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Diseases & Conditions

Non-Hodgkin's Lymphoma

Adult non-Hodgkin lymphoma is a disease in which malignant (cancer) cells form in the lymph system.

The lymph system is part of the immune system and is made up of the following:

  • Lymph: Colorless, watery fluid that travels through the lymph system and carries white blood cells called lymphocytes. Lymphocytes protect the body against infections and the growth of tumors.
  • Lymph vessels: A network of thin tubes that collect lymph from different parts of the body and return it to the bloodstream.
  • Lymph nodes: Small, bean-shaped structures that filter lymph and store white blood cells that help fight infection and disease. Lymph nodes are located along the network of lymph vessels found throughout the body. Clusters of lymph nodes are found in the underarm, pelvis, neck, abdomen, and groin.
  • Spleen: An organ that makes lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is on the left side of the abdomen near the stomach.
  • Thymus: An organ in which lymphocytes grow and multiply. The thymus is in the chest behind the breastbone.
  • Tonsils: Two small masses of lymph tissue at the back of the throat. The tonsils make lymphocytes.
  • Bone marrow: The soft, spongy tissue in the center of large bones. Bone marrow makes white blood cells, red blood cells, and platelets.

Because lymph tissue is found throughout the body, adult non-Hodgkin lymphoma can begin in almost any part of the body. Cancer can spread to the liver and many other organs and tissues.

Non-Hodgkin lymphoma in pregnant women is the same as the disease in non-pregnant women of childbearing age. However, treatment is different for pregnant women. This summary includes information on the treatment of non-Hodgkin lymphoma during pregnancy.

Non-Hodgkin lymphoma can occur in both adults and children. Treatment for children, however, is different than treatment for adults.

There are many different types of lymphoma.

Lymphomas are divided into two general types: Hodgkin lymphoma and non-Hodgkin lymphoma.

Age, gender, and a weakened immune system can affect the risk of developing adult non-Hodgkin lymphoma.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Risk factors for adult non-Hodgkin lymphoma include the following:

  • Being older, male, or white.
    Having one of the following medical conditions:
    • An inherited immune disorder (for example, hypogammaglobulinemia or Wiskott-Aldrich syndrome).
    • An autoimmune disease (for example, rheumatoid arthritis, psoriasis, or Sjögren syndrome).
    • HIV /AIDS.
    • Human T-lymphotrophic virus type I or Epstein-Barr virus.
    • A history of Helicobacter pylori infection.
  • Taking immunosuppressant drugs after an organ transplant.
  • Being exposed to certain pesticides.
  • A diet high in meats and fat.
  • Past treatment for Hodgkin lymphoma.
Possible signs of adult non-Hodgkin lymphoma include fever, sweating, fatigue, and weight loss.

These and other symptoms may be caused by adult non-Hodgkin lymphoma. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

  • Painless swelling in the lymph nodes in the neck, underarm, groin, or stomach.
  • Fever for no known reason.
  • Drenching night sweats.
  • Feeling very tired.
  • Weight loss for no known reason.
  • Skin rash or itchy skin.
  • Pain in the chest, abdomen, or bones for no known reason.
Tests that examine the body and lymph system are used to help detect (find) and diagnose adult non-Hodgkin lymphoma.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
    • The number of red blood cells, white blood cells, and platelets.
    • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
    • The portion of the sample made up of red blood cells.
  • Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.
  • Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the tissue under a microscope to look for cancer cells. One of the following types of biopsies may be done:
    • Excisional biopsy: The removal of an entire lymph node.
    • Incisional biopsy: The removal of part of a lymph node.
    • Core biopsy: The removal of part of a lymph node using a wide needle.
  • Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer.
  • Liver function tests: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by the liver. For non-Hodgkin lymphoma, the blood is checked for an enzyme called lactate dehydrogenase (LDH). LDH levels help determine prognosis (chance of recovery).
Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

  • The stage of the cancer.
  • The type of non-Hodgkin lymphoma.
  • The patient’s age and general health.
  • Whether the lymphoma has just been diagnosed or has recurred (come back).

Prognosis also depends on the level of LDH in the blood.

For non-Hodgkin lymphoma during pregnancy, the treatment options also depend on:

  • The wishes of the patient
  • Which trimester of pregnancy the patient is in.

Some types of non-Hodgkin lymphoma spread more quickly than others do. Most non-Hodgkin lymphomas that occur during pregnancy are aggressive. Delaying treatment of aggressive lymphoma until after the baby is born may lessen the mother's chance of survival. Immediate treatment is often recommended, even during pregnancy.

Stages of Adult Non-Hodgkin Lymphoma

After adult non-Hodgkin lymphoma has been diagnosed, tests are done to find out if cancer cells have spread within the lymph system or to other parts of the body.

The process used to find out the type of cancer and if cancer cells have spread within the lymph system or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage of the disease in order to plan treatment. The following tests and procedures may be used in the staging process:

  • Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Gallium scan: A procedure to detect areas of the body where cells, such as cancer cells, are dividing rapidly. A very small amount of radioactive material, gallium, is injected into a vein and travels through the bloodstream. The gallium collects in the bones or other tissues (organs) and is detected by a scanner.
  • Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer.
  • Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.

For pregnant women with non-Hodgkin lymphoma, staging tests that protect the fetus from the harms of radiation are used. These include MRI, bone marrow aspiration and biopsy, lumbar puncture, and ultrasound, which do not use radiation. An ultrasound exam is a procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

  • Through tissue. Cancer invades the surrounding normal tissue.
  • Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
  • Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

Stages of adult non-Hodgkin lymphoma may include E and S.

Adult non-Hodgkin lymphoma may be described as follows:

  • E: "E" stands for extranodal and means the cancer is found in an area or organ other than the lymph nodes or has spread to tissues beyond, but near, the major lymphatic areas.
  • S: "S" stands for spleen and means the cancer is found in the spleen.
The following stages are used for adult non-Hodgkin lymphoma:

Stage I
Stage I adult non-Hodgkin lymphoma is divided into stage I and stage IE.

  • Stage I: Cancer is found in one or more lymph nodes in one lymph node group.
  • Stage IE: Cancer is found outside the lymph nodes in one organ or area.

Stage II
Stage II adult non-Hodgkin lymphoma is divided into stage II and stage IIE.

  • Stage II: Cancer is found in two or more lymph node groups above or below the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen).
  • Stage IIE: Cancer is found in one or more lymph node groups above or below the diaphragm and outside the lymph nodes in a nearby organ or area.

Stage III
Stage III adult non-Hodgkin lymphoma is divided into stage III, stage IIIE, stage IIIS, and stage IIIS+E.

  • Stage III: Cancer is found in one or more lymph node groups above and below the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen).
  • Stage IIIE: Cancer is found in lymph node groups above and below the diaphragm and outside the lymph nodes in a nearby organ or area.
  • Stage IIIS: Cancer is found in lymph node groups above and below the diaphragm, and in the spleen.
  • Stage IIIS+E: Cancer is found in lymph node groups above and below the diaphragm, outside the lymph nodes in a nearby organ or area, and in the spleen.

Stage IV
In stage IV adult non-Hodgkin lymphoma, the cancer:

  • is found outside the lymph nodes throughout one or more organs, and may be in lymph nodes near those organs; or
  • is found outside the lymph nodes in one organ and has spread to lymph nodes far away from that organ; or
  • is found in the lung, liver, or bone marrow.
Adult non-Hodgkin lymphomas are also described in terms of how fast they grow and the location of affected lymph nodes.

Indolent or aggressive:

  • Indolent lymphomas: These tend to grow and spread slowly and have few symptoms.
  • Aggressive lymphomas: These grow and spread quickly and have severe symptoms. Lymphoblastic lymphoma, diffuse small noncleaved cell lymphoma/Burkitt lymphoma, and mantle cell lymphoma are 3 types of aggressive adult non-Hodgkin lymphoma. Aggressive lymphomas are seen more often in patients who are HIV -positive (AIDS -related lymphoma).

Contiguous or noncontiguous:

  • Contiguous lymphomas: Lymphomas in which the lymph nodes containing cancer are next to each other.
  • Noncontiguous lymphomas: Lymphomas in which the lymph nodes containing cancer are not next to each other, but are on the same side of the diaphragm.

Recurrent Adult Non-Hodgkin Lymphoma

Recurrent adult non-Hodgkin lymphoma is cancer that has recurred (come back) after it has been treated. The lymphoma may come back in the lymph system or in other parts of the body. Indolent lymphoma may come back as aggressive lymphoma. Aggressive lymphoma may come back as indolent lymphoma.

Treatment Option Overview

There are different types of treatment for patients with non-Hodgkin lymphoma.

Different types of treatment are available for patients with non-Hodgkin lymphoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

For pregnant women with non-Hodgkin lymphoma, treatment is carefully chosen to protect the fetus. Treatment decisions are based on the mother’s wishes, the stage of the non-Hodgkin lymphoma, and the age of the fetus. The treatment plan may change as the symptoms, cancer, and pregnancy change. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.

Four types of standard treatment are used:

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells and keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

For pregnant women with non-Hodgkin lymphoma, radiation therapy should be postponed until after delivery, if possible, to avoid any risk to the fetus. If immediate treatment is needed, pregnant women may decide to continue the pregnancy and receive radiation therapy. However, lead used to shield the fetus may not protect it from scattered radiation that could possibly cause cancer in the future.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). To treat certain types of adult non-Hodgkin lymphoma that spread to the brain, CNS prophylaxis (chemotherapy given to kill cancer cells in the brain or spinal cord) may be used. The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Combination chemotherapy is treatment using two or more anticancer drugs. Steroid drugs may be added, to relieve swelling and inflammation.

In pregnant women, the fetus is exposed to chemotherapy when the mother is treated, and some anticancer drugs cause birth defects. Because anticancer drugs are passed to the fetus through the mother, both must be watched closely when chemotherapy is given.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibody therapy is one type of targeted therapy used to treat adult non-Hodgkin lymphoma.

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Monoclonal antibodies that have been joined to radioactive material are called radiolabeled monoclonal antibodies.

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until symptoms appear or change.

New types of treatment are being tested in clinical trials.

This section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Vaccine therapy

Vaccine therapy is a type of biologic therapy. Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy. Vaccine therapy can also be a type of targeted therapy.

High-dose chemotherapy with stem cell transplant

High-dose chemotherapy with stem cell transplant is a method of giving high doses of chemotherapy and replacing blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body’s blood cells.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options for Non-Hodgkin Lymphoma

For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.

Indolent, Stage I and Contiguous Stage II Adult Non-Hodgkin Lymphoma
Treatment of indolent, stage I and contiguous stage II adult non-Hodgkin lymphoma may include the following:

  • Radiation therapy directed at the area where cancer is found.
  • Watchful waiting.
  • Radiation therapy directed at the area where cancer is found and nearby lymph nodes.
  • Chemotherapy with radiation therapy.

Aggressive, Stage I and Contiguous Stage II Adult Non-Hodgkin Lymphoma
Treatment of aggressive, stage I and contiguous stage II adult non-Hodgkin lymphoma may include the following:

  • Combination chemotherapy with or without radiation therapy to areas where cancer is found.
  • A clinical trial of monoclonal antibody therapy and combination chemotherapy with steroids. Radiation therapy may also be given.

Indolent, Noncontiguous Stage II/III/IV Adult Non-Hodgkin Lymphoma
Treatment of indolent, noncontiguous stage II /III /IV adult non-Hodgkin lymphoma may include the following:

  • Watchful waiting for patients who do not have symptoms.
  • Chemotherapy with or without steroids.
  • Combination chemotherapy with steroids.
  • Monoclonal antibody therapy with or without combination chemotherapy.
  • Radiolabeled monoclonal antibody therapy.
  • Radiation therapy directed at the area where cancer is found and nearby lymph nodes, for patients who have stage III disease.
  • A clinical trial of chemotherapy with or without total-body irradiation (radiation therapy to the entire body) or radiolabeled monoclonal antibody therapy, followed by autologous or allogeneic stem cell transplant.
  • A clinical trial of chemotherapy with or without vaccine therapy.

Aggressive, Noncontiguous Stage II/III/IV Adult Non-Hodgkin Lymphoma
Treatment of aggressive, noncontiguous stage II /III /IV adult non-Hodgkin lymphoma may include the following:

  • Combination chemotherapy alone.
  • Combination chemotherapy with radiation therapy or monoclonal antibody therapy.
  • Combination chemotherapy with CNS prophylaxis.
  • A clinical trial of autologous or allogeneic stem cell transplant for patients who are likely to relapse.

Adult Lymphoblastic Lymphoma
Treatment of adult lymphoblastic lymphoma may include the following:

  • Combination chemotherapy and CNS prophylaxis.
  • A clinical trial of autologous or allogeneic stem cell transplant.

Diffuse Small Noncleaved Cell/Burkitt Lymphoma
Treatment of adult diffuse small noncleaved cell/Burkitt lymphoma may include the following:

  • Combination chemotherapy and CNS prophylaxis.
  • A clinical trial of combination chemotherapy.
  • A clinical trial of autologous or allogeneic stem cell transplant.
Non-Hodgkin Lymphoma During Pregnancy

Aggressive Non-Hodgkin Lymphoma During the First Trimester of Pregnancy

When aggressive non-Hodgkin lymphoma is diagnosed in the first trimester of pregnancy, medical oncologists may advise the patient to end her pregnancy so that treatment may begin. Treatment is usually chemotherapy with or without radiation therapy.

Aggressive Non-Hodgkin Lymphoma During the Second and Third Trimester of Pregnancy

When possible, treatment should be postponed until after an early delivery, so that the fetus will not be exposed to anticancer drugs or radiation therapy. However, sometimes the cancer will need to be treated immediately in order to increase the mother's chance of survival.

Indolent Non-Hodgkin Lymphoma During Pregnancy

Women who have indolent (slow-growing) non-Hodgkin lymphoma can usually delay treatment with watchful waiting.

Recurrent Adult Non-Hodgkin Lymphoma

Indolent, Recurrent Adult Non-Hodgkin Lymphoma

Treatment of indolent, recurrent adult non-Hodgkin lymphoma may include the following:

  • Chemotherapy with one or more drugs.
  • Radiation therapy.
  • Radiation therapy and/or chemotherapy as palliative therapy to relieve symptoms and improve quality of life.
  • Monoclonal antibody therapy.
  • A clinical trial of radiolabeled monoclonal antibody therapy.
  • A clinical trial of monoclonal antibody therapy as palliative therapy to relieve symptoms and improve quality of life.
  • A clinical trial of autologous or allogeneic stem cell transplant.

Treatment of indolent lymphoma that comes back as aggressive lymphoma may include the following:

  • A clinical trial of autologous or allogeneic stem cell transplant.
  • A clinical trial of combination chemotherapy followed by radiation therapy or stem cell transplant and radiation therapy.
  • A clinical trial of monoclonal antibody therapy.
  • A clinical trial of radiolabeled monoclonal antibody therapy.

Aggressive, Recurrent Adult Non-Hodgkin Lymphoma

Treatment of aggressive, recurrent adult non-Hodgkin lymphoma may include the following:

  • Stem cell transplant.
  • Monoclonal antibody therapy.
  • A clinical trial of autologous or allogeneic stem cell transplant.
  • A clinical trial of combination chemotherapy followed by radiation therapy or stem cell transplant and radiation therapy.
  • A clinical trial of radiolabeled monoclonal antibody therapy.

Treatment of aggressive lymphoma that comes back as indolent lymphoma may include the following:

  • Chemotherapy.
  • Palliative therapy to relieve symptoms and improve quality of life.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with adult non-Hodgkin lymphoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

For more information from the NCI, please write to this address:

NCI Public Inquiries Office
Suite 3036A
6116 Executive Boulevard, MSC8322
Bethesda, MD 20892-8322

U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. Information about ongoing clinical trials is available from the NCI Web site.

Source: National Institutes of Health; National Cancer Institute

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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 9/10/2009...#6199