• Non-Hodgkin Lymphoma

    Non-Hodgkin lymphoma (NHL) is not just one disease but a group of cancers that originate in cells of the immune system, called lymphocytes.

    • Non-Hodgkin lymphomas often begin in lymph nodes,but may arise in any organ of the body, including kidneys, liver, spleen, bone, bone marrow, skin, and brain.
    • Non-Hodgkin lymphomas occur in both children and adults. However, the particular types of non-Hodgkin lymphoma that are most common in children are different from those in adults, and treatment recommendations and outcomes are different for children than for adults.
    • Non-Hodgkin lymphomas are, as a group, the third most common childhood cancer, accounting for 7 percent of pediatric cancers.
    • More than 80 percent of children and adolescents with non-Hodgkin lymphoma are cured.
    • Non-Hodgkin lymphoma differs from Hodgkin lymphoma in that Hodgkin lymphoma is marked by the presence of Reed-Sternberg cells (mature B cells that are unusually large), but non-Hodgkin lymphomas do not have these cells.

    Types of Non-Hodgkin Lymphoma:

    Non-Hodgkin Lymphoma Treatment at Dana-Farber/Boston Children's

    Children with non-Hodgkin lymphoma are treated at Dana-Farber/Boston Children's through the Lymphoma Treatment Program in our Hematologic Malignancies Center. One of the top pediatric cancer centers worldwide, Dana-Farber/Boston Children’s combines the expertise of a premier cancer center – Dana-Farber Cancer Institute – and a world-class children’s hospital – Boston Children’s Hospital – to provide internationally-renowned care for children with cancers of the blood and immune system.

    What is 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.

    What are the different types of non-Hodgkin lymphoma?

    The World Health Organization (WHO) divides non-Hodgkin lymphoma into different categories based on various features of the lymphoma, such as the type of lymphocyte that has become cancerous. The two types of lymphocytes that most commonly cause lymphomas are B-cells and T-cells. Within each of these cell types, the cancer may grow from immature cells or mature cells. Therefore, most non-Hodgkin lymphomas fall into one of three groups:

    1. mature B-cell lymphomas
    2. mature T-cell lymphomas
    3. immature B- or T-cell lymphomas

    Treatment for non-Hodgkin lymphoma depends on the particular lymphoma diagnosis.

    To determine the correct diagnosis, expert pathologists examine the lymphoma under the microscope and use specialized molecular tests. The pathologist evaluates many features of the cancer, including the size, shape and physical details of the tumor cells, the pattern of how the cells are arranged within the tumor, the presence of certain proteins and gene markers that the tumor cells express, and certain details of how the lymphoma presents in the patient.

    Within the WHO classification of NHL, most non-Hodgkin lymphomas of children and adolescents are one of the following types:

    Mature B-cell lymphomas

    • Burkitt lymphoma is a cancer of mature B-cell lymphocytes. Under the microscope, the lymph node often has a “starry sky” pattern. The lymphoma cells express a marker called CD20 and usually have an abnormality of the c-myc gene that can be detected by specialized testing. This type of lymphoma is a rapidly growing cancer, often involving the lymphatic tissue in the abdomen, neck, tonsils, sinuses, or near the spine. It can also involve the bone marrow and present as a leukemia with tumor cells in the blood.
    • Diffuse large B-cell lymphoma (DLBCL) is another lymphoma of mature B-cell lymphocytes and also expresses the protein marker called CD20. Although this type of lymphoma is more common in adults than in children, it is biologically different in the two age groups and is generally very curable in children and adolescents. In children, this lymphoma is usually treated like Burkitt lymphoma. 
    • Primary mediastinal B-cell lymphoma (PMBL) is another mature B-cell lymphoma that usually presents in the chest (mediastinum) and has features similar to both Hodgkin lymphoma and diffuse large B-cell lymphoma. Like other mature B-cell lymphomas, PMBL expresses the marker CD20 on the tumor cells. PMBL most commonly affects adolescents and young adults and may be treated the same way in both age groups.
    • Rare lymphomas of mature B-cells include pediatric follicular lymphoma and pediatric MALT lymphoma.

    Mature T-cell lymphomas

    • Anaplastic large cell lymphoma (ALCL) arises from mature T-cell lymphocytes. Children with this lymphoma can present with fever and symptoms that mimic other illnesses. The tumor can present in multiple lymph nodes and in the abdomen, chest, bone, and skin. The tumor cells express a marker called CD30 and usually have a rearrangement of a gene called ALK that can be detected by specialized testing.
    • Rare lymphomas of mature T-cells include various types of peripheral T-cell lymphomas and cutaneous T-cell lymphomas.

    Immature B and T-cell lymphomas

    • Lymphoblastic lymphoma arises from immature precursor lymphocyte cells called lymphoblasts. These may be T-cell or B-cell lymphoblasts but more commonly are of the T-cell type. This lymphoma usually presents with a mass in the chest and enlarged lymph nodes in the neck, but it may involve any organ in the body, including skin, bone, bone marrow, and kidneys. B and T lymphoblasts are the same type of cells that cause the most common type of childhood leukemia, acute lymphoblastic leukemia. Lymphoblastic lymphoma is treated in the same way as acute lymphoblastic leukemia.

    Non-Hodgkin lymphoma is sometimes categorized according to where it arises in the body.

    • Primary central nervous system lymphoma (PCNSL) is a rare lymphoma and requires specialized treatment with chemotherapy that can enter the brain and nervous system.
    • Cutaneous lymphomas are lymphomas that are only present in the skin. These are rare lymphomas in children.

    What are the causes and symptoms of non-Hodgkin lymphoma?

    Doctors do not know what causes most cases of non-Hodgkin lymphoma. The majority of instances of NHL in children are not caused by anything that can be prevented.

    There are some known risk factors that might increase a child’s likelihood of developing non-Hodgkin lymphoma. These affect only a small percentage of children. Risk factors include:

    • a weakened immune system due to inborn or acquired immunodeficiency diseases,
    • treatment with immune-suppressive medications,
    • a history of exposure to chemotherapy or radiation therapy for another cancer, or
    • prior infection with Epstein-Barr virus (EBV). In some children, EBV infection may later lead to lymphoma, but most children and adults do not develop lymphoma after an EBV infection.

    Non-Hodgkin lymphoma symptoms

    Non-Hodgkin lymphoma symptoms vary depending on the type of lymphoma (see types of lymphoma section above) and where the lymphoma is located. Sometimes symptoms of generalized illness, such as fever, night sweats, and weight loss, may go along with NHL. These symptoms are referred to as “B” symptoms. Other times, there are no symptoms except an enlarging lymph node or lump. The disease can progress quickly over days to weeks or can have a very slow pace of progression over many months.

    The location where the lymphoma is growing in the body often explains the symptoms.

    • Non-Hodgkin lymphoma in the chest may present with cough, difficulty breathing, especially when lying flat, or swelling of the face and neck.
    • Non-Hodgkin lymphoma in the abdomen may present with swelling of the abdomen, belly pain, decreased appetite, constipation, or obstruction to passing urine.
    • Non-Hodgkin lymphoma next to the spine may present with weakness of the legs, loss of ability to walk, or loss of control over bowel movements or urination.
    • Non-Hodgkin lymphoma in the lymph nodes or skin may present as a slowly growing lump at the site of the tumor, such as in the neck, armpit, groin, or anywhere in the skin, including the scalp.

    Non-Hodgkin lymphoma symptoms may resemble those of other more common medical problems. It is important to have your child evaluated by a qualified medical professional for an accurate diagnosis.

    How is non-Hodgkin lymphoma diagnosed and staged?


    The first step in treating NHL is making an accurate diagnosis. When the symptoms and findings on physical examination raise the possibility of a non-Hodgkin lymphoma diagnosis, laboratory tests and radiology tests will usually be done to help guide how best to determine the diagnosis. To make a definite non-Hodgkin lymphoma diagnosis, a sample of the tumor needs to be obtained for evaluation by the pathologist. This usually is done by having a surgeon or interventional radiology doctor remove a piece of tumor (biopsy). Sometimes the diagnosis may be made by evaluating fluid removed for the chest or abdomen or by removing a small piece of bone marrow to be examined under the microscope.


    The second step in treating NHL is to determine how much the disease has spread within the body. The extent of disease is called the “stage” of the lymphoma. Knowing the stage helps to determine the strength of the treatment that is needed to cure the lymphoma. The process of finding all of the sites of disease in the body is called “staging.” Staging involves doing radiology tests, such as PET, CT, and MRI scans; sampling the bone marrow with a needle into the hip bones; and obtaining spinal fluid with a needle into the space between the bones of the lower spine (lumbar puncture).

    The information learned from the scans and from the bone marrow and spinal fluid evaluations is used to assign a “stage” that describes how extensive the lymphoma is. More than one staging system is used for non-Hodgkin lymphoma. Whereas in adult non-Hodgkin lymphoma, a system called the Ann Arbor Staging System is commonly used, in childhood non-Hodgkin lymphoma, the most common system of staging is the St. Jude/Murphy Staging System. This system is summarized below:

    • Stage I – The tumor is at one site only, except not in the chest, abdomen, or next to the spine or brain.
    • Stage II – The tumor is at two or more sites, all either in the upper half or the lower half of the body, but not in the chest, next to the spine or brain, or in the abdomen (unless completely surgically removed). The division between the upper and lower body is at the breathing muscle called the diaphragm that separates the chest from the abdomen.
    • Stage III – The tumor is at two or more sites in both the upper and lower halves of the body or any tumor in the chest, any tumor in the abdomen that is not removed by surgery, and any tumor next to the spinal cord or brain but does not involve the bone marrow or the central nervous system (the brain or spinal fluid).
    • Stage IV – The tumor is at any location and also is in the bone marrow and/or central nervous system. Stage IV is also subdivided depending on the amount of cancer cells present in the bone marrow. More than 25% lymphoma cells in the bone marrow is generally considered to be leukemia rather than lymphoma.

    Because the common childhood non-Hodgkin lymphomas often are located in the chest, abdomen, or next to the spine or brain, many children with non-Hodgkin lymphoma have stage III or IV disease when they are diagnosed.

    What are the treatments for non-Hodgkin lymphoma?

    The major factor in deciding the treatment strategy for non-Hodgkin lymphoma is the specific type of lymphoma. The other important consideration is whether the cancer is localized to a specific part of the body (low stage; stage I or II) or has spread to different parts of the body (advanced stage; stage III or IV). Generally, stronger treatment is needed for successful treatment of advanced stage lymphoma.

    Non-Hodgkin lymphoma treatment may include:

    • Chemotherapy: By far the most common treatment for non-Hodgkin lymphoma is chemotherapy. Chemotherapy is drug treatment that works by interfering with the cancer cells’ ability to grow or reproduce. Several different chemotherapy drugs are combined to provide the most effective treatment for the lymphoma. Commonly used drugs in the treatment of lymphoma are cyclophosphamide, doxorubicin, vincristine, prednisone, and methotrexate, among others. Different chemotherapy drugs work in different ways. Chemotherapy may be given by mouth, by injection into the muscle or directly into the vein (IV), or as a direct injection into the spinal fluid through a needle (lumbar puncture). Chemotherapy into the spinal fluid is commonly used as part of the treatment of NHL in children.
    • Targeted therapy: Antibodies, immune cell therapies, and drugs that target lymphoma cells directly or help the body’s own immune system to attack the cancer have become important tools in fighting lymphoma. Rituximab is an antibody that targets CD20 on mature B-cell lymphomas. Brentuximab is an antibody-chemotherapy combination that targets lymphomas with CD30 expression, such as Anaplastic Large Cell Lymphoma. Other types of immunotherapy are currently being investigated in the treatment of lymphoma.
    • CAR T-cell therapy: Pediatric B-cell lymphomas, such as Burkitt lymphoma and diffuse large B-cell lymphoma, are usually cured with chemotherapy. However, for patients with lymphoma that does not respond to chemotherapy or that comes back after initial treatment, a cure can be difficult to achieve. CAR (chimeric antigen receptor) T-cell therapy is a promising new treatment for these challenging cases of pediatric non-Hodgkin lymphoma. It works by modifying the patient's own T-cells, a normal part of the body’s immune system, to make cells that hunt and destroy the abnormal cancer cells.
    • Stem cell transplant: When a lymphoma is completely resistant to initial treatment or recurs despite initial treatment, high dose chemotherapy followed by a stem cell transplant may be a good treatment option. In a stem cell transplant for NHL, the transplanted bone marrow is usually the patient's own (autologous), rather than someone else’s (allogeneic).
    • Radiation therapy uses high-energy rays (radiation) from a specialized machine to damage or kill cancer cells and shrink tumors. This type of therapy is not commonly used to treat non-Hodgkin lymphoma in children.
    • Surgery may be needed to biopsy the tumor to make an accurate diagnosis or to confirm that the tumor has responded well to treatment but usually does not have a role in the treatment of pediatric NHL.

    The lymphoma specialists at Dana Farber/Boston Children’s determine the best treatment approach for each child's unique situation based on the type of lymphoma, the extent of the disease, the patient’s medical condition, the patient and family’s preferences, and the most up-to-date medical knowledge about lymphoma therapies.

    What is the latest research on non-Hodgkin lymphoma?

    For many children with cancer, clinical trials – research studies evaluating new treatment approaches – provide state-of-the art treatments and new opportunities for cures. Dana-Farber/Boston Children’s offers many clinical trials. It is possible your child will be eligible to participate in one of our lymphoma clinical trials. Participation in a clinical trial is optional and is never a requirement to receive treatment at Dana-Farber/Boston Children’s.

    In addition to launching our own clinical trials, we also offer trials available through collaborative groups such as the Children's Oncology Group (COG), the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) group, and the Pediatric Oncology Experimental Therapeutics Investigators' Consortium (POETIC). We are the New England Phase I Center of the Children's Oncology Group.

    We have new treatments under investigation, both for newly diagnosed lymphomas and for lymphomas that have come back after initial treatment. New and experimental treatments include monoclonal antibody therapies, antibody-drug conjugates and bispecific antibodies that specifically target tumor cells; small molecule inhibitors that interfere with the way cancer cells grow; checkpoint inhibitors that activate the body’s own immune system to fight the cancer; and selective inhibitors of nuclear export that prevent tumor cells from escaping cell death. Clinical trials to investigate the biology of each child’s lymphoma are available and may help find targets of therapy unique to that lymphoma.

    Clinical Trials

    To learn more about the specific clinical trials that are currently available at the Dana-Farber/Boston Children's:

    What is the long-term outlook for children with non-Hodgkin lymphoma?

    The long-term outlook for children with non-Hodgkin lymphoma is excellent. More than 80 percent of children are cured and can resume a normal life, returning to school, social activities, and athletics, typically within a year after diagnosis.

    Non-Hodgkin lymphoma survivorship care

    All kids who have been treated for cancer require ongoing, specialized care. Through the David B. Perini Jr. Quality of Life Clinic, our cancer survivorship clinic, childhood cancer survivors receive regular, comprehensive follow-up evaluations from their cancer care team. In addition to meeting with your pediatric oncologists, your child may see one of our endocrinologists, cardiologists, neurologists, neuro-psychologists, or alternative/complementary therapy specialists. We also offer patient and family education, psychosocial assessment, genetic counseling, reproductive counseling, and opportunities to speak with other childhood cancer survivors.

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