Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)

Childhood 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 grow 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. The spleen 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, childhood 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 can occur in both adults and children. Treatment for children is different than treatment for adults. (See the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information on treatment in adults.)

There are four major types of childhood non-Hodgkin lymphoma.

The specific type of lymphoma is determined by how the cells look under a microscope. The 4 major types of childhood non-Hodgkin lymphoma are:

  • B-cell non-Hodgkin lymphoma (Burkitt and Burkitt-like lymphoma) and Burkitt leukemia.
  • Diffuse large B-cell lymphoma.
  • Lymphoblastic lymphoma.
  • Anaplastic large cell lymphoma.

There are other types of lymphoma that occur in children. These include the following:

  • Lymphoproliferative disease associated with a weakened immune system.
  • Rare non-Hodgkin lymphomas that are more common in adults than in children.
Signs of childhood non-Hodgkin lymphoma include breathing problems and swollen lymph nodes.

These and other signs may be caused by childhood non-Hodgkin lymphoma or by other conditions. Check with a doctor if your child has any of the following:

  • Trouble breathing.
  • Wheezing.
  • Coughing.
  • High-pitched breathing sounds.
  • Swelling of the head, neck, upper body or arms.
  • Trouble swallowing.
  • Painless swelling of the lymph nodes in the neck, underarm, stomach, or groin.
  • Painless lump or swelling in a testicle.
  • Fever for no known reason.
  • Weight loss for no known reason.
  • Night sweats.
Tests that examine the body and lymph system are used to detect (find) and diagnose childhood 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.
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. One of the following types of biopsies may be done:
    • Excisional biopsy: The removal of an entire lymph node or lump of tissue.
    • Incisional biopsy: The removal of part of a lump, lymph node, or sample of tissue.
    • Core biopsy: The removal of tissue or part of a lymph node using a wide needle.
    • Fine-needle aspiration (FNA) biopsy: The removal of tissue or part of a lymph node using a thin needle.
    • Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone.

      The following tests may be done on the sample of tissue that is removed:

      • Immunohistochemistry: A test that uses antibodies to check for certain antigens in a sample of tissue. The antibody is usually linked to a radioactive substance or a dye that causes the tissue to light up under a microscope. This type of test may be used to tell the difference between different types of cancer.
      • Cytogenetic analysis: A laboratory test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes.
      • Flow cytometry: A laboratory test that measures the number of cells in a sample, the percentage of live cells in a sample, and certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface. The cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The measurements are based on how the light-sensitive dye reacts to the light.
      • FISH (fluorescence in situ hybridization): A laboratory test used to look at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA attach to certain genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light. This type of test is used to find certain gene changes.
      • Immunophenotyping: A process used to identify cells, based on the types of antigens or markers on the surface of the cell. This process is used to diagnose specific types of lymphoma by comparing the cancer cells to normal cells of the immune system.
  • Mediastinoscopy: A surgical procedure to look at the organs, tissues, and lymph nodes between the lungs for abnormal areas. An incision (cut) is made at the top of the breastbone and a mediastinoscope is inserted into the chest. A mediastinoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer.
  • Anterior mediastinotomy: A surgical procedure to look at the organs and tissues between the lungs and between the breastbone and heart for abnormal areas. An incision (cut) is made next to the breastbone and a mediastinoscope is inserted into the chest. A mediastinoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer. This is also called the Chamberlain procedure.
  • Thoracentesis: The removal of fluid from the space between the lining of the chest and the lung, using a needle. A pathologist views the fluid under a microscope to look for cancer cells.
  • Ultrasound exam: 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. The picture can be printed to be looked at later.
  • 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. Sometimes a PET scan and a CT scan are done at the same time. If there is any cancer, this increases the chance that it will be found.
  • 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.
  • 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.
Certain factors affect prognosis (chance of recovery) and treatment options.

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

  • The age of the child.
  • The type of lymphoma.
  • The stage of the cancer.
  • The number of places outside of the lymph nodes to which the cancer has spread.
  • Whether the lymphoma has spread to the bone marrow or central nervous system (brain and spinal cord).
  • Whether there are certain changes in the chromosomes.
  • The type of initial treatment.
  • Whether the lymphoma responds to initial treatment.
  • The patient’s general health.
After childhood 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 if cancer has 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 in order to plan treatment. Some of the tests that are used to diagnose childhood non-Hodgkin lymphoma are also used to stage the disease. The following tests and procedures may be used in the staging process:

  • 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.
  • 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.
  • Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow 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.
  • 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).
There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.
The following stages are used for childhood non-Hodgkin lymphoma:
Stage I

In stage I childhood non-Hodgkin lymphoma, cancer is found:

  • in one group of lymph nodes; or
  • in one area outside the lymph nodes.

No cancer is found in the abdomen or mediastinum (area between the lungs).

Stage II

In stage II childhood non-Hodgkin lymphoma, cancer is found:

  • in one area outside the lymph nodes and in nearby lymph nodes; or
  • in two or more areas above or below the diaphragm, and may or may not have spread to nearby lymph nodes; or
  • to have started in the stomach or intestines and can be completely removed by surgery. Cancer may or may not have spread to certain nearby lymph nodes.
Stage III

In stage III childhood non-Hodgkin lymphoma, cancer is found:

  • in at least one area above the diaphragm and in at least one area below the diaphragm; or
  • to have started in the chest; or
  • to have started in the abdomen and spread throughout the abdomen, and cannot be completely removed by surgery; or
  • in the area around the spine.
Stage IV

In stage IV childhood non-Hodgkin lymphoma, cancer is found in the bone marrow, brain, or cerebrospinal fluid. Cancer may also be found in other parts of the body.

Childhood non-Hodgkin lymphoma is also described as low-stage or high-stage.

Treatment for childhood non-Hodgkin lymphoma is based on whether the cancer is low-stage or high-stage. Low-stage lymphoma has not spread beyond the area in which it began. High-stage lymphoma has spread beyond the area in which it began. Stage I and stage II are usually considered low-stage. Stage III and stage IV are usually considered high-stage.

Recurrent childhood non-Hodgkin lymphoma is cancer that has recurred (come back) after it has been treated. Childhood non-Hodgkin lymphoma may come back in the lymph system or in other parts of the body.

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

Different types of treatment are available for children 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.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with non-Hodgkin lymphoma should have their treatment planned by a team of doctors with expertise in treating childhood cancer.

Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other health care providers who are experts in treating children with non-Hodgkin lymphoma and who specialize in certain areas of medicine. These may include the following specialists:

  • Pediatrician.
  • Radiation oncologist.
  • Pediatric hematologist.
  • Pediatric surgeon.
  • Pediatric nurse specialist.
  • Rehabilitation specialist.
  • Psychologist.
  • Social worker.
Some cancer treatments cause side effects months or years after treatment has ended.

Side effects from cancer treatment that begin during or after treatment and continue for months or years are called late effects. Late effects of cancer treatment may include the following:

  • Physical problems.
  • Changes in mood, feelings, thinking, learning, or memory.
  • Second cancers (new types of cancer).

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the effects cancer treatment can have on your child. (See the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information.)

Four types of standard treatment are used:
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 cerebrospinal fluid (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas. Intrathecal chemotherapy may be used to treat childhood non-Hodgkin lymphoma that has spread, or may spread, to the brain. When used to prevent cancer from spreading to the brain, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis. Intrathecal chemotherapy is given in addition to chemotherapy by mouth or vein. The way the chemotherapy is given depends on the type and stage of the cancer being treated.


Combination chemotherapy is treatment using 2 or more anticancer drugs.

See Drugs Approved for Non-Hodgkin Lymphoma for more information.

Radiation therapy (in certain patients)

Radiation therapy is a cancer treatment that uses high energy x-rays or other types of radiation to kill cancer cells or 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.

High-dose chemotherapy with stem cell transplant

This treatment is a way of giving high doses of chemotherapy and then replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the bone marrow or blood 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.

See Drugs Approved for Non-Hodgkin Lymphoma for more information.

Stem Cell Transplant


Stem cell transplant (Step 1). Blood is taken from a vein in the arm of the donor. The patient or another person may be the donor. The blood flows through a machine that removes the stem cells. Then the blood is returned to the donor through a vein in the other arm.Stem cell transplant (Step 2). The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy (not shown).Stem cell transplant (Step 3). The patient receives stem cells through a catheter placed into a blood vessel in the chest.
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 antibodies and tyrosine kinase inhibitors are two types of targeted therapy being studied in the treatment of childhood 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. Rituximab is used to treat recurrent childhood non-Hodgkin lymphoma.

Tyrosine kinase inhibitors (TKIs) block signals that tumors need to grow. Some TKIs also keep tumors from growing by preventing the growth of new blood vessels to the tumors. Other types of kinase inhibitors, such as crizotinib and temsirolimus, are being studied for childhood non-Hodgkin lymphoma.

See Drugs Approved for Non-Hodgkin Lymphoma for more information.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

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. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

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 child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment of low-stage (stage I or II) non-Hodgkin lymphoma in children and adolescents may include the following:

  • Surgery followed by combination chemotherapy.
  • Surgery and/or radiation therapy for anaplastic large cell lymphoma that affects the skin.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I childhood large cell lymphoma, stage I childhood small noncleaved cell lymphoma, stage I childhood lymphoblastic lymphoma, stage I childhood anaplastic large cell lymphoma, stage II childhood large cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage II childhood lymphoblastic lymphoma and stage II childhood anaplastic large cell 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. Talk with your child's doctor about clinical trials that may be right for your child. General information about clinical trials is available from the NCI Web site.

Treatment for high-stage (stage III or IV) B-cell (Burkitt and Burkitt-like) non-Hodgkin lymphoma in children and adolescents may include the following:

  • Combination chemotherapy.
  • Intrathecal or systemic chemotherapy for cancer in the brain or spinal cord.
  • A clinical trial of combination chemotherapy with or without a monoclonal antibody.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III childhood large cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage IV childhood large cell lymphoma and stage IV childhood small noncleaved cell 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. Talk with your child's doctor about clinical trials that may be right for your child. General information about clinical trials is available from the NCI Web site.

Treatment of high-stage (stage III or IV) lymphoblastic lymphoma in children and adolescents may include the following:

  • Combination chemotherapy with or without radiation therapy to the brain.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III childhood lymphoblastic lymphoma and stage IV childhood lymphoblastic 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. Talk with your child's doctor about clinical trials that may be right for your child. General information about clinical trials is available from the NCI Web site.

Treatment of high-stage (stage III or IV) anaplastic large-cell lymphoma in children and adolescents may include the following:

  • Combination chemotherapy.
  • Intrathecal or systemic chemotherapy for cancer in the brain or spinal cord.
  • A clinical trial of new combination chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III childhood anaplastic large cell lymphoma and stage IV childhood anaplastic large cell 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. Talk with your child's doctor about clinical trials that may be right for your child. General information about clinical trials is available from the NCI Web site.

There is no standard treatment for patients with recurrent childhood non-Hodgkin lymphoma.

All patients with recurrent childhood non-Hodgkin lymphoma should be considered for clinical trials of new treatments.

Burkitt lymphoma and diffuse large B-cell lymphoma

Treatment options for recurrent Burkitt lymphoma and diffuse large B-cell lymphoma include:

  • Combination chemotherapy.
  • Combination chemotherapy and targeted therapy with a monoclonal antibody.
  • High-dose chemotherapy with stem cell transplant.

Lymphoblastic lymphoma

Treatment options for recurrent lymphoblastic lymphoma include:

  • Combination chemotherapy.
  • High-dose chemotherapy with stem cell transplant.
  • A clinical trial of targeted therapy (kinase inhibitor) with combination chemotherapy.

Anaplastic large-cell lymphoma

Treatment options for recurrent anaplastic large cell lymphoma include:

  • Chemotherapy with one or more drugs.
  • High-dose chemotherapy with stem cell transplant.
  • A clinical trial of targeted therapy with a tyrosine kinase inhibitor.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood 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. Talk with your child's doctor about clinical trials that may be right for your child. General information about clinical trials is available from the NCI Web site.

Treatment of lymphoproliferative disease in children and adolescents with weakened immune systems may include the following:

  • Surgery with or without radiation therapy.
  • Combination chemotherapy.
  • Low-dose chemotherapy.
  • A clinical trial of stem cell transplant followed by donor lymphocyte infusion or an infusion of T-cell lymphocytes that have been treated in the laboratory.

For more information from the National Cancer Institute about childhood non-Hodgkin lymphoma, see the following:

For more childhood cancer information and other general cancer resources, see the following:

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Editorial changes were made to this summary.

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2014-06-25