A practical guide to understanding cancer. Understanding. chronic. myeloid. leukaemia

Transcription

1 A practical guide to understanding cancer Understanding chronic myeloid leukaemia

2 Contents 1 Contents About this booklet 3 1 The blood and chronic myeloid leukaemia 5 2 Diagnosing chronic myeloid leukaemia 19 3 Treating chronic myeloid leukaemia 27 4 Living with chronic myeloid leukaemia 59 5 Work and financial support 75 6 Further information 81

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4 About this booklet 3 About this booklet This booklet is about chronic myeloid leukaemia (CML). It is also known as chronic myelogenous leukaemia or chronic granulocytic leukaemia. We hope it answers some of your questions and helps you deal with some of the feelings you may have. We ve also listed other sources of support and information, which we hope you ll find useful. We can t advise you about your own situation. This can only come from your healthcare team, who are familiar with your medical history. In this booklet we ve included quotes from people affected by CML, which you might find helpful. These are taken from the website healthtalkonline.org Turn to pages for some useful addresses and websites, and to page 93 to write down questions for your doctor or nurse. If you d like to discuss this information, call the Macmillan Support Line free on , Monday Friday, 9am 8pm. If you re hard of hearing, you can use textphone , or Text Relay. For non-english speakers, interpreters are available. Alternatively, visit macmillan.org.uk If you find this booklet helpful, you could pass it on to your family and friends. They may also want information to help them support you.

5 4 Understanding chronic myeloid leukaemia

6 The blood and chronic myeloid leukaemia 5 1 The blood and chronic myeloid leukaemia What is leukaemia? 6 The blood 7 About chronic myeloid leukaemia 10 Risk factors and causes 15 Symptoms 16

7 6 Understanding chronic myeloid leukaemia What is leukaemia? Leukaemia is a cancer of the white blood cells. People with leukaemia usually have more white blood cells than normal. These leukaemia cells behave differently from healthy white blood cells. The four main types of leukaemia are: acute lymphoblastic (ALL) acute myeloid (AML) chronic myeloid (CML) chronic lymphocytic (CLL). Each type of leukaemia has its own characteristics and treatment. We have separate information about these different leukaemias, which we can send you.

8 The blood and chronic myeloid leukaemia 7 The blood To help you understand CML and its treatment, it is useful to know a bit about your blood, how it s made and what it does. Blood is made up of blood cells, which move around in a liquid called plasma. Blood cells are made in the bone marrow. This is a spongy material in the middle of our bones particularly in our pelvis, backbone (spine) and breast bone (sternum). Normally, millions of new blood cells are made every day to replace old and worn-out blood cells. All blood cells are made from cells called blood stem cells. There are two types of blood stem cell: lymphoid stem cells, which make a type of white blood cell called lymphocytes myeloid stem cells, which make all the other types of blood cell: red blood cells, platelets, and white blood cells. Blood stem cells in the bone marrow divide and grow to make new blood cells. The new, developing blood cells are called blast cells. They don t look like fully developed cells and they can t do the jobs that fully developed cells do. Usually, blast cells stay in the bone marrow until they have developed into red blood cells, platelets or white blood cells.

9 8 Understanding chronic myeloid leukaemia Stem cell Myeloid stem cell Lymphoid stem cell Red blood cell Platelets Neutrophil B-lymphocyte T-lymphocyte White blood cells How blood cells divide The developed cells are then released into your blood to carry out different functions: Red blood cells contain haemoglobin (Hb), which carries oxygen from your lungs to all the cells in your body. Platelets are very small cells that help your blood clot and prevent bleeding and bruising.

10 The blood and chronic myeloid leukaemia 9 White blood cells fight and prevent infection. There are several types of white blood cell. The two most important types are neutrophils and lymphocytes. Neutrophils are a type of granulocyte. The levels of these cells in your blood are measured in a blood test called a full blood count (FBC). The figures below are a guide to the levels usually found in a healthy person. Type of blood cell Red blood cells (Hb) Levels found in a healthy person g/l (men); g/l (women) Platelets x 10 9 /l White blood cells (WBC) x 10 9 /l Neutrophils x 10 9 /l Lymphocytes x 10 9 /l These figures can vary from hospital to hospital. Your doctor or nurse will be able to tell you which levels they use. The levels can also vary slightly between people from different ethnic groups. The figures might look complicated when they re written down, but in practice they re used in a straightforward way. For example, you ll hear doctors or nurses saying things like, Your haemoglobin is 140, or, Your neutrophils are 4. Most people with CML soon get used to these figures and what they mean. But remember, you can always ask your medical team to explain more if you need to.

11 10 Understanding chronic myeloid leukaemia Chronic myeloid leukaemia CML is a rare cancer. About 700 people in the UK are diagnosed with CML each year. It can occur at any age but is more common in middle-aged and older people. CML usually develops very slowly, which is why it s described as a chronic leukaemia. People with CML make too many granulocytes. These are a type of white blood cell (see pages 7 9). This is why CML is sometimes called chronic granulocytic leukaemia (CGL). In a person with CML, when the granulocytes are looked at under a microscope, they are immature (not fully developed). The granulocytes fill the bone marrow and stop it making enough normal white blood cells, red blood cells and platelets. Over time, these abnormal white blood cells collect in the spleen, making it enlarge. The spleen is an organ on the left side of the tummy, underneath the ribs. The spleen: produces small numbers of lymphocytes stores blood cells destroys older, damaged blood cells. The spleen is part of the lymphatic system (see the diagram opposite). The bone marrow and the lymph nodes (glands) are also part of the lymphatic system.

12 The blood and chronic myeloid leukaemia 11 Neck (cervical) lymph nodes Thymus Armpit (axillary) lymph nodes Spleen Groin (inguinal) lymph nodes The lymphatic system

13 12 Understanding chronic myeloid leukaemia How CML develops All cells have a set of instructions that tell them what to do and when to do it. These instructions are stored inside the cells as genes. Each gene has its own distinct set of instructions. These control how the cell behaves. For example, some genes tell a cell to rest, others tell it to grow, and others tell it to develop into a mature cell so it can perform its functions in the body. The genes are organised into structures called chromosomes. Most cells in the body contain 23 pairs of chromosomes. CML develops when a cell is dividing and, by mistake, a gene gets moved from one chromosome to another. This means two genes that are normally completely separate join together and create a new gene. This new, abnormal fusion gene stops the bone marrow stem cell from developing into a normal blood cell (see pages 7 8). These abnormal cells are the leukaemia cells (blast cells see page 7). When doctors look at the leukaemia cells under a microscope, they can often see a chromosome that looks different. This new chromosome is caused by two genes joining together. It is called the Philadelphia chromosome. The Philadelphia (Ph) chromosome Most people with CML (more than 95% or 95 out of 100) have the Philadelphia chromosome in all their leukaemia cells. This is called Philadelphia chromosome-positive CML, or Ph+ CML. The Philadelphia chromosome isn t inherited, so it is not something you were born with and it can t be passed on to your children.

14 The blood and chronic myeloid leukaemia 13 How the Philadelphia chromosome develops There are 23 pairs of chromosomes in a cell. 22 of them are numbered from The 23 rd pair is responsible for our gender it is called XX in women and XY in men. The Philadelphia chromosome is made when a gene on chromosome 9 (the ABL gene) wrongly attaches to a gene on chromosome 22 (the BCR gene). This creates a new gene called BCR-ABL. Chromosome 9 Chromosome 22 Philadelphia chromosome BCR gene ABL gene Fusion gene (BCR and ABL combined) How the Philadelphia chromosome develops The BCR-ABL gene makes a substance called tyrosine kinase. Too much tyrosine kinase makes cells develop and behave abnormally.

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16 The blood and chronic myeloid leukaemia 15 Risk factors and causes The cause of CML is unknown, but research is going on to find out more. There are a number of factors that might increase your risk of developing CML but, for most people, it isn t clear why it develops. The known risk factors are listed below. Age The risk of developing CML increases slightly with age. Radiation exposure Exposure to very high radiation levels is known to increase the risk of developing CML. For example, accidental exposure can happen after a nuclear accident like Chernobyl. Nobody in the UK is exposed to radiation levels high enough to increase their risk of developing CML. For most people with CML, there s no obvious link to radiation exposure. Sometimes there is publicity about an increase in leukaemia in people who live near nuclear power plants. Research is still going on to see whether there is a definite link, but at the moment there is no evidence of this. Research has also found no links between the risk of adults developing CML and: exposure to electromagnetic fields living near high-voltage electricity cables household radon. Like other cancers, CML is not infectious and cannot be passed on to other people.

17 16 Understanding chronic myeloid leukaemia Symptoms CML develops slowly and many people don t have symptoms in the early stages. It is often discovered by chance when a blood test is done for another reason, for example before an operation or as part of a routine health check. If there are symptoms in the early stages of CML, they develop gradually and are usually mild. The symptoms are usually vague and can easily be confused with the symptoms of more common illnesses, such as flu. If you do have symptoms, they may include the following. Common symptoms Feeling generally tired or unwell. Having a poor appetite and losing weight. Feeling full or tender on the left side of your tummy (abdomen). This is caused by an enlarged spleen (see pages 10 11). Sweating or a high temperature at night. Rarer symptoms Having various infections one after the other. This is caused by a lack of healthy blood cells. Unusual bleeding or bruising. This may include bruising without any obvious cause, bleeding gums, frequent nosebleeds and heavy periods in women. This is caused by a lack of platelets in the blood.

18 The blood and chronic myeloid leukaemia 17 Looking pale and feeling tired or breathless. This is caused by a lack of red blood cells in the blood (anaemia). Aching joints and bones. This happens because there are too many white blood cells collecting in the bone marrow. Enlarged lymph nodes. This happens because leukaemia cells are collecting in the lymph nodes (see pages 10 11) and making them swell. It is usually painless. Small bumps in the skin. Itching. Visual disturbances and headaches. This happens because the tiny blood vessels in the eyes and brain get clogged up with too many white blood cells. Sometimes an optician will notice changes to the blood vessels in the eye before there are any symptoms. If you have any of these symptoms, it is important to see your doctor. But remember that these can be symptoms of many illnesses other than CML. I was having all sorts of different symptoms aching limbs, tiredness, night sweats, headaches. As it went on, it didn t seem quite right. Mark

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20 How CML is diagnosed 19 2 Diagnosing chronic myeloid leukaemia How CML is diagnosed 20 Phases of CML 24

21 20 Understanding chronic myeloid leukaemia How CML is diagnosed There are few, if any, symptoms in the early stages of CML. So it s common for people with CML to be diagnosed by chance when they have a blood test for another reason. There s a photo of someone having a blood test on page 18. If your GP suspects you have CML, they will refer you to a haematologist for further tests. A haematologist is a doctor who specialises in diagnosing and treating blood problems. At the hospital The haematologist will ask you about any illnesses or health problems you ve had. They will also examine you to check whether your lymph nodes, spleen or liver are enlarged. You will also have more blood tests to check the number of different cells in your blood (a full blood count see pages 8 9) and to look for leukaemia cells. If the blood test shows there are leukaemia cells in your blood, the haematologist will arrange further tests to find out which type of leukaemia you have and its extent. The results of these tests will help them plan your treatment.

22 Diagnosing chronic myeloid leukaemia 21 Tests Bone marrow sample A doctor or nurse takes a small sample of bone marrow from the back of the hip bone (pelvis), or occasionally the breast bone (sternum). The sample is sent to a laboratory to be checked for abnormal white blood cells. A haematologist can tell which type of leukaemia you have by identifying the type of abnormal white cell. A sample of bone marrow being taken from the back of the hip bone The procedure can be done on the ward or in the outpatients department. It takes about minutes in total, but taking the bone marrow sample only takes a few minutes. Before the bone marrow sample is taken, you ll be given a local anaesthetic injection to numb the area.

23 22 Understanding chronic myeloid leukaemia The doctor or nurse passes a needle through the skin into the bone. They then draw a small sample of liquid from inside the bone marrow into a syringe. This is called a bone marrow aspirate. It can feel uncomfortable for a few seconds when the liquid marrow is drawn into the syringe. You may also have small core of marrow taken (a trephine biopsy). The doctor or nurse passes a thicker needle through the skin into the bone marrow. When they take the needle out, it contains a small core of bone marrow. You may feel bruised after having a sample of bone marrow taken, and have an ache for a few days. You can ease this by taking mild painkillers. Cytogenetic tests These are tests that look at chromosomes through a microscope: Philadelphia chromosome test The blood and bone marrow sample will be analysed to look for the Philadelphia chromosome (see pages 12 13). This will help doctors decide on the best treatment for you. Polymerase chain reaction (PCR) test This is a blood test that detects the BCR-ABL gene (see page 13), which is usually present in CML. It s a very sensitive test and can detect tiny amounts of leukaemia that can be missed by other tests. Doctors use the PCR test to see how you are responding to treatment.

24 Diagnosing chronic myeloid leukaemia 23 Further tests You may have additional tests, including the following: Chest x-ray This uses x-rays to take a picture of your chest, to check your lungs and heart (see the photo below). Ultrasound scan An ultrasound scan may be done to see whether your liver and spleen are enlarged (see pages 10 11). Ultrasound scans use sound waves to build up a picture of the inside of the body. This is a painless test and only takes a few minutes.

25 24 Understanding chronic myeloid leukaemia Phases of CML CML develops slowly. There are three phases of CML: the chronic phase the accelerated phase the blast phase. Your phase depends on the number of immature cells (blast cells) in your blood and bone marrow (see page 7), and your symptoms. Most people are diagnosed when CML is in the chronic phase. Chronic phase CML develops very slowly in the chronic phase and is often stable for a long time. The chronic phase is sometimes called the stable phase. There may be no symptoms and most people lead a normal life. People in this phase rarely need to go into hospital. They can have treatment as an outpatient and it doesn t usually cause many side effects. They will have regular blood tests to check how well they are responding to treatment. Most people who have treatment in the chronic phase have their leukaemia well-controlled and won t have any symptoms. If they keep taking their treatment, their leukaemia may be kept under control for many years and potentially for the rest of their life.

26 Diagnosing chronic myeloid leukaemia 25 Accelerated phase In some people, CML does not respond as well to treatment. In a small number of people, the leukaemia may progress from the chronic phase to the accelerated phase. Occasionally people may be diagnosed with CML in the accelerated phase. In this phase, there are more blast cells in the blood and bone marrow. You may also develop symptoms such as tiredness, weight loss, bone pain, sweating and a high temperature at night. If you feel unwell or develop new symptoms, let your doctor know. The treatment for the accelerated phase (see page 29) may be more intensive than for the chronic phase, and you may need to spend some time in hospital. Your specialist can tell you more about this. Blast phase After some time in the accelerated phase, the leukaemia may transform into the blast phase. Occasionally people may be diagnosed in the blast phase or progress straight to this from the chronic phase. The blast phase is like an acute leukaemia. In this phase, there are even more blast cells. This phase is sometimes called blast crisis. Remission Remission (a complete response) means the blood and bone marrow go back to normal following treatment. There are different levels of response (see pages 41 43). Relapse Relapse means the leukaemia cells have come back after a time in remission.

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28 Phases of CML 27 3 Treating chronic myeloid leukaemia Treatment overview 28 Targeted therapies 34 Chemotherapy 46 Stem cell transplants 53 Interferon alpha 54 Research clinical trials 56

29 28 Understanding chronic myeloid leukaemia Treatment overview How CML is treated depends on: the phase of the illness your general health how fit you are. Your doctor will discuss the possible treatment options with you, and their advantages and disadvantages. Chronic phase In the chronic phase, the aim of treatment is for your blood count (see pages 8 9) to return to normal, and for you to keep feeling well. This may be for many years possibly for your normal lifespan. You will usually be treated with a tablet called imatinib. This is a type of targeted therapy called a tyrosine kinase (TK) inhibitor (see pages 34 44). TK inhibitors have greatly improved the outlook for people with CML. Many people have been taking imatinib for 10 years or longer without any problems from their leukaemia. If imatinib doesn t work or if you can t take it because you have side effects, other TK inhibitors can be used. These include nilotinib and dasatinib. If you have CML that hasn t responded to TK inhibitor treatment, stem cell transplants (sometimes called bone marrow transplants) may be used (see page 53).

30 Treating chronic myeloid leukaemia 29 Accelerated phase If imatinib or another TK inhibitor hasn t been used in the chronic phase, it can be used in the accelerated phase. If you don t have a TK inhibitor, you ll usually be treated with a combination of chemotherapy drugs (see pages 46 51). These are given by injection into a vein (intravenously). Some people may have a stem cell transplant if they are fit enough (see page 53). Blast phase In the blast phase, the aim of treatment is to reduce symptoms and to try to put your leukaemia back into a second chronic phase. If you ve not had TK inhibitors before, you may be given them. Blast-phase CML is like an acute leukaemia, so you will usually be treated with combinations of chemotherapy drugs used to treat acute leukaemia. If your leukaemia responds well to either TK inhibitors or chemotherapy and you are fit enough, your doctors may recommend a stem cell transplant (see page 53). Supportive treatments Some people have a very high number of white blood cells in their blood when they re 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. You lie on a bed or reclining chair with a plastic tube (cannula) in each arm. Each cannula is connected by a tube to the cell separator. Your blood is removed through one tube and circulated through the cell separator. This removes the white blood cells. The rest of your blood is then returned to your body through the cannula in your other arm. The whole procedure takes a few hours and is not painful.

31 30 Understanding chronic myeloid leukaemia How your treatment is planned Haematologists follow national and international 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 decide on the treatment that s best for you. This multidisciplinary team (MDT) may include: one or more medical doctors who specialise in diseases of the blood (haematologists) specialist nurses who give information and support. It may also include other healthcare professionals, such as a dietitian, physiotherapist, occupational therapist, psychologist or counsellor. The MDT will take a number of factors into account when advising you on the best course of action, including the phase of your leukaemia and your general health. You may be invited to take part in a clinical trial of a new treatment for CML (see pages 56 57).

32 Treating chronic myeloid leukaemia 31 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 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: the type and extent of the treatment its advantages and disadvantages any significant risks or side effects any other treatments that may be available. If you don t understand what you ve been told, let the staff know straight away, so they can explain again. Some leukaemia treatments are complex, so it s not unusual to need repeated explanations. It s a good idea to have a relative or friend with you when the treatment is explained, to help you remember the discussion. You may also find it useful to write a list of questions before your appointment. People sometimes feel that hospital staff are too busy to answer their questions, but it s important for you to know how the treatment is likely to affect you. The staff should be willing to make time for your questions. You can always ask for more time if you feel that you can t make a decision when your treatment is first explained to you. You are 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

33 32 Understanding chronic myeloid leukaemia to tell a doctor or the nurse in charge, so they can record your decision in your medical notes. You don t have to give a reason for not wanting treatment, but it can help to let the staff know your concerns so they can give you the best advice. Second opinion Your multidisciplinary team (MDT) uses national treatment guidelines to decide the most suitable treatment for you. Even so, you may want another medical opinion. If you feel it will be helpful, you can ask either your specialist or GP to refer you to another specialist for a second opinion. Getting a second opinion may delay the start of your treatment, so you and your doctor need to be confident that it will give you useful information. If you do go for a second opinion, it may be a good idea to take a relative or friend with you, and have a list of questions ready, so that you can make sure your concerns are covered during the discussion.

34 Treating chronic myeloid leukaemia 33 The benefits and disadvantages of treatment Many people are frightened at the idea of having leukaemia treatments, particularly because of the side effects that can occur. However, these can usually be controlled with medicines. Treatment can be given for different reasons and the potential benefits will vary depending on your individual situation. If you have been offered treatment in the chronic phase, it will aim to control the leukaemia for a long time and have few side effects. In this case, deciding whether or not to have treatment may not be difficult. However, if you are in the blast phase and have been offered more intensive treatment, it may cause more side effects and have a lower chance of controlling the leukaemia. In this case, it may be more difficult to decide whether or not to go ahead. Making decisions about treatment in these circumstances is always difficult, and you may need to talk to your doctor in detail about whether or not you want to have treatment. If you choose not to have treatment, you can have supportive (palliative) care, with medicines to control any symptoms. If you want to stop your treatment, it s important to tell a doctor or specialist nurse. They can discuss your decision with you and offer you advice. They will also make a record of your decision in your medical notes.

35 34 Understanding chronic myeloid leukaemia Targeted therapies The main treatment for CML uses drugs known as targeted therapies. These work by targeting specific proteins in the leukaemia cells. There are different types of targeted therapy drug. The type used in CML is called a tyrosine kinase (TK) inhibitor. These switch off (inhibit) the effects of the abnormal gene BCR-ABL (see page 13). This means that the leukaemia cells (blast cells) will mature correctly and die. The three TK inhibitor drugs currently used are imatinib, dasatinib and nilotinib. Some newer drugs are also being used. Imatinib (Glivec ) Imatinib is the most common targeted therapy used to treat CML. It can be used in the chronic phase and may also be used in the accelerated or blast phase if it hasn t been used before. Imatinib is a tablet. You take it every day for as long as it is working to control the leukaemia. We can send you more detailed information about imatinib.

36 Treating chronic myeloid leukaemia 35 Nilotinib (Tasigna ) and dasatinib (Sprycel ) Nilotinib and dasatinib are also TK inhibitors. They are used to treat newly diagnosed CML in the chronic or accelerated phase. Dasatinib is also used in the blast phase. You may be prescribed nilotinib or dasatinib if you can t take imatinib because of severe side effects or because it isn t working to control your CML. Nilotinib and dasatinib are tablets. They are taken for as long as they are effective. The National Institute for Health and Care Excellence (NICE) gives guidance to doctors in England and Wales. It has recommended nilotinib as a treatment for CML in the chronic or accelerated phase if imatinib isn t working or has to be discontinued because of side effects. The Scottish Medicines Consortium (SMC) has made the same recommendation for Scotland. Neither NICE or the SMC has recommended dasatinib for the treatment of CML. If you live in Northern Ireland, you can find out from your leukaemia specialist whether nilotinib or dasatinib is available. Your specialist may apply to your health board for individual funding for dasatinib. Or, if you live in England, it may be available through the Cancer Drugs Fund. Your specialist will discuss this with you if they think dasatinib is suitable for you. We can send you more information about dasatinib and nilotinib.

37 36 Understanding chronic myeloid leukaemia Bosutinib (Bosulif ) Bosutinib is a newer TK inhibitor, which may be used if other TK inhibitors have stopped working. Neither NICE or the SMC has recommended bosutinib for the treatment of CML, so it may not be widely available. If you live in Northern Ireland, you can find out from your leukaemia specialist whether bosutinib is available. Ponatinib (Iclusig ) Ponatinib is a newer TK inhibitor. It is only suitable for people with CML who have a particular gene change (mutation) in their CML cells called T315I. Only a few people with CML have this gene change. Ponatinib may not be widely available on the NHS. Your specialist may apply to your health board for individual funding for bosutinib or ponatinib. Or, if you live in England, they may be available through the Cancer Drugs Fund. Your specialist will discuss this with you if they think either of these drugs is suitable for you. We can send you information about what you can do if a treatment isn t available, and about the Cancer Drugs Fund.

38 Targeted therapies 37

39 38 Understanding chronic myeloid leukaemia Side effects of TK inhibitors The side effects of TK inhibitors are usually mild and treatable. They are often more noticeable in the first four weeks of treatment and begin to settle after this. Side effects generally disappear when treatment is stopped. If you have severe side effects, your doctor may ask you to stop taking the drug for a few days. After a short break, you may be able to start taking it again without having the same problems. Occasionally people need to stop treatment because their side effects are too severe. Always let your doctor know if you notice any new side effects or your side effects get worse. We have listed the possible side effects of TK inhibitors over the next few pages. Feeling sick (nausea) This is usually mild. Your doctor may prescribe anti-sickness (anti-emetic) drugs to prevent or reduce this. Let them know if you still feel sick, as they can prescribe another anti-sickness drug that may work better for you. Diarrhoea This can usually be controlled with anti-diarrhoea medicine, but tell your doctor if it s severe or continues. It s important to drink plenty of fluids if you have diarrhoea. Loss of appetite A dietitian or specialist nurse can give you advice and tips on boosting your appetite, coping with eating difficulties and maintaining your weight.

40 Treating chronic myeloid leukaemia 39 Headaches Let your doctor know if you have headaches. They can advise you on which painkillers to take. Muscle, bone and joint pain You may have muscle, joint or bone pain while having your treatment. Your doctor can prescribe painkillers to ease this. Fluid retention This can affect different parts of your body. Your ankles may swell, or you may get swelling around the eyes. Fluid retention often settles without treatment. But if it doesn t, drugs that make you pass more urine (diuretics) can help get rid of some of the fluid. A short course of steroids may also help. Skin changes Your skin may become dry and itchy, or you may develop a mild skin rash. Making sure you drink enough fluids can help. Your doctor can also prescribe medicine or creams to help with this. Tiredness and feeling weak This is common, but it s usually mild. It is important to give yourself plenty of time to rest. Constipation Drinking plenty of fluids, eating a high-fibre diet and doing gentle exercise usually helps relieve constipation. Sometimes you may need to take medicines (laxatives) to stimulate your bowel. Your doctor can prescribe these. Risk of infection TK inhibitors can reduce the number of healthy white blood cells produced by the bone marrow, making you more prone to infection.

41 40 Understanding chronic myeloid leukaemia Contact your doctor straight away if: you develop a high temperature, which may be over 37.5 C (99.5 F) or over 38 C (100.4 F) depending on the hospital s policy follow the advice you have been given by your chemotherapy team you suddenly feel unwell, even with a normal temperature. Bruising or bleeding TK inhibitors can reduce the production of platelets, which help the blood to clot. Tell your doctor if you have any unexplained bruising or bleeding. This may include nosebleeds, bleeding gums, blood spots or rashes on the skin. They will advise you about this and explain any precautions you should take. Anaemia (low number of red blood cells) You may become anaemic. This can make you feel tired and breathless. Tell your doctor or nurse if you have these symptoms. If the number of red blood cells becomes too low, you may need to have a blood transfusion. Your blood count will be monitored regularly while you re having treatment. If your blood cell numbers fall too much, 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. The growth factor G-CSF can stimulate your bone marrow to produce more healthy white blood cells, and erythropoietin can help with the production of red blood cells. We can send you more information about G-CSF and erythropoietin.

42 Treating chronic myeloid leukaemia 41 Contraception and fertility TK inhibitors are a newer type of drug, so there isn t a lot of information about women becoming pregnant or men fathering children while taking them. If you are taking a TK inhibitor, there is a slightly increased risk of damage to a developing baby, so it s strongly recommended that you use contraception while being treated with a TK inhibitor. If you think you may want to have children in the future, talk to your doctor before starting treatment with a TK inhibitor. Monitoring response to treatment When you first start treatment with a TK inhibitor, you will need to go to the clinic every week or so. This is so your doctors can closely monitor how you re responding to treatment, and so they can check for any side effects. As time goes on, you won t need to go to the clinic as often. Eventually you may only need a check-up every 2 3 months. At these check-ups, your doctor will ask about your general health and whether you have had any new symptoms or side effects from treatment. You will usually have blood taken to check the numbers of blood cells (a full blood count) and for a PCR test (see page 22). Sometimes you may also have a bone marrow sample taken (see pages 21 22). Your doctor can tell you how often this might be needed. The results of these tests help your doctors know how well your leukaemia is responding to treatment, so they can make any changes if needed.

43 42 Understanding chronic myeloid leukaemia Levels of response The aim of treatment is to put your CML into remission. Remission means there are no signs of CML in your blood. There are different levels of response, which we ve listed over the next pages. Haematological response The white blood cell count in the blood is usually high when you first develop CML. If there is a haematological response, it means your full blood count has returned to normal and no leukaemia cells can be seen. 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 response within three months of starting imatinib. Cytogenetic response This is the next level of response. It refers to the amount of Philadelphia chromosome in the blood and bone marrow (see pages 12 13). As treatment begins to work, the number of Philadelphia chromosome-positive (Ph+) cells in the blood and bone marrow goes down. To check for a cytogenetic response, you will have a bone marrow sample taken (see pages 21 22). Your doctors will usually examine at least 20 cells from the sample to see whether there has been a cytogenetic response. There are different levels of cytogenetic response the level depends on the amount of Ph+ cells in the bone marrow. It takes longer to get a cytogenetic response than a haematological response. It sometimes takes many months. About 80% of (8 out of 10) people taking imatinib for CML in the chronic phase get a complete cytogenetic response. This means there are no Ph+ cells in the bone marrow.

44 Treating chronic myeloid leukaemia 43 Molecular response Even after you have a cytogenetic response, there can still be leukaemia cells in your blood. Because there may only be one leukaemia cell among thousands of normal blood cells, a very sensitive test is needed to detect the leukaemia cells. The PCR test can detect one leukaemia cell in up to 10,000 normal blood cells. It does this by measuring a substance made by the BCR-ABL gene in the leukaemia cells (see page 13). When you re first diagnosed with CML, you ll have blood taken for PCR testing (see page 22). After diagnosis, you ll have this done around every three months. Because it s so sensitive, the PCR test may keep showing signs of leukaemia for many months after your treatment starts, even though you re feeling well. There are two different levels of molecular response: A major molecular response is when there are tiny amounts of the BCR-ABL gene in the blood. Molecularly undetectable leukaemia means the PCR test cannot detect any of the BCR-ABL gene in your blood.

45 44 Understanding chronic myeloid leukaemia Continuing to take treatment You ll usually keep taking the TK inhibitor for as long as it s controlling your leukaemia. This is important even if your PCR tests don t show any signs of leukaemia. If you find it difficult to remember to take your tablets every day, you may find the following ideas helpful: Take your tablets at the same time you usually do something else, for example when you eat your lunch or dinner. Put your tablets in a place where you ll see them every day. Mark off each dose you take on a calendar, or use a seven-day pill container. Keep a supply of tablets with you when you travel and take your medicine in your carry-on luggage when you fly. Your prescriptions will be organised through the hospital, so you may have to go there to collect the tablets each time you need more. Tell your doctor, nurse or pharmacist if it is difficult for you to get to the hospital. There s a possibility that my tablets could give a lifetime s control. But I do try to keep in mind that there might come a day when I have to seek other options. Chanelle

46 Chemotherapy 45

47 46 Understanding chronic myeloid leukaemia Chemotherapy Chemotherapy uses anti-cancer (cytotoxic) drugs to destroy or damage 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. Chemotherapy for CML Although imatinib is usually the standard treatment for CML, chemotherapy is occasionally used. It s most likely to be used if imatinib or other TK inhibitors aren t effective or cause severe side effects. You may be given chemotherapy when your CML is first diagnosed usually with a tablet. This may be when your doctors are waiting to confirm whether the CML is a type that s likely to respond to a TK inhibitor. In this situation, treatment is usually changed to imatinib once the test results are available. Occasionally you may need more intensive chemotherapy, involving having a combination of drugs into a vein (intravenously). This is usually used for the blast phase (see pages 25 and 29). People who are treated with a stem cell transplant (see page 53) usually have intensive chemotherapy as preparation for the transplant.

48 Treating chronic myeloid leukaemia 47 Chemotherapy tablets Chemotherapy tablets are usually used to treat CML in the chronic phase. The most commonly used drug is hydroxycarbamide. The doctor, nurse or pharmacist will tell you how many tablets to take. You need to be sure you are taking the right dose. You will usually take the tablets every day for as long as they re working, or until test results confirm your CML is likely to respond to a TK inhibitor. The dose of the tablets may be changed depending on the results of regular blood tests. Your treatment may be stopped for a while if your number of white blood cells falls below a certain level. We have more information about hydroxycarbamide. Combination chemotherapy If your CML starts to behave more like an acute leukaemia, or if you are going to have high-dose treatment with a stem cell transplant (see page 53), you will be given more intensive chemotherapy. This generally means a combination of three or four drugs given by injection into a vein (intravenously). Your doctor or specialist nurse will tell you about the drugs and their possible side effects. To make it easier for you to have intravenous chemotherapy, and so you don t need frequent injections, you may have a plastic tube called a central line put into a vein in your chest. Sometimes a PICC (peripherally inserted central venous catheter) line or an implantable port may be used instead of a central line. We can send you more information about central lines, PICC lines and implantable ports.

49 48 Understanding chronic myeloid leukaemia Side effects of chemotherapy If you are taking a single chemotherapy tablet, any side effects you have will usually be mild. Treatment with a combination of two or more chemotherapy drugs may cause more troublesome side effects. Risk of infection Chemotherapy can reduce the number of white blood cells, which help fight infection. If the number of your white blood cells is low you ll be more prone to infections. A low white blood cell count is called neutropenia. Always contact the hospital immediately on the 24-hour contact number you ve been given and speak to a nurse or doctor if: you develop a high temperature, which may be over 37.5 C (99.5 F) or over 38 C (100.4 F) depending on the hospital s policy follow the advice you have been given by your chemotherapy team you suddenly feel unwell, even with a normal temperature you feel shivery and shaky you have any symptoms of an infection, such as a cold, sore throat, cough, passing urine frequently (urine infection), or diarrhoea. If necessary, you ll be given antibiotics to treat any infection. You ll have a blood test before each cycle of chemotherapy to make sure your white blood cells have recovered. Occasionally your treatment may need to be delayed if the number of your white blood cells is still low.

50 Treating chronic myeloid leukaemia 49 Anaemia (reduced number of red blood cells) Chemotherapy may reduce the number of red blood cells (haemoglobin) in your blood. A low level of red blood cells is called anaemia, which can make you feel very tired and lethargic. You may also become breathless. Let your doctor know if you get these effects. Increased bruising and bleeding Chemotherapy can reduce the number of platelets in your blood. Platelets are cells that help the blood to clot. If you develop any unexplained bruising or bleeding, such as nosebleeds, bleeding gums, blood spots or rashes on the skin, contact your doctor or the hospital straight away. Feeling sick Some chemotherapy drugs can make you feel sick (nauseated) or possibly be sick (vomit). Your leukaemia specialist will prescribe anti-sickness (anti-emetic) drugs to prevent this. Let your doctor or nurse know if your anti-sickness drugs are not helping, as there are several different types you can take. We have a fact sheet about nausea and vomiting. Sore mouth Your mouth may become sore (or dry), or you may notice small ulcers during treatment. Some people find that sucking on ice may be soothing. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help to reduce the risk of this happening. Tell your nurse or doctor if you have any of these problems, as they can prescribe mouthwashes and medicine to prevent or clear mouth infections.

51 50 Understanding chronic myeloid leukaemia Tiredness (fatigue) You re likely to become tired and have to take things slowly. Try to pace yourself and save your energy for things that you want to do or that need doing. Balance rest with some physical activity even going for short walks will help increase your energy levels. Our booklet Coping with fatigue has more helpful tips. Hair loss Some chemotherapy drugs may cause hair loss. Some people may have complete hair loss including eyelashes and eyebrows. Others may only experience partial hair loss or thinning. It depends on what chemotherapy drugs you are having (your doctor or nurse can tell you more about what to expect). If you do experience hair loss your hair should start to grow back within about 3 6 months of the end of treatment. It may grow back straighter, curlier, finer, or a slightly different colour than it was before. Your nurse can give you advice about coping with hair loss and how to look after your scalp. Contraception It is not advisable to become pregnant or father a child while having any of the chemotherapy drugs used to treat CML, as they may harm the developing baby. It is important to use effective contraception during your treatment and for up to a year afterwards. You can discuss this with your doctor or specialist nurse. Condoms should be used during sex within the first 48 hours after chemotherapy, to protect your partner from any of the drug that may be present in semen or vaginal fluid. You can discuss this with your doctor.

52 Treating chronic myeloid leukaemia 51 Fertility Some chemotherapy treatments may cause infertility (the inability to become pregnant or to father a child). This may be temporary or permanent, depending on the drugs 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 whether 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. We can send you more information about cancer and fertility.

53 52 Understanding chronic myeloid leukaemia

54 Treating chronic myeloid leukaemia 53 Stem cell transplants A stem cell transplant is mainly used to treat people who haven t responded to treatment with TK inhibitors (see pages 34 44). At least two TK inhibitors are usually used first. If your doctor thinks a stem cell transplant is appropriate for you, they will discuss it with you in more detail. Stem cell transplants are only carried out in specialist cancer treatment centres. A stem cell transplant allows you to have much higher doses of chemotherapy than usual. You may also have radiotherapy (high-energy rays) to the whole body. This can help improve the chances of curing the leukaemia or make a remission last longer. Stem cells are found inside our bone marrow. They make all the red blood cells, white blood cells and platelets in the blood (see page 7 8). There are two types of stem cell transplant: Allogeneic transplants when you are given stem cells from someone else (a donor). Autologous transplants (also known as high-dose treatment with stem cell support) when you are given back your own stem cells. People with CML are almost always treated using stem cells from a donor. We can send you more information about donor stem cell (allogeneic) transplants.

55 54 Understanding chronic myeloid leukaemia Interferon alpha Interferon alpha is a protein normally made by the body during viral infections, such as flu. It can also be made outside the body. If other treatments haven t worked, some people are occasionally given interferon alpha in the chronic phase of CML. Doctors may also use it for women who need treatment and are pregnant or want to become pregnant. You have interferon alpha as an injection under the skin (subcutaneously) 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 you can have them at home. I learned to inject myself properly without hurting myself. It did take me a little while to get the knack of it. Chanelle

56 Treating chronic myeloid leukaemia 55 Side effects Interferon alpha can cause various side effects. Some are similar to the symptoms of flu. They include: chills fever depression weight loss headaches aching in the back, joints and muscles tiredness. Some of these side effects can be reduced by taking a mild painkiller, such as paracetamol, before the injection and before you go to bed. Your doctor can give you further advice. The side effects are most noticeable with the first one or two injections, and usually wear off after that. However, the tiredness may continue. We have more information about interferon alpha.

57 56 Understanding chronic myeloid leukaemia Research clinical trials Leukaemia research trials are carried out to try to find new and better treatments for leukaemia. Trials that are carried out on patients are known as clinical trials. These may be carried out to: test new treatments, such as new chemotherapy drugs or targeted therapies look at new combinations of existing treatments, or change the way they are given to make them more effective or reduce side effects compare the effectiveness of drugs used to control symptoms find out how leukaemia treatments work find out which treatments are the most cost-effective. Trials are the only reliable way to find out if a different type of surgery, chemotherapy, hormone therapy, radiotherapy, or other treatment is better than what is already available. Taking part in a trial You may be asked to take part in a treatment research trial. There can be many benefits in doing this. Trials help to improve knowledge about leukaemia and develop new treatments. You will be carefully monitored during and after the study. Usually, several hospitals around the country take part in these trials. It s important to bear in mind that some treatments that look promising at first are often later found not to be as good as existing treatments or to have side effects that outweigh the benefits.