Diffuse large B-cell lymphoma (DLBCL): Full guide

What is DLBCL?

Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells. B cells are a type of lymphocyte, a white blood cell that makes antibodies to fight infection. B cells live in your lymph nodes, spleen, bone marrow, and other organs.

In DLBCL, large B cells grow out of control and spread in sheets through a lymph node or organ. That is what "diffuse" means. It is the most common type of lymphoma in adults. It is an aggressive lymphoma, which means it grows fast, often over weeks to months.

The most common first sign is a lump that grows quickly in the neck, armpit, or groin. DLBCL can also start outside the lymph nodes, such as in the stomach, bowel, skin, bone, testicle, or brain. Some people have fevers, drenching night sweats, or weight loss without trying. Doctors call these "B symptoms."

DLBCL is most common in people in their 60s and 70s, but it can happen at any age. Most people have no clear cause. A weak immune system, such as from HIV or medicines after an organ transplant, raises the risk. Sometimes a slow-growing lymphoma, such as follicular lymphoma, changes into DLBCL. Because DLBCL grows fast, treatment usually starts soon after diagnosis. The goal is cure. About 6 or 7 out of 10 people are cured with first treatment. If it comes back, newer treatments can still cure some people.

Types and related lymphomas

DLBCL, not otherwise specified

The most common form. "Not otherwise specified" simply means it does not fit one of the special groups below. It is split further by cell of origin (see Lab tests).

Double-hit lymphoma

DLBCL or high-grade B-cell lymphoma where the cells have changes in both the MYC gene and the BCL2 gene. It can grow faster and is more likely to come back. Some care teams use stronger treatment, and clinical trials are a good option.

High-grade B-cell lymphoma

A very fast-growing lymphoma that looks like a cross between DLBCL and Burkitt lymphoma under the microscope. It is often treated like double-hit lymphoma.

Primary mediastinal large B-cell lymphoma

A type that starts in the middle of the chest, most often in young adults, and more often in women. It can press on the large vein in the chest and cause swelling of the face and arms. It is often treated with stronger chemotherapy, and most people are cured.

Transformed lymphoma

DLBCL that grew out of a slow-growing lymphoma, such as follicular lymphoma, marginal zone lymphoma, or CLL. When it comes from CLL, it is called Richter transformation. Treatment depends on what you had before.

Primary CNS lymphoma

Large B-cell lymphoma that starts in the brain, spinal cord, or eyes. It is treated differently, with drugs that can reach the brain, such as high-dose methotrexate.

Large B-cell lymphoma in special sites

DLBCL can start in the testicle, breast, kidney, or adrenal gland. These sites carry a higher risk of spread to the brain, so extra steps to protect the brain may be discussed.

Other subtypes

Rarer forms include T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive DLBCL (linked to the Epstein-Barr virus, often in older adults), and lymphoma linked to HIV. Most are treated much like DLBCL.

Tests you may have

Biopsy

A surgeon removes a lymph node, or a needle takes several thin cores of tissue. A larger sample is best, because the lab needs enough tissue for many tests. A very thin needle sample (fine needle aspiration) alone is usually not enough.

PET-CT scan

A scan that shows active lymphoma, which lights up because it uses more sugar. It finds the stage and is repeated during or after treatment to see how well it worked.

Blood tests

A complete blood count, liver and kidney tests, uric acid, and LDH. LDH is a protein that is often high when lymphoma is growing fast. It is part of the IPI risk score.

Infection tests

Tests for hepatitis B, hepatitis C, and HIV. Rituximab can wake up a hidden hepatitis B infection, so people who have had hepatitis B take an antiviral medicine during treatment.

Heart test

An ultrasound of the heart (echocardiogram) or a similar scan checks how well your heart pumps. This is needed before doxorubicin, a drug that can affect the heart.

Bone marrow biopsy

A needle takes a small sample from the back of the hip bone. Many people do not need it if the PET-CT scan is clear. It may be done if blood counts are low or the scan is unclear.

Brain MRI and spinal tap

If you have a high risk of lymphoma spreading to the brain, or any new nerve symptoms, you may have a brain MRI and a spinal tap (lumbar puncture). A spinal tap takes a small amount of fluid from the lower back to check for lymphoma cells.

Fertility and pregnancy tests

People who could be pregnant get a pregnancy test. Ask about saving sperm or eggs before treatment if you may want children.

Stages and risk scores

The stage tells how far the lymphoma has spread. A high stage does not mean DLBCL cannot be cured. Many people with stage 3 or 4 DLBCL are cured.

Your stage may also have a letter. "A" means no B symptoms. "B" means fever, drenching night sweats, or weight loss. "E" means it has grown into an organ next to a lymph node. "Bulky" means one very large mass.

Doctors also use a risk score called the IPI (International Prognostic Index). You get 1 point for each of 5 features. The total helps your care team understand your risk and choose your treatment. A related score called the CNS-IPI estimates the risk of lymphoma spreading to the brain.

Stage 1

Lymphoma is in one lymph node area, or in one organ outside the lymph nodes.

Stage 2

Lymphoma is in two or more lymph node areas on the same side of the diaphragm. The diaphragm is the muscle under your lungs.

Stage 3

Lymphoma is in lymph nodes both above and below the diaphragm.

Stage 4

Lymphoma has spread more widely into organs such as the bone marrow, liver, lungs, or bone.

Limited vs advanced stage

Stages 1 and 2 without a bulky mass are called limited stage. They often need fewer cycles of treatment. Stages 3 and 4 are called advanced stage.

IPI risk features

Age over 60, stage 3 or 4, a high LDH, lymphoma in more than one organ outside the lymph nodes, and needing help with daily activities (performance status). Each one adds 1 point.

IPI risk groups

A score of 0 or 1 is low risk. A score of 2 or 3 is intermediate risk. A score of 4 or 5 is high risk. People in every group can be cured.

CNS-IPI

Adds lymphoma in the kidneys or adrenal glands to the IPI. A high score means a higher chance of spread to the brain, so your care team may check or protect the brain.

Cell type and gene tests

Lab tests on your biopsy confirm the diagnosis and look for markers and gene changes. Some results help predict how the lymphoma will behave. Others point to medicines that can target it.

You do not need to memorize them. Ask your care team which results matter for you, especially whether you have double-hit lymphoma.

CD20

A marker on almost all DLBCL cells. The antibody rituximab attaches to CD20 and helps the immune system kill the lymphoma cells. Bispecific antibodies such as glofitamab and epcoritamab also target CD20.

Cell of origin (GCB or non-GCB)

Tests sort DLBCL by the kind of B cell it came from. GCB means germinal center B cell. Non-GCB (often called ABC, activated B cell) can be a bit harder to treat. For now, this result does not change first treatment for most people.

MYC, BCL2, and BCL6 genes

A test called FISH looks for rearranged (moved) genes. If MYC and BCL2 are both rearranged, it is called double-hit lymphoma. Many centers test every case, or every case with certain features.

Double expressor

The lymphoma makes high levels of MYC and BCL2 proteins, but without the gene rearrangements. It is more common than double-hit and is usually treated like regular DLBCL.

CD79b

A marker on B cells. Polatuzumab vedotin attaches to CD79b and carries a cancer drug into the cell. No test is needed before using it.

CD19

Another B-cell marker. CAR T-cell therapy, tafasitamab, and loncastuximab tesirine all target CD19.

TP53 changes

Changes in this gene can mean the lymphoma is harder to treat. It is not tested everywhere.

Epstein-Barr virus (EBV)

The lab may check if this virus is inside the lymphoma cells. EBV-positive DLBCL is more common in older adults and in people with weak immune systems.

Main treatments

R-CHOP

The long-standing first treatment for DLBCL. It is rituximab (an antibody) plus 4 drugs: cyclophosphamide, doxorubicin, vincristine, and prednisone (a steroid). It is given by vein every 3 weeks, usually for 6 cycles. People with limited stage and low risk may need only 4 cycles.

Pola-R-CHP

Polatuzumab vedotin, an antibody-drug conjugate, replaces vincristine in R-CHOP. For people with higher-risk DLBCL (an IPI score of 2 or more), it keeps the lymphoma from coming back for longer. It is now a standard first treatment for many people.

Radiation therapy

High-energy beams aimed at one area. It may be added for a bulky mass, for an area still active on the PET scan at the end of chemotherapy, or for lymphoma in a bone. A clear PET scan often means radiation is not needed.

Gentler plans for older or frail adults

People over 80, or with heart or other health problems, may get lower doses (such as R-mini-CHOP) or a plan without doxorubicin. Many older adults are still cured.

Treatment for double-hit and high-grade lymphoma

Some care teams use a stronger plan called DA-EPOCH-R. Others use R-CHOP or pola-R-CHP. No plan has clearly been proven best, so ask about a clinical trial.

Protecting the brain (CNS prophylaxis)

For people at high risk of spread to the brain, such as lymphoma in the testicle, extra steps may be discussed. This can mean chemotherapy given into the spinal fluid or high doses of methotrexate. Experts disagree on how much this helps, so ask about the pros and cons for you.

CAR T-cell therapy

Your own T cells are collected, changed in a lab to find CD19 on lymphoma cells, and given back once. It is the preferred next step if DLBCL does not respond to first treatment or comes back within about a year. It is also used after two or more treatments. Products include axi-cel (Yescarta), liso-cel (Breyanzi), and tisa-cel (Kymriah). It is given at a specialized center.

Stem cell transplant

If DLBCL comes back more than a year after first treatment, a common plan is more chemotherapy (such as R-ICE or R-GDP). If the lymphoma shrinks, high-dose chemotherapy and an autologous stem cell transplant (using your own stem cells) follow. A transplant from a donor is used only for a small number of people.

Bispecific antibodies

These drugs grab a lymphoma cell (through CD20) with one arm and a T cell with the other, so your immune system attacks the cancer. Glofitamab is given by vein for a set number of cycles. Epcoritamab is a shot under the skin. They are off the shelf, so there is no wait for cells to be made. They are used after two or more treatments, including after CAR T-cell therapy, and are being studied earlier.

Other targeted treatments for relapse

Options include polatuzumab with bendamustine and rituximab, tafasitamab with lenalidomide, and loncastuximab tesirine. These may be used when CAR T-cell therapy or transplant is not possible or did not work. Clinical trials are a good option at any step.

Common side effects and what helps

Infections and low white blood cells

Chemotherapy lowers the white blood cells that fight germs, most often about 7 to 12 days after each cycle. Most people get a shot of a growth factor after each cycle to help. Call right away for a fever of 100.4 F (38 C) or higher.

Numbness, tingling, and constipation from vincristine

Vincristine can cause numbness or tingling in the hands and feet, and constipation. Take a stool softener or laxative as your team advises. Tell your team early about tingling, because the dose can be lowered. Polatuzumab can also cause tingling, but usually less.

Infusion reactions

Rituximab can cause chills, fever, itching, or trouble breathing during the first infusion. You get medicine beforehand, and the first infusion is given slowly. Reactions are less common after that.

Heart effects from doxorubicin

Doxorubicin can weaken the heart muscle, more so at higher total doses or in people with heart disease. Your heart is checked before treatment. Report shortness of breath, leg swelling, or a racing heartbeat.

Steroid side effects

Prednisone can cause trouble sleeping, mood changes, high blood sugar, and a big appetite for a few days each cycle. Take it in the morning with food. People with diabetes may need to check sugar more often.

Tumor lysis syndrome

When a lot of lymphoma dies quickly, it can release salts that harm the kidneys. Drink plenty of fluids. You may get a medicine such as allopurinol and extra blood tests in the first days of treatment.

Hair loss, mouth sores, and nausea

Hair usually falls out with R-CHOP and grows back after treatment. Rinse your mouth with salt and baking soda water for sores. Anti-nausea medicine works best taken before you feel sick.

Cytokine release syndrome (CRS) and nerve effects from CAR T and bispecifics

CRS is a strong immune reaction that can cause fever, chills, low blood pressure, or trouble breathing, usually in the first days. Some people have confusion, trouble finding words, or shaking (called ICANS). You will be watched closely. After CAR T, plan to stay near your center for about 2 to 4 weeks with a caregiver, and do not drive for 8 weeks.

Low blood counts and low antibodies after CAR T and bispecifics

Blood counts can stay low for weeks to months. These treatments can also lower antibodies for a long time, raising infection risk. You may take medicines to prevent infection, and some people get IVIG, an infusion of antibodies.

Living with and after DLBCL

After treatment, you will have a PET-CT scan to see if you are in complete remission. Then you will have regular check-ups, often every 3 to 6 months for the first 2 years. Most people do not need routine scans if they feel well and are in remission. Tell your care team about new lumps, fevers, night sweats, or weight loss.

If DLBCL is going to come back, it usually happens in the first 2 years. People who stay in remission for 2 years have a very good chance of being cured. If it does come back, CAR T-cell therapy, bispecific antibodies, and other treatments can still lead to long remissions.

Some treatments can have effects years later. Doxorubicin can affect the heart, so heart-healthy habits matter: do not smoke, stay active, and keep blood pressure, cholesterol, and blood sugar under control. Tingling in the feet may slowly improve. Ask for a written survivorship plan that lists your treatment and the checks you need.

After rituximab, CAR T, or bispecifics, your body may not respond well to vaccines for 6 months or longer. Ask when to get your vaccines again. People around you should stay up to date on theirs. Many people go back to work and normal life after treatment, but tiredness can last for months. It is normal to feel worried or low. Support groups, counselors, and social workers can help you and your family.