What happens if high-grade lymphoma comes back?
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- Ralf Ray
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1 Freephone helpline What happens if high-grade non-hodgkin lymphoma comes back? Non-Hodgkin lymphoma is a cancer of the lymphatic system. There are many different types of non-hodgkin lymphoma. Some develop and grow slowly and these are described as 'low grade' or 'indolent'. Faster-growing non-hodgkin lymphomas are described as 'high grade' or 'aggressive'. This information sheet is for people with high-grade non-hodgkin lymphoma. High-grade non-hodgkin lymphoma is usually treated with chemotherapy and sometimes with radiotherapy too. Unfortunately, not everybody who is treated for high-grade non-hodgkin lymphoma will be cured by their first course of treatment. In some people the lymphoma will come back after the treatment initially seemed to work. This is called a 'relapse'. A smaller number of people will have high-grade non-hodgkin lymphoma that does not respond well to the first course of treatment. When this happens the lymphoma is described as being 'refractory'. In this information sheet we will look at some of the concerns that people in these situations might have: What does it mean if high-grade lymphoma comes back after treatment? (page 2) What does it mean if high-grade lymphoma does not respond well to the initial treatment? (page 2) Your feelings if the lymphoma hasn't gone away or has come back (page 2) What will happen next? (page 3) What treatments are available? (page 3) Where can I get more help and support? (page 5) We have more information about high-grade non-hodgkin lymphomas and about lymphoma treatments in general. Please ring our helpline ( ) or visit our website ( if you have questions that are not answered in this information sheet or if you would like further information on any aspect of your illness. 1/7
2 What does it mean if high-grade lymphoma comes back after treatment? Most people who have treatment for high-grade non-hodgkin lymphoma will go into complete remission. Complete remission means that the lymphoma has been very well controlled. Unfortunately, in some people who have been in complete remission, the lymphoma will come back or start to grow again. This is known as a relapse and people nearly always experience symptoms if this happens either the same symptoms they had before or new ones. Relapse is most likely to happen within 2 years of the end of your first course of treatment. The lymphoma might come back where it was before or it can affect another part of your body. Relapsed high-grade non-hodgkin lymphoma can be treated again. The treatments often work very well and it may still be possible for you to be cured. What does it mean if high-grade lymphoma does not respond well to the initial treatment? A small number of people with high-grade non-hodgkin lymphoma will not respond well to their first course of treatment. Lymphoma that does not go into remission with treatment is known as refractory lymphoma. If the initial treatment has not been as effective as hoped, other treatments may well work better and it is still possible for you to be cured. The treatments that are given for relapsed high-grade non-hodgkin lymphoma can often be used for refractory high-grade non-hodgkin lymphoma too (see pages 3 5). Your feelings if the lymphoma hasn't gone away or has come back Most people being treated for high-grade non-hodgkin lymphoma will hope that the treatment is going to cure them. It is therefore likely to be very disappointing and upsetting to be told that your lymphoma has not responded to the treatment or that it has come back. Everyone will have slightly different feelings when they hear this news. For many people it brings back the whole range of emotions they felt when they were first diagnosed. These emotions are no easier to cope with the second time round, even if the doctors feel that a cure is possible with further treatment and start to plan this with you. Once again, you will need to call on the people and resources you found helpful last time. It is vital to recognise that what you are feeling is natural and to ask for any help you need with the emotional side of your relapse. Our helpline staff are there for you at every stage of your lymphoma, so do ring them if you would like to talk about how you are feeling or if you want to know more about the emotional side of having lymphoma ( ). 2/7
3 What will happen next? If your lymphoma relapses or is refractory, your specialist will want to repeat some of the tests you had to start with, including blood tests and scans. You might have another biopsy. Your further treatment will depend on: which type of high-grade non-hodgkin lymphoma you have your symptoms and your test results your general health and fitness the treatment you had before and how well your lymphoma responded to it how well you coped with the treatment how long it is since you were treated (if your lymphoma has relapsed). Your treatment will be discussed by several expert doctors and nurse specialists at the multidisciplinary team (MDT) meeting. Do let your team know if you have any strong views about your treatment. When your doctor recommends a treatment for you, do not be afraid to ask why they feel it is the best treatment for you. What treatments are available? Chemotherapy Relapsed or refractory high-grade non-hodgkin lymphoma is most often treated with further chemotherapy. If you are fit enough, the chemotherapy you are offered will probably be stronger than your first treatment. This kind of treatment is often called 'salvage chemotherapy'. Once further chemotherapy has controlled the lymphoma again, you might then be offered high-dose chemotherapy and a stem cell transplant (see page 4). Your salvage chemotherapy is likely to contain some drugs that are new to you. Gemcitabine and the 'platinum' drugs (such as cisplatin) are quite commonly given to treat relapsed or refractory high-grade non-hodgkin lymphoma (in regimens such as DHAP or ICE for example). There are a number of different regimens and none of these have been shown to be better than any of the others, so different centres will use different salvage regimens. Often these treatments are given over a few days so you will need to be an inpatient. Your team will explain what the treatment will involve when and how it will be given and the side effects you might experience. As in the initial treatments, an antibody treatment might be included in the salvage regimen, for example rituximab for B-cell non-hodgkin lymphomas. Steroids are also commonly given as part of the treatment, usually in the form of prednisolone or dexamethasone. 3/7
4 For people who are less fit, gentler chemotherapy, but using different drugs from those used initially, may be offered. The aim of this treatment would be to ease any symptoms and control the lymphoma for a while. This kind of treatment is not likely to cure the lymphoma. If you would like to know more about chemotherapy, how it is given and its possible side effects, please ring our helpline ( ) or visit our website ( Radiotherapy Radiotherapy is sometimes used after chemotherapy to treat areas where the lymph nodes were very large (known as bulky disease ). It cannot usually be given again to an area that has already been treated with radiotherapy. If the lymphoma comes back in just one part of the body, where radiotherapy has not been given before, it can be given to that area. If possible, though, your doctors will probably still want to give you chemotherapy first. High-dose chemotherapy and stem cell transplant If your lymphoma has been controlled by more chemotherapy and you are fit enough, you may be offered high-dose chemotherapy and a stem cell transplant. This form of treatment takes several weeks to complete, and for some of that time you will need to stay in hospital. Stem cells are special cells from the bone marrow that can make normal blood cells. A stem cell transplant is a treatment which allows very high doses of anti-lymphoma therapy to be given to you. It is a way of replenishing your healthy bone marrow stem cells after this intensive treatment. When you have a stem cell transplant you first have high doses of chemotherapy (and sometimes also radiotherapy). This treatment causes so much damage to your bone marrow that it might never recover by itself. Instead it is rescued (helped to recover) by the stem cells that are transplanted into you. The stem cells are put back into your bloodstream, just like a blood transfusion. They then settle in your bone marrow where they start to grow and make new blood cells. Stem cell transplants for high-grade non-hodgkin lymphoma are usually autologous. This means that the stem cells used are your own. They are collected, usually after one of your cycles of chemotherapy, and kept frozen until they are needed. If your response to the salvage chemotherapy regimen was good, this will increase the chance that an autologous stem cell transplant will keep the lymphoma in remission for a long period of time. Less often, stem cells from a donor are used this is known as an allogeneic transplant. Allogeneic transplants offer the chance of cure in some people, but they are a very intense form of therapy. Most allogeneic stem cell transplants for lymphoma now use reduced-intensity conditioning (sometimes shortened to RIC or known as a 'mini-transplant'). This means that less treatment is given before the transplant. Although this makes the treatment safer than other allogeneic transplants, it is still not suitable for everyone. 4/7
5 If your high-grade non-hodgkin lymphoma relapses after an autologous stem cell transplant, you might be treated with an allogeneic stem cell transplant. Alternatively, you might be offered treatment with a newer drug (see below). Stem cell transplants carry lots of risks as well as benefits, especially if they are allogeneic. If your doctors are thinking about this form of treatment for you, they will talk to you in detail about it. Please ring our helpline ( ) if you want to talk to someone about stem cell transplants. We also have information about transplants that the helpline can send you. The information can also be downloaded from our website ( New drugs used to treat relapsed high-grade lymphoma New drugs to treat lymphoma are becoming available all the time. Some of these drugs may work differently from chemotherapy because they target biological pathways in the lymphoma cells. They are often described as 'novel agents'. These new drugs have often been used in other lymphomas or blood cancers already, but it might not be known how well they work in your particular type of lymphoma or when a lymphoma needs further treatment. You may therefore be offered one of these newer treatments as part of a clinical trial. In fact, this is often the only way that people can receive one of these drugs. Examples of drugs that are being studied as treatments for relapsed and refractory high-grade lymphomas include brentuximab vedotin (Adcetris ), romidepsin (Istodax ), lenalidomide (Revlimid ), temsirolimus (Torisel ), bortezomib (Velcade ) and ibrutinib. They might be given alone or in combination with other treatments (such as chemotherapy drugs). Taking part in a trial is entirely voluntary and you can always opt to have the standard treatment if you prefer. If you are interested in taking part in a trial, ask your specialist if there might be a suitable one for you. Please ring our helpline ( ) if you would like to talk to someone about taking part in a clinical trial. We produce a booklet on clinical trials please ring the helpline or see our website ( if you would like to receive a copy. Where can I get more help and support? Finding out that the lymphoma hasn't responded to treatment or that it has come back and then having to face another course of treatment is very difficult for most people. You and your loved ones may well need to ask for more help and support at this time. Your hospital team will be able to tell you what to expect from any treatment that is planned. Finding out about your treatment and what is involved, especially if your team is suggesting that you have a transplant, can often help you prepare. 5/7
6 Talking about any concerns you may have is more important than ever at this time. You may be able to talk to your clinical nurse specialist or GP. Some people find that counselling is helpful. Our helpline staff are always happy to listen too and may be able to put you in touch with a 'buddy' someone who has been through the same sort of treatment as you. Please ring our helpline ( ) if you would like to talk to someone about how you are feeling about your lymphoma or if you would like to be put in touch with a Lymphoma Association buddy. Other possible sources of help Maggie s Centres Drop-in centres offer free, comprehensive support for anyone affected by cancer (also online) enquiries@maggiescentres.org British Association for Counselling and Psychotherapy Provides a register of accredited counsellors throughout the UK bacp@bacp.co.uk Macmillan Cancer Support Provides practical, medical, emotional and financial support to people living with cancer (Monday Friday, 9am 8pm) Acknowledgement We are grateful to Dr Paul Fields, consultant haematologist at Guy's and St Thomas' NHS Foundation Trust, London for reviewing this information. We also wish to thank all those people affected by lymphoma who have helped us develop our information. Selected references The full list of references is available on request. Please contact us via (publications@lymphomas.org.uk) or telephone if you would like a copy. Ghielmini, et al. and the panel members of the 1st ESMO Consensus Conference on Malignant Lymphoma. ESMO Guidelines consensus conference on malignant lymphoma 2011: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Annals of Oncology, : Tilly H, et al. and the ESMO Guidelines Working Group. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, (Suppl 7): vii78 vii82. Linch D. Today s treatment of diffuse large B-cell lymphoma in adults. Hematology Education: the education program for the Annual Congress of the European Hematology Association, : /7
7 Murawski N, Pfreundschuh M. New drugs for aggressive B-cell and T-cell lymphomas. Lancet, : Dearden CE, et al. Guidelines for the management of mature T-cell and NK-cell neoplasms (excluding cutaneous T-cell lymphomas). British Journal of Haematology, : Updated August Available at: com/documents/t_nhl_guideline_3_8_13_updated_with_changes_accepted_v1_ rg.pdf (accessed 15 January 2014). Dunleavy K, et al. New strategies in peripheral T-cell lymphoma: understanding tumor biology and developing novel therapies. Clinical Cancer Research, : How we can help you We provide: a Freephone helpline providing information and emotional support (9am 6pm Mondays Thursdays; 9am 5pm Fridays) or information@lymphomas.org.uk booklets and other information about lymphoma (free of charge) a website with forums the opportunity to be put in touch with others affected by lymphoma through our buddy scheme a nationwide network of lymphoma support groups. How you can help us We continually strive to improve our information resources for people affected by lymphoma and we would be interested in any feedback you might have. Please visit or publications@lymphomas.org.uk if you have any comments. Alternatively please phone our helpline on We make every effort to ensure that the information we provide is accurate but it should not be relied upon to reflect the current state of medical research, which is constantly changing. If you are concerned about your health, you should consult your doctor. The Lymphoma Association cannot accept liability for any loss or damage resulting from any inaccuracy in this information or third party information such as information on websites which we link to. Please see our website ( for more information about how we produce our information. Lymphoma Association PO Box 386, Aylesbury, Bucks, HP20 2GA Registered charity no Produced: February 2014 Next planned review: /7
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