Non-Hodgkin lymphoma (NHL) is a term that refers to several, very different types of lymphoma, a cancer of the lymph system. When lymphatic cells mutate (change) and grow uncontrollably, they can form tumors.

The lymph system is made up of thin tubes that branch out to all parts of the body. Its job is to fight infection and disease. The lymph system carries lymph, a colorless fluid containing lymphocytes (white blood cells). Lymphocytes fight germs in the body. B-lymphocytes (also called B-cells) make antibodies to fight bacteria, and T-lymphocytes (also called T-cells) kill viruses and foreign cells and trigger the B-cells to make antibodies.

Groups of bean-shaped organs called lymph nodes are located throughout the body at different sites in the lymph system. Lymph nodes are found in clusters in the abdomen, groin, pelvis, underarms, and neck. Other parts of the lymph system include the spleen, which makes lymphocytes and filters blood; the thymus, an organ under the breastbone; and the tonsils, located in the throat.

Because lymph tissue is found in so many parts of the body, non-Hodgkin lymphoma can start almost anywhere and can spread to almost any organ in the body. It most often begins in the lymph nodes, liver, or spleen, but can also involve the stomach, intestines, skin, thyroid gland, or any other part of the body.

This section covers NHL in children. For information on adult non-Hodgkin lymphoma, please read the Cancer.Net Guide to Non-Hodgkin Lymphoma.

Types of non-Hodgkin lymphoma in children

There are three major categories of non-Hodgkin lymphoma in children. They are distinguished from one another by how the cells look under a microscope.

Burkitt’s lymphoma. This type of B-cell lymphoma affects the bone marrow and is one of the fastest growing cancers. It most often develops in the abdomen and may spread to other organs including the brain. Burkitt’s lymphoma accounts for about 40% of non-Hodgkin lymphoma in children in the United States.

Large cell non-Hodgkin lymphoma (LCL). LCL, which accounts for about 35% of cases, may develop in the throat, abdomen, lymph tissue of the neck, or near the thymus (behind the breastbone). LCL is further classified into subtypes. The most common subtypes of LCL include large B-cell lymphoma (20%), which develops from B-cells, and anaplastic large cell lymphoma (ALCL-15%), which develops from T-cells.

Lymphoblastic lymphoma (LBL). LBL accounts for about 25% of all cases. It most often develops in the chest area behind the breastbone (near the thymus gland) and can spread to the surface of the brain, the bone marrow, other lymph nodes, and the membranes surrounding the heart and lungs. LBL occurs more often in teenagers than in young children. Boys are more likely to develop LBL than girls.

To learn about the cancer terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: Basic Oncology Terms.

In 2008, an estimated 800 children (younger than 20 years old) in the United States will be diagnosed with non-Hodgkin lymphoma. NHL accounts for about 4% of all childhood cancer. It occurs more often in boys than girls. The five-year relative survival rate (the percentage of patients who survive at least five years after the cancer is detected, excluding those who die from other diseases) for non-Hodgkin lymphoma in people younger than 20 is between 70% and 90%, depending on the type of lymphoma.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of this type of cancer, but the actual risk for a particular individual may differ. It is not possible to tell a person how long he or she will live with childhood NHL. Because the survival statistics are measured in five-year (or sometimes one-year) intervals, they may not represent advances made in the treatment or diagnosis of this cancer.

Statistics adapted from the American Cancer Society.

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A risk factor is anything that increases a person’s chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do.

Although the exact cause of non-Hodgkin lymphoma is unknown, some children seem to have a slightly greater risk of developing the disease:

• Those who have had illnesses related to the Epstein-Barr virus (for example, infectious mononucleosis)
  
  
• Those who have acquired immune deficiency syndrome (AIDS)
  
  
• Children who have received an organ transplantation
  
  
• Children born with deficiencies in their immune systems
  
  
• Children who have been treated with certain drugs for other types of cancer
  
  
• In rare cases, children who take dilantin, an antiseizure drug

Children with NHL may experience the following symptoms. Sometimes, people or children with NHL do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom on this list, please talk with your child’s doctor.

The symptoms of non-Hodgkin lymphoma may vary depending on where the cancer starts and what organ is involved.

General symptoms may include:

• Swelling or lumps in the lymph nodes located in the abdomen, groin, neck, or underarm
  
  
• Fever that is not associated with an illness
  
  
• Unexplained weight loss
  
  
• Sweating and chills
  
  
• Extreme fatigue (tiredness)
  

Symptoms related to tumor location may include:

• A distended belly, caused by a large tumor in the abdomen
  
  
• Painful urination and bowel movements, caused by fluid accumulation and a tumor around the kidneys and intestines
  
  
• Difficulty breathing, caused by a tumor in the thymus near the windpipe

A serious symptom of non-Hodgkin lymphoma is superior vena cava syndrome (SVCS). In SVCS, a tumor in the thymus area behind the breastbone squeezes the vein that carries blood from the head and arms to the heart. The head and arms swell as a result. SVCS can affect the brain and is life threatening. Children with SVCS need emergency medical attention.

Doctors use many tests to diagnose cancer and determine if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:

• Age and medical condition
  
  
• The type of cancer suspected
  
  
• Severity of symptoms
  
  
• Previous test results

In addition, the following tests may be used to diagnose non-Hodgkin lymphoma:

The doctor will first perform a physical examination and take a complete medical history to help determine if a person has non-Hodgkin lymphoma.

Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope. Other tests can suggest that cancer is present, but only a biopsy can make a definite diagnosis. The sample removed from the biopsy is analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease). If the tumor is near the surface, the child will be given a local anesthetic to numb the area. If it is deeper inside the body, the doctor will use a general anesthetic. The doctor may perform a fine-needle aspiration biopsy, in which a thin needle attached to a syringe is used to remove some fluid and tissue from a tumor.

Bone marrow aspiration. To determine whether the cancer has spread, the doctor may do a bone marrow aspiration. In this test, a small amount of bone marrow is removed and examined under a microscope. The child’s skin is numbed with a local anesthetic.

Lumbar puncture (spinal tap). A lumbar puncture is a procedure in which a doctor takes a sample of cerebral spinal fluid (CSF) to look for cancer cells, blood, or tumor markers (substances found in higher than normal amounts in the blood, urine, or body tissues of people with certain types of cancer). CSF is the fluid that flows around the brain and the spinal cord. The child will receive an anesthetic to numb the lower back before the procedure.

Cytogenetic analysis. A pathologist may examine the pairs of chromosomes (strings of DNA that contain genes) from the biopsy under the microscope to check for chromosomal abnormalities. This helps the doctor identify the subtype of lymphoma and plan treatment.

Flow cytometry and immunocytochemistry. To determine the subtype of non-Hodgkin lymphoma, the doctor may do two tests: flow cytometry and immunocytochemistry. A flow cytometry involves cells of interest being removed and treated with a fluorescent, dye-equipped antibody that attaches to DNA. The cells are then passed in front of a laser beam, which allows a special computer to measure their DNA level. Higher amounts of DNA than normal may indicate cancer. During an immunocytochemistry test, fluorescent antibodies or immunoperoxidase staining may be used to determine the subtype of non-Hodgkin lymphoma.

Imaging tests

To determine where the cancer is and if it has spread, the doctor may use the following imaging tests:

Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into a vein to provide better detail. CT scans of the chest and abdomen can help find cancer that has spread to the lungs, lymph nodes, and liver.

Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the brain and spinal column. A contrast medium may be injected into a patient’s vein to create a clearer picture. MRIs may create more detailed pictures than CT scans.

X-ray. An x-ray is a picture of the inside of the body. For instance, a chest x-ray can help doctors determine if the cancer has spread to the lungs.

Bone scan. A bone scan uses a radioactive tracer to look at the inside of the bones. The tracer is injected into a patient’s vein. A bone scan can detect injuries to the bones, which could be caused by cancer. It collects in areas of the bone and is detected by a special camera. Healthy bone appears gray to the camera, and areas of injury, such as those caused by cancer, appear dark.

Positron emission tomography (PET) scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient’s body and absorbed by organs or tissues being studied. This substance gives off energy that is detected by a scanner, which produces the images. PET scans are often used to complement information gathered from CT scan, MRI, and physical examination. It can show the difference between benign (noncancerous) shadows and malignant (cancerous tumors) that may not be clear on a CT scan or MRI. The exact accuracy and role of PET scanning in non-Hodgkin lymphoma is not yet clear, although lymphoma-containing masses often show up on PET scans. In the future, a PET scan may help monitor aggressive types of lymphoma and their response to treatment.

To learn more about what to expect during common diagnostic tests, read Cancer.Net: Tests and Procedures.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: Newly Diagnosed.

Staging is a way of describing a cancer, such as where it is located, if or where it has spread, and if it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the cancer's stage, so staging may not be complete until all the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis (chance of recovery). There are different stage descriptions for different types of cancer. Doctors use the following stages to describe non-Hodgkin lymphoma in children:

Stage I: Describes cancer that occurs in only one area outside the chest or abdomen.

Stage II: Describes a tumor that may occur in one area and surrounding lymph nodes, or it may be found in two or more lymph nodes or other areas on the same side of the diaphragm (the thin muscle under the lungs and heart that separates the chest from the abdomen). Or, the tumor began in the digestive system; surrounding lymph nodes may or may not be cancerous.

Stage III: Describes cancer that may occur in tissue or lymph nodes on both sides of the diaphragm. Or, the cancer started in the chest, or it may occur in multiple places the abdomen, or growths may occur around the spine.

Stage IV: Describes cancer that is found in the bone marrow, spinal cord, and/or brain.

Recurrent: Recurrent cancer is cancer that comes back after treatment.

Source: National Cancer Institute

Clinical trials are the standard of care for the treatment of children with cancer. In fact, more than 60% of children with cancer are treated as part of a clinical trial. Clinical trials are research studies that compare the best treatments available (standard treatments) with newer treatments that may be more effective. Cancer in children is rare, so it can be hard for doctors to plan treatments unless they know what has been most effective in other children. Investigating new treatments involves careful monitoring using scientific methods and all participants are followed closely to track progress.

To take advantage of these newer treatments, all children with cancer should be treated at a specialized cancer center. Doctors at these centers have extensive experience in treating children with cancer and have access to the latest research. Many times, a team of doctors treats a child with cancer. Pediatric cancer centers often have extra support services for children and their families, such as nutritionists, social workers, and counselors. Special activities for kids with cancer may also be available.

Three types of treatment are used for non-Hodgkin lymphoma in children: chemotherapy, radiation treatment, and stem cell/bone marrow transplantation. Sometimes, the treatments are used in combination.

The medications used to treat cancer are continually being evaluated. Talking with your child’s doctor is often the best way to learn about the medications they've been prescribed, their purpose, and their potential side effects or interactions with other medications. Learn more about your child’s prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. The most common type of radiation therapy is called external-beam radiation therapy, which is radiation given from a machine outside the body.

Radiation therapy for non-Hodgkin lymphoma is generally used only in emergency or life-threatening situations. For example, it may be used to treat pressure from a tumor on the windpipe or spinal cord. Also, it is used if the lymphoma affects the central nervous system at the time of diagnosis or to prevent recurrence of lymphoma in the central nervous system.

Side effects from radiation therapy include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished.

Stem cell transplantation/bone marrow transplantation

A stem cell transplant is a medical procedure in which diseased bone marrow is replaced by highly specialized cells, called hematopoietic stem cells. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because blood stem cells are typically what is being transplanted, not the actual bone marrow tissue.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO).

In an ALLO transplant, stem cells are obtained from a donor whose tissue matches the patient’s on a genetic level; this testing is called HLA-typing. Most often, a patient’s brother or sister serves as the donor, although unrelated donors can serve as the donor too. Millions of people worldwide have volunteered to donate stem cells for patients who do not have matched family members; matches can be made by searching a computer registry. In addition, a donation of stem cells derived from umbilical cord blood is sometimes considered if family donors are not available.

In an AUTO transplant, the patient’s own stem cells are used. The stem cells are obtained from the patient when he or she is in remission from previous treatment. The stem cells are then frozen until they are needed, usually after the high-dose treatment (explained below) is completed.

In both types, the goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and have replacement blood stem cells create healthy bone marrow. In most stem cell transplants, the patient is treated with high doses of chemotherapy and/or radiation therapy to destroy as many cancer cells as possible. This also destroys the patient’s bone marrow tissue and suppresses the patient’s immune system so that, in an ALLO transplant, the donor cells are not rejected by the body. After the high-dose treatment is given, blood stem cells are infused into the patient’s vein to replace the bone marrow and restore normal blood counts from donor cells. Sometimes, ALLO transplants can also be performed after giving lower doses of chemotherapy and/or radiation therapy that are still sufficient to suppress the immune system and allow growth of the donor cells. (These transplants, sometimes termed “mini-transplants” or “reduced intensity transplants” have less immediate side effects, allowing the procedure to be used for older patients.)

Before recommending transplantation, doctors will talk with the patient about the risks of this treatment and consider several other factors, such as the type of cancer, results of any previous treatment, and patient’s age and general health.

For both ALLO and AUTO transplant types, the replacement cells engraft (begin to make new blood cells) and turn into healthy, blood-producing tissue in 10 days to three weeks. Destroying the patient’s own marrow reduces the body’s natural defenses, temporarily leaving the patient at an increased risk of infection. Until the patient’s immune system is back to normal, patients may need antibiotics and blood transfusions.

In an ALLO transplant, another major risk is that the donor’s cells will recognize the patient’s body as foreign, causing graft-versus-host disease (GVHD). GVHD may be a serious complication of allogeneic transplants and can be fatal. Other side effects may include liver problems, diarrhea, infections, and rashes. However, GVHD can also be a benefit, in that the donor cells can recognize the cancer cells as foreign and destroy these cells, a mechanism that is one of the major reasons why ALLO transplantation generally works so well over the long term. The risk of GVHD can be reduced with exact HLA-type matching and the use of preventative drugs.

In an AUTO transplant, there is little risk of GVHD because the replacement stem cells are the patient’s own cells. However, there is a risk in an autologous transplant that some of the cells that are put back into the patient could still be cancerous.

Learn more by reading the Cancer.Net Feature series Understanding Bone Marrow and Stem Cell Transplantation.

• Whether the tumor came back in the same place or in another part of the body
  
  
• The type of treatment the child had for the original tumor
  
  
• The overall health of the child

The doctor may use chemotherapy or bone marrow/stem cell transplantation, or recommend a clinical trials.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: During Treatment.

Doctors and scientists are always looking for better ways to treat children with non-Hodgkin lymphoma. A clinical trial is a way to test a new treatment to prove that it is safe, effective, and possibly better than a standard treatment. Patients who participate in clinical trials are among the first to receive new treatments before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that finding new drugs and other therapies is the only way to make progress in treating childhood non-Hodgkin lymphoma. Even if they do not benefit directly from the clinical trial, their participation may benefit future children with non-Hodgkin lymphoma.

To join a clinical trial, patients must complete a learning process known as informed consent. During informed consent, the doctor should list all of the patient’s options, so the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different from the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.

Cancer and its treatment can cause a variety of side effects. However, doctors have made major strides in recent years in reducing pain, nausea and vomiting, and other physical side effects of cancer treatments. Many treatments used today are less intensive but as effective as treatments used in the past. Doctors also have many ways to provide relief to patients when such side effects do occur.

Fear of treatment side effects is common after a diagnosis of cancer, but it may be helpful to know that preventing and controlling side effects is a major focus of your health-care team. Before treatment begins, talk with your child’s doctor about possible side effects of the specific treatments you will be receiving. The specific side effects that can occur depend on a variety of factors, including the type of cancer, its location, the individual treatment plan (including the length and dosage of treatment), and the person’s overall health.

Ask your child’s doctor which side effects are most likely to happen (and which are not), when side effects are likely to occur, and how they will be addressed by the health-care team if they do happen. Also, be sure to communicate with the doctor about side effects your child experiences during and after treatment. For more information on the most common side effects of cancer and different treatments, along with ways to prevent or control them, visit Cancer.Net’s section on Managing Side Effects, based on ASCO’s curriculum.

In addition to physical side effects, there may be psychosocial (emotional and social) effects as well. Learn more about the importance of addressing these needs in Cancer.Net’s section on Caring for the Whole Patient.

For more information on late effects or long-term side effects, please read the After Treatment section or talk with your child’s doctor.

The treatment of childhood non-Hodgkin lymphoma often involves prolonged hospital stays during each treatment cycle (one to two weeks). Also, some of the treatments may cause significant mucositis (inflammation of the mucous membranes) that may lead to pain, discomfort, and difficulty eating and drinking.

Most pediatric cancer programs provide emotional support, financial guidance, and social services support to families. These services can reduce the emotional pain and financial discomfort and should be utilized to the fullest extent possible.

After treatment for childhood non-Hodgkin lymphoma ends, talk with your child’s doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your child’s recovery for the coming months and years. All children treated for cancer, including non-Hodgkin lymphoma, should have life-long, follow-up care.

Long-term, follow-up care is critical for all children with non-Hodgkin lymphoma. Even though the risk of recurrence begins to decline after three years, there is still the potential of long-term complications including heart problems and/or infertility. The risk of secondary cancers after treatment of childhood non-Hodgkin lymphoma is also possible, although the risks are only 1% to 2%. Yearly follow-up care by an experienced health-care team is highly encouraged for survivors of childhood non-Hodgkin lymphoma.

Based on the type of treatment the child received, the doctor will determine what examinations and tests are needed to check for long-term side effects, such as heart problems and/or infertility, and the possibility of secondary cancers. Your child’s doctor can recommend the necessary screening tests. Follow-up care should also address the child’s quality of life, including any developmental or emotional concerns. Learn more about Childhood Cancer Survivorship.

The child’s family is encouraged to organize and keep a record of the child’s medical information, so that as the child enters adulthood, he or she has a clear, written history of the diagnosis and details of the treatment given. The doctor’s office can help you compile this, and it should include recommendations from the doctor about the schedule for follow-up care. This information will be valuable to doctors who care for your child during his or her lifetime.

Children who have had cancer can also enhance the quality of their future by following established guidelines for good health into and through adulthood, including not smoking, maintaining a healthy weight, eating a balanced diet, and participating in regular physical activity. Talk with the doctor about developing a plan that is best for your child’s needs.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: After Treatment.

Research for childhood non-Hodgkin lymphoma is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this time. Always discuss all diagnostic and treatment options with your doctor. There are numerous areas of new research in childhood non-Hodgkin lymphoma.

Genetics. One of the most important areas of research involves the genetic predisposition to developing childhood non-Hodgkin lymphoma, and how well genetic subtypes will respond to different treatment.

Biologic Therapy. A second area of research involves monoclonal antibodies (a type of biologic therapy) that are designed to kill lymphoma cells that express a specific protein and spare the rest of normal cells from the toxic effects of chemotherapy. Biologic therapy, also called immunotherapy, is designed to boost the body’s immune system.

Targeted therapies. A third area of research is investigating other forms of targeted therapy that utilize specific drugs that are unique in affecting the normal regulation of the lymphoma cell, while having little effect on the regulation and survival of normal cells.

Expanded use of transplantation. Finally, a fourth area of research involves reduced intensity conditioning therapy (lower doses of chemotherapy and radiation therapy in order to reduce complications following a transplantation) followed by allogeneic stem cell transplantation for patients with recurrent childhood non-Hodgkin lymphoma.

Regular communication with your child’s doctor is important in making informed decisions about his or her health care. Consider asking the following questions of your child’s doctor:

• What type of non-Hodgkin lymphoma has been diagnosed?
  
  
• What is the stage of the disease? What does this mean?
  
  
• What are the treatment options?
  
  
• What clinical trials are open to my child?
  
  
• What treatment plan do you recommend? Why?
  
  
• What chemotherapy will my child receive?
  
  
• Should my child receive a bone marrow/stem cell transplantation?
  
  
• Will my child receive radiation therapy?
  
  
• Will my child need to stay in the hospital?
  
  
• What are the common short-term and long-term side effects from each treatment?
  
  
• What follow-up tests will my child need, and how often will he or she need them?
  
  
• What support services are available to my child? To my family?