Diffuse large B-cell lymphoma (DLBCL)

This page was reviewed under our medical and editorial policy by

Leslie Popplewell, MD, Hematologist, City of Hope | Atlanta

This page was reviewed on June 5, 2023.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Lymphoma is a cancer of the lymphatic system, which is part of the body’s immune system. The cancer starts in cells called lymphocytes, which are white blood cells that help the body fight off infections.

The two main types of lymphocytes are:

B cells: They make antibodies (proteins) that protect the body from bacteria, viruses and other germs.

T cells: They destroy germs or abnormal cells and boost or slow your immune system’s cells.

The majority of non-Hodgkin lymphomas affect B cells, and this is true of DLBCL.

DLBCL gets its name because the malignant B cells are larger than healthy B cells, and they are diffuse, meaning they don’t clump together when seen under a microscope. DLBCL often forms in lymph nodes, although it can start in other parts of the body. It tends to grow quickly, but it also tends to respond well to treatment. As many as 3 out of 4 patients with DLBCL show no signs of their disease after they start treatment, and many have evidence of disease after treatment ends, according to the American Cancer Society.

Most people with DLBCL are older adults. More men than women get DLBCL.

Subtypes of DLBCL

While still rare, primary mediastinal B-cell lymphoma is the most common subtype of DLBCL. It tends to affect young women and typically starts in the mediastinum, which is the area behind the breastbone. It can grow large and make breathing difficult because it presses on the trachea (windpipe), the tube that connects the throat to the lungs. The cancer may also cause complications if it blocks the superior vena cava, which is the large vein that returns blood from the right half of the heart to the head, neck and upper limbs. The blockage may cause the arms and face to swell. Like DLBCL, primary mediastinal B-cell lymphoma is a fast-growing tumor, but it tends to respond well to treatment.

Other subtypes of DLBCL are even rarer but are treated in a similar way. The rarer types of DLBCL include:

  • ALK-positive large B-cell lymphoma
  • Epstein-Barr virus-positive DLBCL
  • Intravascular large B-cell lymphoma
  • Primary mediastinal (thymic) large B-cell lymphoma
  • T-cell/histiocyte-rich large B-cell lymphoma

Causes and risks of DLBCL

Doctors don’t know exactly what causes DLBCL or other non-Hodgkin lymphomas. However, some known risk factors include:

Weakened immune system: The immune system may be weak in patients with an HIV infection or if they take drugs to suppress the immune system after an organ transplant.

Autoimmune diseases: Autoimmune diseases develop when the immune system mistakenly attacks the body’s own healthy cells. People who have some autoimmune diseases such as rheumatoid arthritis may be more susceptible to DLBCL, although doctors don’t know if that’s due to the disease or the immunosuppressive drugs used to treat it.

Family history: Having a family member with DLBCL may slightly raise the risk of getting it, although doctors don’t know if it’s genetic.

How DLBCL is diagnosed

Patients with DLBCL may notice lumps in their neck, armpit or groin, caused by swollen lymph nodes. A diagnosis starts with the doctor asking questions about the patient’s medical history the performing a physical exam.

If you have an enlarged or suspicious lymph node, your doctor will order a lymph node biopsy.

In rare cases, you may need a biopsy of an extranodal tumor, which means it’s located outside the lymph nodes.

During the biopsy, the doctor may remove all or part of the enlarged lymph node. Pathologists, who are experts at diagnosing diseases, will examine the tissue under a microscope to look for cancerous cells. It can take a few days or a few weeks for your doctor to call you with the results.

Your doctor also may perform additional tests or procedures, including:

Signs and symptoms of DLBCL

The first signs of DLBCL tend to be lumps in the groin, armpit or neck. The lumps, which aren’t always painful, are caused by lymphoma cells filling the lymph nodes and making them swell.

Other symptoms include:

  • Drenching night sweats
  • Fevers that come and go for no obvious reason
  • Unexplained weight loss
  • Itching

Other symptoms depend on where the lymphoma is:

  • Abdominal lymphoma can cause stomach pain, diarrhea or bleeding.
  • Chest lymphoma can cause shortness of breath, pain, cough and headaches.

Grades and stages

Oncologists use the grade and stage of the lymphoma to make treatment recommendations. Non-Hodgkin lymphoma is divided into two groups (high grade and low grade) based on how fast the cancer cells grow and spread. Because DLBCL is fast-growing, it’s considered high-grade.

The cancer stage is determined by how many lymph nodes are involved. The more lymph nodes involved, the higher the stage.

Treatment options

Most patients with DLBCL receive a combination of chemotherapy drugs, steroids and immunotherapy. Immunotherapy is a type of treatment that either boosts the immune system or uses cells from immune system that have been reprogrammed to attack the lymphoma cells. Your age, general health and the stage of the lymphoma will determine how intensive this combination, known as chemoimmunotherapy, will be.

The first line of treatment typically combines chemotherapy drugs with a monoclonal antibody (immunotherapy) in a therapy called R-CHOP. Components of R-CHOP include:

  • Rituximab® (a monoclonal antibody that targets a specific protein on the surface of B lymphocytes)
  • Cyclophosphamide
  • Hydroxydaunomycin (doxorubicin hydrochloride)
  • Oncovin® (vincristine sulfate)
  • Prednisone (a steroid)

Patients receive these drugs in cycles, which means they get the treatment on certain days followed by a rest period to let the body recover. Patients with early-stage DLBCL usually require three to four cycles of R-CHOP. If your disease is more advanced, you may need six cycles of R-CHOP. Each cycle is three weeks. The treatment is administered a few times each of these weeks.

If you can’t tolerate the chemoimmunotherapy, your doctor might suggest an R-mini-CHOP treatment to help lessen the side effects.

Other treatment options for some people include:

Intrathecal chemotherapy: This treatment is used if you have lymphoma in your brain or spinal cord. The chemotherapy drugs are delivered directly into your spinal fluid.

Radiotherapy: Your doctor may recommend radiotherapy, which uses high-energy radiation to attack cancer cells, either before or after chemotherapy. Radiotherapy targets lymphoma cells in a particular area of the body. It also may help relieve symptoms such as pain. Your doctor also may suggest radiotherapy before a stem cell or bone marrow transplant.

Stem cell transplant: A stem cell transplant (also called a bone marrow transplant) allows patients to receive higher doses of chemotherapy, which can damage bone marrow where new stem cells are created. There are two types of stem cell transplants: autologous, which uses the patient’s own cells, and allogeneic, which uses a donor’s stem cells (though allogeneic transplants are rarely used to treat DLBCL).

CAR-T cell therapy: This is a kind of immunotherapy. The doctor collects your own immune cells (T cells) and reprograms them in a lab before putting them back in your body. This therapy may be used when other treatments have failed or if lymphoma has come back or is advanced. CAR-T therapy isn’t appropriate for everyone, and it’s only available at certain specialized cancer centers. However, recent clinical trials have shown very promising results as a second-line treatment, according to the New England Journal of Medicine.

Surgery: Surgery is rarely used as a treatment for DLBCL. However, your doctor may recommend surgery to remove a lymph node that is pressing on an organ and causing pain.

While DLBCL is a fast-growing lymphoma, patients often respond well to treatment.You also may want to ask your care team whether joining a clinical trial, where new treatments are compared to standard treatments, would be right for you.

Risk of DLBCL recurrence

It’s sometimes possible to have a recurrence, or relapse, of DLBCL. About 40 percent of patients are likely to relapse, according to the American Society of Clinical Oncology.

Relapse tends to occur within the first two years after treatment, called early relapse. After that time period, relapse, called late relapse, becomes less likely, and is less aggressive.

You’re at increased risk of a recurrence if:

  • You’re older. (The average age at diagnosis is mid-60s.)
  • You had an advanced-stage DLBCL. (With advanced-stage disease, stages 3 or 4, growth is aggressive and has spread outside the lymph nodes, affecting other areas such as the bone marrow, central nervous system, testis, kidney, lungs or liver.)
  • You had more than one area beyond the lymph nodes affected.
  • You have high serum lactate dehydrogenase (LDH) levels.
  • You have certain genetic mutations that may affect relapse and prognosis.
  • Your overall general health is otherwise compromised.

Still, experts haven’t been able to identify all the factors responsible for the higher risk for relapse, and having these factors may not be predictive of a relapse. Depending the level of your risk, you may be monitored for recurrence with surveillance scans.

If your cancer returns, your treatment is likely to be more intense than the first time.

Most often, if your DLBCL returns, your doctors are likely to suggest another chemotherapy regimen. If your lymphoma responds to the chemotherapy, you may be a candidate for a stem cell transplant. However, not everyone is healthy enough to undergo this procedure.

Certain immunotherapies, targeted therapies and clinical trials may also be options for treating recurrent DLBCL.

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