Overview of Burkitt Lymphoma (BL)
Burkitt lymphoma (BL) is the most aggressive subtype of lymphoma, and thought to be the fastest growing – or most aggressive type of cancer.
Because it starts and spreads very quickly, it needs to be treated with intensive chemoimmunotherapy very quickly after diagnosis. However, because chemotherapy works best on fast growing cells, it is very affective at destroying Burkitt Lymphoma cells.
Many people with Burkitt Lymphoma can be cured.
Subtypes of Burkitt Lymphoma
There are different subtypes of lymphoma. Click on the headings below to learn about the different subtypes.
Endemic Burkitt Lymphoma, which is more common in people with an African background, and is the most common lymphoma in African children. It is also more common in people who have had malaria or Epstein-Barr virus (EBV).
Endemic Burkitt Lymphoma often starts in your jaw, or on other bones of your face, but can also start in your abdomen (tummy).
Sporadic Burkitt Lymphoma can occur in any part of the world and like many lymphomas is thought to be more common in people who have had an infection with the Epstein-Barr virus. It often starts in your abdomen, so it can be common to pain or discomfort in your tummy.Â
Sporadic Burkitt Lymphoma can spread to your central nervous system, including your brain and spinal cord, your thyroid gland, tonsils and the bones in your face.
Immunodeficiency-associated Burkitt Lymphoma is more common in people with a weakened immune system, and is found in people who have human immunodeficiency virus (HIV) or who have develop acquired immunodeficiency syndrome (AIDS).
However, this subtype can also develop if you take medications that eaken you immune system such as those taken after an organ transplant or if you have an autoimmune disease.
Understanding B-cell lymphocytes
Burkitt Lymphoma is a cancer of B-cell lymphocytes, so to understand Burkitt Lymphoma you need to know a bit about your B-Cell lymphocytes.
B-Cell lymphocytes:
- Are a type of white blood cell.
- Fight infection and diseases to keep you healthy.Â
- Remember infections you had in the past, so if you get the same infection again, your body’s immune system can fight it more effectively and quickly.Â
- Are made in your bone marrow (the spongy part in the middle of your bones), but usually live in your spleen and your lymph nodes.  Some live in your thymus and blood too.
- Can travel through your lymphatic system, to any part of your body to fight infection or disease.Â
Burkitt Lymphoma develops when some of your B-cells become cancerous. They grow uncontrollably, are abnormal, and do not die when they should. Â
When you have Burkitt Lymphoma, your cancerous B-cell lymphocytes:
- Grow and multiply very quickly.
- Will not work as effectively to fight infections and disease.Â
- Look and behave very differently to your healthy B-cells.Â
- Can cause lymphoma to develop and grow in many parts of your body.
Who is affected by Burkitt lymphoma (BL)?
Burkitt lymphoma affects both children and adults and affects males three times more frequently than it does females. BL accounts for around 30 percent of all childhood lymphomas, where it is most common in children aged between 5 and 10 years and in adults between the age of 30 to 50 years. BL accounts for around 1-2 percent of all lymphomas and mainly occurs in adults aged between 30 to 50 years. Â
The cause of BL is unknown. However, the disease may be associated with viral infections such as human immunodeficiency virus (HIV) and the Epstein-Barr virus (EBV), a common virus that can also cause glandular fever. Not all people who are exposed to these viruses develop BL.
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Occasionally, a lymphoma has features of Burkitt lymphoma (BL) and another type of lymphoma. This might be called a ‘high-grade B-cell non-Hodgkin lymphoma, not otherwise specified’. If this is the case for you, your doctor can tell you if your lymphoma will be treated like Burkitt lymphoma (BL) or a different type of lymphoma.
Symptoms of Burkitt lymphoma (BL)
Burkitt lymphoma (BL) can start anywhere in the body and can have many different symptoms. The symptoms will often depend on where the lymphoma is in the body. BL is often found in the abdomen that can cause abdominal swelling (caused by fluid collecting in the stomach). The most common symptoms of BL can include:
- One or more lumps, which often develop in several parts of your body. These are the lymphoma cells building up in your lymph nodes (glands), causing them to enlarge (swell)
- Abdominal or back pain
- Swelling of the abdomen because of fluid collecting
- Bleeding from the bowel or pain from bowel obstruction (blockage)
- Loss of appetite
- Nausea and diarrhoea
- Fatigue
- Itchy skin
Burkitt lymphoma (BL) can also be located outside of the lymph nodes and is called ‘extranodal’. BL in the bone marrow can cause low blood counts as the lymphoma cells take up the space of normal cells. This may cause:
- Anaemia (low red blood cells that carry oxygen around the body)
- Thrombocytopenia (low platelets helps with bleeding and clotting)
Patients with BL often have bulky disease (large lumps or mass) as this type of lymphoma grows very quickly.
Some patients may have other common symptoms known as B symptoms, that include:
- Night sweats (drenching sleepwear or bedding)
- Persistent fevers (especially at night >38C)
- Unexplained weight lossÂ
Note: it is important to remember that lymph nodes can swell for lots of reasons. Most people with swollen lymph nodes do not have lymphoma, as they swell when we have an infection.
Diagnosis of Burkitt lymphoma (BL)
A biopsy is always required for 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 results can be a difficult time. It may help to talk to family, friends or a specialist nurse. Â
Staging
Once a diagnosis of Burkitt lymphoma (BL) 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.  The staging of lymphoma helps to determine the best treatment for the patient.
There are four stages from stage 1 (lymphoma in one area) through to stage 4 (lymphoma that is widespread).Â
- Early stage means stage 1 and some stage 2 lymphoma. This is also called ‘localised’. Stage 1 or 2 means that the lymphoma is found in one area or a few areas close together.
- Advanced stage means that the lymphoma is stage 3 or stage 4, and it is widespread lymphoma. In most cases, the lymphoma has spread to parts of the body that are far from each other.
Most people who are diagnosed with Burkitt lymphoma (BL) have advanced stage disease at diagnosis, as it is a rapidly growing lymphoma. Â
Advanced stage lymphoma does sound concerning, but lymphoma is a systemic disease meaning it spreads throughout the lymphatic system and nearby tissue and organs easily, unlike solid tumours. Â
What is the ‘grade’ of lymphoma?
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. Burkitt lymphoma is an aggressive lymphoma.Â
Burkitt lymphoma (BL) is normally divided into ‘low-risk’ and ‘high-risk’ based on the stage and other factors including:
- Central nervous system (CNS – brain or spinal) involvement at diagnosis is the strongest risk factor
- Levels of a chemical called ‘lactate dehydrogenase’ (LDH) in the blood
- How the lymphoma is affecting your everyday life
Most people with BL have a high-risk form. However, there are very effective treatments for BL. People with low-risk disease may receive slightly less treatment.
It is important to know the stage and grade of the lymphoma to help the medical team to know what’s the best treatment. Â
Staging scans and tests
The scans and tests needed for staging and before treatment can start may include:
- Positron emission tomography (PET) scanÂ
- Computed tomography (CT) scanÂ
- Bone marrow biopsyÂ
- Lumbar puncture & magnetic resonance imaging (MRI) – If lymphoma is suspected in the brain or spinal cord
Patients may also undergo a number of baseline tests prior to any treatment commencing to check organ functions. These are often repeated during and after the treatment has completed to assess whether the treatment has affected the functioning of organs. Sometimes the treatment and follow-up care may need to be adjusted to help manage side effects. These may include:
- Â Physical examination
- Â Vital observations (blood pressure, temperature, & pulse rate)
- Â Heart scan
- Â Kidney scan
- Â Breathing tests
- Â Blood tests
It may take some time for all the necessary biopsies and tests to be done (an average of 1-3 weeks), but it is important for the doctors to have a complete picture of the lymphoma and the general health of the patient in order to make the best treatment decisionsÂ
Many of the 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.
Prognosis of Burkitt lymphoma (BL)
Burkitt lymphoma (BL) has a very high survival rate using current standard treatments. The treatment is intensive, but many people can be cured. Most children are also cured with current standard treatment and the outcomes are often very good for adults. BL can be harder to treat in older adults who are generally less able to tolerate the intensive treatment required.
Treatment for Burkitt lymphoma (BL)
Once all the results from the biopsy and the staging scans have been completed, the doctor will review these to decide the best possible treatment for a patient.  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.  The following is considered:
- The stage of lymphoma
- Symptoms
- Levels of a chemical called ‘lactate dehydrogenase’ (LDH) in the blood
- How the lymphoma is affecting the patient
- Age
- Past medical history & general health
- Current physical and mental wellbeing
- Patient preference
Before treatment is started it is important that adequate information is provided about the treatment that is planned, the possible side effects and what to expect. Education from the cancer nurses prior to receiving treatment, can be extremely helpful and should include instructions about becoming unwell or needing medical or nursing assistance.
Burkitt lymphoma (BL) is extremely aggressive (fast-growing), where diagnosis, hospitalisation and urgent treatment is needed. However, BL is often very responsive to the current standard intensive combination chemotherapy regimens and cure rates are high. Treatment options are determined based on ‘low’ or ‘high’ risk status. Â
Central nervous system (CNS) involvement at diagnosis is recognised as the strongest risk factor for relapse (disease returns after treatment); therefore, it is recommended treatment regimens for patients who are a higher risk of recurrence include treatment to protect the CNS, which may be given intrathecally (injected into the spinal fluid).
All of the treatments used are very intensive, using high doses of medicines given very frequently. The monoclonal antibody rituximab may be added to any of these regimens. The standard first-line treatments for Burkitt lymphoma (BL) may include:
- CODOX-MÂ (cyclophosphamide, vincristine, doxorubicin, intrathecal cytarabine, methotrexate and rituximab)-Â alternating with cycles of IVAC
- IVACÂ (ifosfamide, etoposide, cytarabine and intrathecal methotrexate)Â or
- DA-EPOCH-R (dose adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin plus intrathecal methotrexate and rituximab)
- Clinical trial participation
Different combination chemotherapy regimens are used to treat BL in children and adolescents. BL is one of the most common types of childhood lymphoma. Younger patients tend to have excellent responses to chemotherapy and particularly high cure rates.Â
For this reason, current research, and studies in the treatment of children is focused on decreasing toxicity by reducing the overall amount of chemotherapy used to treat disease.Â
Common side effects of treatmentÂ
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:
- Anaemia (low red blood cells that carry oxygen around the body)
- Thrombocytopenia (low platelets that help with clotting and bleeding)
- Neutropenia (low white blood cells that help fight infection)
- Nausea and vomiting
- 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 treatmentÂ
- 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
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. Â
The doctor should advise on whether fertilitymay be affected or whether fertility preservation should bedone before the start of treatment.
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:Â Â
- 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 timeÂ
Relapsed or refractory Burkitt lymphoma (BL)
A high percentage of people achieve remission of their Burkitt lymphoma (BL) with first-line standard treatment. However, for some people, the lymphoma returns (relapses) or in the rare cases does not respond to first-line treatment (refractory). People with relapsed or refractory disease BL may have other treatment options (second-line treatment) including:
- Other combination chemotherapy options
- Stem cell transplant (autologous or allogeneic)
- Biological medicinesÂ
- Clinical trial participation
Treatment under Investigation for Burkitt Lymphoma (BL)
There are many treatments that are currently being tested in clinical trials in Australiaand around the world for patients with both newly diagnosed and relapsed lymphoma. Some of these treatments include:
- Brentuximab vedotin (Adcetris) & rituximabÂ
- Alisertib (MLN82737)
- Lenalidomide (RevlimidTM)
- Everolimus (AfinitorTM)
- Panobinostat (FarydakTM)Â
- Vorinostat (ZolinzaTM)
- Pembrolizumab (KeytrudaTM)
- Obinutuzumab (GazyvaTM)
- Venetoclax (VenclextaTM)
What happens after treatment?
 Late Effects Â
Sometimes a side effect from treatment may continue or develop months or years after treatment has completed. This is called a late effect.Â
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
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.Â
