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One of the most common cancers of childhood, non-Hodgkin lymphoma is the group name for all types of lymphomas except Hodgkin lymphoma. Lymphomas are cancers that begin in the body’s lymphatic system, which is part of the body’s immune system.
The lymphatic system transports infection-fighting white blood cells called lymphocytes throughout the body. As a result, lymphoma can start in many places, including the lymph nodes, thymus gland, spleen, abdomen, liver, bone marrow, skin, and bones.
Most non-Hodgkin lymphomas of childhood are different from adult lymphomas. Childhood lymphomas are typically more aggressive, but they are highly treatable.
There are several different types of non-Hodgkin lymphoma depending on the type of lymphocyte it affects – B-cells or T-cells.
Types of childhood non-Hodgkin lymphoma include:
Burkitt lymphoma is an aggressive (fast-growing) disorder of B lymphocytes. It may form in the abdomen, tonsils, testicles, bone, bone marrow, skin, or central nervous system.
There are three main types of Burkitt lymphoma: sporadic, endemic, and immunodeficiency-related. Sporadic Burkitt lymphoma occurs throughout the world, and endemic Burkitt lymphoma occurs in Africa. Immunodeficiency-related Burkitt lymphoma is most often seen in AIDS patients.
A different form of the same disease, Burkitt leukemia may start in the lymph nodes as Burkitt lymphoma and then spread to the blood and bone marrow, or it may start in the blood and bone marrow without forming in the lymph nodes first.
Treatment depends on a number of factors. It could include a combination of chemotherapy drugs or combination chemotherapy with rituximab.
When planning chemotherapy for newly diagnosed disease, the doctor will consider the intensity of dosage needed and how long to give medicines (duration) based on a variety of risk factors such as disease stage, site(s) of disease, and level of lactate dehydrogenase (LDH.) Examples of commonly used medicines to treat childhood Burkitt lymphoma are vincristine, cyclophosphamide, prednisone, Adriamycin, methotrexate, cytarabine, and etoposide. Some patients may also receive rituximab. The duration ranges from 3 to 8 months depending on risk factors.
Relapsed disease is generally treated with chemotherapy and rituximab followed by bone marrow transplant. A common chemotherapy plan used for relapsed disease is RICE (rituximab, ifosfamide, carboplatin, and etoposide). New targeted therapy strategies are currently under investigation.
Prognosis depends on a number of factors, including stage, where the disease is located and the serum level of lactate dehydrogenase (LDH). Levels are higher than normal in some patients with lymphoma. The five-year survival rate for limited stage (Stage I and II) childhood Burkitt lymphoma is more than 90 percent.
The five-year survival rate for more advanced (Stage III or IV) childhood Burkitt lymphoma ranges from about 80 to 90 percent.
Diffuse large B-cell lymphoma occurs more often in adolescents than in children. It is a type of B-cell non-Hodgkin lymphoma that grows quickly in the lymph nodes. The spleen, liver, bone marrow, or other organs are also often affected.
Treatment for childhood diffuse large B-cell lymphoma is generally the same as for Burkitt lymphoma.
Prognosis depends on a number of factors, including the stage of the disease.
The five-year survival rate for limited stage (stage I and II) diffuse large B-cell lymphomas is more than 90 percent.
The five-year survival rate for advanced (stage III or IV) diffuse large B-cell lymphoma ranges from about 80 to 90 percent.
Primary mediastinal large B-cell lymphoma develops from B cells in the mediastinum (the area behind the breastbone). It may spread to nearby organs including the lungs and the sac around the heart. It may also spread to lymph nodes and distant organs including the kidneys. In children and adolescents, primary mediastinal B-cell lymphoma occurs more often in older adolescents.
The long-term, event-free survival rate for childhood primary mediastinal large B-cell lymphoma is about 70 percent. There is a need for improved treatment approaches which may include novel targeted therapy.
Lymphoblastic lymphoma mainly affects T-cell lymphocytes. It usually forms in the mediastinum (the area behind the breastbone). Symptoms include trouble breathing, wheezing, trouble swallowing, or swelling of the head and neck. It may spread to lymph nodes, bone, bone marrow, skin, the central nervous system, abdominal organs, and other areas. Lymphoblastic lymphoma is a lot like acute lymphoblastic leukemia (ALL).
The medicines and treatment schedule used to treat children with lymphoblastic lymphoma is generally derived from regimens developed to treat acute lymphoblastic leukemia. Agents commonly used include vincristine, prednisone, pegaspargase or Erwinia asparaginase, daunorubicin, methotrexate, mercaptopurine, cytarabine and cyclophosphamide. The total duration of therapy is approximately 2 years.
If cancer has spread to the brain and spinal cord, treatment may include radiation and chemotherapy. The pediatric oncologist will review the treatment options including available research protocols.
A clinical trial of chemotherapy with different approaches to prevent spread to the central nervous system may be discussed with parents.
Treatment for recurrent lymphoblastic lymphoma may include chemotherapy or high-dose chemotherapy with hematopoietic cell transplant (also called a bone marrow transplant or stem cell transplant.)
Prognosis depends on a number of factors, including the stage of the disease and the genetic makeup of the cancer.
With intensive treatment, around 90 percent of children with limited stage (stage I or II) lymphoblastic lymphoma can be cured.
The cure rate for more advanced (stage III or IV) lymphoblastic lymphomas is generally higher than 80 percent.
Anaplastic large cell lymphoma mainly affects T-cell lymphocytes. It usually forms in the lymph nodes, skin or bone, and sometimes forms in the gastrointestinal tract, lung, tissue that covers the lungs, and muscle.
Treatment options depend on a number of factors, including stage of the disease and the genetic basis of the cancer. Varied approaches have been used to treat children with anaplastic large cell lymphoma. Chemotherapy agents that are commonly used include cyclophosphamide, doxorubicin, prednisone, vincristine, methotrexate, cytarabine and etoposide. The total duration of therapy ranges from 4 to 12 months.
Treatment options for relapsed anaplastic large cell lymphoma may include chemotherapy, stem cell transplant, a clinical trial of targeted therapy (crizotinib) for children with recurrent anaplastic large cell lymphoma and changes in the ALK gene, a clinical trial with crizotinib with chemotherapy or a clinical trial with an antibody to CD30 linked to another anticancer drug (antibody drug conjugate such as brentuximab vedontine), often referred to as immunotherapy.
The 5-year event-free survival for anaplastic large cell lymphoma is about 70 percent.
Signs and symptoms vary depending on where the disease starts in the body:
Doctors begin to suspect cancer based on the child’s symptoms and from considering the results of a physical examination, medical history and blood tests. Sometimes doctors will order certain diagnostic imaging tests. These tests may be completed at the local doctor’s office, hospital, or at a cancer center.
At the pediatrician’s office, the child will typically receive a physical exam and a medical history will be taken. During the physical exam, the doctor will check general signs of health, including signs of disease, such as lumps or anything else that seems unusual. The eyes, mouth, skin, and ears will be looked at carefully, and a nervous system exam may be done. The doctor may feel the patient’s abdomen for signs of an enlarged spleen or liver.
Blood tests may include a complete blood count (CBC) and blood chemistry study. A CBC looks at the number of red blood cells, white blood cells, platelets, hematocrit, and hemoglobin. During blood chemistry studies, the patient’s blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. A higher or lower than normal amount of a substance can indicate disease.
An X-ray uses a small amount of radiation to take a picture inside a person’s body. X-rays of the chest area will show the heart, lungs, lymph nodes, diaphragm, spine, ribs, collarbone, and breastbone.
Doctors order a biopsy when cancer is suspected. A biopsy is required for diagnosis and will determine exactly what type of lymphoma. During a biopsy, tissue from the suspected tumor is removed and then examined by a pathologist under a microscope.
One of the following types of biopsies may be performed, depending of where the suspected cancer is located:
If lymphoma cells are present, additional tests will be performed on the tissue biopsy to diagnose the specific type of lymphoma. These tests include
Non-Hodgkin lymphomas arise from different cells of the immune system (B lymphocytes, T lymphocytes). The majority of lymphomas (around 80%) arise in developing B-lymphocytes (B-cell lymphomas). The remainder arise in developing T-lymphocytes (T-cell lymphomas).
Immunophenotyping is used to diagnose specific types of lymphoma by comparing the cancer cells to normal cells of the immune system. Immunohistochemistry and flow cytometry are the laboratory tests used to diagnose the specific type of B or T-cell lymphoma.
Immunohistochemistry is a test that uses antibodies to check for certain antigens in a sample of tissue. The antibodies will light up under a microscope.
In flow cytometry, 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 test measures the number of cells, the percentage of live cells, and certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface.
Flow cytometry: This test 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.
Cytogenetic analysis involves laboratory tests that look for certain changes in the chromosomes.
One such test is FISH (fluorescence in situ hybridization). This test looks 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.
After a biopsy confirms cancer, doctors will perform more tests to determine the stage of the disease. The stage indicates whether the cancer has spread to other parts of the body and, if so, how much and how far it has spread. Treatment is planned based on the stage of the cancer. It is very important that lymphoma is staged as quickly as possible because these tumors grow rapidly. The higher the stage of the cancer, the more aggressively it needs to be treated.
Stage 1 and Stage 2 lymphomas are considered limited disease, and Stage 3 and Stage 4 lymphomas and considered advanced.
|Stage||Where Cancer is Found|
|Stage 1||In one group of lymph nodes
In one area outside the lymph nodes
No cancer is found in the abdomen or area between the lungs
|Stage 2||In one area outside the lymph nodes and in nearby lymph nodes
In two or more areas either above or below the diaphragm, and may have spread to nearby lymph nodes
To have started in the stomach or intestines and can be completely removed by surgery. Cancer may have spread to certain nearby lymph nodes.
|Stage 3||In at least one area above the diaphragm and in at least one area below the diaphragm
To have started in the chest
To have started in the abdomen and spread throughout the abdomen
In the area around the spine
|Stage 4||In the bone marrow
In the brain
Other parts of the body.
A bone marrow aspiration and biopsy can determine if the lymphoma has spread to the bone marrow or bone.
Bone marrow aspiration: Doctors will remove bone marrow by inserting a hollow needle into the hipbone. A pathologist will view the bone marrow under a microscope to look for signs of cancer.
Bone marrow biopsy: Doctors will remove a small piece of solid bone marrow to determine if the cancer has spread to the bone. The biopsy is typically performed right before or after the aspiration. Children are usually asleep (sedated) during the procedure or will be given the appropriate amount of pain medication.
A lumbar puncture is used to determine if lymphoma has spread to the central nervous system. The procedure is used to collect cerebrospinal fluid (CSF) from the spinal column. This is done by placing a needle between two bones in the spine and into the CSF around the spinal cord and removing a sample of the fluid. The sample of CSF is checked under a microscope for signs that the cancer has spread to the brain and spinal cord. This procedure is also called an LP or spinal tap. Patients are either asleep during the procedure or are given numbing medication.
Mediastinoscopy and thoracentesis are two tests that may be used in limited cases when a biopsy is needed deep in the chest area.
Mediastinoscopy: a surgical procedure to check for signs of cancer in organs, tissues, and lymph nodes is the chest area. Surgeons make an incision (cut) at the top of the breastbone and insert a mediastinoscope into the chest.
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.
A screening test for HIV (human immunodeficiency virus) is also recommended because lymphomas sometimes develop in patients with this virus. If the test is positive, the patient may require medications to treat HIV.
Chemotherapy is the main treatment for childhood non-Hodgkin lymphoma, and many different types of medicines and combination of medicines are approved for therapy. When determining the best treatment, doctors consider many factors including the subtype of the lymphoma, its stage, how likely it is to respond to chemotherapy, and the treatment protocols available. The physician and medical team will also consider many factors about the patient, including age and if patients have any existing conditions that might affect their reaction to chemotherapy. The pediatric oncologist will discuss options with families.
This type of cancer tends to be aggressive in children, so it is important that treatment begins as soon as possible. The treatment is based on how well the subtype of lymphoma typically responds to initial therapy. It is called risk-adapted therapy. Risk refers to the risk of cancer not responding successfully to treatment – that it is either won’t respond well (refractory) or will return after remission (relapsed).
Patients whose type of lymphoma is typically less responsive to therapies are considered higher-risk. These patients are generally given more intense therapies. On the other hand, patients with a type of lymphoma that is likely to respond to initial therapy will be given medicines that are likely to have fewer side effects. All patients are given medicines and other therapies to help with side effects.
Chemotherapy is the main treatment for childhood non-Hodgkin lymphoma, and many different types of medicines and combination of medicines are approved for therapy. In determining a treatment plan, the physician and medical team will consider the type and stage of the lymphoma, along with many factors about the patient, including age and if patients have any existing conditions that might affect their reaction to chemotherapy.
Chemotherapy for mature B-cell non-Hodgkin lymphoma and anaplastic large cell lymphoma is generally given in cycles. Patients will receive the drug over several weeks and then will rest for a few weeks before beginning another cycle. The number of cycles and the length of treatment vary depending on the type and stage of lymphoma and patient characteristics. Patients with acute lymphoblastic leukemia are given continuous therapy over a two-year period.
In targeted therapy, researchers design drugs that home in on the changes in cancer cells that help the cells grow, divide, and spread and disarm these cells.
Monoclonal antibodies, tyrosine kinase inhibitors, and immunotoxins are three types of therapy being used or studied in the treatment of childhood non-Hodgkin lymphoma.
Monoclonal antibody therapy
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. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.
Rituximab is a monoclonal antibody used to treat several types of childhood non-Hodgkin lymphoma. (NCI) Brentuximab vedotin is a monoclonal antibody combined with an anticancer drug that is used to treat anaplastic large cell lymphoma.
Tyrosine kinase inhibitors
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. Crizotinib is one TKI under study for childhood non-Hodgkin lymphoma.
Immunotoxins can bind to cancer cells and kill them. Denileukin diftitox is an immunotoxin used to treat cutaneous T-cell lymphoma.
Although significant progress has been made in the treatment of children with lymphoma, 25-30% continue to have refractory or recurrent disease, but there are many therapy options in these cases. Most pediatric oncologists consider either intensive chemotherapy with or without treatment with targeted therapy, followed by a hematopoietic cell transplant (also called bone marrow transplant or stem cell transplant) in the majority of cases.
The subtype of lymphoma is an important factor in making treatment decisions for relapsed disease, including what medicines to use or perhaps the type of bone marrow transplant.
The prognosis (chance of recovery) depends upon
Overall five-year survival rates for childhood non-Hodgkin lymphoma can range from about 70 percent to more than 90 percent.
Late effects are side effects that develop after treatment is completed. These include:
Patients should discuss any concerns with their physicians and let them know about any symptoms. Regular, focused follow-up care is extremely important for childhood cancer survivors.
Reviewed: June 2018