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Non-Hodgkin Lymphomas

(Non-Hodgkin's Lymphomas)

By Carol S. Portlock, MD, Professor of Clinical Medicine;Attending Physician, Lymphoma Service, Weill Cornell University Medical College;Memorial Sloan-Kettering Cancer Center

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Non-Hodgkin lymphomas are a diverse group of cancers that develop in B or T cells (lymphocytes).

  • Often, lymph nodes in the neck, under the arms, or in the groin enlarge rapidly and painlessly.

  • People may have pain or shortness of breath or other symptoms when enlarged lymph nodes press on organs.

  • A lymph node biopsy is needed for diagnosis.

  • Treatment may involve radiation therapy, chemotherapy, monoclonal antibodies, or a combination.

  • Most people are cured or survive for many years.

This group of cancers is actually more than 50 different diseases that involve B cells or T cells (lymphocytes), which are types of white blood cell (see Neutrophilic Leukocytosis). 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 (85%) are from B cells. Less than 15% develop from T cells. Non-Hodgkin lymphoma is more common than Hodgkin lymphoma. In the United States, about 70,000 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 or the human immunodeficiency virus (HIV) are at risk of developing non-Hodgkin lymphoma.

Although the cause of 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 HIV. The Epstein-Barr virus is associated with many cases of Burkitt lymphoma (see Burkitt Lymphoma), another type of non-Hodgkin lymphoma.

Leukemias (see Leukemias) also are cancers that involve white blood cells. In leukemia, most of the cancerous white blood cells are in the bloodstream. In lymphoma, 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 leukemia cells in their lymph nodes and organs.


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, so people can develop symptoms related to too few red blood cells, white blood cells, or platelets. Too few red blood cells can cause anemia, leading to fatigue, shortness of breath, and pale skin. Too few white blood cells can lead to infections. Too few platelets may lead to increased bruising or bleeding. Non-Hodgkin lymphomas also commonly invade the bone marrow, 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.

Did You Know...

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

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, most noticeably in the arms and legs

Symptoms of Non-Hodgkin Lymphoma



Difficulty breathing

Swelling of the face

Lymph nodes in the chest are enlarged.

Loss of appetite

Severe constipation

Abdominal pain or distention

Lymph nodes in the abdomen are enlarged.

Progressive swelling of the legs

Lymph vessels in the groin or abdomen are blocked.

Weight loss



Bloating and cramping (indicating malabsorption—nutrients are not absorbed normally into the blood)

Lymphoma cells are invading the small intestine.

Shortness of breath

Chest pain

Cough (indicating fluid accumulation around the lungs, called pleural effusion)

Lymph vessels in the chest are blocked.

Swelling of the face and neck

Blood vessels in the chest are blocked.

Thickened, dark, itchy areas of skin

Lymphoma cells are infiltrating the skin.

Weight loss


Night sweats

The disease is spreading throughout the body.


Shortness of breath

Pale skin (indicating anemia, or too few red blood cells)

One or more of the following occurs:

  • Bleeding into the digestive tract

  • Destruction of red blood cells by an enlarged spleen or by abnormal antibodies

  • Invasion and destruction of bone marrow by lymphoma cells

  • Inability of the bone marrow to produce enough red blood cells because it is damaged by treatment (drugs or radiation therapy)

Susceptibility to severe bacterial infections

Lymphoma cells are invading the bone marrow and lymph nodes, reducing antibody production.

Diagnosis and Classification

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.

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

  • Lack of cure when standard therapies are used

Aggressive lymphomas are characterized by

  • Rapid progression without therapy

  • High rates of cure with standard chemotherapy

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


Many people with non-Hodgkin lymphomas have disease that has spread at the time of diagnosis. In only 10 to 30% of people, the disease is limited to one region. People with these lymphomas undergo similar staging procedures as people with Hodgkin lymphoma (see Hodgkin Lymphoma : Staging). In addition, a bone marrow biopsy is almost always done.

Treatment and Prognosis

For some people with indolent lymphomas, treatment is not needed when the lymphoma is first diagnosed. For people with indolent lymphomas, treatment, when needed, extends life and relieves symptoms for many years. For people with aggressive lymphomas, cure is possible. 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 and II non-Hodgkin lymphomas

People with indolent lymphomas who have very limited disease (stages I and II) are often treated with radiation therapy 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. 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. With this approach, 70 to 90% of people are cured.

Stage III and IV non-Hodgkin lymphomas

Almost all people with indolent lymphomas have stage III or 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.

It is not known which treatment option is best initially, so the choice of treatment is influenced by the extent of disease and the person’s symptoms. Treatment may include therapy with monoclonal antibodies (rituximab) alone or chemotherapy with or without rituximab. These antibodies are given intravenously. Sometimes, the monoclonal antibodies are modified so that they can carry radioactive particles or toxic chemicals directly to the cancer cells in different parts of the body. Treatment usually produces a remission. The average length of remission ranges from 2 years to more than 5 years. When rituximab is combined with chemotherapy, the results of remission are better. Sometimes treatment may also include maintenance therapy (therapy given after the initial treatment to help prevent relapse). The roles of rituximab, combined chemotherapy as well as a type of radiation therapy (called radioimmunotherapy) in maintenance are being studied.

For people with aggressive stage III or IV non-Hodgkin lymphomas, combinations of chemotherapy 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). More than 70% of people with aggressive non-Hodgkin lymphomas at an advanced stage are cured with R-CHOP chemotherapy. Newer 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.


A decision about treatment after a relapse (in which lymphoma cells reappear) depends on the extent of the disease and the symptoms. If non-Hodgkin lymphoma relapses, a type of radiation therapy called radioimmunotherapy is an option. After an initial relapse, remissions tend to become shorter.

Most people who have a relapse of an aggressive lymphoma receive high doses of chemotherapy drugs combined with autologous stem cell transplantation, involving the person's own stem cells (see Stem Cell Transplantation). With this type of treatment, up to 50% of people may be 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.t is not likely that people who have indolent lymphoma will be cured with autologous stem cell transplantation, but it does appear to be the best treatment option.I

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