Quick snapshot of diffuse large B-cell lymphoma (DLBCL) in children
This section is a brief explanation of diffuse large B cell lymphoma (DLBCL) in children aged 0-14 years. For more in depth information review the additional sections below.
What is it?
Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast growing) B-cell non-Hodgkin lymphoma. It develops from B lymphocytes (white blood cells) that grow uncontrollably. These abnormal B lymphocytes gather in the lymph tissue and lymph nodes, within the lymphatic system, which is part of the immune system. Because lymph tissue is found throughout the whole body, DLBCL can start in almost any part of the body and spread to almost any organ or tissue in the body.
Who does it affect?
DLBCL accounts for around 15% of all lymphoma that occur in children. DLBCL is more common in boys than in girls. DLBCL is the most common lymphoma subtype in adults, accounting for around 30% of adult lymphoma cases.
Treatment and prognosis
DLBCL in children has an excellent prognosis (outlook). Around 90% of children are cured after receiving standard chemotherapy and immunotherapy. There is a lot of research going into treating this lymphoma, with an emphasis on investigating how to reduce late effects, or side effects from the toxic therapy that can occur months to years following treatment
Overview of diffuse large B-cell lymphoma (DLBCL) 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.
In DLBCL the lymphoma cells divide and grow uncontrollably or do not die when they should. 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
Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast growing) B-cell non-Hodgkin lymphoma. DLBCL accounts for around 15% of all lymphomas that occur in children. DLBCL is the most common lymphoma in adults, accounting for around 30% of all lymphoma cases in adults.
DLBCL develops from mature B-cells from either the germinal centre of a lymph node, or from B-cells known as activated B-cells. Therefore, there are two most common types of DLBCL:
- Germinal Centre B-cell (GCB)
- Activated B-cell (ABC)
The exact cause of DLBCL in children is not known. Most of the time there is no reasonable explanation for where or how a child has contracted cancer and there is no evidence that suggests parents and carers/guardians could have prevented the lymphoma from developing, or caused it.
Who is affected by diffuse large B-cell lymphoma (DLBCL)?
Diffuse large B-cell lymphoma (DLBCL) can occur in people of any age or gender. DLBCL is most commonly seen in older children and young adults (people 10 – 20 years of age). It occurs more frequently in boys than girls.
The cause of DLBCL is not known. There is nothing that you have done or haven’t done that has caused this . It is not infectious and cannot be passed onto other people.
While the possible causes of DLBCL are not obvious, there are some risk factors that have been associated with lymphoma. Not all people who have these risk factors will go on to develop DLBCL. The risk factors include (although the risk is still very low):
- Previous infection with Epstein-Barr virus (EBV) – that virus is the common cause of glandular fever
- Weakened immune system due to an inherited immune deficiency disease (autoimmune disease such as dyskeratosis congenita, systemic lupus, rheumatoid arthritis)
- HIV infection
- Immunosuppressant medication that is taken to prevent rejection after an organ transplant
- Having a brother or sister with lymphoma (especially twins) has been suggested to have a rare family genetic link to the disease (this is very rare and it is not recommended for families to have genetic testing)
Having a child diagnosed with lymphoma can be a very stressful and emotional experience, there is no right or wrong reaction. It is often devastating and shocking, it is important to allow yourself and your family time to process and grieve. It is also important that you do not carry the weight of this diagnosis on your own, there are a number of support organisations that are here to help you and your family during this time, click here to find out more about support for families who have a child or young person with lymphoma.
Types of diffuse large B-cell lymphoma (DLBCL) in children
Diffuse large B-cell lymphoma (DLBCL) can f be divided into subtypes based on the type of B-cell it has grown from (termed “cell of origin”).
- Germinal Centre B-cell lymphoma (GBC): GCB-type is more common in paediatric patients than ABC-type. Young people are more likely to get GCB-type disease (80-95% in 0-20 years) than adults and it is associated with improved outcomes compared to the ABC-type.
- Activated B-cell Lymphoma (ABC): ABC-type comes from post-germinal centre (of the cell) locations because it is a more mature B-cell malignancy. It is called ABC-type because the B-cells have been activated and are working as frontline contributors to the immune responses.
DLBCL can be classified as either germinal centre B-cell (GCB) or activated B-cell (ABC). The pathologist examining your lymph node biopsy can tell the difference between these by looking for certain proteins on the lymphoma cells. At present, this information is not used to direct treatment. However, scientists are carrying out research to find out if different treatments are effective against different types of DLBCL that develop from different cells.
Symptoms of diffuse large B-cell lymphoma (DLBCL) in children
The first symptoms that most people notice is a lump or multiple lumps that don’t go away after several weeks. 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.
There is a rare type of lymphoma which presents with a mediastinal mass, it is known as primary mediastinal large B-cell lymphoma (PMBCL). This lymphoma used to be classified as a subtype of DLBCL but has since been reclassified. PMBCL is when lymphoma originates from thymic B-cells. The thymus is a lymphoid organ located directly behind the sternum (chest).
The most common symptoms of DLBCL include:
- 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
- Itchy skin (pruritus)
B symptoms is a term that describes the following symptoms :
- Night sweats (especially at night, where you might need to change their sleepwear and bedding)
- Persistent fevers
- Unexplained weight loss
Approximately 20% of children with DLBCL present with a mass in the upper chest. This is called a “mediastinal mass”. , A mass in the chest can cause shortness of breath, a cough or swelling of the head and neck due to the tumour pressing on the windpipe or large veins above the heart.
It is important to note that many of these symptoms are related to causes other than cancer This means lymphoma can be difficult for doctors to diagnose.
Diagnosis of diffuse large B-cell lymphoma (DLBCL)
A biopsy is always required for a diagnosis of diffuse large B-cell lymphoma. 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.
Generally, either a core biopsy or an excisional node biopsy is the best investigative option. This is to ensure the doctors collect an adequate amount of tissue to complete the necessary testing for a diagnosis.
Waiting for results can be a difficult time. It may help to talk to your family, friends or a specialist nurse.
Staging of diffuse large B-cell lymphoma (DLBCL)
Once a diagnosis of DLBCL is made, further tests are required to see where else in the body the lymphoma is located . This is called staging. The staging of the lymphoma helps the doctor to determine the best treatment for your child .
There are 4 stages, from stage 1 (lymphoma in one area) through to stage 4 (lymphoma that is widespread or advanced).
- Early stage means stage 1 and some stage 2 lymphomas. This may also be called ‘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 DLBCL.
T ests required may 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 (only usually done if evidence of advanced disease)
- Lumbar puncture – If lymphoma is suspected in the brain or spinal cord
Your child may also undergo a number of baseline tests prior to starting any treatment. This is to check organ function. These may be repeated during and after treatment to assess whether the treatment has affected organ function. The tests required may include; ;
- Physical examination
- Vital observations (Blood pressure, temperature, & pulse rate)
- Heart scan
- Kidney scan
- Breathing tests
- Blood 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 diffuse large B-cell lymphoma (DLBCL)
DLBCL in children has an excellent prognosis (outlook). Around 9 out of every 10 (90%) children are cured after receiving standard chemotherapy and immunotherapy. There is a lot of research looking into treating this lymphoma, with an emphasis on investigating how to reduce late effects, or side effects from the toxic therapy that can occur months to years after treatment .
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
Treatment of diffuse large B-cell 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 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 DLBCL is a fast-growing lymphoma, it needs to be treated quickly – often within days to weeks of a diagnosis. DLBCL treatment includes a combination of chemotherapy and immunotherapy
Some adolescent DLBCL patients might be treated with the adult chemotherapy regimen called R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, & prednisolone). This will often depend on whether your child is being treated within a paediatric hospital or an adult hospital.
Standard paediatric treatment for early stage DLBCL (stage I-IIA):
- BFM-90/95: 2 – 4 cycles of chemotherapy based on disease stage
- Protocol drug agents include: cyclophosphamide, cytarabine, methotrexate, mercaptopurine, vincristine, pegaspargase, prednisolone, pirarubicin, dexamethasone.
- COG-C5961: 2 – 4 cycles of chemotherapy based on disease stage
Standard paediatric treatment for advanced stage DLBCL (stage IIB-IVB):
- COG-C5961: 4 – 8 cycles of chemotherapy based on disease stage
- Protocol drug agents include: cyclophosphamide, cytarabine, doxorubicin hydrochloride, etoposide, methotrexate, prednisolone, vincristine.
- BFM-90/95: 4 – 6 cycles of chemotherapy based on disease stage
- Protocol drug agents include: cyclophosphamide, cytarabine, methotrexate, mercaptopurine, vincristine, pegaspargase, prednisolone, pirarubicin, dexamethasone.
Common side effects of treatment
The treatment for DLBCL 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 diffuse large B-cell lymphoma 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
Your medical team, doctor, cancer nurse or pharmacist, should provide you with information about your treatment, the common side effects, what symptoms to report and who to contact. If not, please ask these questions.
Some treatments for lymphoma can reduce fertility. 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.
Your doctor should advise on whether fertility may be affected Speak to the doctor and/or specialist cancer nurse prior to treatment starting about whether fertility will be affected.
For more information or advice about paediatric DLBCL , treatment, side effects, supports available or how to navigate the hospital system, please contact the lymphoma care nurse support line on 1800 953 081 or email us at firstname.lastname@example.org
Once treatment has completed, your child will have staging scans. These scans are to review how well the treatment has worked. The scans will show the doctors how the lymphoma has responded to treatment. This is termed the response to treatment and can be described as 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)
Your child will then need to be followed up by their doctor with regular follow-up appointments, usually every 3-6 months. These appointments are important so that the medical team can check how well they are recovering from treatment. These appointments provide a good opportunity for you to talk to the doctor or nurse about any concerns you have. The medical team will want to know how your child and you are 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
Your child is likely to have a physical examination and blood tests at each appointment . 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 is well, the appointments may become less frequent over time.
Relapsed or refractory management of DLBCL
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, DLBCL 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, these include:
- High dose combination chemotherapy followed by autologous stem cell transplant or an allogeneic stem cell transplant (not suitable for all people)
- Combination chemotherapy
- Clinical trial participation
When a person is suspected to have relapsed disease, 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. Some of these treatments include:
- Many trials are studying reducing the toxicity profile and late effects of the chemotherapy treatments
- CAR T-cell therapy
- Copanlisib (ALIQOPATM – PI3K inhibitor)
- Venetoclax (VENCLEXTATM – BCL2 inhibitor)
- Temsirolimus (TORISOLTM)
- CUDC-907 (novel targeted therapy)
What happens after treatment?
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 information, go to the ‘late effects’ section to learn more about some of the early and late effects that can occur from treatment for lymphoma.
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. 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 diffuse large B-cell lymphoma (DLBCL) receive regular follow-up and monitoring.