Low grade non-hodgkin Lymphoma

Transcription

1 Low grade non-hodgkin Lymphoma The knowledge to challenge lymphatic cancers

2 The Lymphoma Association provides: freephone helpline emotional support for those affected by lymphomas information about lymphomas and their treatments audio and video library telephone links to others with similar experience of lymphoma quarterly newsletter network of support groups national and regional patient conferences website Lymphoma Nurse Specialists Publisher: Lymphoma Association Author: Catriona Gilmour Hamilton

3 Introduction and acknowledgements You may be someone with low grade non-hodgkin lymphoma. Perhaps someone close to you has recently been diagnosed. You are not alone. Approximately 3000 the monster turned out to be not as fearsome as I had imagined new cases of low grade non-hodgkin lymphoma are diagnosed in the UK each year. Not many people have heard of the illness before their own diagnosis. Low grade non-hodgkin lymphoma can occur at any stage in life, but it is more common in those aged over 50. It is one of the most common cancers in those aged over 75. Low grade non-hodgkin lymphomas are a complex group of cancers that are quite different from other, more aggressive, lymphomas. In many ways, having low grade lymphoma is different to what you might expect of having cancer. This booklet aims to explain what low grade lymphomas are, how they behave and what to expect of treatment. It can be possible to enjoy good quality of life with low grade lymphoma for prolonged periods of time. We hope that this booklet helps you to face the challenge ahead. The Lymphoma Association produces a separate booklet about living with lymphoma, including information about feelings, diet, exercise and complementary therapies. Should you require further information about anything you read in this booklet, or if there is anything you wish to discuss in more detail, please call our helpline. 1

4 This booklet is a revision of a booklet first published in We are grateful to Dr Christopher MacNamara, Consultant Haematologist, Royal Free Hospital NHS Trust, for his assistance in the revision of this booklet. We would like to acknowledge the continued support of our many expert advisors, whose ongoing contributions help us in the development of our publications. In addition to our expert advisors, we have referred to textbooks and scientific papers in the compilation of this booklet. You will find these listed at the end of the booklet. 2

5 Contents 5 How to use this booklet 7 Part One: Introduction to lymphomas 7 The lymphatic system 8 What are lymphomas? 8 How do lymphomas develop? 9 How will it affect my body? 9 Cause of lymphoma? 10 The symptoms of lymphoma 11 Diagnosis 12 Staging tests 15 What do the stages mean? 17 Summary 19 Part Two: Low grade non-hodgkin lymphomas 19 Classification 20 What is meant by low grade or indolent? 21 How will low grade lymphoma affect me? 24 Summary 25 The low grade non-hodgkin lymphomas 26 Follicular lymphoma 28 Chronic lymphocytic leukaemia / small lymphocytic lymphoma 30 Cutaneous lymphomas 30 Lymphoplasmacytic lymphoma 32 Marginal zone lymphomas 32 MALT lymphoma 34 Splenic marginal zone lymphoma 35 Waldenström s macroglobulinaemia 3

6 37 Part Three:Treatment options for low grade non-hodgkin lymphoma 37 Aims of treatment 38 The treatment of early stage disease 38 Watch and wait for advanced stage disease 40 Treatments for advanced stage disease 41 Combination chemotherapy + rituximab 42 Combination chemotherapy on its own 43 Purine analogues 43 Rituximab on its own 43 Rituximab maintenance therapy 44 Oral chemotherapy 44 Radioimmunotherapy 45 Steroids 45 High dose therapy and stem cell transplantation 46 Clinical trials and the future 49 Summary 51 Part Four: Practicalities of treatment 51 About your hospital 52 How is chemotherapy given? 54 How is monoclonal antibody therapy given? 54 How is radiotherapy given? 56 Summary 57 Side effects of treatment 62 Tips for coping with side effects 69 Summary 70 What happens following treatment? 71 Other useful organisations 74 Selected references 4

7 How to use this booklet This booklet has been divided into four parts. You don t have to read it all at once! You might like to read a bit at a time and come back to it when you want to find out more Part One gives an introduction to lymphomas. It deals with: What lymphomas are The symptoms of lymphoma How lymphoma is diagnosed The tests you will have. Part Two discusses the low grade non-hodgkin lymphomas in more detail. It deals with: How lymphomas are classified How low grade non-hodgkin lymphoma behaves The different kinds of low grade non-hodgkin lymphoma and how they affect you. Part Three discusses the different treatments in use for low grade non-hodgkin lymphoma. It deals with: Treatment for early stage disease Treatments for advanced disease. Part Four discusses the practicalities of treatment. It deals with: How chemotherapy is given How antibody therapy is given How radiotherapy is given The side effects of treatment Your hospital Follow up after treatment. Important! Read this bit 5

8 You will see things written in different ways throughout the booklet. This is what they mean: Words written like this discuss what is included in the paragraphs to follow The arrow bullet points give you directions to other parts of the booklet with more information on a particular subject. The helpline logo indicates that you can call our helpline for more information on this subject. Words written in a paragraph like this are summaries of the section above. You might want to just read these bits of the booklet to get the most important points. 6

9 Part One: Introduction to lymphomas 1 This part of the booklet will begin with: The lymphatic system What lymphoma is and how lymphoma develops The cause of lymphoma The symptoms of lymphoma The lymphatic system The lymphatic system is a complex network of tubes, glands and other organs such as the spleen. The tubes are called lymph vessels. The glands are called lymph nodes. We have lymph nodes and lymph vessels throughout our bodies. The lymph nodes are often found in groups, particularly under the arms, in the neck and in the groin. The lymphatic system is part of the body s natural defence against infection the immune system. The lymphatic system helps to transport cells and waste products from place to place around your body. They are carried in a clear fluid called lymph. The lymph moves through the lymph vessels and lymph nodes. The lymph nodes are an important part of your immune system. Your lymph nodes kick start your body s defence against infection. The lymph carries white blood cells called lymphocytes. Lymphocytes help our bodies to fight infection. 7

10 What are lymphomas? Lymphomas are cancers of the lymphatic system. Lymphomas develop when the white blood cells we mentioned before the lymphocytes become cancerous. Lymphoma is not just one illness. It is a word used to describe a wide range of diseases that all start with a cancerous lymphocyte. Lymphomas were first identified in the 19th century by Dr Thomas Hodgkin. Lymphomas are described as either Hodgkin lymphoma (Hodgkin s disease), or non-hodgkin lymphoma. Non-Hodgkin lymphomas can be fast growing (high grade or aggressive ) or slow growing (low grade or indolent ). Each year, about 10,000 people in the UK are diagnosed with non-hodgkin lymphoma. Around 3000 of these are low grade lymphomas. Non-hodgkin lymphoma is the 6th most common cancer in the UK. It is slightly more common in men. It can occur at any age, but it is more common in those aged 50 and over. How do lymphomas develop? Lymphocytes are constantly dividing to make new lymphocytes. Cell division and cell death are controlled by very complex chemical and genetic messages. Lymphomas occur when something goes wrong with this messaging system. Some of the lymphocytes start to divide in an abnormal way, or do not die when they should. These abnormal lymphocytes reproduce to make more abnormal cells, and collect to form lumps. Most commonly, these lumps form in the lymph nodes. They can grow in other parts of the body too. 8

11 How will it affect my body? The abnormal lymphocytes can spread to other lymph nodes in all parts of the body. They can also spread to organs and tissues outside the lymphatic system and start to grow there too. Like all cancers, lymphoma will damage the health of the individual, and this will get worse if the illness is not treated. The lymphoma cells take up energy and nutrients that are needed by healthy cells. Lymphoma cells are produced instead of the normal lymphocytes. Lymphoma cells prevent healthy organs from doing their usual job. This means that the person s health will suffer depending on where the lymphoma is. For example, lymphoma in the bone marrow might mean that the body can t produce enough blood cells. Tumours can press on surrounding tissues and organs too, causing discomfort and damage. Cause of lymphoma? The cause of lymphoma remains unknown. There is no evidence to suggest that anything you have done or not done has caused your lymphoma. You can t catch lymphoma from someone and you can t give it to someone else. You did not inherit the lymphoma from your parents. Some people are more at risk of lymphoma because of other medical conditions, in particular conditions that affect the immune system. People who are on long-term drugs after an organ transplant are more at risk of certain types of lymphoma. Those living with HIV and AIDS are more at risk of developing some types of lymphoma. This does not mean that you will develop HIV or AIDS if you have lymphoma. 9

12 Some kinds of lymphoma are related to common viruses. Research studies have investigated possible causes of lymphoma, such as chemicals present in the working environment. But it will be a long time before scientists understand this subject properly. The symptoms of lymphoma There are many potential symptoms of lymphoma. Low grade lymphoma often causes few symptoms. Many people have no symptoms at all. For this reason, people often have advanced disease by the time they find out something is wrong. The most common symptom of lymphoma is a painless lump or swelling in the neck, armpit or groin. Sometimes there are lumps in more than one place. These lumps may come and go with low grade non-hodgkin lymphoma. Other symptoms include: Unusual tiredness or fatigue Excessive sweating especially at night Persistent flu-like symptoms Fevers Difficulty shaking off infections Unexplained weight loss Loss of appetite Abdominal pain A cough or breathlessness A persistent itch all over. Sometimes people can have lymphomas in other parts of the body. A person s symptoms may vary depending on where their lymphoma is. 10

13 The next section will discuss: Diagnosis How lymphoma is diagnosed The tests you will have The different stages of lymphoma Diagnosis means finding out what is wrong. In most cases, it is not possible for a GP to confirm whether or not you have lymphoma not even from a blood test. For this reason, your GP will refer you to a specialist at your local hospital for further tests. Sometimes you will see a number of different people who each specialise in different aspects of your care. Biopsy You will almost certainly have a biopsy. In most cases a biopsy is the only way to tell whether or not a lump is lymphoma. A biopsy means the removal of cells for close examination under a microscope. These cells can be taken from an enlarged lymph node. They can also be taken from other tissues such as the bone marrow, or any tissue that seems to have something wrong with it. Usually a whole enlarged lymph node will be removed. This involves having a general anaesthetic and a short stay in hospital. Occasionally the cells will be taken using a needle and a local anaesthetic. Often several doctors have a look at the biopsy. Other tests are performed on the cells. These tests give information about changes in cell DNA, and proteins that can be found on the cell surface. This information helps to determine what kind of lymphoma it is. These tests can take several days. 11

14 The diagnosis of non-hodgkin lymphoma can be difficult. Pathologists who work in General Hospitals may only see a few cases a year. It is now recommended that suspected cases of non-hodgkin lymphoma be reviewed in specialised laboratories. Expert pathologists will then check to make sure they agree with the diagnosis. Staging tests The next step is to find out whether other parts of the body are involved. This process is known as staging. Staging involves a number of other tests, some of which are described below. Don t worry if you don t have all of these tests. Sometimes the most common tests are all that are needed to find out about your lymphoma. Most of these tests will be done as an outpatient. In other words, you will not have to remain in hospital overnight. Blood tests Blood tests will give your specialist information about your general health. Blood tests check things like your liver and kidney function. Other blood tests give an indication of how your general health might be affected by your lymphoma. For example, your blood count gives information about the red cells, white cells and platelets in your blood. In some cases, your doctors may wish to test you for HIV. This is because some cases of lymphoma are related to HIV. You will have blood tests at regular intervals during your treatment and afterwards. 12

15 Bone Marrow Biopsy The bone marrow is spongy, jelly-like tissue found in the middle of the large bones in our bodies. The bone marrow makes our blood cells. It is common for lymphoma cells to be found in the bone marrow. A bone marrow biopsy may be needed to see if this is the case. This procedure involves taking a sample of bone marrow through a large needle. The needle is usually inserted through the skin into the bone of your pelvis (your hip bone) using a local anaesthetic. The procedure usually takes about minutes. Although doctors use a local anaesthetic, this can be a painful procedure. You may need to take pain-killers before and after your bone marrow biopsy. Sedatives can help too. Ask your specialist for advice about what to take. You may hear this test referred to as bone marrow aspirate or bone marrow trephine. Both are types of bone marrow biopsy. A bone marrow trephine takes more tissue, which gives your doctor more information about the structure of the marrow and the cells within it. X-rays X-rays can be used to look at various parts of your body. For example, a chest X-ray may be used to see if there are any enlarged lymph nodes in your chest. X-rays are painless and shouldn t take longer than a few minutes. Scans Scans give a more detailed picture of the body s internal organs and lymph nodes. A CT scan or CAT scan involves lying on a bench that moves your body into a cylinder-shaped camera. The camera takes 13

16 computerised pictures of your insides. Unlike X-rays, which give a see-through picture from front to back, CT scans give a picture of your body in cross section from top to bottom. As the bench moves, the camera takes pictures of the different layers of your body. You may be asked not to eat or drink on the morning of the scan. Most people will be given a liquid to drink, or an injection into a vein, at the time of the scan. These are to make it easier to see some of your internal organs. The drink or injection might make you feel hot all over but this usually only lasts a few minutes. Tell someone if you feel this way. If you are allergic to iodine, or if you have asthma, it is important that you tell the people doing the test before you have the drink or injection. The scan is painless, and takes 5 20 minutes. You will be asked to lie quite still while the pictures are being taken. MRI (or NMR) scans are similar to CT scans, except they give a slightly different image of the internal structures of your body. MRI is particularly good at imaging certain tissues such as the brain. Like having a CT scan, you are asked to lie on a table that moves you into a cylinder. The cylinder measures magnetic waves as they pass through your body. This test takes about an hour and is painless, but can be very noisy and you may feel claustrophobic. Because the cylinder uses a magnet, you should take off all metal jewellery beforehand. You should also let the technicians know if you have any other metal implants, such as a replaced hip or a pacemaker. Sometimes metal staples are used instead of stitches after an operation, so mention this if you still have them in after your biopsy. PET scans give more detailed information about cell activity. They measure the rate at which cells take up and process a radioactive form of sugar. This can help doctors to distinguish 14

17 between cancerous and non-cancerous cells. More active cells, like cancer cells, will absorb the sugar more readily than surrounding tissue. This creates energy that is picked up by the camera. You may hear this referred to as PET/CT. This is because new machines combine a PET scan with a CT scan to give more anatomical detail. You will have an injection before the PET/CT scan. This injection is the sugar that will create the pictures of your cells. You will be asked to rest for up to an hour after this injection. This is to give it time to be absorbed. PET/CT scans take about an hour. PET/CT scans are not commonly used to diagnose lymphoma at the moment. They are more often used as part of follow up after treatment. Doctors are continuing to find out more about how best to use PET scans in lymphoma treatment. The NHS is working towards having a PET/CT scanner for every cancer network in the UK. But at present, PET/CT scanning is not widely available. An ultrasound scan may be used to check the inside of your abdomen. This scan uses sound waves that bounce off internal organs to create an image. You will be positioned on your back, and a gel rubbed onto your stomach. A technician will then pass an instrument over the gel to produce a picture on a small screen. It is a painless procedure and takes about a quarter of an hour. What do the stages mean? Once all the test results are ready, your doctor will be able to tell which parts of your body are affected by your lymphoma. This is called the stage of your disease. The different stages are described in the following table. 15

18 Stage 1 Stage 2 Stage 3 Stage 4 One group of lymph nodes is affected on one side of the diaphragm Two or more groups of lymph nodes are affected on one side of the diaphragm Lymph nodes are affected on both sides of the diaphragm Lymphoma can be found on both sides of the diaphragm and in organs outside the lymphatic system or in the bone marrow In addition to the stage, you may also hear the letters A or B used to describe your illness. This refers to whether or not you ve had significant weight loss, drenching night sweats or unexplained fevers. B means that you have had one or more of these symptoms and A means that you have not. Most people with low grade lymphoma will have disease at stage 3 or 4 by the time they are diagnosed. This is because the disease grows slowly and it might be a long time before you notice something is wrong. These tests can take a couple of weeks to complete. This might seem a long time, but the information being collected is very important. Your doctor needs to know as much as possible about your illness before choosing the treatment that will be best for you. It can be frustrating and worrying to have to wait before you find out more, and you may find this time difficult. In the case of low grade lymphoma, it is not likely that your illness will change significantly during the time it takes to complete your tests. 16

19 Summary Lymphomas are cancers of the lymphatic system. There are many different types of lymphoma. Lymphomas develop when a kind of white blood cell called a lymphocyte becomes malignant. Lymphomas are described as either Hodgkin lymphoma (Hodgkin s disease), or non-hodgkin lymphoma. Non- Hodgkin lymphomas can be fast growing (high grade or aggressive ) or slow growing (low grade, or indolent ). Lymphomas often cause very few symptoms. The most common symptom is a lump or swelling. Lymphomas are diagnosed following a biopsy of a lump, which means taking some of the cells to look at under the microscope. After this, you will have lots of other tests to find out what parts of the body are involved. These include scans and blood tests, and sometimes bone marrow biopsy. The results of these tests will tell your specialist the stage of your illness. 17

20 18

21 Part Two: Low grade non-hodgkin lymphomas 2 This part of the booklet will discuss low grade non-hodgkin lymphoma in more detail. The first section will discuss: Classification of lymphomas What is meant by low grade or indolent lymphoma How low grade lymphomas behave relapse and remission Classification There are many different types of lymphoma. The process of classification means sorting all the different lymphomas into particular groups. Your biopsy will help with this process. Tests carried out on your lymphoma cells, which take a much more detailed look at the cell s properties, will also help with classification. Classification depends on: what type of lymphocyte has become cancerous what the cells and surrounding tissue looks like under the microscope what molecules or proteins are on the cell what changes may have happened to the cell genes, or DNA. 19

22 The classification of your lymphoma is very important. It gives your specialist vital information about your illness, and how it might behave, in particular: whether it is growing quickly or slowly whether particular parts of your body might be at risk what treatment might be best for you. T-cells and B-cells Lymphocytes are either B-cells or T-cells. Low grade non- Hodgkin lymphomas are either B-cell lymphomas or T-cell lymphomas, depending on which lymphocyte has become cancerous. B-cells and T-cells are so called because they grow to maturity in different parts of the body. B-cells mature in the bone marrow. T-cells mature in the thymus gland in your chest. B-cells and T-cells act in different ways to protect our bodies from infection and illness. Most non-hodgkin lymphomas come from B-cells. B-cell lymphomas are about 10 times more common than T-cell lymphomas. What is meant by low grade or indolent? Lymphomas are described as low grade if the cells appear to be dividing slowly. Low grade non-hodgkin lymphomas are also called indolent lymphomas. Generally speaking, the size of a cell gives an indication of its growth rate. Most lymphomas are a mixture of small and large cells. Small cells reproduce more slowly than large cells. The higher the proportion of small cells the more slow growing the disease is likely to be, and vice versa. 20

23 This rate of cell division will vary from person to person. No two people are identical, even if on paper their lymphomas are the same. The growth of low grade non-hodgkin lymphoma can fluctuate. There will be times when the disease is more active than others. There are several different low grade lymphomas, which will be discussed later in this section. How will low grade lymphoma affect me? The discussion below talks about the most common low grade non-hodgkin lymphomas. Other kinds of low grade non-hodgkin lymphoma might behave differently. You might want to check this with your specialist. Early stage low grade non-hodgkin lymphoma stage 1 or 2 may have little impact on how you feel. This will depend on which lymph nodes are affected, and what tissues are nearby. Early stage disease usually causes few symptoms. It is more likely to go away completely after treatment. Advanced low grade non-hodgkin lymphoma stage 3 or 4 is different. It is, in some ways, not what people expect of having cancer. It often behaves like a long term condition. There are times when it needs treatment, and times when it does not, but it is less likely to go away altogether. Doctors describe this behaviour as a relapsing and remitting course. What is meant by remission and relapse? Remission is a term used to describe a disease being reduced or eliminated completely. Doctors usually describe different types of remission. A complete remission is where no evidence of the disease is present. Important! Read this bit 21

24 A partial remission is where the disease has been significantly reduced but not removed altogether. Sometimes doctors talk of good partial remissions, or even very good partial remissions to describe degrees of response to treatment. Relapse is the term used when a disease returns after an absence or flares up after a quiet period. What does this mean in practice? Early stage low grade lymphoma stage 1 or 2 can occasionally be cured. In this case there is a chance that the treatment will remove the lymphoma completely that the person will go into complete remission and that the lymphoma will not return. Early stage low grade lymphoma is uncommon. Advanced low grade lymphoma stage 3 or 4 behaves differently. It may go into remission, but it is likely to relapse again and need treatment at some time in the future. People with advanced low grade lymphoma are more likely to have partial remissions than complete remissions. In other words, it may reduce significantly following treatment, but is less likely to go away completely. The intervals between treatments are likely to become shorter over time. Treatments that have worked for you in the past may not work as well next time round. Because it does not tend to go away completely, and because it requires treatment at increasingly regular intervals, advanced low grade lymphoma is not usually considered to be a curable disease. For these reasons, specialists aim to manage the disease rather than get rid of it completely. This can often be done very successfully. The aim of treating advanced low grade lymphoma is to induce the best possible remission for as long as possible with the least possible side effects. In other words, your 22

25 specialist will aim to keep the disease under control with a minimum of disruption to quality of life and health. It should be stressed that improvements in treatment mean that cure of advanced low grade lymphoma is a realistic goal for the longer term future. Recent additions to chemotherapy mean that more people diagnosed today have a better chance of good quality long term remission. It is also important to point out that people with advanced low grade lymphoma often live for many years with the disease, and enjoy good quality of life. What is meant by transformation? Sometimes a person s lymphoma can change as it relapses. Low grade lymphoma is usually a mixture of different cells, some that grow faster than others. Sometimes this mixture changes, and the proportion of faster growing cells increases. This means that the disease becomes more like a high grade lymphoma. This is known as transformation. This change can occur in some places but not in others, meaning that a person might have some lumps that are low grade, and some lumps that are high grade. If your doctor suspects that your lymphoma has changed, you may need to have another biopsy. In these cases the lymphoma will be treated as a high grade lymphoma, usually with combination chemotherapy as described on pages

26 Summary Classification of non-hodgkin lymphoma depends on what kind of cell has become cancerous, the characteristics of that cell, and whether the lymphoma grows quickly or slowly. Low grade or indolent lymphomas grow more slowly. Early stage low grade non-hodgkin lymphoma can be cured. Advanced low grade non-hodgkin lymphoma is more difficult to cure completely. It tends to come and go, requiring treatment at regular intervals. The aim of treatment for advanced low grade non- Hodgkin lymphoma is to get as good a remission as possible with the minimum impact on quality of life. Many people with advanced low grade non-hodgkin lymphoma will live with the illness for a long time and enjoy good quality of life. 24

27 The low grade non-hodgkin lymphomas There are many different types of low grade non-hodgkin lymphoma. They differ in the parts of the body involved, the way they are likely to affect you, and the way they are treated. The following pages discuss some of the low grade lymphomas. For each lymphoma you will find a table that discusses: What the term means Who gets it How the illness might affect you How it might be treated Follicular lymphoma is the most common type of low grade lymphoma. It is likely that the discussion of follicular lymphoma will be relevant to you, but you should confirm this with your specialist. Important! Read this bit We would like to stress that it may be confusing or distressing to read about illnesses that are not relevant to your situation. 25

28 Follicular lymphoma What does it mean? Who gets it? The cells of follicular lymphoma have a characteristic appearance under the microscope. Follicles or clumps of irregular size and shape replace the normal structure of a lymph node. Follicular lymphoma is the most common type of low grade lymphoma. It is estimated that follicular lymphoma represents about 22% of all non- Hodgkin lymphomas. Follicular lymphoma is more common in people aged over 50. Most people with follicular lymphoma are aged 65 and over. It is slightly more common in men. How will it affect me? Follicular lymphoma tends to grow slowly in most cases. It usually causes few symptoms in the early stages. The most common symptom is enlargement of lymph nodes, often in more than one place. Sometimes the size of these lymph nodes will fluctuate. Most people will have advanced disease before symptoms develop. About 80% 85% of patients have disease at stage 3 or 4 when they are first seen by their doctor. It is common for follicular lymphoma to involve the spleen and bone marrow. This might cause problems with your blood count. For example, you may experience anemia, or shortage of red blood cells. Follicular lymphoma tends to behave like a chronic condition, meaning that there are times when it is active and times when it is less active. 26

29 How is it treated? Many people live with follicular lymphoma for long periods of time when it does not need treatment. Treatment will be given when the disease worsens or when it causes problems for your general health. It will usually need to be treated more than once. Intervals between treatments tend to become shorter with time. Most cases of follicular lymphoma will have a mixture of small and large cells. The higher the proportion of small cells you have, the slower your disease is likely to grow. Sometimes follicular lymphoma will be graded from 1 3. The different grades refer to the proportions of small and large cells. Grade 3 tends to grow more quickly than Grade 1 or 2. In over 90% of people with follicular lymphoma, the cancer cells have a protein called CD20 on their surface. This protein is very significant because it is commonly used as a target for immunotherapy and radioimmunotherapy. Follicular lymphoma may not need treatment initially. For those that need treatment there are many different options. Follicular lymphoma can be treated with different types of chemotherapy, with antibody therapy and sometimes with radiotherapy. Very occasionally more intensive treatments will be used, including high dose therapy and stem cell transplantation. This is usually reserved for people with disease that might be more aggressive. You will find treatment discussed in more detail on pages

30 Chronic lymphocytic leukaemia / small lymphocytic lymphoma You may be thinking that leukaemia and lymphoma are different things, and to a large extent you would be correct. In theory, lymphoma is a disease primarily of the lymph nodes, and leukaemia is a disease that primarily affects the blood. In practice, the two are very similar and often almost impossible to distinguish from one another. They are both diseases of blood cells with the tendency to involve the same parts of the body. What does it mean? Chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma are terms used for the same condition. Small lymphocytic lymphoma (SLL) tends to be used when the lymph nodes are more prominently involved. The words refer to the behaviour of the illness. Chronic means something that is slow growing and tends not to go away completely. The names also refer to the kind of cells that are seen under the microscope. CLL/SLL is distinguished by particular formations of cells in the bone marrow and lymph nodes. For further information about leukaemia, you may wish to contact Cancerbackup or the Leukaemia Research Fund. You will find their details at the end of this booklet. Who gets it? How will it affect me? CLL/SLL tends to affect people in later life. It is more likely to occur in those aged over 60. CLL/SLL is a slow growing illness. Many people live with it for a long time and die of something else. People with CLL/SLL often have no symptoms at all. The most common symptom of CLL/SLL is enlargement of the lymph nodes in lots of parts of the body. 28

31 How is it treated? Some people will experience B symptoms unexplained weight loss, night sweats and fevers. CLL/SLL commonly involves the bone marrow. The cancerous cells can also be found in the blood. It often involves the liver and the spleen. Disease in the bone marrow and the spleen can cause changes to your blood count. In other words, it alters the numbers of healthy blood cells in your blood. You may have a shortage of red blood cells (anemia), or a shortage of platelets (thrombocytopenia). Anemia causes fatigue, can cause aches and pains and can make you short of breath. People with anemia often look very pale. Thrombocytopenia means that you are more likely to have problems with bleeding. Changes to your blood mean that, unlike other lymphomas, CLL/SLL may be found following a routine blood test, even if you have no symptoms. In a minority of people CLL/SLL will change to become a faster growing disease. People with CLL who feel well often need no treatment. Treatment for CLL involves chemotherapy and sometimes antibody therapies. You will find these treatments discussed in more detail on pages

32 Cutaneous lymphomas Some low grade non-hodgkin lymphomas begin in, and may be confined to the skin. These diseases are quite different to other lymphomas in the way they behave, how they affect you, and how they are treated. Because they are so different to other low grade lymphomas, the cutaneous lymphomas are discussed in a separate document. Lymphoplasmacytic lymphoma What does it mean? Lymphoplasmacytic refers to the kind of cells that can be seen under the microscope. In this case you can see lymphocytes that look like another cell type a plasma cell. The Lymphoma Association produces a information sheet about cutaneous lymphomas. Please telephone the helpline for a copy. Lymphoplasmacytic lymphomas are a group of similar illnesses that have a tendency to behave in particular ways. They are also referred to as lymphoplasmacytoid lymphomas. Waldenström s macroglobulinaemia (WM) is a subtype of lymphoplasmacytic lymphoma. The term macroglobulinaemia refers to the presence in the blood of a large abnormal protein or globulin. This protein is produced by the cancerous cell. How will it affect me? Lymphoplasmacytic lymphoma is less likely to produce typical lymphoma symptoms such as weight loss, fevers and night sweats. Lymphoplasmacytic lymphoma is similar to chronic lymphocytic leukaemia because cancerous cells can sometimes be found in the blood. 30

33 It will always involve the bone marrow and is more likely to involve the spleen. Lymphoplasmacytic lymphoma can cause you to become anemic. This means a shortage of healthy red blood cells. Anemia causes fatigue, can cause aches and pains and can make you short of breath. People with anemia often look very pale. Lymphoplasmacytic lymphoma is likely to produce abnormal proteins or globulins that circulate in the blood. In high concentrations these proteins can cause problems due to hyperviscosity. This means that the protein makes the blood too thick. It makes it harder for the blood to get through small blood vessels, and causes raised pressure in the blood vessels. This may cause a variety of symptoms, including nose bleeds, confusion and visual disturbance. In some cases it can cause more serious problems. Your specialist will carefully monitor the levels of these proteins. How is it treated? Lymphoplasmacytic lymphoma is treated in a number of different ways according to individual circumstances. In some cases it will need no treatment. Other people may have treatment with chemotherapy and/or antibody therapy. 31

34 Marginal zone lymphomas Marginal zone lymphoma refers to a group of lymphomas that make up around 10% of all non-hodgkin lymphomas. They can grow in the lymph nodes, but they usually occur outside the lymphatic system. The most common marginal zone lymphomas are MALT lymphoma and splenic lymphoma. MALT lymphoma and splenic lymphoma are quite different from other low grade lymphomas in their behaviour and treatment. MALT lymphoma What does it mean? Who gets it? MALT stands for mucosa-associated lymphoid tissue. These are lymphomas that begin to grow in the mucous membrane. The mucous membrane is a moist soft tissue that lines many parts of the body. MALT lymphomas can occur at any age, but they typically affect people of middle age and older. They represent about 8% of all non-hodgkin lymphomas. MALT lymphoma is more common in women. MALT lymphomas are more likely to occur in people who have had particular diseases. For example, MALT lymphomas of the stomach occur following infection with a bacterium called helicobacter pylori. MALT lymphoma of the thyroid usually occurs in people who ve had a disease called Hashimoto s thyroiditis. MALT lymphoma in other tissues is more common in people with Sjogren s syndrome. How will it affect me? The symptoms of MALT lymphoma will depend on what part of your body is affected. 32

35 How is it treated? MALT lymphoma can grow in a number of places, including the stomach, the thyroid gland, the salivary gland, the lung, the tear glands and other parts of the eye. MALT lymphoma may be confined to the tissue where it first started to grow. In some cases it spreads further and may involve the lymph nodes or bone marrow. The most common place for MALT lymphoma to grow is the stomach. People with MALT lymphoma in the stomach usually experience symptoms of indigestion or abdominal pain. It is most often diagnosed following an endoscopy. This is a procedure that involves putting an instrument down the oesophagus and into the stomach to have a look and take a biopsy. MALT lymphomas in other places will cause lumps, inflammation, irritation and discomfort in the area. MALT lymphoma in the lung may cause cough and shortness of breath. MALT lymphoma in the tear gland will make the eye very watery. MALT lymphomas are less likely to cause the typical symptoms of lymphoma such as weight loss, fevers and night sweats. The treatment of MALT lymphoma will depend on the parts of the body involved. In some cases MALT lymphoma may need no initial treatment. It is thought that MALT lymphoma of the stomach is caused by infection with a bacterium called Helicobacter pylori. In its early stages it can respond to treatment with antibiotics. You will find these treatments discussed in more detail on pages

36 The antibiotics are used to treat the bacterial infection and the lymphoma regresses as a result. If the lymphoma doesn t respond to this type of treatment, or if it has spread beyond the lining of the stomach at the time of diagnosis, several treatments may be used. These may include surgery, chemotherapy and antibody therapy. MALT lymphomas in other parts of the body will be treated in different ways depending on where it is and whether or not it is confined to one area. Possible treatments include surgery, chemotherapy, antibody therapy and radiotherapy. Splenic marginal zone lymphoma What does it mean? Splenic marginal zone lymphoma is so called because it usually begins in the spleen. Sometimes doctors use the term villous lymphocytes when describing this type of lymphoma. This refers to particular cells that can be found in the circulating blood. Who gets it? How will it affect me? Splenic lymphoma is more likely to occur in later life. Splenic lymphoma is usually a slow growing disease. Enlargement of the spleen means that the spleen does too much of what it is supposed to do. In good health, your spleen takes away excess blood cells. If the spleen is diseased, it can take away too many blood cells. This can mean that you have a shortage of blood cells, in particular a shortage of red blood cells (anemia) or a shortage of platelets (thrombocytopenia). 34

37 Anemia causes fatigue, can cause aches and pains and can make you short of breath. People with anemia often look very pale. Thrombocytopenia will make you more prone to bleeding problems. Splenic lymphoma may be confined to the spleen. It can also spread beyond the spleen to involve other tissues, in particular the bone marrow and lymph nodes. How is it treated? Splenic lymphoma may be treated in several ways, including chemotherapy, surgery and antibody therapy. Some people may require no treatment for prolonged periods. Waldenström s macroglobulinaemia For a discussion of Waldenström s macroglobulinaemia see lymphoplasmacytic lymphomas on page

38 36

39 Part Three: Treatment options for low grade non-hodgkin lymphoma 3 This part of the booklet will discuss the different treatments used for low grade non-hodgkin lymphoma. It will discuss: Aims of treatment The treatment of early stage disease The treatments for advanced disease Clinical trials and the future Aims of treatment The aim of treating low grade non-hodgkin lymphoma is to achieve a good quality prolonged remission with good quality of life. Some people with stage 1 or 2 low grade non-hodgkin lymphoma have a chance of going into a permanent complete remission. For these people, the aim of treating early stage disease will be to cure it. For most people with stage 3 or 4 low grade non-hodgkin lymphoma the aim of treatment will be to control the disease. Advanced disease has a higher tendency to relapse, and is difficult to cure completely. This means that you are likely to need treatment at regular intervals. Until now, doctors have treated advanced low grade non- Hodgkin lymphoma as a chronic condition. But there is reason to expect that this situation is changing. Recent important developments in treatment mean the chance of better quality 37

40 remissions, and remissions that last longer. With time, there may be evidence to suggest that people are living longer as a result. Many experts are confident that in the future advanced low grade lymphoma may be regarded as a potentially curable cancer. The treatment of early stage disease Between 15% and 20% of people with low grade lymphoma have disease at Stage 1 or 2 at the time they first see their doctor. This means that, after completing all of the normal tests, the disease can only be found in one or two groups of lymph nodes. The standard treatment for people who have early stage disease is radiotherapy to the affected lymph nodes and to the surrounding groups of nodes. Surgery to remove all the lymph nodes in the area is not the best treatment. Some lymphoma cells will be left behind after surgery and this means the lymphoma has a good chance of coming back. If the disease comes back at some point in the future it will then be treated in the same way as advanced stage disease. Some doctors suggest that people with early stage disease might benefit from adding short course chemotherapy, or antibody therapies to radiotherapy. Clinical trials will be needed to provide more information about this. Watch and wait for advanced stage disease Many people who have stage 3 4 low grade non-hodgkin lymphoma do not require immediate treatment. Treatment may not be necessary if you: are well have no B symptoms 38

41 have small lymph nodes which are not obviously enlarging rapidly have no threat to major organ function, including bone marrow function. If this applies to you, your doctor might recommend watch and wait. This means exactly what it says. You will be watched, meaning regular outpatient appointments to check on your illness and how you are feeling. You and your specialist will wait until your illness changes before considering treatment. You will be encouraged to keep your specialist informed of any change in how you are feeling. Appointments can be changed if you feel the need to see your doctor sooner. In a scientific study, watch and wait has been compared with immediate treatment with chemotherapy. The people not treated initially did just as well as those who had intensive chemotherapy. They were also spared the side effects of chemotherapy. For people who are suitable for a watch and wait policy the average time from diagnosis to starting treatment is about 18 months. However, some people can carry on for many years without needing any treatment. It can be difficult to have a cancer that is not having active treatment. Many people find it hard to understand why no treatment is the best thing to do. It doesn t mean that you are too old, or that your disease is too advanced to treat. It means that it might be best to save yourself the side effects of treatment until the illness becomes worse. Evidence suggests that no treatment is just as good as treatment for people who are otherwise feeling well. If you would like to talk about watch and wait please telephone our helpline. It is important to be aware that this advice may change. Current clinical trials may provide information that will change the treatment of people with no symptoms. You will find current research referred to on page

42 Treatments for advanced stage disease Your specialist will recommend starting treatment when: your lymph nodes begin to enlarge you develop B symptoms or begin to feel more unwell tests show that your major organs or bone marrow are affected. It is likely that you will need treatment more than once, and that you will experience different types of treatment over a period of time. The average time between treatments is 2 3 years. There are several treatments in routine use for advanced low grade lymphoma. These are discussed on the following pages. There are a number of things that will be considered when deciding which of these treatments will be best for you: 1. What kind of lymphoma you have. Some lymphomas respond better to certain kinds of treatment than others. Some treatments are not suitable for all lymphomas. 2. Whether you have been treated before. Certain treatments are recommended for those who are having treatment for the first time. Others are suitable for people who are having a second or third course of treatment. 3. Side effects. Side effects of treatment may play a major role in deciding what treatment is best for you. This is particularly the case for those in later life who may have other health problems. Your specialists will need to ensure that you will be able to tolerate the side effects, and to ensure that your treatment does not do more harm than good. 4. Previous treatment. If you have failed to respond to a treatment previously, or if it had a very short-lived response, a different form of treatment is likely to be used next time. 40

43 5. Need for a rapid response. If there are severe symptoms, or evidence of problems with a major organ, it is important to ensure that the disease responds quickly to treatment. Some therapies produce a more rapid response than others. 6. Convenience. The frequency of hospital visits, need for admission, and total duration of treatment will be important factors when making a treatment choice. Combination chemotherapy + rituximab Rituximab in addition to combination chemotherapy is recommended as standard first treatment for people with B-cell low grade non-hodgkin lymphoma who have not been treated before. Recent research has demonstrated that the addition of rituximab to combination chemotherapy is superior to chemotherapy alone. It means a better response to treatment and, for some people, an improvement in overall survival. This may be recommended for you if you are eligible. Eligible means that: you have advanced B-cell follicular lymphoma your lymphoma produces the protein CD20 you are fit enough to cope with the side effects of combination intravenous chemotherapy. Combination chemotherapy means giving several drugs together. The idea is to expose the lymphoma cells to a number of drugs that each act in different ways. The drugs are given as a combination of tablets and drugs given through a drip, or as an injection into a tube in your vein. Combination chemotherapy does not usually involve staying in hospital. You usually visit the hospital for a few hours on each day of the treatment. In some cases, admission to hospital may be necessary. Rituximab is a monoclonal antibody therapy. A monoclonal antibody is a protein made to target something called an 41

44 antigen that is found on a cell surface. Rituximab targets an antigen called CD20. CD20 is found on the surface of B-lymphocytes, including the cancerous cells of a B-cell lymphoma. The antibody attaches itself to the antigen. This helps the cell to die, and helps your immune system to attack it. Rituximab is different to chemotherapy because it targets only one kind of cell. This means that there is no damage to other healthy cells. Rituximab is most often given with a combination of drugs called CVP (R-CVP). CVP uses the drugs cyclophosphomide, vincristine, and prednisolone. This combination is given as intravenous injections and tablets, at three or four week intervals. A full course of treatment is usually 6 to 8 cycles, meaning treatment over a period of about 6 to 8 months. Doctors also use rituximab in combination with CHOP chemotherapy (R-CHOP). CHOP uses the drugs cyclophosphamide, hydroxydaunorubicin (or doxorubicin), oncovin (or vincristine) and prednisolone. This combination is also given as intravenous injections plus tablets, usually at three week intervals for a total of 6 to 8 cycles. The addition of the drug hydroxydaunorubicin means that CHOP has more side effects than CVP. R-CHOP is not suitable for everyone. Rituximab can also be added to other combinations of chemotherapy. R-CVP and R-CHOP are those most commonly used. Combination chemotherapy on its own Sometimes combination chemotherapy is used on its own. CHOP and CVP are both used for low grade lymphoma. There are a number of other combinations in regular use. The chemotherapy you have will depend on the kind of lymphoma you have, and on how you have responded to previous treatments. 42

45 Purine analogues Some intravenous chemotherapy combinations are based on particular types of drugs called purine analogues. This group of chemotherapy drugs includes fludarabine and cladribine. Most experience in treating low grade lymphoma has been with fludarabine. It is common in the treatment of chronic lymphocytic leukaemia. Fludarabine can be given as an intravenous injection or in tablet form. It is usually given as daily injections or tablets for 3 to 5 consecutive days, once every 3 to 4 weeks. A standard course is 6 to 8 cycles of therapy. Fludarabine is often used in combination with other drugs, such as in FMD chemotherapy (fludarabine, mitoxantrone, dexamethasone) or FCM (fludarabine, cyclophosphamide, mitoxantrone). Doctors are investigating the use of fludarabine and its combinations with rituximab. Rituximab on its own Rituximab can be used on its own for people who have relapsed more than once following chemotherapy, or for people whose lymphoma does not respond to chemotherapy. It can also be used for people who are unable to cope with the toxic side effects of chemotherapy because of other health problems. Rituximab maintenance therapy Rituximab is given as a maintenance treatment after chemotherapy to people who go into remission. Research confirms that using rituximab in this way helps to significantly prolong remission, meaning that people can enjoy longer periods of improved quality of life. Rituximab maintenance might be suitable for you if: you have stage III IV B-cell follicular lymphoma you have relapsed following an earlier course of treatment you go into remission following another course of chemotherapy or R-chemotherapy. 43

46 Maintenance rituximab is given once every 3 months. At the moment, it is given for a maximum period of 2 years. Current clinical trials will provide evidence about whether rituximab should be given to maintain remission following your first course of treatment. Oral chemotherapy Oral chemotherapy chemotherapy taken as a tablet has always been a common treatment for low grade lymphoma. The side effects of tablet chemotherapy are often relatively easy to tolerate. This makes tablet chemotherapy a good option for anyone who is not fit enough to cope with intravenous combination chemotherapy. The most frequently used tablet is a drug called chlorambucil. It is taken every day for two weeks, followed by two weeks off, and then repeated. A full course of treatment is usually about 6 months, but may sometimes be longer. Another drug called cyclophosphamide is sometimes used in a similar way to chlorambucil. Radioimmunotherapy Radioimmunotherapy is a combination of antibody therapy and radiotherapy. A tiny radioactive particle is attached to an antibody that targets an antigen on the B-lymphocyte. The action of the antibody which helps the cell to die is combined with the delivery of a dose of radiation direct to the lymphoma cell. Radioimmunotherapy is different from conventional chemotherapy or radiotherapy, because it targets the B- lymphocyte in particular, and avoids damage to healthy cells. Zevalin is one radiolabelled antibody that is being used in a number of UK hospitals. Another drug name is Bexxar. The Lymphoma Association produces a information sheet about radioimmunotherapy. Please telephone the helpline for a copy. 44 Recent research suggests that radioimmunotherapy might prolong remission when given after a course of chemotherapy.

47 Radioimmunotherapy may also be used for people who have relapsed following earlier treatments with chemotherapy and rituximab, or for people whose lymphoma does not respond to other treatments. At present, radioimmunotherapy is not widely used in NHS hospitals. Steroids The word steroid refers to a large family of similar drugs. They are all drugs that imitate hormones produced naturally by the body. Steroids may be given with chemotherapy or on their own. The most commonly used steroid is called prednisolone. Steroids can be taken as tablets or sometimes given intravenously. Steroids are not a long-term treatment for lymphoma, but they are very effective in controlling symptoms, and reducing the disease quickly. Steroids are useful for people who are not well enough for chemotherapy, or for use in symptom control. High dose therapy and stem cell transplantation Occasionally, some specialists recommend treatment with high dose therapy and stem cell transplantation as a first treatment or as a treatment to follow standard chemotherapy. It is thought that the high dose therapy may produce a good quality prolonged remission. Stem cell transplants mean that chemotherapy can be given in higher doses than usual. Treatment for lymphoma causes damage to the cells of your bone marrow, which makes the cells of the blood. The large doses of chemotherapy kill all the cells of your bone marrow, so your bone marrow needs help to recover. Your bone marrow recovers with a transfusion, or a transplant, of cells. These cells are called stem cells. They are the primitive 45

48 cells that have the potential to grow into all the different cells of your body. Following the transplant, they find their way back to your bone marrow, and replace the damaged cells. The long-term effect of high dose therapy for low grade non- Hodgkin lymphoma is still unclear. It is not a treatment that everyone can tolerate because of the high doses of drugs and the pronounced side effects. Doctors are still learning about how best to use stem cell transplant in low grade lymphoma. To date, stem cell transplant has not been compared with other treatments that aim to prolong remission. Clinical trials and the future Clinical trials are scientific studies that test the success of different treatments. They are very important in improving the future treatment of people with lymphoma. You may be invited to take part in one. Not all hospitals conduct clinical trials. This may be something to discuss with your doctor when planning treatment. Clinical trials for lymphoma usually involve comparing a standard treatment with another, newer, type of treatment. In these cases, you are allocated to one of two groups at random. You will not be able to choose which of the treatments you receive. Sometimes trials for low grade non-hodgkin lymphoma involve the use of a less well known treatment on its own. These trials are for people who have already had other standard treatments. The Lymphoma Association can provide more information about stem cell and bone marrow transplants and clinical trials. Please telephone our helpline. If you take part in a trial, you will be given information about the reasons for the trial and the drugs you will have. Clinical trials often involve more tests and scans. People involved in trials also have access to specialist research staff for information during treatment and afterwards. 46

49 There will be no pressure placed on you to take part in a trial if you do not wish to. You can always opt to have the standard treatment if you prefer. Your care will not be compromised if you don t want to be in a trial. The past decade has seen huge changes in the treatment of advanced low grade non-hodgkin lymphoma. All of this progress is the result of clinical trials. The following are examples of current areas of research. More about rituximab Research continues to improve the way we use the treatments we already know about. This includes looking at the use of rituximab. Some important areas of study that could mean further progress in the near future include: should rituximab therapy be used instead of watch and wait? should rituximab maintenance therapy be used after someone s first course of treatment? should rituximab maintenance be given for longer than 2 years? Is it safe to continue for longer than 2 years? Donor transplants Donor stem cell transplants may prove to be an important treatment for people with low grade lymphoma. By using reduced intensity conditioning meaning lower doses of chemotherapy and radiotherapy donor transplants may be safer for older people for whom high dose therapy would be too risky. The cells from a donor are like giving you a transplant of a new immune system. These new immune cells will mount an attack against your lymphoma cells. This is known as the graft versus lymphoma effect. Donor transplants are usually only used for people who have relapsed following other treatments. 47

50 New antibodies Following the success of rituximab, new monoclonal antibodies are in development to target other antigens on the surface of the lymphoma cell. Early clinical trials are looking at whether they work, and how they might be combined with other treatments. These include: anti CD80 therapy galiximab anti CD22 Epratuzumab anti CD40 SGN-40 Vaccination therapy In recent years, research has increased our understanding of how our immune systems react or don t react to cancer cells. Lymphoma cells have certain unique proteins or antigens that are found on the cell surface. For some reason, the immune system sometimes fails to respond to the presence of these antigens. It is thought that, using the antigen, a vaccine might be prepared. The vaccine would help the immune system identify the lymphoma cells, and kill them. In this way, it may be possible to prevent spread of disease or relapse. Vaccination therapy has been under investigation for several years. Vaccines are not currently available for routine use in lymphoma therapy. 48

51 Summary Early stage low grade lymphoma is potentially curable with radiotherapy to the affected lymph nodes. If it comes back it will then be treated as for advanced low grade lymphoma. If you feel well, and there is no immediate threat to your general health, your disease may need no treatment to begin with. Your specialist will observe you and begin treatment when necessary. This is called watch and wait. Treatment will be recommended if your lumps enlarge quickly, if your symptoms become difficult to manage, or if there is a threat to a major organ such as your bone marrow. You are likely to need more than one course of treatment, and you are likely to experience different kinds of treatment. There are many potential treatments for advanced low grade non-hodgkin lymphoma. The most common first treatment is rituximab + combination chemotherapy. Other treatments include combination chemotherapy alone, tablet chemotherapy, and radioimmunotherapy. Rituximab on its own is also used to maintain remission. At the moment, rituximab maintenance therapy is given after a second course of chemotherapy. Current clinical trials are finding out more about maintenance rituximab. Your treatment will be chosen according to your individual circumstances. Clinical trials continue to find out more about treating low grade lymphoma. You may be invited to take part in a clinical trial. 49

52 50

53 Part Four: Practicalities of treatment 4 This part of the booklet will discuss: Your hospital How chemotherapy is given How antibody therapy is given How radiotherapy is given Side effects of treatment What happens after treatment About your hospital People with lymphoma may be treated at local hospitals or at larger hospitals with cancer centres. Sometimes people will have their treatment shared between the two. Your GP, or the doctor who finds out that you have lymphoma, will send you to the nearest hospital with a lymphoma specialist. Don t worry if you are having treatment at a small hospital. Larger hospitals do not necessarily have better results. A lymphoma specialist might be a haematologist (someone who specialises in diseases of blood cells) or an oncologist (someone who specialises in cancers). Lymphoma experts come from both these fields of medicine. Clinical Nurse Specialists also play an important role in the care of people with lymphoma. Your doctor will not mind if you want to ask questions about your treatment hospital. Some of the questions you might like to ask are: 51

54 Will your doctor have links with other lymphoma specialists? Does the hospital have a clinical nurse specialist or other specialist cancer nurse? Does the hospital have a laboratory on site for fast blood test results? Does the hospital have close links with specialist lymphoma pathologists? Does the hospital participate in clinical trials? What other experts are there to help if you need them? For example, will you be able to see a counsellor if you need to? The Lymphoma Association has an information sheet giving general advice about how to find the best place for treatment. Please telephone the helpline for a copy. How is chemotherapy given? The word chemotherapy literally means treatment with drugs. Drugs for cancer are called cytotoxic drugs because they kill cells: cyto means cell, and toxic means poisonous. Chemotherapy works by interrupting the reproductive cycle of the lymphoma cell. Different chemotherapy drugs do this in different ways. Chemotherapy drugs particularly target cells that divide quickly. Chemotherapy for lymphoma often involves giving more than one kind of drug. This increases the chances of killing as many cancer cells as possible. Many people with low grade non-hodgkin lymphoma will have chemotherapy taken as a tablet. The hospital pharmacy will prepare your tablets for you to take home. You will have regular checkups during the time you are taking them. You will find the side effects of chemotherapy discussed on pages

55 Other chemotherapy for low grade non-hodgkin lymphoma is given intravenously. This means through a tube into one of your veins. This involves coming to hospital to have treatment. Chemotherapy is usually given over a period of several months. The exact timetable for your treatment will depend on what kind of chemotherapy you are having. You will be given information about your treatment and what side effects to expect. Intravenous chemotherapy Intravenous chemotherapy for low grade lymphoma is usually given as an outpatient. This means you will visit hospital on the day of treatment but go home afterwards. In some cases admission to hospital may be necessary. This might be because of treatment side effects. You may, for example, have a very low blood count and develop an infection. Admission might also be necessary because certain drug combinations are known to cause more severe side effects. Intravenous drugs are delivered through a small tube that is put into one of your veins. The nurse or doctor will often use a vein on the back of your hand or in your lower arm. A needle is put in first, and then taken out, leaving a soft tube resting in the vein. This is secured with adhesive to keep it in position. Usually, this tube will be taken out before you go home and another one put in next time. On some occasions people will have intravenous chemotherapy through a central line. A central line is a more permanent intravenous tube. It sits in a larger vein further inside your body. Central lines are relatively uncommon for people with low grade lymphoma. Intravenous drugs are usually given as an infusion, or a drip. They are mixed with another fluid in a bag, and the bag is set 53

56 up to drip into the tube in your arm over a period of time. The bag of fluid needs to be kept higher than your arm, and it will usually be hung on a pole. The poles are often mobile, so you can walk around while the drip is connected. You might need to go to the toilet more often because of the extra fluid. Drugs are often given using machines that regulate the flow of liquid. They are boxes that attach to the pole, and the intravenous tube is fed through them. They can beep from time to time if something is not right. This might sound alarming at the time, but don t worry. The flow of fluid stops until the problem is sorted out. How is monoclonal antibody therapy given? Rituximab is given as a drip in the same way as other intravenous drugs. The first infusion is given quite slowly to help prevent side effects. This usually takes around 4 6 hours. Subsequent infusions may be given over a shorter period of time if you do not have significant side effects. Rituximab is usually given as an outpatient, so you don t have to stay in hospital. Sometimes people are asked to stay in hospital following the first infusion of rituximab. Radioimmunotherapy antibody therapy + radioactive isotope is given as a single injection following a short course of rituximab. How is radiotherapy given? Radiotherapy uses high energy rays directed through the enlarged lymph nodes. These rays are similar to the rays used when taking an X-ray, but they are delivered in much higher doses. The rays stop the cells from dividing and kill them. Radiotherapy is used for some people with low grade non- Hodgkin lymphoma. It may be used as a treatment on its own for early stage disease. Side effects of radiotherapy are discussed on pages

57 Radiotherapy is usually given daily Monday to Friday, and you will be able to go home after each treatment. Treatment usually takes 4 6 weeks. A radiotherapy department can feel like quite a high-tech and impersonal environment, with big machines and no windows. It can be unnerving at first, particularly as you will be left alone for some of the time. The first stage of treatment is planning. This may involve more than one visit to the department before treatment starts. The radiographer will mark your skin with a marker pen. These marks need to remain visible throughout treatment. During treatment, you will be carefully positioned on a narrow table and asked to stay very still. The radiographer may cover certain parts of your body that do not need treatment. The lights in the radiation room are dimmed while you are getting into position. You will be left alone for the time it takes to give the treatment. The radiographer will be watching from a room next door. You will be able to hear what they say and they can hear you. The length of time treatment takes will depend on your individual situation, but it will be somewhere between 5 and 20 minutes. This kind of radiotherapy does not make you radioactive, and there will be no risk to those close to you. The radiotherapy itself is completely painless, but it can have uncomfortable side effects. 55

58 Summary Lymphoma is treated by either a haematologist or an oncologist. Most treatment for low grade non-hodgkin lymphoma is given as an outpatient. In some instances hospital admission will be required. Chemotherapy for low grade non-hodgkin lymphoma is given as a tablet or intravenously. Intravenous chemotherapy may be given via a central line, which is a more permanent intravenous tube. Antibody therapy is given intravenously. Sometimes hospital admission is needed for the first dose of antibody therapy. Radiotherapy may be used for treating low grade non- Hodgkin lymphoma, especially for early stage disease. Radiotherapy is given on weekdays over a course of several weeks. 56

59 Side effects of treatment This part of the booklet discusses: Common side effects of treatment Tips for coping with side effects The text written in italics refers to side effects of radiotherapy. Common side effects Side effects occur because lymphoma treatments damage healthy cells as well as lymphoma cells. The side effects of chemotherapy will depend on what drugs you are having. You will be given information about what to expect. The side effects of radiotherapy will depend on what part of your body is being treated. You will be given information about what to expect and how to take care of yourself. You may find that you have no side effects to start with but that they become more obvious towards the end of your course of treatment. Most treatment side effects are short term. Some may be long-term or permanent. Your doctors should discuss this with you before treatment starts. People in later life, in particular those who have other medical problems, are likely to experience greater difficulty with side effects. Damage to the bone marrow The most important side effect of chemotherapy is damage to the bone marrow. The bone marrow is responsible for producing the body's blood cells. These include white blood cells that help us to fight infection, red blood cells that carry oxygen and platelets that stop us bleeding. These cells are measured using a blood test called a blood count. For information about the longterm side effects of treatment please telephone our helpline. The Lymphoma Association produces a document discussing the treatment of lymphoma in later life. Please telephone the helpline for a copy. 57

60 Chemotherapy can cause neutropenia, or a shortage of white cells called neutrophils. This means you will be more at risk of infection during your treatment. You will be most at risk from about 7 10 days after each dose. A low white cell count can last for some time. You should contact your hospital immediately if you develop signs of an infection. Signs of infection are listed in the table on page 63. Important! Read this bit If you develop an infection, or if your white cell count is too low, it may be necessary to delay treatment for a short period to give your blood count a chance to recover. You may have to stay in hospital during this time. Chemotherapy can also cause anemia, or a shortage of red blood cells. This is particularly the case with low grade non- Hodgkin lymphoma because the disease itself may have caused anemia to start with. Sometimes chemotherapy causes thrombocytopenia, or a shortage of platelets. This will make you more susceptible to bruising and bleeding. Your blood count can be affected by radiotherapy too, and you will be more at risk of infection during treatment. Change in taste, loss of appetite and sore mouth Most people find that they have some problems with eating and diet. For example, food may start to taste different. You may lose your appetite. You may find that nausea or a sore mouth makes it difficult to eat. You may experience loss of weight. If you are having radiotherapy to the chest or neck, you may also find that swallowing becomes difficult. Radiotherapy to the upper neck or head will cause a sore mouth. 58

61 Nausea and vomiting Some chemotherapy drugs may make you feel sick or nauseous after treatment. You might vomit too. You will be given anti-sickness drugs to help. These are called anti-emetics. Tell your specialist or nurse how you are feeling. If the drugs don t work, tell someone. Sometimes a change in the antisickness drug is needed if the first drug doesn't work. Sometimes radiotherapy can make you feel sick, in particular if your abdominal area is being treated. It may help to have anti-sickness medications before treatment starts. Fatigue Fatigue is one of the most common experiences for people with lymphoma. Cancer related fatigue is quite different from normal tiredness. It can mean that you find it difficult to concentrate or make decisions. You might be short tempered. You might sometimes feel too tired to do even simple things, like watching television. Fatigue can be difficult to describe, and you may find that other people even your doctors don t really understand it. Fatigue is thought to be the result of a combination of factors, including your treatment, the impact of your illness on your body, a low red cell count (anemia) and anxiety. It may take some months following treatment before your fatigue goes away. Fatigue is associated with both chemotherapy and radiotherapy. For more information about fatigue, please telephone our helpline. Hair loss Chemotherapy drugs commonly cause hair loss. This means that you may lose some or all of your hair. Hair loss will start within a couple of weeks of starting treatment. It can come out in large quantities, and this can be very distressing. 59

62 Hair loss will only be short term, and your hair will grow back after treatment has finished. It usually starts to grow back within a month or two of treatment finishing. It might take 6 to 12 months for it to return to normal. If you are having radiotherapy, hair loss should only occur in the area to be treated. This hair loss will be temporary, and hair will start to grow back a few months after treatment. Sore mouth Chemotherapy drugs may give you a sore mouth. This is because the chemotherapy damages the cells of the lining of your mouth. You will be more at risk of mouth ulcers and infections. This is called mucositis. It can be very uncomfortable. If you are having radiotherapy to the head, neck or upper chest you may find that your mouth or throat becomes sore. Sore skin The skin in the radiotherapy treatment area can become pink, dry and itchy. If you have dark skin it might become darker. Sometimes it becomes blistered, a bit like sunburn. This is particularly likely to occur in folds of skin such as under the breast or in the groin. Skin reactions usually peak a few days after the end of treatment and then start to heal. You will be given instructions about caring for your skin. Peripheral neuropathy Some chemotherapy drugs cause damage to the nerves that carry information about touch, temperature, pain and sensation. The drugs can also damage the nerves involved in muscle movement. This is called peripheral neuropathy. Peripheral neuropathy is usually related to a particular group of drugs, which includes vincristine and vinblastine. Peripheral neuropathy commonly affects the nerves in your hands and feet, but you might feel it in other places too. It can cause pins and needles, pain and numbness. It sometimes 60

63 causes clumsiness and problems with balance. Sometimes it produces increased sensitivity to heat. Symptoms of peripheral neuropathy usually develop soon after you start treatment. For most people these will be temporary. Some people will experience long-term or permanent damage. Not everyone will get peripheral neuropathy. If you do experience symptoms, tell your doctor. Your doctors might make a change to your treatment to prevent it getting worse. Bladder problems The drugs cyclophosphamide and ifosfamide can cause irritation and bleeding from the lining of the bladder and the kidneys. You will have to drink lots of extra fluid with these treatments. You may have extra fluid through your drip. A drug called Mesna can be given to prevent bladder and kidney complications. It is given with ifosphamide and sometimes with cyclophosphamide. Your nurses may check your urine for signs of blood. If you notice blood in your urine, you should tell someone straight away. Ask your team for advice about prevention of bladder problems. Reduced fertility Some treatments for lymphoma may reduce your fertility. This is particularly the case with certain chemotherapy drugs, with radiotherapy to the groin, and with high dose chemotherapy used in bone marrow and stem cell transplant. Your specialist should discuss this with you before treatment starts, but it will not be possible to say for certain how your fertility might be affected. Men may wish to consider storing sperm prior to treatment. The options for women are more limited. Reduced fertility in women is related to age. Women closer to the age of normal menopause are more likely to experience 61

64 reduced fertility, and may experience early menopause. You may find that your periods become irregular, or stop altogether, during treatment. Doctors will advise that women with lymphoma do not become pregnant during the time of their treatment. You should continue to use contraceptives during treatment. Side effects of monoclonal antibody therapy The most common side effects of antibody therapy are shivers, fevers, headache and flu-like symptoms. These are more common with the first infusion. The first infusion is given slowly to reduce side effects. You will be given paracetamol and antihistamines to prevent side effects. Occasionally people have more serious side effects and your doctor may decide to discontinue antibody therapy. For more information about dealing with side effects please telephone our helpline. Tips for coping with side effects The tables on the following pages give information about coping with side effects. It is important to let your medical team know about your side effects. Tell them if any of the side effects change during your treatment. Your doctors and nurses won t always ask how you are feeling, and they might assume you are OK if you don t say anything. There are usually things that can be done to help with side effects. 62

65 Side effect Low white cell count neutropenia What to do Contact the hospital if you develop signs of infection such as: fever, temperature above 38 o C, chills and sweating, mouth sores and ulcers, cough or sore throat, redness or swelling around sores on the skin, diarrhoea, burning sensation when passing urine, unusual vaginal discharge or itching. Wash well and regularly. Wash hands before meals, after using the toilet, after using public facilities. Avoid places where infection risk is increased, such as swimming pools. Avoid foods that contain lots of live bacteria. These include: runny cheeses, take aways, raw or undercooked eggs, peppercorns, undercooked meats and fish, paté. Ask your nurse for information on clean diets. Don t keep food for longer than 24 hours in the fridge. Take care when handling pets avoid bites or scratches and wash your hands afterwards. Wear gloves for gardening. Low red cell count anemia Tell your doctor if you are fatigued, if you feel short of breath, abnormally tired or have abnormal aches and pains. Ask about what treatment you might have for anemia. 63

66 Side effect Low platelet count thromobocytop enia Change in taste and loss of appetite What to do Report bruising, bleeding. Notify doctors immediately if you feel very unwell, faint or clammy. Avoid contact sports or very vigorous exercise. Take care to avoid injury when doing day to day things like cooking and gardening. Try to eat little and often and avoid big meals. Eat whenever you are hungry whether or not this is your usual mealtime. Avoid things you don t like. Try foods that taste stronger marinated foods, savoury rather than sweet. Eat food warm rather than hot. Have a ready supply of things that are quick and easy to prepare. Try to supplement your diet with nutritious drinks, but not at the same time. Take drinks through a straw. Eat with others in a pleasant environment. Take exercise where possible. Rinse mouth before meals and practice good mouth hygiene. 64

67 Side effect Constipation What to do Ask your doctor if your treatment might cause constipation, and ask for advice about using laxatives to prevent it. Make sure you drink plenty. Try a hot drink in the mornings. Eat a high fibre diet if possible. Take gentle exercise. Diarrhoea Ensure adequate fluid intake. Ask your doctor for treatment for diarrhoea. Fatigue Take regular light exercise, such as walking. Take regular rests or short naps throughout the day. Ask your doctor if you are anemic, and whether any treatment will help your anemia. Plan your activities: do a bit less of what is less important, and plan the important things for when you have more energy. Accept offers of help with day to day tasks. Aim for a good night s sleep on a regular basis. Eat well. Make time to see friends and take part in normal social activities. 65

68 Side effect Feeling sick What to do Take anti sickness drugs. Tell someone if they don t work. Try travel sickness wrist bands from the pharmacy. These prevent nausea by using acupressure points. Try relaxation techniques. Avoid cooking smells and seek help with preparing meals. Eat smaller meals, cold or at room temperature. Keep surroundings as peaceful and clean as possible, and encourage fresh air. Hair loss Have hair cut short before treatment starts. Discuss wigs with the hospital team, or try hats or scarves. Avoid using heated rollers or hairdryers, avoid chemical treatments such as perms and hair dyes. Avoid things that pull at your hair such as rollers and tight elastics. Use wide toothed combs and soft bristled hair brushes. Protect the skin of your scalp from becoming dry. Avoid exposure to heat and cold. Wearing a hair net or towelling turban to bed will help to collect hair lost overnight. Use make up, jewellery and accessories to give you more confidence. 66

69 Side effect Peripheral neuropathy What to do Tell your doctors if you have pins and needles or loss of feeling in fingers and toes, loss of balance, abdominal pain or constipation. Take care to avoid injury to fingers and toes, which will be less sensitive than usual: avoid extreme temperatures, wear gloves for gardening, take care when cooking. Keep your feet and hands warm as cold can make symptoms worse. Try gentle massage and exercise of fingers and toes by flexing and stretching for a few minutes four times a day. Wear comfortable shoes avoid high heels or shoes that are tight. Inspect your feet regularly to check for damaged skin in parts that are numb, particularly on the soles of your feet and around toenails. Sore mouth, sore throat Visit your dentist before starting treatment. Practice good oral hygiene the hospital may prescribe special mouthwashes for use at home. Avoid mouthwashes containing salt or alcohol. Use a soft bristled toothbrush. Avoid alcohol and tobacco. Rinse mouth after meals. Keep your lips moist with lip creams. Vaseline works well and is easy to find. 67

70 Side effect What to do Avoid hot, spicy foods or foods coarse in texture. Cool, easy to swallow things can help, like ice cream and yoghurt. Sip drinks through a straw. Ask for pain killers or other medication to help. Sore skin Ask your team for instructions about looking after your skin. Do not use creams unless recommended by your specialist. Avoid soaps, talcum powder and deodorants. Avoid rubbing the skin. If bathing, use lukewarm water and pat dry with a towel. Men having radiotherapy to the head or neck should use electric razors rather than wet shaving, or avoid shaving altogether. Avoid exposure to sun and wind. 68

71 Summary There are many potential side effects of treatment. Your side effects will depend on what kind of treatment you are having. You should be given information about what side effects to expect. Most side effects of treatment are short-term. They should improve within weeks of finishing treatment. Some side effects may be permanent. You are likely to have more difficulty with side effects if you are older, or if you have other medical problems. You should tell the team at the hospital immediately if you develop signs of infection. You should keep the hospital team informed of any side effects you have. 69

72 What happens following treatment? People with low grade lymphoma usually attend a clinic for follow-up appointments on a regular basis. Appointments are generally every 3 to 6 months, or sometimes less frequent, depending on the individual. Don t feel that you have to wait until your next appointment if you feel worried about anything. Most specialists will encourage you to bring your appointment forward if you experience changes in how you are feeling. You may find that it helps to talk to your GP if you are concerned. He or she can be a valuable source of support and advice closer to home. whilst it is obviously not something to be recommended, having NHL has given me new insights and appreciation of life. I have done my best to pass these positive benefits on to others, so that they too realise that life must be cherished and enjoyed not taken for granted and endured! The Lymphoma Association produces information about living with lymphoma, including information about diet, exercise, dealing with feelings and relationships. Please telephone the helpline for further information. 70

73 Other useful organisations Benefits Enquiry Line Tel: Website: British Association for Counselling and Psychotherapy BACP House Albert Street Rugby Warwickshire CV21 2SG Tel: Website: Will provide a list of accredited counsellors in your area. Cancerbackup 3 Bath Place Rivington Square London EC2A 3JR Tel: Website: via website. Providers of information about all cancers, cancer treatments and living with cancer. Cancerbackup merged with Macmillan Cancer Support in Cancer Counselling Trust Caspari House 1 Noel Road London N1 8HQ Tel:

74 Website: Providers of face-to-face and telephone counselling services. Cancer Research UK 61 Lincolns Inn Field London WC2A 3PX Tel: Website: via website. Provide information on all cancers. Also largest voluntary provider of funding for cancer research. Carers UK Glasshouse Yard London EC1A 4JS Tel: Website: Free and confidential information for carers. Depression Alliance 212 Spitfire Studios Collier Street London N1 9BE Tel: Website: Provides information about the symptoms and treatment of depression, national and local groups. 72

75 Hospice Information St Christopher's Hospice Lawrie Park Rd Sydenham London SE26 6DZ Help the Hospices Hospice House Britannia Street London WC1X 9JG Tel: Website: via website. Providers of information about hospice and palliative care services. Leukaemia Research Fund 43 Great Ormond Street London WC1N 3J J Tel: Website: [email protected] Funds research into the causes and treatment of leukaemia, lymphoma and related diseases. Publish booklets on a range of subjects. Macmillan Cancer Support 89 Albert Embankment London SE1 7UQ Website: [email protected] Macmillan provide practical and financial support to those affected by cancer. They also provide funding for cancer health professionals. Macmillan can also provide information about cancer. Macmillan s information service is now provided by Cancerbackup, following a recent merger between the two organisations. 73

76 Selected references Textbooks: Hancock, B.W., McLennan, K., Armitage J.O., (eds.), Malignant Lymphoma, London: Hodder Arnold, 2000 Otto, SE., Oncology Nursing:Third edition, St Louis: Mosby, 2000 Provan D, Chisholm M, Duncombe A, et al., Oxford Handbook of Clinical Haematology: Second Edition, Oxford: Oxford University Press, 2004 Journal articles: Abbot, B., Chronic Lymphocytic Leukemia: Recent Advances in Diagnosis and Treatment, January 2006, The Oncologist,Vol. 11, No. 1, Adamsen, L. et al, The effect of a multidimensional exercise intervention on physical capacity, well being and quality of life in cancer patients undergoing chemotherapy, in Supportive Care in Cancer, 2006 Feb;14(2): Ardeshna, K.M. et al, Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced stage non-hodgkin lymphoma. A randomised controlled trial, The Lancet, 2003, August 16,Vol 362, Issue 9383 Evans, L.S., Hancock, B.W., Non-Hodgkin lymphomas, The Lancet, Volume 352, July 12, 2003 Incidence of non-hodgkin lymphoma, UK, 2002, accessed August 2006 Illidge,T and Chan, C., How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies?, Leukaemia Lymphoma, 2008 Jul;49(7): Gerwitz AM,Winder JN, and Zuckerman K (eds) Haematology 2007: American Society of Haematology Education Programme Book, ASH, December 2007 [90Y]-ibritumomab tiuxetan ([90Y]-ibritumomab tiuxetan) consolidation of first remission in advanced stage follicular NHL: First results of the international randomized Phase 3 First-line Indolent Trial (FIT) in 414 Patients. Abstract# 643. Data presented at the American Society of Hematology (ASH) Annual Meeting in December Van Oers, M.H., Rituximab maintenance therapy: a step forward in follicular lymphoma, Haematologica, 2007 Jun;92(6): Incidence of non-hodgkin lymphoma, UK, 2004, accessed July

77 About our publications: The Lymphoma Association is committed to the provision of high quality information for people with lymphoma, their families and friends. We produce our information in accordance with nationally recognised guidelines. These include the DISCERN tool for information about treatments, the NHS Toolkit for producing patient information, and the Campaign for Plain English guidelines. Our publications are written by experienced medical writers, in close collaboration with medical advisors with expertise in the appropriate field. Textbooks and professional journals are consulted to ensure that information is as up to date as possible. References are provided where they have been used. Some publications are written by professionals themselves, acting on guidance provided by the Lymphoma Association. Our publications are reviewed every two years and updated as necessary. Our publications are reviewed by a panel of volunteers with experience of lymphoma. Publications are also reviewed by members of the Lymphoma Association helpline team, who have many years collective experience of supporting those with lymphoma. In some instances, our publications are funded by educational grants from pharmaceutical companies. These sponsors do not have any involvement in the content of a publication. They are not invited to see the content and have no editorial input. 75

78 76

79 The information in this booklet can be made available in large print

80 Helpline open 9am-6pm Monday - Thursday, 9am-5pm Friday Lymphoma Association PO Box 386, Aylesbury Bucks HP20 2GA Administration: Lymphoma Association ISBN This edition is due to be revised in 2010 Registered Charity No All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, or recording in any information storage or retrieval system without permission in writing from the Lymphoma Association.