Overview of lymphoblastic lymphoma (LL)
Lymphoblastic Lymphoma (LL) is a rare aggressive (fast-growing) non-Hodgkin lymphoma (NHL). It is very rare and accounts for around 2% of all NHL. LL develops from either B-lymphoblasts (B-lymphoblastic lymphoma) or T-lymphoblasts (T-lymphoblastic lymphoma).
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.
The difference between the lymphoma and leukaemia depends entirely on where the highest percentage of cancer cells are found at diagnosis.
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 cells 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)
Lymphoblastic lymphoma has a good prognosis, roughly 85% of young people achieve complete remission after current standard first-line treatment using chemotherapy. Those who are over the age of 40 years, have a worse outlook of around 45-50% cure rate with first-line standard treatment. Research is constantly aiming to improve long-term survival rates and there are clinical trials investigating how to achieve this.
Who is affected by lymphoblastic lymphoma?
Lymphoblastic lymphoma (LL) can affect anyone of any age. It is more common in males than females. LL is more common in children and young adults (average age 20 years), and under the age of 35 years. Those who are diagnosed over the age of 40 years can have a higher chance of relapse than younger people.
The cause of lymphoblastic lymphoma is not known. As with other cancers, it is not infectious and it cannot be passed onto other people. While the possible causes of LL are not obvious, there are risk factors that are associated with the development of LL.
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) 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 (LL) 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-cell lymphoblastic lymphomas account for around 90% of adult lymphoblastic lymphomas. The T-cells often come from the thymus (an organ in the upper chest behind the sternum). Because of the location of the thymus, lymph nodes in the upper body are commonly affected. People often present to their doctor with a mass in the upper chest region. This mass is known as a mediastinal (chest area) mass. This lymphoma arises from immature lymphocyte cells which are on the path to becoming mature T-cell lymphocytes.
Precursor B-cell lymphoblastic lymphoma
Precursor B-cell lymphoblastic lymphoma is less common than B-acute lymphoblastic leukaemia (B-ALL). The lymphoma cells develop from early immature B-cell lymphocytes. People often present to their doctor with both affected lymph nodes and extranodal (tissue outside of the lymph nodes). Extranodal site involvement could be the presence of lymphoma cells in the skin, bone, central nervous system or bone marrow.
Symptoms of lymphoblastic lymphoma
The first symptoms that most people notice is a lump or several lumps that do not go away after several weeks. You might feel one or more lumps in the neck, armpit or groin. These lumps are swollen lymph nodes, where abnormal lymphocytes are growing uncontrollably. These lumps often start in one part of the 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 (widespread disease), 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 may include:
- Painless swelling of lymph nodes in the neck, underarm, groin or chest
- Easy bruising
- Pallor (paleness of skin)
- Shortness of breath – due to enlarged lymph nodes in the chest
- 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 and are sometimes difficult for doctors to diagnose.
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 can be done under general anaesthetic or local anaesthetic depending on location.
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.
A bone marrow biopsy (BMA) and peripheral blood collection are also required for a diagnosis of lymphoblastic lymphoma – in order to distinguish it from acute 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 family, friends or a specialist nurse.
Staging, tests and scans
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 to decide on the best treatment.
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 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 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.
Some of the tests needed can include:
- 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
- Lumbar puncture
- Bone marrow biopsy
- Blood tests (such as: full blood count, blood chemistry and erythrocyte sedimentation rate (ESR) to look for evidence of inflammation)
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:
- 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 (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 this has had on the body.
Prognosis of lymphoblastic lymphoma
Lymphoblastic lymphoma has a very good prognosis, with most patients responding very well to treatment and achieving 85% cure. Those who are diagnosed over the age of 40 years have a worse outcome than younger patients, of 45-50% cure rate.
Long-term survival and treatment options depend on a range of factors, including:
- age 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 doctor about your individual disease, treatment options and prognosis.
Treatment of lymphoblastic 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. 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 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
- Age, 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 chemotherapy
- Maintenance phase chemotherapy
The standard first-line chemotherapy protocols used can include:
- Hyper CVAD (cyclophosphamide, Doxorubicin, Vincristine, Cytarabine, Methotrexate, Dexamethasone)
- BFM 2000 (Prednisone, Methotrexate, Daunorubicin, Vincristine, Asparaginase, Mercaptopurine, Cyclophosphamide, Cytarabine, Dexamethasone, Doxorubicin, Tioguanine, Etoposide, Ifosfamide) *This protocol is used in young adults (25 years and younger).
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 (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
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 whether fertility may be affected or whether fertility preservation should be done before the start of treatment.
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 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 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 and can include:
- High dose combination chemotherapy followed by either:
- Autologous stem cell transplant
- Allogeneic stem cell transplant.
- Combination chemotherapy
- Clinical trial participation
If a relapse is suspected another biopsy needs to be done often with the same staging tests that were explained above in the staging section.
Treatment under investigation for lymphoblastic lymphoma (LL)
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 lymphoma. For a list of the current treatments that are being investigated include:
- Chimeric antigen receptor T-cell therapy (CAR-T-cell 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.
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.