Diffuse Large B cell (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. DLBCL is an aggressive ( fast-growing) lymphoma and has a good chance of being cured.

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Diffuse Large B Cell Lymphoma (DLBCL) Fact Sheet PDF

Overview of diffuse large B-cell lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) B-cell non-Hodgkin lymphoma.  It is the most common subtype of lymphoma, accounting for around 30% of all lymphoma cases and affects around 2,000 Australians each year.

Why is it called diffuse large B-cell lymphoma DLBCL)?

It is called diffuse large B-cell lymphoma (DLBCL) because:

  • It develops from abnormal B-cells
  • The abnormal B-cells are larger than normal, healthy cells
  • The abnormal B-cells are spread out (diffuse) rather than grouped together when they’re examined under a microscope

DLBCL can occur in lymph nodes (nodal) or outside of the lymphatic system (extranodal) in the gastrointestinal tract, testes, thyroid, skin, breast, bone or brain.  About 70% of DLBCL are nodal, and 30% extranodal(30% of cases) at diagnosis, that usually indicates advanced stage disease.

Who is affected? 

Diffuse large B-cell lymphoma (DLBCL) affects both men and women (although slightly higher in men) and over half the cases are aged in people over 60 years. However, DLBC can also be diagnosed in children, adolescents and young adults. Treatments can also be different depending on the age of the person being treated.

In most cases the cause of lymphoma is not known but on some rare occasions there are some risk factors associated between DLBCL and conditions affecting the immune system. These risk factors may include autoimmune conditions, HIV and organ transplantation. 

There is also a slightly increased risk of developing DLBCL if there is a family member with lymphoma, if hepatitis C has been diagnosed or if you were overweight as a child.  However, most people with these characteristics never develop lymphoma.

Sometimes DLBCL can be diagnosed after an indolent (slow growing) lymphoma has transformed (changed) into DLBCL.  Transformation is a rare occurrence but can occur in patients diagnosed with follicular lymphoma or chronic lymphocytic leukaemia/small lymphocytic lymphoma.

For more info see
Transformed Lymphoma

Treatment and prognosis 

DLBCL is usually treated with the aim to cure.  DLBCL usually responds well to immunochemotherapy, and many patients achieve a complete remission, with around 70 percent achieving this with standard first line treatment. The prognosis depends on the stage, subtype of DLBCL, general health and toxicities that can occur with treatment.

Main subtypes of diffuse large B-cell lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) can further be divided into subtypes based on the type of B-cell it has grown from termed “cell of origin”.  DLBCL can be classified as either:

  • Germinal Centre B-cell (GCB): Patients with GCB type DLBCL generally have a better outcome compared to non-GCB type.  GCB subtype has a complete response (CR) rate of about 70% to standard therapy.
  • Activated B-cell (ABC): has a more aggressive and worse prognosis when treated with standard therapy.  The complete response (CR) rate with standard therapy for ABC-type DLBCL is not more than 30% with a high chance of relapse within two years following treatment. Patients with ABC subtype may benefit from participating in a clinical trial.

The doctor examining the lymph node biopsy can identify the difference between GCB and BC by the staining for certain proteins on the surface of the lymphoma cells.  At present, this information is not always used to determine the initial treatment.  However, research is currently underway to find out if different treatments are effective against different types of DLBCL that develop from different cells. This research may change how the subtypes will be treated in the future 

Once the cell of origin (GCB or ABC) has been determined, further testing can be done to determine if the DLBCL is another subtype called high-grade lymphoma (double or triple-hit) lymphoma or a double-expressor DLBCL.

Rare types of diffuse large B-cell lymphoma and other large B-cell lymphomas include:

  • Primary mediastinal large B-cell lymphoma
  • T-cell/histiocyte large B-cell lymphoma
  • EBV-positive DLBCL not otherwise specified
  • ALK-positive large B-cell lymphoma
  • Intravascular large B-cell lymphoma
  • Double-hit and triple-hit lymphoma
  • Primary Central Nervous System lymphoma
  • Cutaneous (skin) B-cell lymphoma

Primary mediastinal large B-cell lymphoma (PMBCL)

Primary mediastinal B-cell lymphoma (PMBCL) is a rare aggressive (fast-growing) type of B-cell non-Hodgkin lymphoma (NHL), that represents 2-4% of all NHLs.  PMBCL is a subtype of large B-cell lymphoma (LBCL).

PMBCL develops when the body makes abnormal B-cells. (also called B-lymphocytes) that develop in a part of the lymphatic system called the thymus gland. These abnormal B-cells cells grow and build up in the space behind the chest-rib cage and between the lungs, known as the mediastinum.

The mediastinum contains vital organs, including the thymus, heart, oesophagus (gullet), trachea(windpipe) and major blood vessels. It may spread to other organs such as the lungs, pericardium, liver, gastrointestinal tract, ovaries, adrenal glands and central nervous system. 

The causes of PMBCL are not known and like other cancers, it is not infectious and cannot be passed onto other people.  It mainly occurs between the ages of 25 to 40 years but it may also occur in older children. It is more common in women than in men.

PMBCL is usually treated with the aim to cure and usually responds well to immunochemotherapy treatment with many patients achieving a  complete response.  The prognosis depends on the stage, general health, treatment and the adverse side effects that can occur with treatment.  

The treatment and management of PMBCL is more intense than the treatment for DLBCL

For more info see
Primary Mediastinal B – cell lymphoma (PMBCL)

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL)

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare subtype of diffuse large B cell lymphoma (DLBCL) and is characterised by malignant B-cells with an infiltrate of reactive T lymphocytes. It is about 1-3 percent of all DLBCLs. Under the microscope, T-cell/histiocyte-rich large B-cell lymphoma can look like nodular lymphocyte predominant Hodgkin lymphoma and classical Hodgkin lymphoma, although the clinical presentation and the behaviour of these two lymphomas are very different.

 T-cell histiocyte-rich large B-cell lymphoma occurs in younger patients and predominantly affects men (approximately 75%) more than women. The average age of diagnosis is 40-50 years.

The most common symptoms are:

  • Swollen lymph nodes
  • Swelling of liver or spleen, which can cause tummy (abdominal) swelling and discomfort
  • Feeling generally unwell

B symptoms can also be present in some patients and can include:

  • Fever
  • Night sweats 
  • Unexplained weight loss

Standard treatment for THRLBCL is the same as for diffuse large B-cell lymphoma (DLBCL).

EBV-positive DLBCL not otherwise specified

This subtype of diffuse large B-cell lymphoma (DLBCL) typically develops in people over 50 years of age, although it can affect younger people too. It is linked to a virus called Epstein-Barr virus (EBV), which affects B-cells. Only a very small number of people who have had EBV go on to develop lymphoma. The reason is unknown.

Symptoms of EBV-positive diffuse large B-cell lymphoma (DLBCL) depends on where the lymphoma is growing:

  • Lymphoma growing outside the lymph nodes (extranodal lymphoma), most commonly the skin, lungs, tonsils or stomach 
  • Lymphoma only in the lymph nodes (nodal)

Standard treatment is the same as for diffuse large B-cell lymphoma (DLBCL), not otherwise specified.

ALK-positive large B-cell lymphoma

This is a very rare subtype of diffuse large B-cell lymphoma (DLBCL) that can affect people of any age and is more common in men. The lymphoma cells have a mutation that means they make a protein called ‘anaplastic large-cell kinase’ (ALK). Unlike other types of DLBCL they don’t usually make a protein called CD20, so rituximab (CD20 monoclonal antibody) does not work for the treatment of this lymphoma.

Standard treatment for this lymphoma is the same as for DLBCL not otherwise specified but without rituximab.

Intravascular large B-cell lymphoma

This is a rare form of an extranodal (outside of the lymph nodes) non-Hodgkin lymphoma (NHL). This lymphoma mainly affects older adults. Most typical age of diagnosis is 50-70 years of age. This subtype occurs equally in both men and women. The lymphoma cells are found within the lumina (inside lining) of small blood vessels called capillaries.

Intravascular large B-cell lymphoma does not usually cause enlarged lymph nodes. The exact symptoms depend on which capillaries are affected. Symptoms may include:

  • Central nervous system symptoms for example confusion, seizures, dizziness or weakness
  • Reddened patches or lumps on skin

B symptoms can include:

  • Fever
  • Drenching night sweats
  • Unexplained weight loss
  • Enlarged liver or spleen

Standard treatment is the same as diffuse large B-cell lymphoma (DLBCL) not otherwise specified.

Double-hit and triple-hit lymphoma

Double-hit lymphoma (and triple-hit lymphoma) is an aggressive (fast-growing) lymphoma with signs and symptoms that may be similar to those of diffuse large B-cell lymphoma.  Most double-hit or triple-hit lymphomas are similar to a type of lymphoma called diffuse large B-cell lymphoma (DLBCL), although some are more like Burkitt lymphoma. Occasionally, they develop from follicular lymphoma (a low-grade non-Hodgkin lymphoma that can sometimes change, or transform, into a faster-growing lymphoma.

Double-hit lymphoma (DHL) has an Incidence reported to be approximately 5%-10% of all people who are diagnosed with diffuse large B-cell lymphoma (DLBCL). Triple-hit lymphoma is estimated to be approximately 2% of all diffuse large B-cell lymphomas. 

There is a poorer prognosis when treated with standard chemoimmunotherapy, that is used in the treatment of diffuse large B-cell lymphoma.  Because double-hit lymphoma is a fairly new classification of lymphoma, ongoing research is helping doctors learn more about the best ways to treat this disease.  

The treatment and management of DHL is more intense than diffuse large B-cell lymphoma 

For more info see
Double Hit Lymphoma

Double expresser lymphoma (DEL)

Double expresser lymphoma (DEL) is an aggressive B-cell non-Hodgkin lymphoma (NHL). Double expresser lymphoma is a subtype of diffuse large B-cell lymphoma (DLBCL) with increased expression of MYC and BCL2 proteins not related to underlying chromosomal rearrangements.

This does not imply that a patient has double-hit lymphoma (DHL) and these double expresser lymphomas (DEL) generally are thought to have a better prognosis than the double-hit lymphomas, but less favourable prognosis to the standard diffuse large B-cell lymphoma.

Double expressor lymphomas occur in around a third of all DLBCL cases and is more often associated with the ABC subtype of DLBCL, where the double-hit lymphomas occurs more in the GCB subtype of DLBCL.

There is not a standard treatment, however many doctors treat DEL as a high-grade lymphoma with a more intense (stronger) treatment involving chemotherapy and immunotherapy.

Primary central nervous system lymphoma (PCNSL)

Primary Central Nervous System Lymphoma (PCNSL) is an aggressive (fast growing) rare subtype of non-Hodgkin lymphoma (NHL).

It is called Primary Central Nervous System Lymphoma (PCNSL) as the lymphoma cells form in the brain and/or spinal cord. In more than 90% of cases it is a B-cell lymphoma that may develop in the brain, spinal cord, eye or leptomeninges (the inner two membranes surrounding the brain and spinal cord).The most common site is in the brain.

When lymphoma has originated in other parts of the body and at some stage has spread to the brain or spinal cord it is referred to as secondary CNS lymphoma (SCNSL)

People are most likely to be affected in their fifties and sixties. The average age at diagnosis is around 60, however it can occur at any age. The cause of PCNSL is unknown as is the case of many lymphomas.

Treatment strategies for CNS lymphoma have improved greatly over recent years. PCNSL can be difficult to treat and some treatments have a risk of causing long-term neurological problems (problems with the brain and eyes).

The treatment and management of PCNSL is slightly different to diffuse large B-cell lymphoma.

Cutaneous (skin) B-cell lymphoma (CBCL)

Cutaneous (skin) lymphomas are lymphomas that develop in the skin and have not affected any other areas of the body at the time they are diagnosed.  Cutaneous B-cell lymphoma (CBCL) are skin lymphomas that develop from B-cells.  There are also cutaneous T-cell lymphomas 

A lymphoma that starts somewhere else in the body and then spreads to the skin is not a skin lymphoma.  If you have a lymphoma that has spread to the skin, our information on the particular type of lymphoma that you have been diagnosed with will be more relevant for you.

The main symptom of CBCL is a lump or lumps on the skin.  CBCL is a very rare subtype of lymphoma, accounting for less than 1% of all lymphomas.  Researchers do not know what causes skin lymphoma.

The treatment and management of CBCL is different to the treatment of diffuse large B-cell lymphoma.

For more info see
Cutaneous B-cell lymphoma (CBCL)

Symptoms of diffuse large B-cell lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBC) can start anywhere in the body and can have many different symptoms. The exact symptoms they cause can depend on the type of lymphoma and where it is in the body. Most symptoms of lymphoma can also be symptoms of many other illnesses. Because the symptoms can be very general, it can be hard to diagnose however the most common symptoms include:

  • Painless rapid swelling of lumps, mainly in the neck, groin or armpit
  • Fatigue 
  • Loss of appetite
  • Stomach or abdominal discomfort or pain, diarrhoea, or bleeding
  • Shortness of breath
  • Pain

B symptoms can include:

  • Night sweats (drenching sleepwear or bedding)
  • Persistent fevers (especially at night >38C)
  • Unexplained weight loss
  • Itchy skin (all over the body)

It is important to tell the doctor about all symptoms as it can influence the decision around the type of treatment and how soon it needs to start.

For more info see
Symptoms of Lymphoma

Diagnosis of DLBC lymphoma

biopsy is always required for the diagnosis of lymphoma. A biopsy is a surgical procedure to remove part of or all of an affected lymph node or other tissue to look under the microscope by a pathologist to see what the cells look like.  The biopsy can be done under local or a general anaesthetic depending on what part of the body is being biopsied.  The biopsy can be done one of three ways:

  • Fine needle aspirate
  • Core needle biopsy
  • Excisional node biopsy

 An excisional node biopsy is the best investigative option, as it collects the most adequate amount of tissue to be able to do the necessary testing for a diagnosis.

Waiting for test results can be a difficult time.  It may help to talk to family, friends or a specialist cancer nurse.

For more info see
Tests, Diagnosis and Staging

Staging of DLBCL lymphoma

Once a diagnosis of diffuse large B-cell lymphoma (DLBCL) is made, there are further tests that are required to see where else in the body the lymphoma has affected or is located.  This is called staging. 

There are four stages from stage 1 (lymphoma in one area) through to stage 4 (lymphoma that is widespread). 

  • Early stage means stage 1 and some stage 2 lymphoma.   This can also be referred to as ‘localised’.  Stage 1 or 2 means that the lymphoma is found in one area or a few areas close together.
  • Advanced stage means the lymphoma is stage 3 and stage 4, as the lymphoma is widespread. 

Approximately 75% of patients diagnosed with DLBCL present with advanced stage disease (stage 3-4), and around 25% with limited or early stage disease (stage 1-2).  It is important to know the stage and grade of the lymphoma as this information helps the medical team to select the best treatment.  

What grade is DLBC 

Lymphomas are also often grouped as either indolent or aggressive. Indolent lymphomas are usually slow growing and aggressive lymphomas are fast growing.  The grade is also referred to as the clinical behaviour of the lymphoma.  Diffuse large B-cell lymphoma (DLBCL) a high-grade lymphoma.  

Staging scans and tests

The scans and tests needed for staging DLBCL before treatment can start may include:

  • Positron emission tomography (PET) scan
  • Computed tomography (CT) scan
  • Bone Marrow Biopsy
  • Lumbar puncture (if there is a high risk of brain or spinal cord involvement)

Several baseline tests prior to any treatment commencing can also be given to check organ function. These are often repeated during and after treatment is completed to assess whether the treatment has affected the function of any organs. Sometimes treatment and follow up care may need to be adjusted to help manage any adverse side effects.  The baseline tests may include:

  • Physical examination
  • Vital observations (blood pressure, temperature & pulse rate)
  • Heart scan
  • Kidney scan
  • Breathing tests
  • Blood tests

It may take some time for all the necessary biopsies and tests to be done (sometimes an average of 1-3 weeks), but it is important for  doctors to have a complete picture of the  lymphoma and health of the patient  in order to make the best treatment decisions .

Many of these staging and organ function tests are done again after treatment to check whether the lymphoma treatment has worked and the effect this has had on the body.

For more info see
Staging Scans & Tests

Prognosis of diffuse large B-cell lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is usually treated with the aim to cure.  DLBCL usually responds well to immunochemotherapy, and many people will achieve a complete remission, with around 70 percent achieving this with standard first line  treatment. The prognosis depends on the stage, subtype of DLBCL,  general health and adverse side effects that can occur from the treatment.

Treatment for diffuse large B-cell lymphoma (DLBCL)

After a review of all of the results from the biopsy and the staging scans have been completed, the doctor will decide the best possible treatment.  At some cancer centres, the doctor will also meet with a team of specialists to discuss the best treatment and this is called a multidisciplinary team (MDT) meeting.  

Treating clinicians will take into consideration many factors before starting treatment and this can include the following:

  • The stage and grade of lymphoma
  • Symptoms (the size and location of the lymphoma)
  • How the lymphoma is affecting parts of the body
  • Age
  • Past medical history & general health
  • Current physical and mental wellbeing
  • Personal preferences

The doctor and/or cancer nurse will explain the treatment plan and the possible side-effects. It is important the treatment plan is fully understood by the patient/carer and questions are answered 

Because diffuse large B-cell lymphoma (DLBCL) is a fast-growing lymphoma treatment will need to start as soon as possible after all upfront tests have been completed .

Standard first-line treatment for DLBCL

The standard first-line treatment for DLBCL includes a combination of chemotherapy (including an anthracycline drug – doxorubicin) and an immunotherapy (rituximab). This is called Immunochemotherapy. Chemotherapy is a treatment that uses drugs to kill cancer cells. Immunotherapy is a treatment of giving antibodies that are made in a laboratory to target an antigen on the surface of a cancer cell.

 The standard treatment (first-line treatment) treatment for DLBCL can include: 

  • R-CHOP (combination of Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone)
  • R-EPOCH (combination of rituximab, etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin)
  • High dose methotrexate (only for patients that are high risk or suspected of lymphoma in the brain or spinal cord – this is 2 cycles that is given after the combination chemoimmunotherapy) 
  • Radiotherapy (usually after chemotherapy)
  • A combination of other different treatments
  • Clinical trial participation

CNS prophylaxis in diffuse large B-cell lymphoma (DLBCL)

Around 1 in 20 people who have DLBCL can have a relapse in their central nervous system (CNS – brain and spinal cord) after going into remission.  If this happens, the lymphoma can be difficult to treat.

If the doctor feels there is a high risk of DLBCL affecting the  CNS, treatments can be given  to try and prevent this.  This is called ‘CNS prophylaxis’.  Most patients do not need CNS prophylaxis.

Common side effects of DLBC treatment 

There are many different side effects of the treatment and these are dependent on the treatment that has been given.  The treating doctor and/or cancer nurse can explain the specific side effects prior to the treatment.  Some of the more common side effects of treatment may include:

Some of the more common side effects of treatment for diffuse large B-cell lymphoma (DLBCL) may include:

  • Anaemia (low red blood cells carry oxygen around the body)
  • Thrombocytopenia (low platelets that help bleeding and clotting)
  • Neutropenia (low white blood cells help with immunity)
  • Nausea and vomiting
  • Bowel problems such as constipation or diarrhoea
  • Fatigue (tiredness or lack of energy
  • Reduced fertility

The medical team, doctor, cancer nurse or pharmacist, should provide information about:

  • What treatment will be given
  • What are the common and possible side effects for the treatment
  • What side effects do you need to report to the medical team
  • What are the contact numbers, and where to attend in case of emergency 7 days a week and 24 hours per day
For more info see
Side effects of treatment

Fertility preservation

Some treatments for lymphoma can reduce fertility and this is more likely with certain chemotherapy protocols (combinations of drugs) and high-dose chemotherapy used before a stem cell transplant.  Radiotherapy to the pelvis also increases the likelihood of reduced fertility.  Some antibody therapies may also affect fertility, but this is less clear.  

The doctor should advise on whether  fertility may be affected or whether  fertility preservation should be done before the  treatment has started. Patients should always ask about fertility preservation before treatments starts if this is important to them. 

Follow-up care 

Once treatment has completed, post treatment staging scans are done to review how well the treatment has worked.  The scans will show the doctor if there has been a:

  • Complete response (CR or no signs of lymphoma remain) or a
  • Partial response (PR or there is still lymphoma present, but it has reduced in size)  

If all goes well regular follow-up appointments will be made for every 3-6 months to monitor the below:  

  • Review the effectiveness of the treatment
  • Monitor any ongoing side effects from the treatment
  • Monitor for any late effects from treatment over time
  • Monitor signs of the lymphoma relapsing

These appointments are also important so that the patient can raise any concerns that they may need to discuss with the medical team. A physical examination and blood tests are also standard tests for these appointments.  Apart from immediately after treatment to review how the treatment has worked, scans are not usually done unless there is a reason for them. For some patient’s appointments may become less frequent over time.

Relapsed or refractory management of diffuse large B-cell lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) usually responds well to Immunochemotherapy, but in some people the lymphoma comes back (relapses) or in rare cases does not respond to initial first-line treatment (refractory). If this happens, there are other treatments (second-line treatment) that can be successful. 

If a relapse is suspected another biopsy need to be done often with the same staging tests that were explained above in the staging section. 

The second-line or third-line treatments can include:

  • A stem cell transplant (although this treatment is not suitable for everyone)
  • Combination of other treatments
  • Clinical trial participation 
  • Chimeric antigen receptor (CAR) T-cell therapy (after 2 lines of treatment)
For more info see
Relapsed and Refractory Lymphoma

Treatment under investigation for diffuse large B-cell lymphoma (DLBCL)

There are many treatments that are currently being tested in clinical trials for patients with both newly diagnosed and relapsed lymphoma.  Some of the treatments that are currently being investigated in clinical trials in Australia and around the world for DLBC include:

  • Chimeric antigen receptor (CAR) T-cell therapy
  • Bispecific T-cell engaging antibodies
  • Macrophage checkpoint inhibitors
  • Polatuzumab vedotin
  • Combination therapies

For the latest information on new treatments under investigation see the diffuse large B-cell lymphoma fact sheet PDF

For more info see
Understanding Clinical Trials

What happens after treatment 

Late effects

Sometimes a side effect from treatment may continue or develop months or years after treatment has completed. 

Finishing treatment

Late Effects  

Sometimes a side effect from treatment may continue or develop months or years after treatment has completed.  This is called a late effect. 

For more info see
Late Effects

Finishing treatment

This can be a challenging time for many people and some of the common concerns can be related to:

  • Physical
  • Mental wellbeing
  • Emotional health
  • Relationships
  • Work, study, and social activities
For more info see
Finishing Treatment

Health and wellbeing

A healthy lifestyle, or some positive lifestyle changes after treatment can be a great help after the treatment has been finished.  Making small changes such as eating and increasing fitness can improve health and wellbeing and help the body to recover.  There are many self-care strategies that can help during the recovery phase.

For more info see
Health & Wellbeing

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