Overview of Burkitt lymphoma (BL) in children
Lymphomas are a group of cancers of the lymphatic system. Lymphoma occurs when lymphocytes, which are a type of white blood cell, gain a DNA mutation. The role of lymphocytes is to fight infection, as part of the body’s immune system. There are B-lymphocytes (B-cells) and T-lymphocytes (T-cells) that play different roles.
The lymphoma cells then divide and grow uncontrollably or do not die when they should. Lymphoma has a build-up of abnormal lymphocytes. There are two main types of lymphoma. They are called Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Lymphomas are further divided into:
- Indolent (slow growing) lymphoma
- Aggressive (fast-growing) lymphoma
- B-cell lymphoma are abnormal B-cell lymphocytes & are the most common. B-cell lymphomas account for around 85% of all lymphomas
- T-cell lymphoma are abnormal T-cell lymphocytes. T-cell lymphomas account for around 15% of all lymphomas
Burkitt’s lymphoma is an aggressive (fast-growing) B-cell non-Hodgkin lymphoma. The abnormal B-cells (lymphoma cells) usually build up in lymph nodes, but they can affect other parts of the body including the bone marrow, the spleen, blood, skin and almost any organ or tissue.
The abnormal cells in Burkitt lymphoma (BL) grow rapidly due to the nature of their DNA mutations. One of the hallmarks of this subtype of lymphoma is known as the C-MYC translocation. This DNA rearrangement of the C-MYC gene on chromosome 8, is a large contributor to the lymphoma being especially fast growing.
There are three types of Burkitt lymphoma (BL). Each subtype of BL have different clinical features that include:
- Endemic (African)
- Sporadic (non-African)
Why is it called ‘Burkitt’ lymphoma?
Burkitt lymphoma (BL) is named after Dennis Burkitt who was a medical researcher in Uganda in the 1950’s. Mr. Burkitt found that this type of lymphoma was widespread in equatorial Africa and did a lot of the initial clinical recording of its occurrence and prevalence.
Since then, subsequent studies have revealed that this same tumour was occurring in places such as Europe and North America. Burkitt lymphoma (BL) is now recognised worldwide, accounting for around 30% of all childhood lymphoma cases.
Who does it affect?
Burkitt lymphoma accounts for around 40% of childhood non-Hodgkin lymphoma in Australia. Burkitt lymphoma (BL) is more common in boys than girls. The average age of diagnosis in children is 5 -10 years of age. In adults the average age of onset is between 35 – 50 years.
In most cases of Burkitt lymphoma (BL), the cause is not known. There is nothing that you have done or haven’t done that has caused this for your child. It is not infectious and cannot be passed onto other people. What we do know is that special proteins or genes are damaged (become mutated) and then grow uncontrollably.
Types of Burkitt Lymphoma (BL)
Burkitt lymphoma (BL) can be divided into three different types. The different types of Burkitt lymphoma and treated the same. The three types of Burkitt lymphoma (BL) include:
- Endemic (African)
- Sporadic (non-African)
- Occurring most commonly in children 4 to 7 years of age.
- It affects boys twice as often as girls.
- This subtype is strongly associated with Epstein-Barr virus (EBV) and chronic malaria.
- Children most often have lymphoma that involve the jaw or facial bones, although other extranodal disease sites such as the abdomen, ovaries, kidney or breast are also common.
- Endemic Burkitt lymphoma is rare outside of Africa.
- Occurring in children and young people who can live anywhere around the world. This type of BL accounts for around 30-50% of all Burkitt lymphoma cases in children.
- This subtype is more common in boys than in girls.
- This subtype less frequently affects the facial bones and presents more commonly in the abdomen causing swelling and discomfort in this region.
- Children can present with bilateral breast masses. These symptoms may be confused with puberty or pregnancy.
- There is a high risk of spread to the central nervous system (brain and/or spinal cord).
- Other organs and tissue may also be affected such as the thyroid and tonsils, and the facial bones may also be involved.
- This subtype of BL is mostly associated with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS).
- Immunodeficiency-related Burkitt lymphoma can occur in patients who have inherited immune deficiencies or those who take immunosuppressive medications to prevent rejection after organ transplant.
- It is more common for this subtype to involve the nodal (lymph nodes) and bone marrow at diagnosis.
There is a high risk that all subtypes of BL can involve the central nervous system.
Symptoms of Burkitt Lymphoma (BL)
The first symptoms that most people notice is a rapidly growing tumour in the abdomen, head or neck. These lumps develop and do not go away. You might feel one or more lumps on your child’s neck, armpit or groin. These lumps are swollen lymph nodes, where abnormal lymphocytes are growing. These lumps often start in one part of a child’s body, usually the head, neck or chest and then tend to spread in a predictable manner from one part of the lymphatic system to the next. In advanced stages, the disease can spread to the lungs, liver, bones, bone marrow or other organs.
The common symptoms of Burkitt lymphoma include:
- Persistent infections
- Painless swelling of lymph nodes in the neck, underarm, groin or chest
- Shortness of breath – due to enlarged lymph nodes in the chest or mediastinal mass
- Cough (usually dry cough)
- Difficulty recovering from an infection
B symptoms are what doctors call the following symptoms and some children may have them and can include:
- Night sweats (especially at night, where you might need to change their sleepwear and bedding)
- Persistent fevers
- Unexplained weight loss
- Itchy skin (pruritus)
It is important to note that many of these symptoms can relate to causes other than cancer. It can be difficult sometimes for doctors to diagnose BL straight away as it is a rare condition.
Diagnosis of Burkitt lymphoma
A biopsy is always required for a diagnosis of Burkitt lymphoma (BL). A biopsy is an operation to remove a lymph node or other abnormal tissue to look at it under the microscope by a pathologist. The biopsy is usually done under general anaesthetic for children to help reduce distress.
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.
Staging of Burkitt lymphoma
Once a diagnosis of Burkitt lymphoma (BL) is made, further tests are required to see where else in the body the lymphoma is located or has been affected. This is called staging. The staging of the lymphoma helps the doctor to determine the best treatment for your child
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 lymphomas. This may also referred to ‘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, and it is widespread lymphoma. In most cases, the lymphoma has spread to parts of the body that are far from each other.
‘Advanced’ stage lymphoma does sound concerning, but lymphoma is what is known as a system cancer. It can spread throughout the lymphatic system and nearby tissue. This is why systemic treatment (chemotherapy) is needed to treat Burkitt’s lymphoma.
Some of the tests needed can include:
- Blood tests (such as: full blood count, blood chemistry and erythrocyte sedimentation rate (ESR) to look for evidence of inflammation)
- Chest x-ray – these images will help identify presence of disease in the chest
- Positron emission tomography (PET) scan – done to understand all sites of disease in the body before treatment starts
- Computed tomography (CT) scan
- Bone marrow biopsy
- Lumbar puncture
Your child may also undergo a number of baseline tests prior to any treatment commencing to check organ function. These are often repeated during and after treatment has completed to assess whether the treatment has affected organ function. Sometimes treatment and follow-up care may need to be adjusted to help manage any adverse side effects. These may include:
- Physical examination
- Vital observations (Blood pressure, temperature, & pulse rate)
- Heart scan
- Kidney scan
- Breathing tests
Many of these staging and organ function tests are done again after treatment to check whether the lymphoma treatment has worked and to monitor the effect treatment has had on the body.
Prognosis of Burkitt Lymphoma (BL)
Burkitt lymphoma has a very good prognosis, with most patients responding very well to standard first-line chemotherapy treatment. Children with Burkitt lymphoma achieve a cure in around 90% of cases. If a cure is not achieved in first-line treatment, there are further treatment options that can be successful.
Long-term survival and treatment options depend on a range of factors, including:
- Age of your child at diagnosis
- Extent or stage of the cancer
- Appearance of the lymphoma cells under the microscope (the shape, function and structure of the cells)
- How the lymphoma responds to treatment
Talk to your child’s doctor about your child’s individual disease, treatment options and prognosis.
Treatment of Burkitt Lymphoma
Once all of the results from the biopsy and the staging scans have been completed, the doctor will review these to decide the best possible treatment for your child. At some cancer centres, the doctor will also meet with a team of specialists to discuss the best treatment option. This is called a multidisciplinary team (MDT) meeting.
The doctors will take into consideration many factors about your child’s lymphoma and general health to decide when and what treatment is required. This is based on:
- The stage and grade of the lymphoma
- Age, past medical history & general health
- Current physical and mental wellbeing
- Social Circumstances
- Family preferences
Since Burkitt lymphoma is a rapidly growing lymphoma, treatment may need to start within days to weeks of a diagnosis being made.
The standard treatment for patients with Burkitt lymphoma (BL) is a combination of chemotherapy and may also includean immunotherapy, with some patients also receiving radiotherapy. There are two chemotherapy regimen options, depending on various factors, that the doctor may recommend.
The standard treatments for Burkitt lymphoma in children may include:
- R-COPADM: rituximab, cyclophosphamide, vincristine, methotrexate, cytarabine, Prednisolone, doxorubicin, etoposide.
- SFOP LMB 89: cyclophosphamide, vincristine, methotrexate, doxorubicin), cytarabine, etoposide
Other variations of chemotherapy protocols used in paediatric Burkitt lymphoma include:
- CHOP: cyclophosphamide, daunorubicin, vincristine and prednisolone
- COPAD: cyclophosphamide, cytarabine, doxorubicin, vincristine, etoposide, Prednisolone
- COPADM: cyclophosphamide, methotrexate, cytarabine, doxorubicin, vincristine, etoposide
Common side effects of treatment
The treatment for Burkitt lymphoma comes with the risk of developing many different side effects. Each treatment regime has individual side effects and your treating doctor and/or specialist cancer nurse will explain these to you and your child prior to starting treatment.
Some of the more common side effects of treatment for Burkitt’s Lymphoma (not all) include:
- Anaemia (low red blood cells)
- Thrombocytopenia (low platelets)
- Neutropenia (low white blood cells)
- Nausea and vomiting
- Bowel problems such constipation and diarrhoea
- Reduced fertility
The medical team, doctor, cancer nurse or pharmacist, should provide you with information about the treatment, the common side effects, what symptoms to report and who to contact. If not, please ask these questions.
For more information contact the lymphoma care nurse support line on 1800 953 081 or email us at email@example.com
The treatment for Hodgkin lymphoma can affect your child’s fertility. Although many males and females go on to have children later in life after treatment, it is important that you discuss the risks on their fertility and what is available to help preserve their fertility before treatment starts.
Once treatment has completed, your child will have post treatment staging scans to review how well the treatment has worked and if there is a complete response (CR or no signs of lymphoma remain) or partial response (PR or there is still lymphoma present, but it has reduced in size).
If a complete remission has been achieved there will be follows ups with the doctor usually every 3-6 months. These appointments are important so that the medical team can check how well the recovery is from treatment. They are also a good opportunity for you to talk to the doctor or nurse about any concerns you may have. The medical team will want to know how your child is feeling both physically and mentally, and to:
- 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
Physical examination and blood tests for these appointments and apart from immediately after treatment to review how the treatment has worked, scans are not usually done unless there is a particular reason for them. If your child stays well, their appointments may become less frequent over time.
Relapsed or Refractory Burkitt lymphoma
Relapsed lymphoma is when the cancer has come back, refractory lymphoma is when the cancer is not responding to first line treatments. For some children and young people, Burkitt lymphoma returns and in some rare cases it does not respond to initial treatment (refractory). For these patients there are other treatments that can be successful, and may include:
- High dose combination chemotherapy followed by autologous (own) stem cell transplant or small groups of patients may receive an allogeneic (donor) stem cell transplant
- Combination chemotherapy
- Clinical trial participation
If a relapse is suspected , often the same staging exams are done, which include the tests that were stated above in the ‘diagnosis and staging’ section.
Treatment under investigation
There are many treatments that are currently being tested in clinical trials around the world for patients with both newly diagnosed and relapsed lymphoma. As Burkitt lymphoma has a very good cure rate, many studies are being done to try to keep the high cure rate but reduce the long term side effects of treatment. Some of these treatments include:
- Brentuximab vedotin (Adcetris) & rituximab
- Pembrolizumab (KeytrudaTM)
What happens after Treatment?
Sometimes a side effect from treatment may continue or can develop months or years after treatment has completed. This is called a late effect.
Children and adolescents may have treatment-related side effects that can appear months or years after treatment, including problems with bone growth and development of sex organs in males, infertility, and thyroid, heart and lung diseases.
Some patients who survive childhood Hodgkin lymphoma may develop a secondary cancer after diagnosis, primarily breast cancer, non-Hodgkin lymphoma, thyroid cancer or acute leukaemia, sometimes many years later. Many current treatment regimens and research studies now focus on trying to decrease the risk for these late effects.
For these reasons it is important the survivors of Hodgkin lymphoma receive regular follow-up and monitoring. It is also important that young people find a good GP that they can see regularly.