Diffuse large B-cell lymphoma (DLBCL)

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What is DLBCL?

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma – between 4,500 and 5,000 people are diagnosed with DLBCL each year in the UK.

DLBCL is a high-grade non-Hodgkin lymphoma that has developed from B cells. It is called ‘diffuse large B-cell lymphoma’ because when it is examined under a microscope the cancerous lymphocytes are abnormally large and they are spread diffusely throughout the biopsy specimen rather than being found in clusters.

Sometimes DLBCL develops in people who have had a slower-growing lymphoma in the past – their low-grade lymphoma has changed into a more quickly growing DLBCL. This is called ‘transformation’.

Who gets DLBCL and why?

DLBCL can develop at any age, but it is more common in people aged over 50. It is slightly more common in men. It is not known what causes DLBCL to develop.  

What are the symptoms of DLBCL?

The first symptom of DLBCL is often one or more swollen glands, which are enlarged lymph nodes. These are most common in the neck, armpit or groin. They can grow quite quickly, over a period of a few weeks. They are not usually painful.

DLBCL can develop in internal lymph nodes and this can cause symptoms too. For example, enlarged nodes in the chest can cause a cough or breathlessness.

It is quite common for people with DLBCL to have lymphoma in extranodal sites, for example in the:

  • head and neck – in the salivary glands, mouth, nasal sinuses, brain, eye or thyroid gland
  • chest and abdomen – in the lung, stomach, bowel, kidney, bladder, liver or spleen
  • breast, testis or skin.

Your symptoms will depend on how much the lymphoma is pressing on or affecting the functioning of these parts of the body. For example, DLBCL in the stomach or the bowel can cause abdominal discomfort or pain, diarrhoea or bleeding.

Some people with DLBCL experience fevers, night sweats or unexplained loss of weight (the B symptoms). Fatigue and loss of appetite are also quite common, and some people experience severe itching. 

Tests for DLBCL

DLBCL is usually diagnosed by taking a biopsy of an enlarged lymph node or of another part of the body that the doctors think could be affected. The biopsy will be examined under the microscope and possibly by further specialised laboratory tests. These tests look for changes in the genes and proteins of the abnormal cells.

The results of the biopsy will confirm the diagnosis and may give more information about your lymphoma. For example, there are at least two subtypes of DLBCL that can be detected using these tests, including the: 
  • ‘germinal centre B-cell-like’ or GCB subtype
  • ‘activated B-cell-like’ or ABC subtype. 

The subtype you have can affect which treatment will work most effectively.

You will have a physical examination and some more tests to:

  • find out the stage of the lymphoma
  • assess your general health.

What are the stages of DLBCL?

Stage I

One group of lymph nodes is affected

Stage II

Two or more groups of lymph nodes are affected on one side of the diaphragm

Stage III

Lymph nodes are affected on both sides of the diaphragm

Stage IV

Lymphoma can be found in organs outside the lymphatic system or in the bone marrow

‘B’ is added to the stage number if there have been any B symptoms; ‘A’ means there have not been any B symptoms. ‘E’ means there is extranodal lymphoma and an ‘X’ means the lymph nodes are very enlarged.

Some people will have early-stage DLBCL at the time of diagnosis, meaning their lymphoma is:

  • stage IA, or
  • stage IIA without very enlarged lymph nodes.

Most people will have advanced DLBCL at diagnosis, meaning their lymphoma is:

  • stage II with very enlarged lymph nodes
  • stage III, or
  • stage IV.

How is DLBCL treated?

When the medical team plan how best to treat you, they will consider:

  • the stage of the lymphoma
  • the biopsy and blood test results
  • where in the body the lymphoma has developed
  • your age and general health.

DLBCL can be treated with: 

These treatments are given with the aim of curing the lymphoma. 

Treatment of early-stage DLBCL

Most people with early-stage DLBCL will be treated with a short course of immunochemotherapy followed by involved-field radiotherapy.

The most commonly used immunochemotherapy regimen is R-CHOP, which is:

combined with three chemotherapy drugs:

  • cyclophosphamide
  • hydroxydaunorubicin
  • vincristine (Oncovin®)

and a steroid:

  • prednisolone.

Immunochemotherapy for early-stage DLBCL is given over a period of 3–4 months and most people will have two to four cycles of R-CHOP altogether. 

The radiotherapy is usually given after the course of chemotherapy. Very occasionally, radiotherapy is used on its own if someone with early-stage DLBCL is unable to tolerate chemotherapy, for example if they are very elderly or frail or if they have severe heart or lung disease. 

Treatment of advanced DLBCL

Advanced DLBCL is usually treated with a course of R-CHOP over a period of 6–8 months. Six (or, less commonly, eight) cycles of treatment are usually given.

Sometimes stronger regimens are used, such as:

  • R-CHEOP – in which etoposide is added to R-CHOP
  • R-CODOX-M / R-IVAC – which contains rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate, etoposide, ifosfamide and cytarabine.

Gentler regimens are sometimes used for people who are not fit enough to tolerate these strong treatments, for example:

  • 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 hydroxydaunorubicin
  • R-CEOP – which uses etoposide* in place of hydroxydaunorubicin.

* These drugs may be safer if someone has heart problems for example.

Involved-field radiotherapy is not used commonly to treat advanced-stage DLBCL unless your response to the chemotherapy was disappointing or the affected lymph nodes were very enlarged before treatment began. 

CNS prophylaxis in DLBCL

There are some people who are considered to be at particular risk of the lymphoma spreading to the brain and spinal cord (the ‘central nervous system’ or CNS). For example, this is a risk if you have DLBCL in:

  • the sinuses or around the eye
  • the testis
  • the breast
  • two or more extranodal sites at once.

If you are judged to be at risk of spread to the CNS you will be given a chemotherapy drug, usually methotrexate, directly into the fluid surrounding the CNS (the cerebrospinal fluid) during a lumbar puncture. This is called ‘intrathecal chemotherapy’. When this treatment is used preventatively it is known as ‘CNS prophylaxis’. Sometimes CNS prophylaxis is given into a vein instead of into the cerebrospinal fluid, either with the early cycles of immunochemotherapy or after the immunochemotherapy is finished.

Follow-up after treatment

A CT scan is usually done part-way through treatment and again at the end of treatment to check how well the lymphoma has responded. A PET/CT scan might also be done after finishing the treatment. A biopsy, bone marrow biopsy or lumbar puncture are sometimes also repeated after the treatment finishes.

After the treatment is finished you will be seen in the outpatient clinic every 3 months at first, then every 6 months after a year or so for a further 2 years, and eventually once a year. How long this follow-up lasts will depend on your type of DLBCL and what treatments you had. The duration of follow-up also varies from centre to centre but people are usually followed up for 2–5 years.

You will have blood tests done in the clinic at the earlier check-ups. X-rays and scans are not done routinely during follow-up but you will have these if the specialist feels they would be helpful. 

What happens if DLBCL comes back?

For many people with DLBCL, the lymphoma is cured by these initial treatments, but sometimes the lymphoma is refractory or it relapses. Relapse is most likely to happen within 2 years of the end of the first treatment.

If the lymphoma relapses:

  • it usually causes symptoms
  • it can come back where it was before or it can come back in another part of the body
  • some of the tests for DLBCL will be repeated.

Further treatment can lead to another remission or even cure and is planned on the basis of:

  • your symptoms
  • the results of the tests
  • your general health and age.

Another important factor that will be considered will be:

  • the type of treatment that you have already had, and how well that treatment worked.

Salvage treatments

Most people with refractory or relapsed DLBCL will be offered more treatment. This is known as ‘salvage treatment’. Examples of salvage regimens used for DLBCL are:

  • R-DHAP – rituximab with dexamethasone, cytarabine and cisplatin
  • R-ICE – rituximab with ifosfamide, carboplatin and etoposide
  • R-GEM-P – rituximab, gemcitabine, cisplatin and methylprednisolone
  • R-GEM-OX – rituximab, gemcitabine and oxaliplatin.

These treatments aim to get the lymphoma into remission again. If the lymphoma responds well to salvage therapy the next option might be high-dose chemotherapy and a stem cell transplant, but only people whose general health is fairly good would be offered this type of treatment.

High-dose chemotherapy and stem cell transplant

In this treatment, high doses of chemotherapy drugs are given, followed by an infusion of stem cells to ‘rescue’ the bone marrow from the harmful effects of the chemotherapy.

There are two kinds of stem cell transplant:

Autologous stem cell transplants usually involve a stay in hospital of 2–4 weeks and can lead to a long remission from the DLBCL.

Allogeneic transplants can sometimes cure DLBCL but this is a more intense and riskier treatment that involves a longer hospital stay. Allogeneic transplants are only suitable for people whose general health is good. An allogeneic transplant is sometimes used to treat DLBCL that has:

  • relapsed early after the initial treatment, or
  • relapsed after an autologous transplant.

Newer treatments for DLBCL

New treatments are being developed all the time for the treatment of lymphoma. These take many years to become available and their effectiveness and safety are tested in clinical trials. Some newer treatments are only available in clinical trials. Two clinical trials that are testing new treatments for DLBCL are:

  • The REMoDL-B trial – this trial is testing a drug called bortezomib to see if adding it to R-CHOP in the initial treatment of DLBCL makes relapse less likely. The researchers on this trial are also looking at whether having the GCB or the ABC type  of DLBCL makes any difference to how well the bortezomib works.
  • The INCA trial – in this trial researchers are looking at whether adding a drug called inotuzumab ozogamicin to R-CVP (a combination of rituximab with cyclophosphamide, vincristine and prednisolone) is an effective treatment for older people with DLBCL who cannot be given R-CHOP because they have heart disease.

Rare types of DLBCL

There are a few rare types of DLBCL. Only about 1 in 20 people with DLBCL will have one of these types. These lymphomas cause different symptoms from the common type of DLBCL but the tests and treatments used are the same.

T-cell/histiocyte-rich large B-cell lymphoma

What are the special features of this kind of large B-cell lymphoma?

  • Biopsy specimens of this lymphoma show three types of cancerous cells – as well as the large B cells the pathologist will see T cells and histiocytes (another kind of immune cell). 

Who gets this type of lymphoma?

  • This lymphoma mainly affects middle-aged men but it can affect men and women of any age.

What are the symptoms?

People with this lymphoma can:

  • have swollen glands (lymph nodes)
  • develop swelling of the liver or spleen, which can cause abdominal swelling and discomfort
  • feel generally unwell, with B symptoms.

What is the treatment?

  • The most common initial treatment is R-CHOP.
  • High-dose chemotherapy and stem cell transplantation can be used to treat this lymphoma if it relapses.

EBV-positive DLBCL of the elderly

What are the special features of this kind of large B-cell lymphoma?

  • It is thought this lymphoma develops when a virus called the Epstein–Barr virus (EBV) interferes with the body’s immune system. This lymphoma is therefore also sometimes called ‘age-related EBV-associated B-cell lymphoproliferative disorder’.

Who gets this type of lymphoma?

  • The average age when this lymphoma develops is the early to mid-70s. It is slightly more common in men.

What are the symptoms?

  • This lymphoma can first appear as swollen glands (lymph nodes).
  • It can also develop in extranodal sites, most commonly in the skin, lung, tonsils or stomach. The symptoms it causes will depend on exactly where it has developed.

What is the treatment?

  • R-CHOP is the usual initial treatment.

Primary mediastinal large B-cell lymphoma (PMBL)

What are the special features of this kind of large B-cell lymphoma?

  • PMBL develops in the mediastinum, which is the area in the middle of the chest, behind the sternum (the breastbone).

Who gets this type of lymphoma?

  • PMBL usually affects young adults – the average age of people who develop this lymphoma is 35 and it is more common in women.

What are the symptoms?

  • PMBL can cause problems by pressing on the lungs or gullet or on the large vein that takes blood back from the body to the heart (the superior vena cava). It can also lead to collections of fluid around the heart (a pericardial effusion) or the lung (a pleural effusion). Possible early symptoms are:
    – breathlessness
    – cough
    – difficulty swallowing
    – swelling of the neck and face
    – headaches
    – dizziness.

What is the treatment?

  • PMBL is treated with R-CHOP or with a more intensive regimen like R-CODOX-M / R-IVAC, sometimes followed by a course of involved-field radiotherapy.
  • High-dose chemotherapy and stem cell transplantation can be used to treat PMBL if it relapses.

Intravascular large B-cell lymphoma

What are the special features of this kind of large B-cell lymphoma?

  • In this lymphoma the cancerous lymphocytes are found within small blood vessels called ‘capillaries’.

Who gets this type of lymphoma?

  • This lymphoma occurs mainly in older adults – people in their mid-60s on average.

What are the symptoms?

  • The symptoms depend on which capillaries are affected, but possible symptoms include:
    – nervous system symptoms such as confusion, seizures, dizziness or weakness
    – reddened patches or lumps in the skin
    – B symptoms.

What is the treatment?

  • Intravascular lymphoma is usually treated with R-CHOP.
  • If the lymphoma has affected the nervous system, chemotherapy with methotrexate or cytarabine is often given too.
  • If just one area of skin is affected it might be treated with radiotherapy.
  • A course of high-dose chemotherapy and a stem cell transplant are options for people whose general health is good enough.

Double-hit DLBCL

What are the special features of this kind of large B-cell lymphoma?

  • Double-hit lymphomas are lymphomas that carry two genetic abnormalities in the cancerous lymphocytes. In double-hit DLBCL tests show abnormalities in the MYC and BCL2 genes. Sometimes this kind of lymphoma is described as a ‘grey zone’ or ‘intermediate’ lymphoma.

Who gets this type of lymphoma?

  • The average age of people who develop these lymphomas is about 70.

What are the symptoms?

  • Double-hit lymphomas commonly affect extranodal sites as well as lymph nodes so cause a wide variety of symptoms as well as lumps (enlarged lymph nodes).

What is the treatment?

  • Double-hit lymphomas are usually treated with R-CHOP or with a more intensive chemotherapy regimen such as R-CODOX-M / R-IVAC.
  • High-dose chemotherapy and a stem cell transplant might also be recommended.

Sources used

The full list of sources used in the preparation of this information is available on request. Please contact us by email (publications@lymphomas.org.uk) or telephone (01296 619409) if you would like a copy.

Fields PA, Linch DC. Treatment of the elderly patient with diffuse large B cell lymphoma. British Journal of Haematology, 2012. 157: 159–170.

Mey U, et al. Diagnosis and treatment of diffuse large B-cell lymphoma. Swiss Medical Weekly, 2012. 142: w13511.

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, 2012. 23 (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, 2011. 5: 210–216.

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.


With thanks to Dr Paul Fields, Consultant Haematologist at Guy’s and St Thomas’ NHS Foundation Trust, London; and to the people affected by lymphoma who reviewed this information.

Content last reviewed: August 2013

Next planned review: August 2016
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