Overview of lymphoblastic lymphoma in children
Lymphoblastic lymphoma (LL) is a rare aggressive (fast-growing) non-Hodgkin lymphoma. LL develops from either B-lymphoblasts (leading to B-lymphoblastic lymphoma/B-LL) or T-lymphoblasts (leading to T-lymphoblastic lymphoma/T-LL).
A lymphoblast is an immature cell that can develop into a mature lymphocyte. B-lymphoblasts are immature B-lymphocytes and T-lymphoblasts are immature T-lymphocytes. T-cell lymphoblastic lymphoma is more common than B-cell lymphoblastic lymphoma.
What is the difference between lymphoblastic lymphoma and leukaemia?
Acute lymphoblastic lymphoma and acute lymphoblastic leukaemia are very similar in both clinical behaviour and appearance under a microscope. The cancerous immature white blood cells are the same and develop from the same cell.
Criteria for a diagnosis of lymphoblastic lymphoma includes:
- Less than 25% of the bone marrow will show cancer
- There are often other sites of involvement such as lymph nodes
- The lymphoma can affect other parts of the body including the spleen, thymus, blood, skin and almost any organ or tissue
- Can be either B-cell or T-cells affected (cell of origin)
Criteria for a diagnosis of acute lymphoblastic leukaemia:
- More than 25% of the healthy bone marrow will have been replaced with malignant lymphoblastic cells
- There will be malignant lymphoblast cells (commonly called blast cells) present in peripheral blood samples
- Can be either B-cell or T-cell affected (cell of origin)
Location & cell of origin
Type of lymphocyte most commonly affected
B-cell or T-cell
B-cell or T-cell
Where the cancer is located
Lymphoblastic lymphoma has a good prognosis, where around 85% of children are cured after standard first-line treatment.
Who is affected by lymphoblastic lymphoma?
Lymphoma is the 3rd most common cancer in Australian children aged 0– 14 years. Lymphoma accounts for 7% of childhood cancers, and it is third most common cancer in children aged 0-14 years, behind leukaemia and brain or central nervous system (CNS) cancer.
Non-Hodgkin Lymphoma accounts for around 5% of all childhood cancers of this age group and lymphoblastic lymphoma accounts for around 25-30% of childhood non-Hodgkin lymphoma cases diagnosed each year. Lymphoblastic lymphoma is one of the three most common types of NHL in children.
Lymphoblastic lymphoma (LL) can affect anyone of any age but is most common in people aged under 35 years, with the median age at diagnosis being 20 years. It is twice as common in boys than girls at this age. Lymphoma is very rare in younger children, but it becomes more common in older children (10-14 years) and increases with age.
In most cases of lymphoblastic lymphoma, 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.
While the possible causes of your child’s lymphoblastic lymphoma are not known, there are some risk factors that have been associated with this lymphoma. It is important to note that the majority of people who have these risk factors do NOT develop lymphoblastic lymphoma.
These risk factors may include:
- Previous infection with Epstein-Barr virus (EBV) – this virus is the common cause of glandular fever
- Weakened immune system due to an inherited immune deficiency disease (autoimmune disease)
- HIV infection
- Immunosuppressant medication that is taken to prevent rejection after an organ transplant
- Having a brother or sister with Hodgkin lymphoma (especially twins), it has been suggested to a rare family genetic link to the disease (although very rare and not recommended for families to have genetic testing)
- Most people do not have any family history
Types of lymphoblastic lymphoma (LL)
Lymphoblastic Lymphoma can be divided into either B-cell or T-cell lymphoblastic lymphoma. Both subtypes generally present in similar ways to one another, their presentation is also very similar to acute lymphoblastic leukaemia (ALL).
Precursor T-cell lymphoblastic lymphoma
- Precursor T-lymphoblastic lymphomas comprise roughly 70%-80% of childhood lymphoblastic lymphomas.
- Majority of cases originate in the thymus (an organ in the upper chest behind the breast-bone). Children often present with what is known as a mediastinal mass, which is a mass in the area behind the breast bone but in front of the windpipe.
- This mediastinal mass can cause shortness of breath – a sign of the lymphoma.
- Upper torso lymph node involvement is common
- This lymphoma arises from immature lymphoid cells which are on the path to becoming mature T-cells.
Precursor B-cell lymphoblastic lymphoma
- Precursor B-lymphoblastic lymphoma accounts for approximately 20%-30% of childhood Lymphoblastic lymphomas.
- It is far less common than B-cell acute lymphoblastic leukaemia (B-ALL).
- It is derived from immature B-lymphoblasts.
- It often begins in lymph nodes outside the mediastinum, more commonly seen in the lymph nodes of the neck, tonsils and sometimes presents with skin tumours arising on the scalp of young children.
- It is generally seen to be slower growing than T-cell lymphoblastic lymphoma.
Symptoms of lymphoblastic lymphoma (LL)
The first symptoms that most people notice is a lump or several 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 uncontrollably. These lumps often start in one part of a child’s body, usually the head, neck or chest and then often 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. Around 50-75% of patients have lymphoma that affects the mediastinal (chest) area.
The common symptoms of Lymphoblastic lymphoma include:
- Painless swelling of lymph nodes in the neck, underarm, groin or chest
- Pallor (paleness of skin)
- Easy bruising
- Persistent infections
- Shortness of breath – due to enlarged lymph nodes in the chest (mediastinal)
- Cough (usually dry cough)
- Difficulty recovering from an infection
- Itchy skin (pruritus)
B symptoms are what doctors call the following symptoms and can include:
- Night sweats (especially at night, drenching sleepwear and bedding)
- Persistent fevers
- Unexplained weight loss
It is important to note that many of these symptoms are related to causes other than cancer This means it can sometimes be difficult for doctors to diagnose.
Diagnosis of lymphoblastic lymphoma (LL)
A biopsy is always required for a diagnosis of Lymphoblastic 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.
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.
A bone marrow biopsy (BMA – bone marrow aspirate) is required for a diagnosis of lymphoblastic lymphoma – in order to distinguish it from lymphoblastic leukaemia. A BMA is a procedure to collect cells from the bone marrow, these cells are generally collected from the back of the pelvic bone.
Waiting for results can be a difficult time. It may help to talk to your family, friends or a specialist nurse.
Staging of lymphoblastic lymphoma (LL)
Once a diagnosis of Lymphoblastic lymphoma (LL) 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 on the best treatment.
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 lymphoblastic lymphoma.
Tests 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 active lymphoma in the body before treatment starts
- Computed tomography (CT) scan
- Bone marrow biopsy
- Lumbar puncture
Patients may also undergo a number of baseline tests prior to starting any treatment. This is to check organ function. These tests 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
It may take some time for all of 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 decisions.
Many of the staging and organ function tests are done again after treatment to check whether the lymphoma treatment has worked and the effect that has had on the body.
Prognosis of lymphoblastic lymphoma (LL)
Lymphoblastic lymphoma (LL) has a good prognosis, with most patients responding very well to treatment and achieving 85% cure. Those who do not respond completely to standard first-line treatment or relapse (comes back), there are still treatments available to still potentially cure.
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
- Lymphoma biology, which includes
- the patterns of the lymphoma cells
- how different the lymphoma cells are from normal cells
- how fast the lymphoma cells are growing.
Talk to your child’s doctor about your child’s individual disease, treatment options and prognosis.
Treatment of lymphoblastic lymphoma (LL) in children
Once all of the results from the biopsy and the staging scans have been completed, the doctor will review these to decide the best treatment. 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 the lymphoma and general health of the patient to decide when and what treatment is required. This is based on:
- The stage and grade of the lymphoma
- Past medical history & general health
- Current physical and mental wellbeing
- Social Circumstances
- Family preferences
Since lymphoblastic lymphoma is a rapidly growing lymphoma, treatment may need to start within a few days after a diagnosis. Treatment protocols for lymphoblastic lymphoma are generally the same protocols used to treat acute lymphoblastic leukaemia, because of the similarities in the diseases.
The majority of treatment pathways will include:
- Induction phase, which uses intensive multi-agent chemotherapy
- Consolidation phase of chemotherapy
- Maintenance phase therapy
The standard first-line chemotherapy protocols used can include:
- AALL0932: (methotrexate, vincristine, cytarabine, dexamethasone, peg asparaginase, mercaptopurine, doxorubicin, cyclophosphamide, thioguanine)
- BFM 2000: (prednisone, methotrexate, daunorubicin, vincristine, asparaginase, mercaptopurine, cyclophosphamide, cytarabine, dexamethasone, doxorubicin, tioguanine, etoposide, ifosfamide)
- Clinical trial participation
Common side effects of 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:
- 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 (lack of energy)
- Reduced fertility
Your medical team, doctor, cancer nurse or pharmacist, should provide you with 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
Some treatments for lymphoma can reduce fertility and this is more likely with certain chemotherapy regimens (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 you on whether fertility may be affected or whether fertility preservation should be done before the start of treatment.
For more information and advice about your diagnosis, 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 email@example.com
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 you 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. If all is going well, the appointments may become less frequent over time. However, contact the medical team if you have any concerns in between these appointments.
Relapsed or refractory management of lymphoblastic 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, Lymphoblastic 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, these may include:
- High dose combination chemotherapy followed by either:
- Autologous stem cell transplant
- Allogeneic stem cell transplant
- Combination chemotherapy
- Clinical trial participation
If a relapse (comes back) is suspected another biopsy needs to be done often with the same staging tests that were explained above in the staging section.
Current treatment under Investigation
There are many treatments that are currently being tested in clinical trials in Australia and around the world for patients with both newly diagnosed and relapsed or refractory lymphoblastic lymphoma. These include:
- Chimeric antigen receptor (CAR) T-cell therapy
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.
This can be a challenging time for many people and some of the common concerns can be related to:
- Mental wellbeing
- Emotional health
- 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.