Overview of primary mediastinal B-cell lymphoma (PMBCL
Primary mediastinal B-cell lymphoma (PMBCL) is a rare aggressive (fast-growing) type of B-cell non-Hodgkin lymphoma (NHL), that represents 2-4% of all NHLs. PMBCL is a subtype of large B-cell lymphoma (LBCL). It is called PMBCL because the lymphoma develops primarily (firstly) within the mediastinal area of the body.
PMBCL develops when the body makes abnormal B-cells. (also called B-lymphocytes) that develop in a part of the lymphatic system called the thymus gland. These abnormal B-cells cells grow and build up in the space behind the chest-rib cage and between the lungs, known as the mediastinum.
The mediastinum contains vital organs, including the thymus, heart, oesophagus (gullet), trachea(windpipe) and major blood vessels. It may spread to other organs such as the lungs, pericardium, liver, gastrointestinal tract, ovaries, adrenal glands and central nervous system.
Primary mediastinal B-cell lymphoma (PMBCL) is usually treated with the aim to cure. PMBCL usually responds well to immunochemotherapy treatment, and many people go into complete response. The prognosis depends on the stage, general health, treatment and the adverse side effects that can occur with treatment.
Who is affected by primary mediastinal B-cell lymphoma (PMBCL)
The causes of primary mediastinal B-cell lymphoma (PMBCL) are not known and like other cancers, it is not infectious and cannot be passed onto other people. It mainly occurs in people aged between 25 to 40 years of age, but it may occur in older children. It is more common in women than in men.
Symptoms of primary mediastinal B-cell lymphoma (PMBCL)
Primary mediastinal B-cell lymphoma (PMBCL) mainly starts in the mediastinum (chest area). For this reason, many symptoms may be caused by the lymphoma pressing on structures in the chest. These symptoms may cause:
- Pain or aching in the chest
- Swelling of neck and face
- Headaches that are worse when bending forward
- More visible chest veins
Some of these symptoms can be caused by lymphoma pressing on a large vein in the chest, called the superior vena cava (SVC). This vein carries all the blood from the upper half of the body to the heart. If pressure on the SVC blocks the blood from flowing along it, doctors call this superior vena cava obstruction (SVCO).
B symptoms can include the following symptoms and some patients may experience these:
- Night sweats (drenching sleepwear and bedding)
- Persistent fevers (especially at night >38C)
- Unexplained weight loss
Diagnosis and staging of PMBCL
A biopsy is always required for diagnosis of primary B-cell lymphoma (PMBCL). A biopsy is a surgical procedure to remove part of or all of an affected lymph node or other abnormal tissue to look at it under the microscope by a pathologist to see what the cells look like.
Because of the common location of PMBCL, the biopsy may require keyhole surgery “mediastinoscopy” so sufficient material can be collected to be certain of the lymphoma subtype. The biopsy can be done one of three ways:
- Fine needle aspirate
- Core needle biopsy
- Excisional node biopsy
Waiting for results can be a difficult time and it may help to talk to family, friends or a specialist cancer nurse.
Staging of PMBCL
Once a diagnosis of primary mediastinal B-cell lymphoma (PMBCL) is made, there are further tests that are required to see where else in the body the lymphoma has affected or is located. This is called staging. Doctors can also use the term bulky disease to describe tumours in the chest that are 10cm across or bigger. The staging of the lymphoma helps the doctor to decide the best treatment for the patient.
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.
PMBCL can be diagnosed at an advanced stage as it is a rapidly growing lymphoma.
What is the ‘grade’ of PMBCL
Lymphomas are also often grouped as either indolent or aggressive. Indolent lymphomas are usually slow growing and aggressive lymphomas are fast growing. The grade is also referred to as the clinical behaviour of the lymphoma. PMBCL is a high-grade lymphoma.
It is important to know the stage and grade of PMBCL to help the medical team to determine the best treatment for each patient. Many of these staging scans and tests are repeated during and after treatment to check how well the treatment is working.
Staging scans and tests for primary mediastinal B-cell lymphoma (PMBCL) can 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.
It is important to note that lymphoma is what is known as a systemic cancer. It can spread throughout the lymphatic system and nearby tissue and organs. Many patients are diagnosed at an advanced stage and the lymphoma can still be successfully treated. Lymphoma is very unlike advanced stage solid tumour cancers, such as bowel or lung cancer.
Prognosis of PMBCL
Primary mediastinal B-cell lymphoma (PMBCL) is usually treated with the aim to cure. PMBCL usually responds well to immunochemotherapy treatment, and many people go into complete a complete remission. The prognosis can depend on the stage, general health, treatments and adverse side effects that can occur with treatment.
Treatment for primary mediastinal B-cell lymphoma (PMBCL)
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 following will be taken into consideration:
- 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
Primary mediastinal B-cell lymphoma (PMBCL) is a fast-growing lymphoma and treatment needs to start quickly (within 1-3 weeks, depending on symptoms). A combination of chemotherapy and immunotherapy are used to treat PMBCL. This is called immunochemotherapy. Chemotherapy is a treatment that uses drugs to kill cancer cells. Immunotherapy is a treatment of giving antibodies (monoclonal antibodies) that are made in a laboratory to target an antigen on the surface of a cancer cell.
The standard first line treatment for PMBCL may include:
- DA-EPOCH-R (combinations of etoposide, vincristine, cyclophosphamide, doxorubicin, prednisolone and Rituximab). DA stands for ‘dose adjusted’ as the dose of drugs can be adjusted depending on how your body responds to the treatment.
- R-CHOP (combination of Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)
- A combination of different treatments
- Radiotherapy: This is a treatment that uses radiation to destroy cancer cells. Radiation is often given post chemotherapy treatment
- Clinical trial participation
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 very helpful and should include instructions about becoming unwell or needing medical or nursing assistance.
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 carry oxygen around the body)
- Thrombocytopenia (low platelets that help bleeding and clotting)
- Neutropenia (low white blood cells help with immunity)
- Nausea and vomiting
- Bowel problems such as constipation or diarrhoea
- Fatigue (tiredness or lack of energy
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 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.
Patients should be advised on whether fertilitymay be affected.
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 primary mediastinal B-cell lymphoma (PMBCL)
Primary mediastinal B-cell lymphoma (PMBCL) usually responds well to Immunochemotherapy, but sometimes the lymphoma comes back (relapses) or in rare cases does not respond to the initial first-line treatment (refractory). There are other treatments (second-line treatment) that can be successful. These second-line treatments can include:
- A stem cell transplant (although this treatment is not suitable for everyone)
- Pembrolizumab as a monotherapy for refractory, or following two prior therapies for relapsed Primary mediastinal B-cell Lymphoma in adults and children (not on PBS)
- Chimeric antigen receptor T-cell therapy (CAR T) (after 2 prior therapies)
Treatments 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 for PMBC include:
- Brentuximab Vedotin (AdcetrisTM)
- Ibrutinib (IbruvicaTM)
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.