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Non-Hodgkin Lymphomas

(Non-Hodgkin's Lymphomas)


Peter Martin

, MD, Weill Cornell Medicine;

John P. Leonard

, MD, Weill Cornell Medicine

Reviewed/Revised Jun 2022 | Modified Sep 2022
Topic Resources

Non-Hodgkin lymphomas are actually more than 50 different diseases that involve B cell or T cell lymphocytes. Each of these lymphomas has a distinct appearance under the microscope, a different cell pattern, and a different pattern of symptoms and progression. Most non-Hodgkin lymphomas (80 to 85%) are from B cells. Less than 15 to 20% develop from T cells.

Non-Hodgkin lymphoma is more common than Hodgkin lymphoma. It is the 6th most common cancer in the United States and causes 4% of all cancer deaths. It is more common as people get older.

In the United States, over 80,000 new cases are diagnosed every year, and the number of new cases is increasing, especially among older people and people whose immune system is not functioning normally. People who have had organ transplants and some people who have been infected with hepatitis C virus or the human immunodeficiency virus (HIV) are at risk of developing non-Hodgkin lymphoma.

Leukemias Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more also are cancers that involve white blood cells. In leukemias, most of the cancerous white blood cells are in the bloodstream and bone marrow. In lymphomas, most of the cancerous white blood cells are within lymph nodes and organs such as the spleen and liver. However, leukemia and non-Hodgkin lymphoma sometimes overlap because people with lymphoma may have cancerous white blood cells in their bloodstream and people with leukemia may have cancer cells in their lymph nodes and organs.

Non-Hodgkin Lymphoma

Did You Know...

  • Non-Hodgkin lymphomas are actually a group of more than 50 different diseases.

Causes of Non-Hodgkin Lymphomas

Although the cause of most non-Hodgkin lymphomas is not known, evidence strongly supports a role for viruses in some of the less common types. A rare type of rapidly progressive non-Hodgkin lymphoma, which occurs in southern Japan and the Caribbean, may result from infection with human T-cell lymphotropic virus 1 (HTLV-1), a retrovirus similar to human immunodeficiency virus (HIV) Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and is treated with antiretroviral medications. If untreated, it can cause... read more Human Immunodeficiency Virus (HIV) Infection . The Epstein-Barr virus Infectious Mononucleosis Epstein-Barr virus causes a number of diseases, including infectious mononucleosis. The virus is spread through kissing. Symptoms vary, but the most common are extreme fatigue, fever, sore throat... read more Infectious Mononucleosis is associated with Burkitt lymphoma Burkitt Lymphoma Burkitt lymphoma is a very fast-growing non-Hodgkin lymphoma, a cancer of white blood cells that originates from B cells (B lymphocytes). Lymphomas (see also Overview of Lymphoma) are cancers... read more Burkitt Lymphoma , another type of non-Hodgkin lymphoma. Other suspected viral causes include hepatitis C virus Overview of Hepatitis Hepatitis is inflammation of the liver. (See also Overview of Acute Viral Hepatitis and Overview of Chronic Hepatitis.) Hepatitis is common throughout the world. Hepatitis can be Acute (short-lived) read more , Kaposi sarcoma Kaposi Sarcoma Kaposi sarcoma is a skin cancer that causes multiple flat pink, red, or purple patches or bumps on the skin. It is caused by human herpesvirus type 8 infection. One or a few spots may appear... read more Kaposi Sarcoma , and herpes virus Overview of Herpesvirus Infections Some common viral infections are caused by a group of viruses called herpesviruses. Eight different types of herpesviruses infect people: Three herpesviruses— herpes simplex virus type 1, herpes... read more . People with HIV are at increased risk of developing some subtypes of non-Hodgkin lymphoma. Bacteria such as Helicobacter pylori Helicobacter pylori Infection Helicobacter pylori (H. pylori) infection is a bacterial infection that causes stomach inflammation ( gastritis), peptic ulcer disease, and certain types of stomach cancer. The... read more also increase lymphoma risk, especially in the stomach.

Other people at risk for non-Hodgkin lymphoma include those with

Symptoms of Non-Hodgkin Lymphomas

The first symptom is often rapid and usually painless enlargement of lymph nodes in the neck, under the arms, or in the groin. Enlarged lymph nodes within the chest may press against airways, causing cough and difficulty breathing, or press against blood vessels in the chest, causing swelling of the face, neck, and arms (superior vena cava syndrome). Deep lymph nodes within the abdomen may press against various organs, causing loss of appetite, constipation, abdominal pain, or progressive swelling of the legs.

Some lymphomas can appear in the bloodstream and bone marrow.

Lymphoma cells in the bone marrow may interfere with the ability of the bone marrow to produce enough normal blood cells.

Non-Hodgkin lymphomas can also invade the digestive tract, skin, and occasionally the nervous system, causing various symptoms. Some people have persistent fever without an evident cause, the so-called fever of unknown origin. This type of fever commonly reflects an advanced stage of disease.

In children, the first symptoms—anemia, rashes, and neurologic symptoms, such as weakness and abnormal sensation—are likely to be caused by infiltration of lymphoma cells into the bone marrow, blood, skin, intestine, brain, and spinal cord. Lymph nodes that become enlarged are usually deep ones, leading to the following:

  • Accumulation of fluid around the lungs, which causes difficulty in breathing

  • Pressure on the intestine, which causes loss of appetite or vomiting

  • Blocked lymph vessels, which causes fluid retention called lymphedema, most noticeably in the arms and legs


Diagnosis and Classification

  • Lymph node biopsy

Doctors suspect non-Hodgkin lymphoma when a person with no apparent infection develops persistent and painless enlargement of lymph nodes that lasts for several weeks. Sometimes enlarged lymph nodes deep within the chest or abdomen are found unexpectedly when a chest x-ray or computed tomography (CT) is done for another reason.

Doctors do a biopsy of an enlarged lymph node to diagnose non-Hodgkin lymphomas and to distinguish them from Hodgkin lymphoma and other disorders that cause enlarged lymph nodes.

The type of biopsy depends on which node is enlarged and how much tissue is needed. Doctors must remove enough tissue to be able to distinguish non-Hodgkin lymphoma from other disorders that can cause lymph node enlargement, including Hodgkin lymphomas, infections, inflammation, or other cancers. The best way to obtain enough tissue is with an excisional biopsy (a small incision made to remove a piece of the lymph node). Occasionally, when an enlarged lymph node is close to the body's surface, a sufficient amount of tissue can be obtained by inserting a hollow needle (usually under ultrasound or CT guidance) through the skin and into the lymph node (core needle biopsy). When an enlarged lymph node is deep inside the abdomen or chest, surgery may be needed to obtain a piece of tissue.

Although more than 50 different disorders can be called non-Hodgkin lymphomas, doctors sometimes group them into two broad categories.

Indolent lymphomas are characterized by

  • A long survival period (many years)

  • Rapid response to many treatments

  • Variable periods of remission but lack of cure with current standard therapies

Aggressive lymphomas are characterized by

  • Rapid progression without therapy

  • High rates of cure with standard chemotherapy but short survival when cure is not achieved

Although non-Hodgkin lymphomas are usually diseases of middle-aged and older people, children and young adults may develop lymphomas. Lymphomas that develop in children and young adults are commonly aggressive subtypes.

Staging of Non-Hodgkin Lymphomas

  • Imaging studies

  • Bone marrow biopsy

  • Blood tests (including tests of liver and kidney function)

Bone marrow biopsy Bone Marrow Examination Red blood cells, most white blood cells, and platelets are produced in the bone marrow, the soft fatty tissue inside bone cavities. Sometimes a sample of bone marrow must be examined to determine... read more may be done, particularly when the blood tests show anemia or low platelet counts. In some types of non-Hodgkin lymphoma, the PET-CT can reliably detect bone marrow involvement, so a bone marrow biopsy may not always be necessary. In other types of non-Hodgkin lymphoma, the PET-CT cannot reliably detect bone marrow involvement and a bone marrow biopsy may be needed if staging would change the choice of treatment.

The disease is classified into four stages based on the extent of its spread (I, II, III, IV). The higher the number, the more the lymphoma has spread.

Limited stage disease includes stages I and II; advanced stage disease includes stages III and IV. In stages I and II, if non-Hodgkin lymphoma is present in an organ outside the lymph system, it is classified as stage IE or IIE. Bulky disease is the term used when there is a tumor mass in the chest, the size of which may be different for different types of lymphomas.


Treatment of Non-Hodgkin Lymphomas

  • Chemotherapy, radiation therapy, or both

  • Immunotherapy (drugs made up of antibodies that attack cancer cells), with or without chemotherapy

  • Sometimes stem cell transplantation

The treatment of non-Hodgkin lymphoma varies widely based on the subtype.

For some people with indolent lymphomas, treatment is not needed when the lymphoma is first diagnosed. Studies show that waiting does not compromise outcome and prevents the patient from being exposed to side effects of treatment earlier than necessary. For people with indolent lymphomas, treatment, when needed, extends life and relieves symptoms for many years.

For people with aggressive lymphomas, cure is possible and therefore waiting without treatment is not usually done.

The likelihood of a cure or long-term survival depends on the type of non-Hodgkin lymphoma and the stage when treatment starts. It is somewhat of a paradox that indolent lymphomas usually respond readily to treatment by going into remission (in which the disease is under control), often followed by long-term survival, but the disease usually is not cured. In contrast, aggressive non-Hodgkin lymphomas, which usually require very intensive treatment to achieve remission, have a good chance of being cured.

Stage I non-Hodgkin lymphomas: Limited disease

People with indolent lymphomas who have very limited disease (stage I) are often treated with radiation therapy Radiation Therapy for Cancer Radiation is a form of intense energy generated by a radioactive substance, such as cobalt, or by specialized equipment, such as an atomic particle (linear) accelerator. Radiation preferentially... read more limited to the site of the lymphoma and adjacent areas. With this approach, most people do not have a disease recurrence in the irradiated area, but non-Hodgkin lymphomas can recur elsewhere in the body as long as 10 years after treatment, so people require long-term monitoring. People with aggressive lymphomas at a very early stage need to be treated with combination chemotherapy and sometimes radiation therapy.

Stage II non-Hodgkin lymphomas: Limited or advanced disease

Stage II non-Hodgkin lymphoma usually behaves like limited disease (stage I) but sometimes behaves like advanced disease. Doctors choose the treatment depending on the disease behavior.

Stages III to IV non-Hodgkin lymphomas: Advanced disease

Almost all people with indolent lymphomas have stage II to IV disease. They do not always require treatment initially, but they are monitored for evidence of lymphoma progression, which could signal a need for therapy, sometimes years after the initial diagnosis. There is no evidence that early treatment extends survival in people with indolent lymphomas at more advanced stages. If the disease begins to progress, there are many treatment choices.

Multiple treatment options exist, and the choice of treatment may depend on a variety of factors, including the lymphoma subtype, the extent of spread, and the person’s symptoms, and co-existing medical conditions. Treatment may include therapy with monoclonal antibodies (such as rituximab) alone or combined with chemotherapy Chemotherapy and Other Systemic Cancer Treatments Systemic treatments are those that have effects throughout the body rather than being applied directly to the cancer. Chemotherapy is a form of systemic treatment that uses drugs to kill cancer... read more . Most treatments are given intravenously. Sometimes, oral drugs are used. Treatment usually produces a remission. The average length of remission depends on the intensity of the treatment. Sometimes treatment may also include maintenance therapy (therapy given after the initial treatment to help prevent relapse).

For people with aggressive lymphomas, stage II to IV, combinations of chemotherapy Combination Cancer Therapy Cancer drugs are most effective when given in combination. The rationale for combination therapy is to use drugs that work by different mechanisms, thereby decreasing the likelihood that resistant... read more drugs are given promptly, often together with rituximab. Many potentially effective combinations of chemotherapy drugs are available. Combinations of chemotherapy drugs are often given names created by using the initial letter of each drug that is included. For example, one of the oldest and still one of the most commonly used combinations is known as CHOP (cyclophosphamide, [hydroxy]doxorubicin, vincristine [Oncovin], and prednisone). Rituximab has been shown to improve the outcome of CHOP and is now routinely added to the combination (R-CHOP). About 60 to 70% of people with aggressive non-Hodgkin lymphomas at an advanced stage are cured with R-CHOP chemotherapy. Other combinations of drugs are being studied. Chemotherapy, which often causes different types of blood cells to decrease in number, is sometimes better tolerated if special proteins (called growth factors) are also given to stimulate growth and development of blood cells.

Did You Know...

  • Combinations of chemotherapy drugs are often named by combining the initial letter of each drug name.

Posttreatment strategies

After radiation therapy, there is an increased risk of secondary cancers occurring 10 or more years after treatment in organs that were in the radiation field. Leukemias Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more may develop in some people many years after successful treatment for non-Hodgkin lymphoma, regardless of the treatment used.

After treatment has been finished, people should have regular doctor's examinations and tests to look for return of the lymphoma (post-treatment surveillance). The type of tests depends on the patient's risk factors and type of treatment they received.


Most people who have a relapse of an aggressive lymphoma receive high doses of chemotherapy drugs combined with autologous stem cell transplantation Stem Cell Transplantation Stem cell transplantation is the removal of stem cells (undifferentiated cells) from a healthy person and their injection into someone who has a serious blood disorder. (See also Overview of... read more , involving the person's own stem cells. With this type of treatment, some people are cured. Sometimes stem cells from a sibling or even an unrelated donor (allogeneic transplant) can be used, but this type of transplantation has a greater risk of complications. Sometimes people are offered treatment with chimeric antigen receptor (CAR) T cells, which are T cells that have been genetically engineered to fight against lymphoma.

More Information

The following is an English-language resource that may be useful. Please note THE MANUAL is not responsible for the content of this resource.

Drugs Mentioned In This Article

Generic Name Select Brand Names
RIABNI, Rituxan, RUXIENCE, truxima
Cyclophosphamide, Cytoxan, Neosar
Adriamycin, Adriamycin PFS, Adriamycin RDF, Rubex
Oncovin, Vincasar PFS
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
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