Non-Hodgkin’s lymphoma (NHL) is a cancer of the lymphatic system, part of the body’s immune system. It occurs when tumors develop from white blood cells known as lymphocytes.

Many types of cancers can spread to the lymph nodes, but only cancers that start in the lymph tissue are considered lymphomas.

NHL is more common than Hodgkin’s lymphoma.

The main difference between Hodgkin’s lymphoma and NHL is the presence of a type of atypical cell called the Reed-Sternberg cell. This cell is only present in Hodgkin’s lymphoma. In addition, Hodgkin’s lymphoma and NHL have very different treatment options.

Non-Hodgkin’s lymphoma types

There are many different types of NHL, and they’re classified by how the cells look under a microscope. Most types of NHL are categorized as either B-cell lymphoma or T-cell lymphoma.

The American Cancer Society (ACS) estimates that around 85 percent of NHL cases in the United States are B-cell lymphomas.

The most common types of B-cell lymphomas are diffuse large B-cell lymphoma and follicular lymphoma. Diffuse large B-cell lymphoma accounts for around 1 out of every 3 cases, and follicular lymphoma accounts for around 1 out of every 5 cases.

The less common types of B-cell lymphoma include:

The ACS estimates that T-cell lymphomas make up less than 15 percent of lymphomas in the United States. Natural killer cells cause fewer than 1 percent of lymphomas in the United States.

Non-Hodgkin’s lymphoma in children vs. adults

The most common types of NHL in children and teens are different from those in adults. In adolescents, almost all NHLs are aggressive, meaning they tend to grow quickly.

The most common types in children and teens are:

The most common types in adults are:

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The symptoms of NHL may include:

The term “B symptoms” refers to symptoms that play a significant role in predicting the severity, outlook, and staging of NHL and Hodgkin’s lymphoma. The B symptoms are:

  • fever
  • drenching night sweats
  • losing more than 10 percent of your body weight over 6 months

Always contact your doctor any time you experience persistent symptoms that concern you.

Lymphoma affects the body’s lymphatic system, which helps fight infections and diseases. The lymphatic system also helps keep fluid moving throughout the body.

Lymphomas can start anywhere where lymph tissue is found. They can also affect the skin.

Major sites of lymph tissue include the:

Researchers have linked NHL to several risk factors, but the exact cause of these cancers is still unknown.

NHL is a blood cancer that develops and originates in the lymphatic system. It develops from different types of white blood cells (lymphocytes) called B cells, T cells, or natural killer cells.

  • B cells (B lymphocytes). B cells help protect the body against bacteria and viruses by making proteins called antibodies.
  • T cells (T lymphocytes). T cells are a group of several cell types. Some T cells destroy pathogens or unusual cells in the body. Others help boost the activity of other immune system cells.
  • Natural killer cells (NK cells). Natural killer cells are in the same family as B cells and T cells. They control and limit the spread of several types of tumors and microbial infections.

NHL has been linked to changes in parts of your DNA called chromosomes. When chromosomal changes — known as translocations, mutations, or deletions — occur, the body begins to make unusual lymphocytes. These atypical lymphocytes continue to grow and divide, enlarging the lymph nodes and causing cancerous tumors.

These chromosomal changes are sometimes the result of DNA mutations inherited from a parent or from gene changes that are acquired throughout your life. Gene changes may occur because of exposure to radiation, certain cancer-causing chemicals, or infections.

Gene changes appear to happen more as we age, which might explain the prevalence of lymphomas in older people. However, gene changes often occur for no apparent reason.

Many people with NHL have no obvious risk factors. It’s also possible to have multiple risk factors and never develop NHL.

Some factors that may increase your NHL risk are included below:

  • Older age. Most people are at least 60 years old when diagnosed.
  • Gender. The risk of NHL is higher in men than women.
  • Family history. Having a first degree relative (parent, child, or sibling) with NHL increases your risk of developing it.
  • Carrying more weight. A 2015 research review suggests that having obesity or overweight might increase your risk of certain types of NHL.
  • Having breast implants. In rare instances, some people with breast implants can develop a type of anaplastic cell lymphoma in their breast.
  • Exposure to certain chemicals. Weed and insect killers may be associated with a higher risk of NHL. Additional research is needed.
  • Radiation exposure. Survivors of atomic bombs and nuclear reactor accidents are at an increased risk of developing NHL and several other types of cancer.
  • Conditions that weaken the immune system. Some autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease, and celiac disease, have been linked with an increased risk of NHL. Having HIV also increases the risk of certain types of NHL, including diffuse large B-cell lymphoma.
  • Infections that cause chronic immune stimulation. Examples of these infections include hepatitis C, Chlamydophila psittaci, and Helicobacter pylori. They may increase a person’s lymphoma risk by forcing the immune system to be constantly active.
  • Infections that affect lymphocyte DNA. Epstein-Barr virus and Helicobacter pylori infection are two of the infections that help transform lymphocytes into cancer cells.

White people in the United States are also more likely than African American people and Asian American people to develop NHL.

Doctors use a number of tests to diagnose NHL.

Physical exams can be used to check the size and condition of your lymph nodes. Physical exams can also detect an enlarged liver or spleen.

Your lymph nodes will swell any time your body is fighting an infection. Your doctor may order blood and urine tests to determine what type of infection your body is fighting.

Imaging tests such as the following can help your doctor look for tumors and stage the cancer:

During a biopsy, your doctor can remove a portion of the lymph node for testing. This can definitively identify NHL. A bone marrow biopsy can help your doctor determine if the disease has spread.

Doctors also use blood tests to determine how advanced the lymphoma is.

Treatment for NHL depends on your age, the type of NHL you have, and the stage of your NHL.

Immediate treatment isn’t always necessary. Your doctor may just monitor NHL that’s growing slowly and isn’t causing symptoms. Treatment can wait until the disease progresses.

More aggressive forms of NHL can be treated in several ways.

Some of the medications listed below were originally formulated to treat other conditions. The Food and Drug Administration (FDA) hasn’t approved all of them for the treatment of NHL, but your doctor may still prescribe them. This is known as off-label drug use.

Off-label drug use

Off-label drug use means that a drug that’s been approved by the FDA for one purpose is used for a different purpose that hasn’t been approved.

However, a doctor can still use the drug for that purpose. This is because the FDA regulates the testing and approval of medications, but not how doctors use them to treat their patients.

So, your doctor can prescribe a drug in whatever way they think is best for your care.

Chemotherapy

Chemotherapy kills cancer cells.

It can be administered orally or by injection. There are multiple types of chemotherapy drugs that are divided into different groups based on how they work:

  • Alkylating agents. Alkylating agents include cyclophosphamide (Cytoxan), chlorambucil (Leukeran), bendamustine (Bendeka, Treanda), and ifosfamide (Ifex).
  • Corticosteroids. Corticosteroids include prednisone (Prednisone Intensol, Rayos) and dexamethasone (Hemady).
  • Platinum drugs. Platinum drugs are made using the heavy metal. They include cisplatin, carboplatin, and oxaliplatin (Eloxatin).
  • Purine analogs. Purine analogs include fludarabine, pentostatin (Nipent), and cladribine (Mavenclad).
  • Antimetabolites. Antimetabolites include cytarabine, gemcitabine (Infugem), methotrexate (Trexall), and pralatrexate (Folotyn).
  • Anthracyclines. Anthracyclines are antibiotic drugs. They include doxorubicin (Doxil).
  • Miscellaneous. Other chemotherapy drugs include vincristine (Marqibo), mitoxantrone, etoposide, and bleomycin.

Chemotherapy may be used alone or with other treatments. Learn more about the different types of chemotherapy drugs.

Radiation therapy

Radiation therapy involves the use of high-powered beams of energy to kill cancer cells and get rid of tumors. Radiation can be used alone or with other treatments.

Stem cell transplant

A stem cell transplant allows your doctor to use higher doses of chemotherapy. This treatment kills stem cells as well as cancer cells. Then, your doctor uses a transplant to return healthy cells to the body.

Your doctor can transplant either your own cells or they can use donor cells. Your cells must be harvested in advance and frozen if your cells are going to be used in the transplant.

Immunotherapy

Immunotherapy is a treatment that boosts the immune system or uses human-made versions of immune system antibodies to kill lymphoma cells or slow their growth. There are several types of antibody treatments.

Monoclonal antibodies are proteins that treat cancer cells by attacking a specific target. They include:

  • Antibodies that target the CD19 antigen. CD19 is a protein on the surface of B cells. Examples of these drugs include tafasitamab (Monjuvi).
  • Antibodies that target the CD20 antigen. CD20 is a protein on the surface of B cells. These drugs include rituximab (Rituxan), obinutuzumab (Gazyva), ofatumumab (Arzerra), and ibritumomab tiuxetan (Zevalin).
  • Antibodies that target the CD30 antigen. CD30 is a protein on the surface of T cells. Examples of these drugs include brentuximab vedotin (Adcetris).
  • Antibodies that target the CD52 antigen. CD52 is a protein on the surface of T cells. Examples of these drugs include alemtuzumab (Campath).
  • Antibodies that target the CD79b antigen. Examples of these drugs include polatuzumab vedotin (Polivy).

Immunomodulating drugs, such as thalidomide (Thalomid) and lenalidomide (Revlimid), are used to treat lymphoma by changing certain parts of the immune system.

Chimeric antigen receptor (CAR) T cell therapy is a treatment where T cells are removed from a person’s blood and altered in the lab to have specific receptors on their surface. These receptors can then attach to proteins on the surface of cancerous lymphoma cells, which enables them to destroy the cells.

Targeted drug therapy

Targeted drug therapy can sometimes work when standard chemotherapy drugs don’t.

Monoclonal antibodies are a type of targeted drug therapy. Other types include:

  • proteasome inhibitors, such as bortezomib (Velcade)
  • histone deacetylase inhibitors, such as belinostat (Beleodaq)
  • Bruton’s tyrosine kinase inhibitors, such as ibrutinib (Imbruvica) and acalabrutinib (Calquence)
  • phosphoinositide 3-kinase inhibitors, such as idelalisib (Zydelig) and duvelisib (Copiktra)
  • enhancer of zeste homolog 2 inhibitors, such as tazemetostat (Tazverik)
  • nuclear export inhibitors, such as selinexor (Xpovio)

There’s no known way to prevent NHL. It may be possible to lower your risk for the condition by avoiding known risk factors such as obesity and HIV:

  • Using barrier methods each time you engage in sexual activity can lower your chances of contracting HIV.
  • Avoiding intravenous drug use or using clean needles when injecting drugs can lower your chances of contracting HIV or hepatitis C.
  • The following actions can help prevent obesity and may protect against lymphoma:

However, some important risk factors, such as age and family history, are fixed and can’t be changed.

Survival rates for people with NHL vary. Your outlook will depend on:

  • your age
  • your overall health
  • the type of NHL you have
  • how soon the NHL is discovered
  • how the cancer responds to treatment

People with slower-growing cancers can live a long time.

However, sometimes, NHL isn’t found until it’s in the advanced stages.

Aggressive forms of NHL can usually be treated, but cancer found in later stages can be difficult to treat. In these cases, the cancer may have spread so much that the goal of treatment is to prevent the cancer from growing more.

Connect with a doctor if you have both symptoms of NHL and known risk factors for the condition. Early diagnosis and prompt medical treatment can help improve your overall outlook.