Overview of splenic marginal zone lymphoma (splenic MZL)
Splenic marginal zone lymphoma (splenic MZL) is an indolent (slow growing) non-Hodgkin lymphoma (NHL). SMZL is rare, accounting for around 1% of all NHLs. Most patients have an enlarged spleen and abnormal blood cell counts.
The spleen is an organ that is part of the immune system and is one of the organs of the lymphatic system. The spleen is involved in fighting infections, is a filter for the blood, destroys old red blood cells and stores white blood cells and platelets. It is usually around the size of a pear and sits in the upper left-hand side of the abdomen to the left of the stomach. When the spleen is enlarged it might feel like a lump at the top of your stomach.
It can sometimes affect the lymph nodes of the abdomen (stomach), but in most cases splenic MZL does not affect the lymph nodes.
Splenic MZL is an indolent (slow growing) lymphoma and treatments are used to keep the lymphoma under control, rather than to cure it. There are some good treatments for splenic MZL, and it can be controlled for many years with several courses of treatment.
What is the spleen?
Who is affected by splenic marginal zone lymphoma (MZL)?
Splenic marginal zone lymphoma (splenic MZL) is a rare form of lymphoma, involving the spleen, bone marrow and often the blood. It affects both men and women, although more common in men, and it most common in people who are middle aged or elderly, with the average age at diagnosis of 65 years. It is uncommon before the age of 50 years.
It is not usually clear why splenic MZL develops, although it has been associated with people who have been diagnosed with the hepatitis C virus (HCV) or other autoimmune disorders. However, it is important to note that NOT all people diagnosed with these will go on to develop splenic MZL.
Symptoms of splenic marginal zone lymphoma (MZL)
The most common symptom of splenic marginal zone lymphoma (splenic MZL) is an enlarged spleen (splenomegaly), that the doctor may notice that it is bigger than it should be during a physical examination of the stomach or abnormal cells are found when a blood test is done for another reason. There is usually involvement of the blood and bone marrow at the time of diagnosis, with the only other symptom being fatigue.
When the spleen is enlarged it might feel like a lump at the top of the stomach and may cause a feeling of a full stomach, even after small meals, and/or abdominal pain or discomfort. The doctor may be able to feel that the spleen is enlarged when they feel the abdomen. An enlarged spleen may also mean it is not functioning properly. This can cause anaemia and thrombocytopenia and this is discussed in more detail below.
The bone marrow is the spongy tissue in the centre of bones where blood cells are made. If lymphoma cells build up in the bone marrow it may not be able to make enough blood cells. This in addition to the spleen not functioning properly can lead to:
- Anaemia: a shortage of red blood cells which may cause tiredness and/or short of breath
- Thrombocytopenia: a shortage of platelets which may cause bleeding or bruising more easily
Some people with splenic MZL produce abnormal proteins that clump together especially when it is cold, these are called ‘cryoglobulins’. This can lead to poor circulation, headaches, confusion, nosebleeds and blurred vision.
Another group of symptoms called B symptoms can include:
- Night sweats (drenching sleepwear or bedding)
- Persistent fevers (especially at night >38C)
- Unexplained weight loss
It is important the doctor is aware of all symptoms as it can influence the decision around the type of treatment and when to start.
Diagnosis and staging of splenic marginal zone lymphoma (MZL)
Splenic marginal zone lymphoma (MZL) can be difficult to diagnose. It can look similar to other types of lymphoma, such as Waldenstrom’s macroglobulinemia. It can be diagnosed using a combination of blood tests and a bone marrow biopsy.
- Blood tests to check blood cell counts and look for abnormal lymphocytes and antibodies in your blood
- A Bone marrow biopsy is a procedure that involves taking a sample of bone marrow, usually from the hip bone. The biopsy is generally done using a local anaesthetic. The doctors will remove a small amount of liquid from inside the bone marrow and a small core of bone to test for the presence of lymphoma.
The doctor may also suggest an operation to remove an enlarged spleen and it is called a ‘splenectomy’. It is possible to live without a spleen, but precautions are needed to help prevent and fight off infections.
Waiting for results can be a difficult time. It may help to talk to family, friends, or a specialist nurse.
Staging of splenic marginal zone lymphoma (splenic MZL)
Once a diagnosis of SMZL is made, further tests are required to see where else in the body the lymphoma has affected or is located. This is called staging. The staging of the lymphoma helps the clinician decide 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 can also be referred to as ‘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. In most cases, the lymphoma has spread to many parts of the body that are far from each other.
What is the ‘grade’ of splenic MZL
Lymphomas are also often grouped as either indolent (slow growing)or aggressive (fast growing). The grade is also referred to as the clinical behaviour of the lymphoma. It is important to know the stage and grade of the lymphoma to determine the best treatment.
Staging scans and tests
The scans and tests needed for staging and before treatment can start may include:
- Positron emission tomography (PET) scan
- Computed tomography (CT) scan
- Bone marrow biopsy
- 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:
- 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.
Splenic MZL is a low-grade lymphoma. Most people have advanced disease at diagnosis as the bone marrow is usually affected. Effective treatment is available to treat advanced splenic MZL. The doctor will use the results of the biopsy, staging and baseline tests to choose the best treatment.
Prognosis of splenic marginal zone lymphoma (splenic MZL)
Splenic marginal zone lymphoma (splenic MZL) develops slowly and in most cases, it responds well to treatment. However, this is an indolent lymphoma, and this means that it often relapses (comes back). If relapse does occur it can usually be treated again to keep it under control. An individual’s prognosis is also based on the grade and stage of the lymphoma.
Occasionally some patients with splenic MZL can change (transform) into a fast-growing type of lymphoma. This happens in around 1-2 people in every 10 people with splenic MZL (very rarely).
If a transformed lymphoma is suspected another biopsy should be done to check for fast-growing cells. Transformed nodal MZL is treated in the same way as fast-growing non-Hodgkin lymphoma, such as diffuse large B-cell lymphoma.
Treatment of splenic marginal zone lymphoma (splenic MZL)
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 stage of lymphoma
- Symptoms (including the size and location of the lymphoma)
- How the lymphoma is affecting the body
- Past medical history & general health
- Current physical and mental wellbeing
- Patient preferences
Treatment for splenic MZL varies depending on the stage and what symptoms are present. Patients who have the hepatitis C virus, are likely to be offered antiviral treatment. Clearing the infection might also clear the lymphoma. If this is the case than additional treatment may not be needed.
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.
Watch and wait (active monitoring)
If the splenic MZL is not causing any symptoms or only minor one’s treatment may not start straight away. Instead, the doctor can suggest a watch and wait approach and the patient is monitored closely and treatment is saved until it is needed. This approach avoids the side effects of treatment for as long as possible. Delaying treatment in this way does not affect how well it works when the treatment is needed, or survival time
If the spleen is very enlarged and the blood counts are very low, the medical team might recommend that an operation to remove the spleen (a splenectomy), if it hasn’t already been removed. This can relieve symptoms very quickly. After having the spleen removed, the body is less able to fight infections, so precautions are taken to reduce the risk of infections. Long-term antibiotic treatment may also be needed.
If the symptoms are being caused by abnormal antibodies in the bloodstream, steroidsmay be prescribed and may be included as part of the chemotherapy regimen
Other standard treatment options for splenic MZL include:
- Radiotherapy to the spleen
- Rituximab with or without chemotherapy
- Chemoimmunotherapy combinations
- R-CVP chemoimmunotherapy (cyclophosphamide, vincristine & prednisolone)
- Rituximab and chlorambucil
- R-CHOP chemoimmunotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine & prednisolone)
- 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 (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
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 splenic MZL
After treatment, the majority of patients can have a period of remission (no signs of lymphoma or the lymphoma is under control). However, splenic MZL often relapses (comes back) and treatment is given with the aim of achieving a remission again. Experts are discovering new and more effective treatments that are increasing the length of remissions. At that time, the choice of treatment will depend on several factors including:
- The type of treatment already received.
- Time taken to relapse
- General health and age
- Stage of splenic MZL at relapse
- Patient preferences
This pattern may repeat itself over many years. Experts are discovering new and more effective treatments that are increasing the length of remissions. The treatment options for Relapsed splenic MZL may include:
- Watch and Wait (active monitoring)
- Splenectomy – an operation to remove the spleen
- Chemotherapy only
- Immunotherapy only
- Autologous Stem Cell Transplant (ASCT) – This treatment approach may be considered if the lymphoma has relapsed very quickly after the initial treatment. This may be unsuitable for some patients.
- Clinical trial participation
Transformed splenic MZL
Sometimes splenic MZL transforms (changes) into an aggressive (fast-growing) type of lymphoma that happens in around 5-10% of cases. If a transformation is suspected a biopsy will be needed to confirm this
If splenic MZL transforms it is usually treated like a diffuse large B-cell lymphoma (an aggressive lymphoma). Transformed lymphoma will need a different type of treatment.
Treatments 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 splenic MZL.
Some treatments that are currently under investigation to treat splenic MZL include:
- BTK inhibitors such as ibrutinib, acalabrutinib & zanubrutinib, that block signals that B-cells send to help them stay alive and divide.
- PI3K inhibitors such as idelalisib, umbralisib and copanlisib, that block a protein involved in the growth and survival of lymphoma cells
- Immunomodulators such as lenalidamide which change how the immune system works
- New antibody treatments such as obinutuzumab, which bind to proteins on the surface of lymphoma cells to help the own immune system destroy them
What happens after treatment?
Sometimes a side effect from treatment may continue or develop months or years after treatment has completed.
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.