Diffuse Large B-Cell Lymphoma Stage IV

Stage 4 diffuse large B-cell lymphoma is an advanced form of blood cancer where the disease has spread beyond the lymphatic system to other organs of the body. Despite its aggressive nature, this cancer often responds well to treatment, and many people can achieve remission or even be cured.

Table of contents

• What is diffuse large B-cell lymphoma?
• Understanding stage 4 disease
• Symptoms
• Diagnosis and tests
• Types of DLBCL
• Treatment
• Outlook and survival

What is diffuse large B-cell lymphoma?

Diffuse large B-cell lymphoma, often called DLBCL, is a blood cancer that affects a type of white blood cell known as B cells (also called B lymphocytes). These cells are normally part of your immune system and help your body fight infections^[1].

DLBCL is the most common type of non-Hodgkin lymphoma, which is a cancer of the lymphatic system. The lymphatic system is a network of tissues, vessels, and organs that help fight infection and maintain your body’s fluid balance^[2][3].

The disease is called “diffuse large B-cell lymphoma” for specific reasons. It develops from abnormal B cells that are larger than normal, healthy B cells. These abnormal cells spread out (diffuse) rather than being grouped together in one spot^[1][7].

DLBCL is considered a fast-growing or high-grade lymphoma, meaning it can develop and progress quickly. While this sounds frightening, the aggressive nature also means the cancer often responds well to treatment. In fact, DLBCL is often curable, especially when caught and treated early^[3].

Understanding stage 4 disease

At stage 4, DLBCL is at its most advanced level. This means the cancer has spread to at least one other organ outside of your lymphatic system^[2][6].

With DLBCL, cancerous B cells may first appear in your lymph nodes. However, they can also appear in virtually any organ throughout your body. Common locations include the gastrointestinal tract (stomach and intestines), liver, lungs, bone marrow, thyroid, skin, breast, bone, or brain^[3].

Stage 4 indicates that the cancer is widespread or metastatic, meaning it has traveled from where it started to other parts of the body^[6].

Symptoms

The most common symptom people notice with diffuse large B-cell lymphoma is painless swelling in the lymph nodes. These swollen nodes usually appear as lumps in the neck, armpits, or groin. The lumps typically don’t go away and may seem to be getting larger over time. They are usually not painful, though they can be in some cases^[3][7].

Because DLBCL is fast-growing, symptoms can start or get worse in just a few weeks^[7].

About 30% of people with DLBCL experience what doctors call “B symptoms”. These include^[3][7]:

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

Some people may also experience unexplained itching all over their body^[7].

When DLBCL grows outside the lymph nodes, the symptoms depend on where it develops. For example, if DLBCL grows in your stomach or intestines, you might have abdominal pain, diarrhea, or bleeding. If it grows in your chest, you might feel short of breath or develop a cough^[7].

Having these symptoms doesn’t necessarily mean you have lymphoma. However, you should contact a healthcare provider anytime you notice changes in your body that last for several weeks^[3].

Diagnosis and tests

Diagnosing diffuse large B-cell lymphoma often begins with a physical exam. Your doctor will check for swollen lymph nodes in your neck, underarms, and groin, and will also check for an enlarged spleen or liver^[4].

The main test to diagnose lymphoma is a biopsy. This involves removing part or all of a swollen lymph node or taking a sample of tissue from another affected area. The sample is sent to a laboratory where a specialist examines it under a microscope to look for cancer cells^[4][7].

You will likely have blood tests to check for lymphoma cells and measure levels of substances like lactate dehydrogenase (LDH), which is often higher in people with lymphoma. Blood tests can also check for viruses, including Epstein-Barr virus, HIV, hepatitis B, and hepatitis C^[4].

Imaging tests create pictures of the inside of your body and can show the location and extent of the lymphoma. These tests might include^[4][7]:

• CT scans (computed tomography scans)
• MRI (magnetic resonance imaging)
• PET scans (positron emission tomography scans)

Your doctor may also recommend a bone marrow biopsy. This procedure collects cells from the bone marrow (the soft matter inside bones where blood cells are made) to check if lymphoma has spread there. The samples are typically taken from the hip bone^[4].

Some people may also have a lumbar puncture (spinal tap) to check for lymphoma cells in the fluid around the brain and spinal cord^[7].

Types of DLBCL

The World Health Organization has identified over a dozen different types of DLBCL. Each type has unique characteristics that help doctors understand how the cancer will likely progress and respond to treatment^[3][6].

Doctors classify DLBCL types based on several factors, including genetic changes in the cancer cells, where in the body the lymphoma starts, and whether there is an association with a virus^[3].

One important classification system divides DLBCL by its cell of origin (COO)^[6]:

• Germinal center B-cell-like (GCB): Originates in B cells that are undergoing specialization in the germinal center of the lymph node
• Activated B-cell-like (ABC): Originates in B cells within the germinal center that have already been activated but are not fully matured

Some DLBCL types are classified by where they develop in the body. For example, primary CNS lymphoma starts in the central nervous system (brain and spinal cord), while primary mediastinal B-cell lymphoma starts in the center of the chest^[3].

Genetic subtypes include double-hit lymphoma (DHL), which is linked to genetic changes in the MYC gene along with either the BCL2 or BCL6 gene. Triple-hit lymphoma (THL) involves changes in the MYC, BCL2, and BCL6 genes^[6].

Some types are associated with specific viruses. For example, people with EBV-positive DLBCL have an Epstein-Barr virus infection^[3].

Most people do not have a specific subtype and are diagnosed with DLBCL not otherwise specified (DLBCL NOS)^[7].

Treatment

Because DLBCL can advance quickly, it usually requires immediate treatment. Treatment typically begins soon after diagnosis^[11].

The most widely used treatment for DLBCL is a combination of chemotherapy drugs and a targeted therapy called rituximab. This approach is often referred to as chemoimmunotherapy^[7].

The standard treatment regimen is called R-CHOP. This stands for rituximab (Rituxan), cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone. R-CHOP is usually given in 21-day cycles (once every 21 days) for an average of 6 cycles. However, the length and number of cycles can vary based on your individual disease and health status^[11].

Sometimes doctors use different regimens. R-CHOEP adds another chemotherapy drug called etoposide to R-CHOP. R-EPOCH involves the same drugs as R-CHOP but they are given as a continuous infusion over 4 days. R-EPOCH may be preferred in certain cases, such as when DLBCL is related to HIV infection^[11].

Another option is polatuzumab vedotin-piiq (Polivy) combined with rituximab, cyclophosphamide, doxorubicin, and prednisone^[11].

In some cases, treatment may also involve radiation therapy, particularly for limited stage disease^[11].

When doctors consider a person at high risk for the cancer spreading to the brain and spinal cord, they may recommend CNS prophylaxis. This preventive treatment involves injecting chemotherapy drugs directly into the spinal cord fluid. This procedure, called intrathecal chemotherapy, allows anticancer drugs direct access to the central nervous system^[6][14].

If the cancer returns after initial treatment or doesn’t respond well, doctors may recommend different therapies. These can include different chemotherapy regimens or a bone marrow transplant (also called a stem cell transplant)^[16].

Outlook and survival

Although DLBCL is aggressive, it is often treatable and can be cured, especially with early diagnosis and treatment^[3].

Many patients can be cured with R-CHOP therapy, which is the current standard treatment. The combined drugs often eliminate DLBCL signs and symptoms^[3][10].

According to estimates, the one-year survival rate for all patients diagnosed with lymphoma similar to DLBCL is about 92%, and the five-year survival rate is about 86%. For people with stage 4 disease, the survival rate is lower, but even at stage 4, many people can beat the disease^[22].

Despite recent progress in improving survival, the outcome for nearly 40% of DLBCL patients remains challenging^[10]. Medical researchers are actively studying new treatments for DLBCL, particularly for cases where the cancer returns or doesn’t respond to initial treatment^[3].

Your individual outlook depends on many factors, including the specific type of DLBCL you have, how far the cancer has spread, your age, overall health, and how well the cancer responds to treatment. Your healthcare provider can give you more personalized information about your specific situation^[3].