Diffuse Large B-Cell Lymphoma Stage III

Diffuse large B-cell lymphoma stage III is a fast-growing blood cancer affecting the lymphatic system, requiring immediate treatment with powerful drug combinations that can often lead to remission and cure.

Table of contents

• What is diffuse large B-cell lymphoma?
• Parts of the body affected
• Signs and symptoms
• What causes this condition
• How it is diagnosed
• Treatment approaches
• Outlook and survival

What is diffuse large B-cell lymphoma?

Diffuse large B-cell lymphoma, or DLBCL, is a blood cancer that involves changes in B cells, a particular type of white blood cell (also called lymphocytes). It is the most common form of aggressive non-Hodgkin lymphoma and a type of B-cell lymphoma^[1][2].

DLBCL affects your lymphatic system. Your lymphatic system is a network of tissues, vessels and organs that help fight infection in your body. Normal B cells are a part of that infection-fighting network. But with DLBCL, healthy B cells change into fast-growing cancer cells that overtake healthy ones. They are no longer able to fight off infection-causing invaders, like viruses and bacteria^[1].

The name “diffuse large B-cell lymphoma” comes from three key features. It develops from abnormal B cells. The abnormal cells are larger than normal, healthy B cells. And the abnormal cells are spread out (diffuse) rather than grouped together^[2].

It is the most common type of lymphoma. Each year about 5,000 people are diagnosed with DLBCL in the UK, making up more than 40 out of 100 cases (40%) of non-Hodgkin lymphoma in adults. DLBCL is more common in males than females^[3]. According to the National Cancer Institute, in 2020, about 6 people in 100,000 received a DLBCL diagnosis^[1].

Although it is aggressive, DLBCL is often treatable and curable, especially with early diagnosis and treatment^[1].

Parts of the body affected

• Lymph nodes
• Gastrointestinal tract
• Thyroid
• Skin
• Breast
• Bone
• Brain
• Central nervous system
• Chest (mediastinum)

With diffuse large B-cell lymphoma, cancerous B cells may appear in your lymph nodes. But they may also appear in virtually any organ, including your gastrointestinal tract, thyroid, skin, breast, bone or brain^[1]. Approximately 40% of the patients have involvement of extranodal sites, the most common of which is the gastrointestinal tract^[10].

Signs and symptoms

Symptoms can start or get worse in just a few weeks. The most common symptom is one or more painless swellings in the neck, armpit, or groin. These swellings are enlarged lymph nodes. They usually appear as a lump that doesn’t go away and seems to be getting larger. The lump isn’t usually painful, but it can be. They can grow very quickly^[1][3].

About 30% of people with DLBCL have what doctors call “B symptoms,” which include^[1][3]:

• A fever above 103 degrees Fahrenheit (39.5 degrees Celsius) that lasts longer than two days or comes and goes
• Unexplained weight loss that involves losing more than 10% of your body weight over six months
• Heavy night sweats (so intense that it drenches your sheets)

Some people may also have unexplained itching^[3]. You might have other general symptoms such as high temperatures that come and go with no obvious cause^[3].

DLBCL can develop outside the lymph nodes. The symptoms you have depend on where it grows. For example, DLBCL growing in your tummy (abdomen) or bowel might cause pain, diarrhea or bleeding. DLBCL growing in your chest might cause breathlessness or a cough^[3].

Having these symptoms doesn’t necessarily mean you have diffuse large B-cell lymphoma. That said, you should contact a healthcare provider anytime you notice changes in your body that last for several weeks^[1].

What causes this condition

Diffuse large B-cell lymphoma happens when B cells mutate (change). These are acquired genetic mutations, meaning you develop them during your lifetime instead of being born with them^[1].

The B-cell lymphomas result from the malignant proliferation of B cells during their various stages of development. Like any other malignancy, B-cell lymphomas can result from the genetic mutations affecting the proto-oncogenes and tumor suppressor genes. However, the environment within the lymph nodes can also promote the development of lymphoma^[4].

Genetic alterations in the BCL6 gene can be seen in 20% to 40% of the patients. Certain infectious agents can directly manipulate the DNA, as seen in cases where the Epstein-Barr virus DNA is transported into the B-cell nucleus, thus altering the B-cell growth and development^[4].

Chronic immunodeficiency of T cells and B-cell stimulation can be a possible cause for non-Hodgkin lymphoma in human immunodeficiency virus (HIV) infected patients. HIV is a risk factor for neoplasm development, as it decreases the hosts’ ability to regulate malignant cells. Likewise, immunosuppressive medication used in transplant patients is a risk factor for the development of B-cell lymphomas^[4].

How it is diagnosed

Diffuse large B-cell lymphoma diagnosis often begins with a physical exam that checks for swollen lymph nodes in the neck, underarms and groin and an enlarged spleen or liver^[8].

The main test to diagnose lymphoma is a lymph node biopsy. A doctor removes part or all of the swollen lymph node. They send it to the laboratory for a specialist to look at it under a microscope^[3]. A biopsy is a procedure to remove a sample of tissue for testing in a lab. In the lab, tests may show whether you have diffuse large B-cell lymphoma^[8].

You might also have some blood tests. Blood tests can sometimes show whether lymphoma cells are present. Blood tests may be used to test for viruses, including Epstein-Barr virus, HIV, hepatitis B and hepatitis C. Blood tests also measure levels of lactate dehydrogenase (LDH), which is often higher in people with lymphoma^[3][8].

If your doctor diagnoses lymphoma, you might have further tests. These might include^[3][8]:

• A PET-CT scan (a type of imaging test that makes pictures of the body)
• A bone marrow test to check if you have lymphoma cells in your bone marrow
• An MRI scan to look at your head or spine
• A lumbar puncture to check for lymphoma cells in the fluid around your brain and spine

Imaging tests make pictures of the body. They can show the location and extent of diffuse large B-cell lymphoma. Tests might include MRI, CT and positron emission tomography (PET) scan^[8].

Bone marrow aspiration and biopsy are procedures to collect cells from the bone marrow for testing. Bone marrow is the soft matter inside bones where blood cells are made. The samples are typically taken from the hip bone. The samples go to a lab for testing^[8].

Treatment approaches

Since DLBCL can advance quickly, it usually requires immediate treatment^[11]. Healthcare providers typically treat it with a combination of cancer drugs. The combined drugs often eliminate DLBCL signs and symptoms^[1].

The most widely used treatment for DLBCL presently is the combination known as R-CHOP. This stands for rituximab (Rituxan), cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone. R-CHOP is the standard treatment for DLBCL and achieves cures in approximately two thirds of patients^[11][13].

The R-CHOP regimen is usually given in 21-day cycles (once every 21 days) for an average of 6 cycles. However, the length and number of cycles given can vary based on the patient’s individual disease and health status. In certain cases 14-day cycles may be used, and for limited stage disease (Stage I or II) 3-4 cycles may be used followed by radiation therapy^[11].

A combination of chemotherapy and the monoclonal antibody rituximab (Rituxan), with or without radiation therapy, can lead to disease remission in a large number of patients with this form of lymphoma^[11].

Sometimes an additional chemotherapy drug, etoposide, is added to the R-CHOP regimen, resulting in a drug combination called R-CHOEP. A related regimen, called R-EPOCH, involves the same drugs administered as a continuous infusion over 4 days. There are some cases in which R-EPOCH may be the preferred regimen, as in HIV-related DLBCL^[11].

Another treatment option for DLBCL is polatuzumab vedotin-piiq (Polivy) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP)^[11][12].

In some cases, treatment may involve radiation therapy^[11]. For patients who do not respond to standard treatment or whose disease comes back, other options are increasingly available, including CAR T-cell therapy, which is a type of treatment that uses the patient’s own immune cells to fight the cancer^[6][13].

Your doctor or nurse will tell you how many cycles of treatment you will need. A cycle is a period of treatment followed by a period of rest. Typically, people have 6 cycles of chemoimmunotherapy, given every 3 weeks^[12].

Outlook and survival

Diffuse large B-cell lymphoma can now be cured in more than 50% of patients^[17]. Based on studies between 2014 and 2020, 65 percent of people with DLBCL live for at least five years after diagnosis^[16].

Your prognosis is an estimate of how your condition is likely to progress and what your outcome may look like. It describes your likelihood of responding to treatment, recovering, and surviving. Your prognosis is partly determined by the DLBCL survival rate, a statistical tool used by oncology specialists to measure how long people with DLBCL tend to live after receiving their cancer diagnosis^[16].

Several factors affect your prognosis. Younger adults tend to have a better outlook compared with older adults. For instance, according to the National Cancer Institute, about 80 percent of those under age 55 will live for five years or more. About 70 percent of people between 55 and 64 will live at least five years. About 55 percent of those 65 or older will live five years or more^[16].

Healthcare providers use a measurement called performance status to describe the degree to which a person is affected by their lymphoma. Performance status estimates how well a person can complete daily activities such as taking care of themselves, doing things around the house, walking, and working. If you have a better performance status score while living with DLBCL, you are likely to have a better prognosis^[16].

A lymphoma’s stage describes how much cancer there is in the body. Health experts classify DLBCL into stages based on how many lymph nodes or organs contain cancer cells. The more cancer-containing lymph nodes you have, the later your lymphoma stage^[16].

Some studies have found that people with coexisting autoimmune disorders such as Sjӧgren’s syndrome, rheumatoid arthritis, and systemic lupus erythematosus tend to have a worse DLBCL prognosis. Health experts don’t know for sure why autoimmune disorders may influence lymphoma outlook. It may be that people with these conditions tend to have worse performance status^[16].

Findings on a positron emission tomographic scan at the end of therapy are the best predictors of a good treatment outcome^[17].