On this page
- What is diffuse large B-cell lymphoma (DLBCL)?
- Who gets DLBCL and why?
- What are the symptoms of DLBCL?
- How is DLBCL diagnosed?
- What is the outlook for people with DLBCL?
- How is DLBCL treated?
- What are the potential side effects of treatment?
- What happens if DLBCL comes back or doesn’t respond to treatment?
- What newer drugs are there for DLBCL?
- What does follow-up involve?
- What rare types of DLBCL are there?
- What is diffuse large B-cell lymphoma (DLBCL)? (page 1)
- Who gets DLBCL and why? (page 3)
- What are the symptoms of DLBCL? (page 3)
- How is DLBCL diagnosed? (page 4)
- What is the outlook for people with DLBCL? (page 6)
- How is DLBCL treated? (page 6)
- What are the potential side effects of treatment? (page 8)
- What happens if DLBCL comes back or doesn’t respond to treatment? (page 9)
- What newer drugs are there for DLBCL? (page 10)
- What does follow-up involve? (page 11)
- What rare types of DLBCL are there? (page 11)
Lymphoma is a cancer of the lymphatic system, which is part of your immune system. It develops when lymphocytes (a type of white blood cell) start to divide in an uncontrolled way. There are 2 main types of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells). Lymphoma can develop from either of these cells, but most lymphomas develop from B cells.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of high-grade (fast-growing) non-Hodgkin lymphoma. There are several features that give DLBCL its name:
- it develops from abnormal B cells
- the abnormal cells are larger than normal, healthy B cells
- the abnormal cells are spread diffusely (spaced out rather than grouped together) throughout the tumour and wipe out the normal structure of the lymph node (gland).
Figure 1. Cells from a biopsy of DLBCL showing abnormal, large cells spread diffusely
The vast majority of people have the most common type of DLBCL, which is described on this page. Some people have a rare type of DLBCL that has different features to the most common type. These differences can be seen under a microscope and in tests on the lymphoma cells. They can cause different symptoms, but they are all usually treated in the same way.
Rare types of DLBCL include:
- T-cell/histiocyte-rich large B-cell lymphoma
- EBV-positive DLBCL of the elderly
- primary mediastinal (thymic) large B-cell lymphoma
- intravascular large B-cell lymphoma
- ALK-positive large B-cell lymphoma.
Very rare types of large B-cell lymphoma can develop in people with severe immune system problems like human immunodeficiency virus (HIV), eg plasmablastic lymphoma.
If DLBCL starts in your central nervous system (CNS; brain and spinal cord), it is a primary CNS lymphoma.
Some types of DLBCL only affect the skin. We have separate information about skin lymphoma.
Around 4,800 people are diagnosed with DLBCL each year in the UK. It can occur at any age, including in children, but the risk of developing DLBCL increases with age. Most people diagnosed with DLBCL are 65 or over. DLBCL affects slightly more men than women.
In most cases, the causes of DLBCL are not known but research shows that:
- you cannot catch lymphoma
- you did not inherit it from your parents
- you cannot pass it on to others.
Rarely, there is an association between DLBCL and disorders of the immune system. These include:
- autoimmune disorders like rheumatoid arthritis and systemic lupus erythematosus (DLBCL can develop as a result of chronic (long-term) inflammation)
- organ transplantation.
However, most people with these disorders never develop lymphoma and most cases of DLBCL are not related to an underlying immune disorder.
Sometimes DLBCL develops in people who have had a low-grade (slow-growing) lymphoma in the past – their lymphoma transforms (changes) into a quicker growing DLBCL. If this is the case for you, you might also find our information on transformation helpful.
Most people with DLBCL first notice painless lumps, often in their neck, armpit or groin. These are enlarged lymph nodes (swollen glands). They can grow quite quickly, over just a few weeks.
DLBCL can develop in lymph nodes deep inside your body where they can’t be felt from the outside. It is quite common for people with DLBCL to have lymphoma in extranodal sites (areas outside the lymph node). Large lumps can form – this is known as ‘bulky disease’.
DLBCL can be hard to diagnose as people have different symptoms depending what organs and tissues their lymphoma is affecting, for example:
- DLBCL in your stomach or bowel can cause abdominal (tummy) discomfort or pain, diarrhoea or bleeding
- DLBCL in your chest can cause a cough or breathlessness.
Some people with DLBCL experience fevers, night sweats and unexplained weight loss. These are known as ‘B symptoms’.
DLBCL is usually diagnosed from a biopsy (sample of tissue taken to see if lymphoma cells are present). Doctors take the biopsy from an enlarged lymph node or another part of the body where they think lymphoma could be growing. The whole lymph node or tumour, or just a small part of it, might be removed.
The biopsy is then examined under a microscope by an expert pathologist. If the pathologist suspects you might have lymphoma, more tests are done on the sample to find out what type of lymphoma you have. Occasionally, a second biopsy is needed if there was not enough tissue from the first biopsy to make a diagnosis.
Waiting for your test results is a worrying time, but it is very important that the diagnosis is correct so that you can have the best treatment.
Other tests might be done to give your doctor more information about the lymphoma. For example, there are several subtypes of DLBCL that can be detected:
- germinal centre B-cell-like or GCB subtype
- non-GCB types, usually activated B-cell-like (ABC subtype).
At the moment, most people with DLBCL have the same treatment. However, researchers are continuing to unpick the biology of lymphoma cells with the aim of identifying people who are more likely to respond to certain treatments. We have regular updates on clinical trials and advances in lymphoma research in our magazine, Lymphoma matters.
You have other tests to:
- find out which parts of your body the lymphoma is growing in
- look at your general health, including how well organs like your heart and kidneys are working.
This is called ‘staging’.
The tests you have are part of ‘staging’ the lymphoma – working out how far it has spread and how much of your body is affected. Staging is important because it helps your doctor plan the best treatment for you.
This section is about staging of DLBCL in adults. NHL, including DLBCL, is staged differently in under-18s. If you need information about staging in this age group, you can find it on our page about NHL in children.
There are 4 main stages of DLBCL:
- stage 1: 1 group of lymph nodes affected
- stage 2: 2 or more groups of lymph nodes affected either above or below the diaphragm (muscle that separates the chest from the abdomen)
- stage 3: lymph nodes affected on both sides of the diaphragm
- stage 4: lymphoma is found in organs outside the lymphatic system or in the bone marrow.
Sometimes, doctors use Roman numerals for these – stage I, II, III and IV.
You may have a letter added to your stage:
- ‘A’ means you have not had any B symptoms
- ‘B’ means you have B symptoms (fever, night sweats, weight loss)
- ‘E’ means you have extranodal lymphoma (outside of the lymph nodes).
You might also be told if you have ‘bulky’ disease (large lumps of lymphoma). Occasionally, an ‘X’ is added to your stage if you have bulky disease.
Stage 1A and stage 2A are known as ‘early-stage’ DLBCL. ‘Advanced-stage’ DLBCL is stage 3 and stage 4. Most people have advanced‑stage DLBCL when they are diagnosed.
At any stage, DLBCL is usually treated with the aim of curing it. Your outlook depends on the stage of the lymphoma and your general health. Researchers are beginning to unpick the differences between distinct subtypes of DLBCL. This will help them to identify people who are most likely to benefit from certain treatments.
Your doctor is best placed to advise you on your outlook based on your individual circumstances. They can use the results of your tests and consider other individual factors, like your age and symptoms, to predict how likely you are to respond to a particular treatment. These factors are called ‘risk factors’.
Your doctor might calculate a prognostic score using the International Prognostic Index (IPI), which takes several different risk factors into account. Your score on the IPI or your risk factors are used to plan your treatment.
High-grade lymphomas often respond well to treatment and many people go into remission (no evidence of lymphoma). In general, more people with early-stage DLBCL go into remission than people with advanced-stage DLBCL.
Survival statistics can be confusing as they don’t tell you what your individual outlook is – they only tell you how a group of people with the same diagnosis did over a period of time. Remember that treatments are improving all the time and survival statistics are usually measured over 5 or 10 years after treatment. Consider also that these statistics only tell you how people did in the past. Those people may have received treatment different to yours. Because of this variability, many people do not find survival statistics helpful.
When your medical team plan how best to treat you, they consider several factors, including:
- the stage of the lymphoma
- information about the lymphoma from your biopsy and blood test results
- where in your body the lymphoma developed and what tissues and organs it is affecting
- your general health.
Some hospitals give scans part-way through treatment to see how you are responding.
If you are under 18, or are a parent or carer of someone under 18 who has DLBCL, our section on non-Hodgkin lymphoma in children has more information on treatment in this age group. Young people (up to 24) with DLBCL might also find our section on lymphoma in young people useful.
The most commonly used chemotherapy regimen (combination of drugs) is CHOP, which includes:
- 3 chemotherapy drugs: cyclophosphamide, hydroxydaunorubicin (doxorubicin) and vincristine (Oncovin®)
- prednisolone (a steroid).
The drugs are given in cycles, with treatment given on certain days followed by a rest period for your body to recover before the next cycle. Each cycle usually takes 3 weeks. Most people with early-stage DLBCL have 2–4 cycles of CHOP or R-CHOP. If you have very large lymph nodes (bulky disease), your doctor might recommend you have 4–6 cycles of chemotherapy before your radiotherapy.
You have most of the drugs given intravenously (into a vein). Prednisolone is given as tablets. Most people come into hospital to have their treatment and don’t need to stay overnight.
You may have radiotherapy to the area affected by lymphoma after your course of chemo-immunotherapy. Very occasionally, radiotherapy is used on its own if you are not well enough to have chemotherapy, eg if you have severe heart or lung disease.
If you have DLBCL in an area difficult to treat with radiotherapy, you might be treated with a longer course of chemotherapy.
Advanced-stage DLBCL (stage 3 and 4) is usually treated with a longer course of R-CHOP. A total of 6-8 cycles of treatment are given.
- R-CODOX-M / R-IVAC – which contains rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate, etoposide, ifosfamide and cytarabine.
- DA-EPOCH-R – which contains dose-adjusted etoposide, prednisolone, vincristine,
- cyclophosphamide and doxorubicin.
Some people are not well enough to have strong chemotherapy. Others have health problems, such as heart problems, that mean CHOP is not suitable for them. A different regimen is given in these cases, eg:
- R-miniCHOP – in which the dosage of each drug is reduced or some of the drugs might be left out
- R-GCVP – which uses gemcitabine in place of doxorubicin
- R-CEOP – which uses etoposide in place of doxorubicin.
Most people with advanced-stage DLBCL do not have radiotherapy as their lymphoma is widespread rather than localised to 1 or few areas. However, you might have radiotherapy if:
- you have localised lymphoma left after your chemotherapy
- you have bulky disease – the radiotherapy can help prevent the lymphoma relapsing (coming back) in these areas.
Your doctor might suggest a newer drug. These are usually only available through a clinical trial.
Around 1 in 20 people have DLBCL that relapses in their central nervous system (CNS, which includes your brain and spinal cord) after going into remission. If this happens, the lymphoma is very difficult to treat.
If you are considered to be at high risk of the lymphoma relapsing in your CNS, you might be given preventative treatment – ‘CNS prophylaxis’. Most chemotherapy cannot reach your brain or spinal cord, so any lymphoma cells remaining there could grow and cause the lymphoma in your CNS.
In CNS prophylaxis, you are given drugs that reach the CNS. You might have intrathecal chemotherapy, where a drug like methotrexate is given by lumbar puncture directly into the fluid surrounding your spine. Some people have CNS prophylaxis intravenously. CNS prophylaxis might be given during your chemo-immunotherapy or after you have finished chemo-immunotherapy.
All medical treatments can have unwanted effects on the body (side effects). Each type of treatment and each drug has different possible side effects. They also affect everyone differently. It is not possible to tell exactly how your treatment will affect you. Ask your medical team for information on the possible side effects for the treatments you are having.
If you experience side effects, tell your medical team. They can offer advice and treatments that might help.
Some treatments for lymphoma can affect your fertility. If this is a concern for you, your medical team can give you more information on the risks of the treatment they are recommending. There may be options for preserving your fertility.
Side effects can also develop long after treatment has finished. These are called ‘late effects’. Chemotherapy can cause late effects like heart problems or increase your risk of developing a second cancer later in life. The risks of chemotherapy have to be weighed up with the benefits of using the most effective treatment. Talk to your medical team if you have any concerns.
You are likely to have a scan at the end of treatment to see how well you have responded. Many people respond well to their first treatment for DLBCL and go into complete remission. However, some people need more treatment, for example:
- the lymphoma might be reduced but not completely cleared
- the lymphoma might be refractory to treatment (it did not get better).
Sometimes, the lymphoma relapses (comes back) after successful treatment. Relapse is most likely to happen within 2 years of the end of the first treatment. As time goes on, lymphoma is less likely to relapse.
Most people who have relapsed or refractory lymphoma are offered other treatments. This is sometimes known as ‘salvage’ treatment.
If you are well enough, your doctor might suggest you have high-dose chemo-immunotherapy. The aim of this type of treatment is to reduce the lymphoma and then increase your chance of remission using a stem cell transplant. A stem cell transplant works best if the lymphoma responds at least partially to the high-dose therapy.
Most people have an autologous stem cell transplant (using your own cells). In some cases, you might be given an allogeneic (donor) stem cell transplant. For example, if you relapse after an autologous stem cell transplant or the doctors were unable to collect enough of your own stem cells.
There are several different chemo-immunotherapy regimens used for people who need more intensive (strong) treatment. Most people are given a platinum-based regimen, eg:
- R-GDP – rituximab with gemcitabine, dexamethasone and cisplatin
- R-DHAP – rituximab with dexamethasone, cytarabine and cisplatin
- R-ICE – rituximab with ifosfamide, carboplatin and etoposide.
If you are not well enough for a stem cell transplant, you might still be able to have chemo-immunotherapy.
There are also many newer drugs in development for DLBCL. Your doctor might suggest you take part in a clinical trial to give you access to a newer drug.
Drugs being tested in DLBCL, but not yet approved in the UK include:
- drugs that block signals or the function of control proteins within the lymphoma cells, which, depending how they work, can be grouped as:
- newer antibodies against CD20, the protein targeted also by rituximab, eg obinutuzumab (Gazyva®)
- antibody-drug conjugates, which join a strong anti-cancer drug to an antibody to deliver the drug directly to the cancer cells, eg brentuximab vedotin (Adcertins®), inotuzumab ozogamicin and polatuzumab vedotin
- immunomodulatory drugs, which affect the activity of your immune system, eg lenalidomide (Revlimid®)
- immune checkpoint inhibitors, which allow your immune system to recognise and kill the lymphoma cells, eg nivolumab and pembrolizumab
- newer chemotherapy drugs, eg pixantrone Pixurvi®).
We have only included drugs in later phases of testing here. There are other drugs in early phase clinical trials and new drugs are being developed and tested all the time.
Another growing research area is CAR T-cell therapy. It involves engineering your own immune cells to recognise and attack your lymphoma cells. There is a lot of interest in this area, but trials are still in early phases.
What is a clinical trial and how can I take part?
A clinical trial is a scientific study testing new medical treatments. Clinical trials are very important in improving future treatments for people with lymphoma. If you are interested in taking part in a clinical trial, ask your doctor if there is a trial that might be suitable for you. You might be referred to another centre if there is a suitable trial that your hospital is not taking part in. You don’t have to take part in a clinical trial if you don’t want to. If you don’t enter a trial, you are still treated with the best available treatment.
Note that trials are opening and closing all the time. Some drugs are being tested in trials that are already closed to new participants. You may not be suitable for a clinical trial, even if it is recruiting people with the type of lymphoma you have. There are many other factors that determine whether you can enter a trial or not, like your general health, other medical conditions and other drugs you are taking or have taken in the past.
You have a scan at the end of treatment to see how you have responded. This is usually a PET/CT scan. Sometimes it is hard to tell whether any lumps in your body after treatment are scar tissue or lymphoma. A PET/CT scan shows areas of active (growing) lymphoma.
You might need other tests after treatment finishes. Your doctor can use the results of the scan and other tests, if needed, to see if you are remission (no evidence of lymphoma) or if you need further treatment.
When you are in remission after treatment, you have regular follow-up appointments. These are to check that:
- you are recovering well from treatment
- you have no signs of relapse
- you are not developing any late effects (side effects that develop months or years after treatment).
At each appointment, your doctor examines you and asks if you have any concerns or symptoms. You might have blood tests. You are unlikely to have a scan unless you have troubling symptoms.
You are likely to be seen every 3 months at first. After a year, your appointments might be every 6 months. The risk of the DLBCL relapsing is highest in the first 2 years. As time goes on, relapse becomes less likely and you are seen less often. Hospitals differ in how long they normally follow-up for. The length of your follow-up also depends on your individual circumstances, eg what type of DLBCL you’ve had and what treatments you’ve had. People are usually followed up for 2–5 years after treatment for DLBCL.
There are a few rare types of DLBCL, including:
- T-cell/histiocyte-rich large B-cell lymphoma
- EBV-positive DLBCL of the elderly
- Primary mediastinal large B-cell lymphoma (PMBL)
- Intravascular large B-cell lymphoma
- ALK-positive large B-cell lymphoma.
If you do not have one of these rare types of DLBCL, you might want to skip this section.
T-cell/histiocyte-rich large B-cell lymphoma mainly affects middle-aged men but it can affect men and women of any age.
In your biopsy, you have a small proportion of large B cells together with T cells and often histiocytes (another kind of immune cell). T-cell/histiocyte-rich large B-cell lymphoma can look like Hodgkin lymphoma under a microscope. It is important that is diagnosed accurately, so you can have the most effective treatment.
The most common symptoms are:
- swollen lymph nodes (glands)
- swelling of the liver or spleen, which can cause abdominal (tummy) swelling and discomfort
- feeling generally unwell, with B symptoms (fever, night sweats and unexplained weight loss).
This type of lymphoma develops in people over 50, with an average age of early- to mid-70s. It is slightly more common in men.
It is thought this lymphoma develops when the Epstein–Barr virus (EBV) interferes with the body’s immune system. This lymphoma is sometimes called ‘age-related EBV-associated B-cell lymphoproliferative disorder’.
Many people in the world are infected by EBV and the infection does not usually cause any symptoms. It is not known why some people with EBV get lymphoma.
Your symptoms depend where the lymphoma is growing:
- Most people (7 in 10) have lymphoma in extranodal (outside the lymph nodes) sites, most commonly the skin, lung, tonsils or stomach.
- Some people (3 in 10) have this lymphoma only in the lymph nodes.
Primary mediastinal large B-cell lymphoma usually affects young adults. The average age of people who develop this lymphoma is 35. It is more common in women.
The lymphoma starts growing in the mediastinum, which is the area in the middle of the chest, behind the sternum (the breastbone). There is often a large lump of lymphoma (bulky disease). It can spread to lymph nodes.
PMBL can cause problems by pressing on the lungs, gullet or superior vena cava (the large vein that takes blood back from the body to the heart). It can also lead to collections of fluid around the heart (pericardial effusion) or the lung (pleural effusion). Possible early symptoms are:
- difficulty swallowing
- swelling of the neck and face
Your doctor might recommend a more intensive chemotherapy regimen for this particular type of lymphoma, eg dose-adjusted EPOCH. Your doctor can give you more information about the risks and benefits of this approach.
This lymphoma occurs mainly in older adults – people in their mid-60s on average. A similar number of men and women are affected. The cancerous lymphocytes are found within small blood vessels called ‘capillaries’.
Your symptoms depend on which capillaries are affected. Possible symptoms include:
- nervous system symptoms such as confusion, seizures, dizziness or weakness
- reddened patches or lumps in the skin
- B symptoms (fever, night sweats, unexplained weight loss).
If the lymphoma only affects your skin, you might be treated with radiotherapy alone.
This very rare type of DLBCL affects people from all age groups. It occurs mainly in men. The lymphoma cells have a mutation that makes them express a protein called ‘anaplastic large-cell kinase (ALK)’ on their surface. They don’t usually have CD20 on their surface so rituximab does not work for this type of lymphoma.
Most people have enlarged lymph nodes (swollen glands) but the lymphoma can grow in the mediastinum (centre of the chest) or at extranodal sites (outside of the lymph nodes).
The full list of sources used in the preparation of this information is available on request. Please contact us by email on firstname.lastname@example.org or telephone on 01296 619409 if you would like a copy.
Swerdlow SH, et al (editors). WHO classification of tumours of haematopoietic and lymphoid tissues. 4th edition. 2008. International Agency for Research on Cancer (IARC), Lyon, France.
Chaganti S, et al. BCSH guidelines for the management of diffuse large B-cell lymphoma. Published 2016. Available at: www.bit.do/bsh-guidelines (Accessed May 2016).
Tilly H, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2015; 26: v116-v125. Available at: www.bit.do/dlbcl-esmo (Accessed May 2016).
Draft NICE guidance on Non-Hodgkin’s Lymphoma: Diagnosis and Management. Available at: www.bit.do/draft-nice-nhl (Accessed April 2016).
Cancer Research UK. Non-Hodgkin lymphoma statistics. Available at: www.bit.do/cruk-nhl-stats (Accessed May 2016).
With thanks to the following people for reviewing this information:
- Dr Robert Marcus, Consultant Haematologist at King’s College Hospital NHS Trust, London
- Dr Daniel Hodson, MRC Clinician Scientist Fellow, University of Cambridge.
We would also like to thank the members of our Reader Panel who gave their time to review this information.
The image of DLBCL cells was kindly provided by Dr Daniel Hodson, as above, and Dr Hesham Eldaly, Consultant Histopathologist, Addenbrooke’s Hospital, Cambridge.
Content last reviewed: July 2016
Next planned review: July 2019
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