What Exactly is Primary Mediastinal B-Cell Lymphoma?

Primary Mediastinal B-Cell Lymphoma (or PMBCL for short), is a very rare form of cancer. At this point, I think I have found and read every article or scientific study written about PMBCL. There are not that many in fact, as it was only designated as its own entity in 2008 (prior to this it was simply considered a form of DLBCL – Diffuse large B-cell Lymphoma).

This post will be very technical. For those who are interested in the scientific aspects of what is going on inside of me, read ahead.

Introduction

Primary mediastinal B-cell lymphoma (PMBCL) is a cancer of mature B-lymphocytes. It is a form of non-Hodgkin lymphoma, which is a type of cancer that originates in cells of the immune system, called lymphocytes. PMBCL usually starts in the area of the thymus, in a part of the upper chest called the mediastinum.

PMBCL constitutes approximately 3% of all non-Hodgkin lymphomas. It affects mainly young adults (median age of 35), predominantly women, with a  (female/male ratio of 2 to 1). No risk factors(viral, genetic or environmental) for PMBCL have been identified to date.

How PMBCL is Identified

PMBCL typically presents as a large, fast-growing tumor with invasion usually limited to the anterior-upper mediastinum although it tends to infiltrate adjacent thoracic structures like the chest wall, pleura, lungs, pericardium, and heart causing pleural/pericardial effusion in approximately 30–50 % of cases. The disease is mainly locally advanced, meaning that it tends to spread to nearby lymph nodes, but not to other parts of the body. Enlarged lymph nodes localized outside the mediastinum are rarely found. Bone marrow infiltration is seen in few cases, but usually rare.

80% of patients have clinical stage I and II and 75 % of them have bulky disease with a tumor mass exceeding 10 cm. I was fortunate in that I caught mine earlier than most people, with a tumor size of 8.5cm and without the many symptoms below other than a chronic cough. I am technically stage II, due to several nearby lymph nodes also being affected.

Typical symptoms such as cough, rapid breathing, vein thrombosis, chest pain, or painful swallowing are related to the tumor mass, with a history of complaints for usually less than three months. Approximately half of the patients present with upper vena cava syndrome, a medical emergency that happens when blood flow through the superior vena cava (svc), a major blood vessel to the head, is obstructed.

Systemic symptoms, mainly weight loss and fever, are relatively rare and they affect less than 20 % of patients. These are referred to as ‘B’ symptoms in Lymphoma, and for example, if I had night sweats and fever, I would be classified as Stage IIB.

Pathology

This is a very complex area where scientists get down to the molecular level of the tumor cells – its also an area where a lot of modern research is focused on. Pathologists use something called lmmunohistochemical stains to test the tumor cells and see if they are positive or negative in order for them to identify the type of cancer. In my case, for example, I am positive in CD20, CD23, CD30 (these are just 3 of about 15 markers), which helps the pathologist identify the cancer type and differentiate it from others. If this isn’t enough for you, read more about this process here. Below is an image of PMBCL under a microscope.

Prognosis

PMBCL is a curable cancer. Given that it is quite rare, there is not a tremendous amount of data about survival rates, but there is some. It has also greatly improved since the introduction of Rituximab, a type of antibody therapy that targets and attaches to the CD20 protein found on the surface of blood cells with cancer. In 2012, one study showed an overall survival (OS) of 97 % and
progression-free survival (PFS) 89 % at four years. A more recent study, which promotes the newer, more aggressive chemotherapy regimen I will be doing (DA-EPOCH-R), followed 51 patients for an average of 5 years. They had an event free survival of 93% and 97% overall survival rate. Only three of the 51 patients had evidence of disease after chemotherapy.

So the outlook is good, although not perfect.

What are the treatments for primary mediastinal B-cell lymphoma?

PMBCL has a protein, called CD20, on the surface of the cancer cells. Rituximab is an immunotherapy drug that targets the CD20 protein. Modern treatments for PMBL include rituximab, along with chemotherapy. Traditionally, radiation therapy has been part of treatment for this disease, but as the last study linked to mentions, the use of DA-EPOCH-R often eliminates the need for post chemotherapy radiation. Read more about DA-EPOCH-R compared to other treatments for lymphoma here.

The most commonly used treatment regimen for PMBCL is called dose-adjusted EPOCH-R. This chemotherapy regimen is given as a 96-hour long continuous infusion into an intravenous line, once every three weeks for six courses (18 weeks total). The doses of the chemotherapy drugs are adjusted according to blood tests that are done in between treatment courses. The drugs that are included in this treatment are etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. A drug called filgrastim is used to help the body’s white blood cells recover quickly after each course of chemotherapy.

My Treatment

I will receive the first cycle of the DA-EPOCH-R treatment starting on Monday. DA-EPOCH-R has been shown to have a higher cure rate than previous treatments, however it does come with a higher risk of toxicity. DA-EPOCH-R’s other advantage, and why it is now the preferred treatment (at least in the US), is because using radiation post-chemotherapy creates long-term issues and secondary cancers (remember the average diagnosis age is in the 30s). DA-EPOCH-R has been shown to eliminate the need for post-chemotherapy radiation in the majority of patients.

The first 5 days out of every 21-day cycle, I will be going to the treatment center to receive treatment. When I leave on Day 1 and until I complete Day 5, I will have a chemo pump or infusion pump that I will take home with me to keep me company and remind me of all the healing I am doing!

If all goes according to plan, my last day of chemotherapy will be on June 5th, and I’ll complete the 18 week treatment program on June 22nd. 6 weeks later I’ll do another PET Scan, discover that I am cancer free and on my way to a full recovery!