Diffuse large B-cell lymphoma is an aggressive cancer that arises from the lymphocytes (a type of white blood cell). It is the most common subtype of non-Hodgkin lymphoma, representing between 25% and 30% of all lymphoma diagnoses each year in the United States.

Diffuse large B-cell lymphoma is more common among men than women. It’s also most commonly diagnosed in older adults.

Although diffuse large B-cell lymphoma is a fast-growing cancer frequently diagnosed at advanced stages, it often responds well to treatment. About 75% of patients treated initially for this type of cancer respond well to standard chemotherapy-based therapy, and many people are cured of the condition.

Newer therapies, such new forms of immunotherapy, are available to patients who don’t respond to initial treatment (more on that below).

Diffuse large B-cell lymphoma is an aggressive type of cancer that often responds well to treatment. It typically occurs in older adults, although it may be diagnosed at any age, even during childhood.

This type of lymphoma develops within white blood cells, known as lymphocytes. It spreads through the body in the bloodstream, often allowing the condition to advance without being detected.

There are two main types of lymphocytes: B cells and T cells, both of which are part of the immune system. T cells are important in establishing and maintaining immune responses, while B cells create antibodies that help prevent and manage infections.

When a person has diffuse large B-cell lymphoma, their B cells develop abnormally. The cells don’t respond to the body’s instructions to keep them a certain size, so they grow bigger than usual. These overly large B cells multiply more rapidly, leading to swollen or enlarged lymph nodes. One or more lymph nodes—and other body parts—may be affected.

People with diffuse large B-cell lymphoma may notice that their lymph nodes feel swollen or have noticeable masses in areas with lymph nodes, such as in the neck, under the arms, or groin. Diffuse large B-cell lymphoma may also grow inside organs—including the stomach, liver, intestines, bone marrow, kidney and/or the skin.

There is increasing recognition that diffuse large B cell lymphoma is a diverse condition likely made up of several lymphoma subtypes. For example, germinal center B-cell subtype, activated B-cell subtype, and primary mediastinal B-cell lymphoma have unique presentations and may respond differently to the growing number of treatment options.

Although doctors aren’t sure what causes diffuse large B-cell lymphoma, those with baseline immune dysregulation and/or chronic infections may be at greater risk. There is increasing recognition of frequent genetic changes present in diffuse large B-cell lymphomas, with more than 70 different genetic mutations linked to diffuse large B-cell lymphoma. In some cases, diffuse large B-cell lymphoma may develop in patients with previously diagnosed or undiagnosed low-grade B-cell lymphoma.

People with diffuse large B-cell lymphoma may experience:

• An enlarged lymph node or large mass in the neck, abdomen, armpit or groin
• Pain at the site of an enlarged lymph node or large mass
• Fever
• Night sweats
• Weight loss
• Enlarged liver and/or spleen
• Fatigue
• Shortness of breath
• Loss of appetite

People at increased risk of diffuse large B-cell lymphoma have:

• A family history of lymphoma
• HIV
• Epstein-Barr virus
• History of a low-grade B-cell lymphoma or chronic lymphocytic leukemia
• A personal history of chemotherapy or radiation
• Prior exposure to certain pesticides or dyes
• Autoimmune disorders

Doctors can diagnose diffuse large B-cell lymphoma after learning about a patient’s medical history, performing a physical exam, or obtaining diagnostic studies (blood work and/or imaging) that raise concern for possible lymphoma. Ultimately, a biopsy of the involved site is required to make a lymphoma diagnosis and help further classify the lymphoma subtype.

When you share your medical history with the doctor, let them know if there’s a personal or family history of lymphoma or if you have had chemotherapy or radiation therapy treatments for another type of cancer. If you have an autoimmune disease or are living with HIV, tell the doctor. You should also describe your symptoms, letting the doctor know how long you have noticed a swollen lymph node or other mass, how long you’ve experienced fatigue, when you began losing weight unintentionally, and how much you have lost, if applicable.

During a physical exam, doctors should examine your head, neck, armpits, abdomen, and groin to see if any lymph nodes feel swollen. They should also feel the abdomen to see if the spleen and/or liver are enlarged.

Different diagnostic tests may reveal that a patient has diffuse large B-cell lymphoma, including:

• Blood tests. A complete blood count (CBC) may be ordered to determine if the correct proportions of red, white blood cells, and platelets are present, and if there are any abnormalities in the blood. Blood tests are also helpful in ruling out other conditions, such as HIV or hepatitis.
• Biopsy. Doctors surgically remove part or all of an enlarged lymph node to check for the presence of cancer cells. If the skin or digestive system is also involved, they may biopsy those areas as well.
• Bone marrow biopsy. Doctors may also retrieve a sample of bone marrow to check for abnormalities or involvement by lymphoma.
• Molecular testing. If the biopsy specimen suggests diffuse large B-cell lymphoma, other molecular studies may be performed, looking for genetic changes. Those with multiple genetic changes are sometimes referred to as “double-hit” or “triple-hit” diffuse large B-cell lymphoma, which may warrant more intensive treatment options.
• Imaging tests. Doctors may offer a computed tomography (CT) scan or a positron emission tomography (PET) scan to determine the stage of a patient’s diffuse large B-cell lymphoma. A CT scan can show whether any lymph nodes or organs are enlarged. A PET scan uses a small amount of injected radiotracer to identify cancer cells anywhere in the body; areas of lymphoma then light up on the scan.

When a patient is diagnosed with diffuse large B-cell lymphoma, doctors often administer a treatment known as R-CHOP: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. More recently, an antibody-drug conjugate (polatuzumab vedotin) may be substituted for the vincristine (Pola-R-CHP regimen). These combination regimens use several chemotherapy drugs along with rituximab, a monoclonal antibody. Monoclonal antibodies recognize a protein on the surface of lymphoma cells, working alongside the chemotherapy drugs to kill or damage cancer cells.

Patients with higher risk diffuse large B-cell lymphoma with multiple genetic changes (i.e. double hit lymphoma) may benefit from using a more intensive chemotherapy regimen than standard R-CHOP.

Doctors may prescribe radiation therapy after R-CHOP or another therapy, especially if the initial lymphoma involved only one to two nearby areas in the body. Further, radiation may be incorporated in diffuse large B-cell lymphoma that did not fully respond to standard chemotherapy.

Some patients don’t respond to initial treatments, with or without radiation therapy. In other patients, the cancer returns months or years after the initial treatment. In these cases, different therapies may help, including:

• Autologous stem cell transplantation, during which doctors remove a patient’s stem cells from the bone marrow or blood, freeze them, and store them temporarily. The patient then undergoes high levels of chemotherapy to kill cancer cells in the body. After this step, doctors thaw the patient’s stem cells and return them to the body via infusion so that they may produce blood cells again.
• Chimeric antigen receptor (CAR) T-cell therapy, a new type of immunotherapy. It helps to boost the effectiveness of the immune system’s T cells, which fight infection. The procedure requires doctors to remove some of the patient’s blood so that a gene within the T cells (a type of white blood cell) can be altered to enable the T cells to identify a protein on lymphoma cells. These altered or “educated” T cells are then reinfused into the body and can expand to help eradicate lymphoma cells.

Many individuals with diffuse large B-cell lymphoma are cured within four to five months of combined chemotherapy and rituximab. However, patients receiving therapy for diffuse large B-cell lymphoma can experience serious complications, including infections and organ dysfunction.

Individuals that do not achieve a remission with first-line therapy are more difficult to treat. However, new non-chemotherapy options are increasingly available and improving outcomes for even the most difficult-to-treatment lymphoma. Because diffuse large B-cell lymphoma may recur months or years after treatment, patients commonly follow up with their oncologist for ongoing surveillance for many years.

“Smilow Cancer Center offers a large integrated network of clinic sites, providing convenient and compressive care to patients and their families,” says Smilow Cancer Hospital oncologist Scott Huntington, MD, MPH. “Smilow has the expertise to make sophisticated diagnoses and ensure delivery of the best treatment available for each patient. Most patients can receive their treatment, including clinical trial options, at their nearby Smilow clinic. However, for those with a more challenging-to-treat diffuse large B-cell lymphoma, Smilow Cancer Hospital is a critical resource for delivering novel immunotherapies, including important cellular therapies. As the only NCI-designated Comprehensive Cancer Center in Connecticut, Smilow is committed to delivering the highest quality of care, advancing science, and achieving the best outcomes for patients with lymphoma.”