get a cytogenetic remission than a haematological remission. About 8 out of 10 people taking imatinib for CML in the chronic phase get a cytogenetic remission.
Major molecular response (MMR)
A major molecular response (MMR) is the next goal of treatment after a person gets a cytogenetic remission.
Even after someone has a cytogenetic remission there can still be leukaemia cells in his or her blood. But, because there may be only one leukaemia cell in among many thousands of normal blood cells, a very sensitive test is needed to detect the leukaemia.
The polymerase chain reaction (PCR) blood test is able to detect one leukaemia cell in up to one million (1,000,000) normal blood cells. It does this by measuring a substance (transcript) made by the Bcr-Abl gene in the leukaemia cells.
When you’re first diagnosed and about every three months afterwards, you’ll have blood taken for PCR testing. Because it’s so sensitive the PCR test may continue to show up signs of leukaemia for many months after your treatment starts even though you’re feeling well.
If your PCR test shows that the numbers of Bcr-Abl transcripts in your blood have decreased to at least 1000 times less than when you were first diagnosed, this is called a major molecular response. In people who have a major molecular response, the risk of the CML relapsing while treatment continues seems to be very low indeed.
Complete molecular response (undetectable transcripts)
If the PCR test can’t detect any Bcr-Abl transcripts this is called a complete molecular response. It’s also sometimes called ‘undetectable transcripts’ as it’s likely that there are still tiny amounts of leukaemia in your system that can’t be detected by PCR.
Continuing to take imatinib
You’ll usually keep taking imatinib for as long as it’s working to control the leukaemia. This is important even if your PCR blood tests don’t show up any signs of leukaemia after you’ve been taking imatinib for a while.
There is a risk that if you stop treatment or change your dose without your doctor’s advice, leukaemia cells may develop again and not respond as well to treatment in future.
It can be difficult to remember to take a tablet every day. You may find it helps to build taking your imatinib into your daily routine so that it becomes a habit.
Other tyrosine kinase inhibitors, Dasatinib and Nilotinib
In addition to imatinib there are other tyrosine kinase inhibitors called dasatinib (Sprycel®) and nilotinib (Tasigna®) that are licensed to treat Philadelphia chromosome positive CML (Ph+CML).
These drugs work in a similar way to imatinib and tend to have similar side effects. They may be helpful for people who can’t take imatinib because of severe side effects or because it isn’t working to control their CML.
Dasatinib and nilotinib are newer drugs, and aren’t yet widely available across the UK. The National Institute for Health and Clinical Excellence (NICE), the organisation that gives guidance on what new treatments should be available on the NHS in England and Wales, is looking at both these treatments. Its guidance is expected sometime in 2010.
The Scottish Medicines Consortium (SMC), the body that makes decisions for Scotland, has said both dasatinib and nilotinib should be available in Scotland for use in people who have Ph+CML in chronic phase for whom imatinib isn’t working or who have too many problems with side effects from it.
If you are prescribed one of these drugs you‘ll be monitored in the same way as people taking imatinib.
Chemotherapy for chronic myeloid leukaemia
Chemotherapy is the use of anti-cancer (cytotoxic) drugs, which work by destroying or damaging the leukaemia cells. The drugs circulate in the blood and can reach leukaemia cells all over the body.
Although imatinib is the standard treatment for CML, chemotherapy is occasionally used. It‘s most likely to be used if imatinib and closely-related drugs such as dasatinib aren’t effective or cause unacceptable side effects.
Some people are given chemotherapy, usually with a tablet, when their CML is first diagnosed. This may happen when doctors are waiting for the results of tests to confirm the CML is of a type that is likely to respond to imatinib. In this situation treatment is usually changed to imatinib once the test results are available.
Often chemotherapy involves taking a tablet and this causes only mild side effects. But, sometimes more intensive chemotherapy, involving a combination of drugs given into a vein, is needed. And this causes more troublesome side effects.
People who are treated with a stem cell transplant usually have intensive chemotherapy as preparation for the transplant.
Chemotherapy tablets
When chemotherapy is used to treat CML in chronic phase it’s usually given as tablets. The most commonly used tablet is hydroxycarbamide. These are often taken every day for as long as they are working. The dose of the tablets is changed depending on the results of regular blood tests.
Treatment may be interrupted for a time if the number of white blood cells falls below a certain level. For most people the side effects from the tablets are mild. The drug most commonly used is hydroxycarbamide.
Combination chemotherapy
If CML starts to behave more like an acute leukaemia, more intensive chemotherapy is the main treatment. It generally consists of a combination of three or four drugs given by injection into a vein (intravenously).
To make giving the chemotherapy easier and so that you can avoid having frequent injections, a plastic tube (called a central line) may be put into a vein in your chest. Alternatively a PICC line (peripherally inserted central venous catheter) or implantable port may be used.
Central line
The central line is put in under a general or local anaesthetic.
A small cut is made in the skin over your chest, and a thin flexible plastic tube is placed under your skin and into a large vein in your chest. 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 and fluids and collect blood samples.
It can stay in for months and the nurses will show you how to look after it to prevent blockages or infections.
A central line
PICC line
A PICC line is a long, fine tube put into a vein in the crook of your arm and threaded up into a larger vein leading to your heart.
Implantable port
An implantable port (also known as a portocath) is a thin, soft plastic tube that is put into a large vein in the chest. It has an opening (port) just under the skin on your chest or arm.
Side effects of chemotherapy
The number and degree of side effects you have will depend on the dose you’re given and on whether you have just one type of chemotherapy tablet or a combination of drugs.
Side effects are generally more severe if higher doses are used or when several chemotherapy drugs are given together.
The main side effects may include:
Although they may be hard to bear at the time, these side effects will disappear once your treatment is over.
Contraception while on chemotherapy
It’s important to take effective contraceptive precautions when you’re having chemotherapy, as the chemotherapy drugs might harm the baby if you or your partner becomes pregnant.
Fertility issues while on chemotherapy
Unfortunately, some chemotherapy treatments may cause infertility. Infertility is the inability to become pregnant or to father a child. This may be temporary or permanent, depending on the drugs that you have.
If you think that you may want to have children in the future, talk to your doctors about this before starting chemotherapy treatment. They will be able to tell you if your fertility is likely to be affected. You can then make an informed decision about your options.
If you have a partner it’s a good idea for both of you to be there during these discussions. Don’t be afraid to ask your doctor or specialist nurse any questions.
JASCAP information booklet on chemotherapy discusses the treatment and its side effects in more detail. Information about individual drugs and their particular side effects is also available.
High-dose treatment with stem cell support for CML
High-dose treatment with a stem cell transplant may benefit some people with CML.
If your doctor thinks that a transplant is necessary or possible for you, they will discuss it with you in more detail. Stem cell transplants are generally only carried out in specialist cancer treatment centres. A stem cell transplant allows you to have much higher doses of chemotherapy than usual. This can help to improve the chances of curing the leukaemia, or make a remission last longer.
Stem cells are blood cells at the very earliest stage of development in the bone marrow. They are mainly collected (harvested) from the blood, but can also be collected from the bone marrow. The stem cells can be donated by someone else (an allogeneic transplant), or you can use your own stem cells (known as an autologous transplant).
The aim of this transplant is to give you a source of healthy bone marrow and to try to completely cure the leukaemia.
In an allogeneic transplant, stem cells are donated by someone else and given to you. The most suitable donor is usually a brother or a sister whose bone marrow is a close match to your own. Occasionally it’s possible to use bone marrow from someone who isn’t related to you, if tests have shown that their white blood cells are a good match with yours. The Anthony Nolan Trust and British Bone Marrow Registry both maintain registers of bone marrow donors in the UK.
In CML, an allogeneic transplant is usually carried out during the chronic phase, when the disease is stable.
A transplant may be used after the blast phase has been treated and you are in remission but it wouldn’t usually be used as treatment for the blast phase.
High-dose treatment
The first stage of the treatment destroys your own bone marrow completely. This is done with high doses of chemotherapy, sometimes combined with radiotherapy (high-energy rays). After this treatment the donated stem cells are given to you through a drip into your central line.
The new stem cells, known as the graft, take a few weeks to settle in your bone marrow and start making the blood cells you need. Because you’re very vulnerable to infections during this time, certain precautions will be taken to protect you until your white cell count has recovered. You’ll be looked after in a room on your own and may be given antibiotics to help to prevent infections.
The hospital or specialist centre where you are treated will have its own policies on how to care for you during this time and your doctor or nurse will discuss this with you beforehand.
Graft versus host disease – a complication of allogenic transplant
Your doctors and nurses will watch you carefully during the transplant and for some months afterwards, for any signs of the new marrow reacting against your own body tissue (this is called graft versus host disease – GvHD). This can occur at any time after your transplant. It doesn’t mean that your transplant hasn’t worked but it can cause various problems including diarrhoea, rashes and liver damage. Your doctor will prescribe drugs to help prevent the graft reacting to your body.
White blood cells from your donor (donor lymphocyte infusion)
After an allogeneic transplant, your doctors will monitor your blood closely for leukaemia cells. Having a small number of remaining leukaemia cells may be one of the reasons why CML comes back in some people after an allogeneic transplant.
One way of getting rid of these leukaemia cells is to have treatment with a type of white blood cell called lymphocytes taken from your donor. The lymphocytes help your immune system to reject the remaining leukaemic cells (known as the graft versus leukaemia effect – GvL). They can be collected from your donor especially for this reason, or they may be taken and stored when the stem cells are originally collected.
The lymphocytes are given through a drip into one of your veins (intravenously). This can be done in the outpatient department. Some people may need to have it done up to three or four times. Sometimes having a donor lymphocyte infusion can cause you to develop graft versus host disease.
Autologous Transplant - Using your own stem cells
Collecting the stem cells
The stem cells are taken while you are free of any signs of the disease (in remission). A substance called G-CSF will be given to you as an injection after a course of chemotherapy. G-CSF stimulates the stem cells to spill over from the bone marrow into the blood so that they can be collected from your blood.
High-dose treatment and recovery
You’re given very high doses of chemotherapy, with or without radiotherapy (high- energy rays). Your own stem cells are then given back to you to ‘rescue’ you from the effects of the high-dose treatment and give you a source of healthy stem cells.
Interferon alpha for chronic myeloid leukaemia
Interferon alpha is a protein normally produced by the body during viral infections, such as flu. It may occasionally be given in the chronic phase of CML if other treatments haven’t worked.
Interferon alpha is given as an injection under the skin using a very fine needle. The injections are slightly uncomfortable. You or a relative or friend can be taught how to give these injections so that they can be done at home.
Side effects of Interferon alpha
Interferon alpha can cause a range of side effects and some are similar to the symptoms of flu, including:
Some of these side effects can be reduced by taking a mild painkiller before the injection. Your doctor can prescribe these. The side effects are most noticeable with the first one or two injections and usually wear off after that, although the tiredness often continues.
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