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

Childhood Hodgkin lymphoma is a type of cancer that develops in the lymph system. The lymph system is part of the immune system. It helps protect the body from infection and disease.

The lymph system is made up of the following:

• Lymph: Colorless, watery fluid that travels through the lymph vessels and carries T and B lymphocytes. Lymphocytes are a type of white blood cell.
• Lymph vessels: A network of thin tubes that collect lymph from different parts of the body and return it to the bloodstream.
• Lymph nodes: Small, bean-shaped structures that filter lymph and store white blood cells that help fight infection and disease. Lymph nodes are found along a network of lymph vessels throughout the body. Groups of lymph nodes are found in the neck, underarm, mediastinum (the area between the lungs), abdomen, pelvis, and groin. Hodgkin lymphoma most commonly forms in the lymph nodes above the diaphragm.
• Spleen: An organ that makes lymphocytes, stores red blood cells and lymphocytes, filters the blood, and destroys old blood cells. The spleen is on the left side of the abdomen near the stomach.
• Thymus: An organ in which T lymphocytes mature and multiply. The thymus is in the chest behind the breastbone.
• Bone marrow: The soft, spongy tissue in the center of certain bones, such as the hip bone and breastbone. White blood cells, red blood cells, and platelets are made in the bone marrow.
• Tonsils: Two small masses of lymph tissue at the back of the throat. There is one tonsil on each side of the throat.

Bits of lymph tissue are also found in other parts of the body such as the lining of the gastrointestinal tract, bronchus, and skin.

There are two general types of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. This summary is about the treatment of childhood Hodgkin lymphoma.

Hodgkin lymphoma occurs most often in adolescents 15 to 19 years of age. The treatment for children and adolescents is different than treatment for adults.

The two main types of childhood Hodgkin lymphoma are classic and nodular lymphocyte-predominant.

The two main types of childhood Hodgkin lymphoma are:

• Classic Hodgkin lymphoma. This is the most common type of Hodgkin lymphoma. It occurs most often in adolescents. When a sample of lymph node tissue is looked at under a microscope, Hodgkin lymphoma cancer cells, called Reed-Sternberg cells, may be seen.

  Classic Hodgkin lymphoma is divided into four subtypes, based on how the cancer cells look under a microscope:

  • Nodular-sclerosing Hodgkin lymphoma occurs most often in older children and adolescents. It is common to have a chest mass at diagnosis.
  • Mixed cellularity Hodgkin lymphoma most often occurs in children younger than 10 years of age. It is linked to a history of Epstein-Barr virus (EBV) infection and often occurs in the lymph nodes of the neck.
  • Lymphocyte-rich classic Hodgkin lymphoma is rare in children. When a sample of lymph node tissue is looked at under a microscope, there are Reed-Sternberg cells and many normal lymphocytes and other blood cells.
  • Lymphocyte-depleted Hodgkin lymphoma is rare in children and occurs most often in adults or adults with the human immunodeficiency virus (HIV). When a sample of lymph node tissue is looked at under a microscope, there are many large, oddly shaped cancer cells and few normal lymphocytes and other blood cells.
• Nodular lymphocyte-predominant Hodgkin lymphoma. This type of Hodgkin lymphoma is less common than classic Hodgkin lymphoma. It most often occurs in children younger than 10 years of age. When a sample of lymph node tissue is looked at under a microscope, the cancer cells look like "popcorn" because of their shape. Nodular lymphocyte-predominant Hodgkin lymphoma often occurs as a swollen lymph node in the neck, underarm, or groin. Most individuals do not have any other signs or symptoms of cancer at diagnosis.

Epstein-Barr virus infection and a family history of Hodgkin lymphoma can increase the risk of childhood Hodgkin lymphoma.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your child’s doctor if you think your child may be at risk.

Risk factors for childhood Hodgkin lymphoma include the following:

• Being infected with the Epstein-Barr virus (EBV).
• Having a personal history of mononucleosis ("mono").
• Being infected with the human immunodeficiency virus (HIV).
• Having certain diseases of the immune system, such as autoimmune lymphoproliferative syndrome.
• Having a weakened immune system after an organ transplant or from medicine given after a transplant to stop the organ from being rejected by the body.
• Having a parent, brother, or sister with a personal history of Hodgkin lymphoma.

Being exposed to common infections in early childhood may decrease the risk of Hodgkin lymphoma in children because of the effect it has on the immune system.

Signs of childhood Hodgkin lymphoma include swollen lymph nodes, fever, drenching night sweats, and weight loss.

The signs and symptoms of Hodgkin lymphoma depend on where the cancer forms in the body and the size of the cancer. These and other signs and symptoms may be caused by childhood Hodgkin lymphoma or by other conditions. Check with your child's doctor if your child has any of the following:

• Painless, swollen lymph nodes near the collarbone or in the neck, chest, underarm, or groin.
• Fever for no known reason.
• Weight loss for no known reason.
• Drenching night sweats.
• Feeling very tired.
• Anorexia.
• Itchy skin.
• Coughing.
• Trouble breathing, especially when lying down.
• Pain in the lymph nodes after drinking alcohol.

Fever for no known reason, weight loss for no known reason, or drenching night sweats are called B symptoms. B symptoms are an important part of staging Hodgkin lymphoma and understanding the patient's chance of recovery.

Tests that examine the lymph system and other parts of the body are used to diagnose and stage childhood Hodgkin lymphoma.

Tests and procedures that make pictures of the lymph system and other parts of the body help diagnose childhood Hodgkin lymphoma and show how far the cancer has spread. The process used to find if cancer cells have spread outside the lymph system is called staging. To plan treatment, it is important to know if cancer has spread to other parts of the body.

These tests and procedures may include the following:

• Physical exam and health 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 blood 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, including albumin, by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
• Sedimentation rate: A procedure in which a sample of blood is drawn and checked for the rate at which the red blood cells settle to the bottom of the test tube. The sedimentation rate is a measure of how much inflammation is in the body. A higher than normal sedimentation rate may be a sign of lymphoma. Also called erythrocyte sedimentation rate, sed rate, or ESR.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the neck, chest, abdomen, or pelvis, 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.

• 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, such as the lymph nodes. This procedure is also called nuclear magnetic resonance imaging (NMRI).

• 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.
• Bone marrow aspiration and biopsy: The removal of bone marrow and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow and bone under a microscope to look for abnormal cells. Bone marrow aspiration and biopsy is done for patients with advanced disease and/or B symptoms.

• Lymph node biopsy:The removal of all or part of one or more lymph nodes. The lymph node may be removed during an image-guided CT scan or a thoracoscopy, mediastinoscopy, or laparoscopy. One of the following types ofbiopsies may be done:
  • Excisionalbiopsy: The removal of an entire lymph node.
  • Incisionalbiopsy: The removal of part of a lymph node.
  • Corebiopsy: The removal of tissue from a lymph node using a wide needle.

  A pathologist views the lymph node tissue under a microscope to check for cancer cells called Reed-Sternberg cells. Reed-Sternberg cells are common in classic Hodgkin lymphoma.

  The following test may be done on tissue that was removed:

  • Immunophenotyping: A laboratory test that uses antibodies to identify cancer cells based on the types of antigens or markers on the surface of the cells. This test is used to help diagnose specific types of lymphoma.

After childhood 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. The results of the tests and procedures done to diagnose and stage Hodgkin lymphoma are used to help make decisions about treatment.

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 Hodgkin lymphoma:

Stage I

Stage I is divided into stage I and stage IE.

• Stage I: Cancer is found in one of the following places in the lymph system:
  • One or more lymph nodes in one lymph node group.
  • Waldeyer's ring.
  • Thymus.
  • Spleen.
• Stage IE: Cancer is found outside the lymph system in one organ or area.

Stage II

Stage II is divided into stage II and stage IIE.

• Stage II: Cancer is found in two or more lymph node groups either above or below the diaphragm (the thin muscle below the lungs that helps breathing and separates the chest from the abdomen).

• Stage IIE: Cancer is found in one or more lymph node groups either above or below the diaphragm and outside the lymph nodes in a nearby organ or area.

Stage III

Stage III is divided into stage III, stage IIIE, stage IIIS, and stage IIIE,S.

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

Stage IV

In stage IV, the cancer:

• is found outside the lymph nodes throughout one or more organs, and may be in lymph nodes near those organs; or
• is found outside the lymph nodes in one organ and has spread to areas far away from that organ; or
• is found in the lung, liver, bone marrow, or cerebrospinal fluid (CSF). The cancer has not spread to the lung, liver, bone marrow, or CSF from nearby areas.

In addition to the stage number, the letters A, B, E, or S may be noted.

The letters A, B, E, or S may be used to further describe the stage of childhood Hodgkin lymphoma.

• A: The patient does not have B symptoms (fever, weight loss, or drenching night sweats).
• B: The patient has B symptoms.
• E: Cancer is found in an organ or tissue that is not part of the lymph system but which may be next to an area of the lymph system affected by the cancer.
• S: Cancer is found in the spleen.

Childhood Hodgkin lymphoma is treated according to risk groups.

Untreated childhood Hodgkin lymphoma is divided into risk groups based on the stage, size of the tumor, and whether the patient has B symptoms (fever, weight loss, or drenching night sweats). The risk group describes the likelihood that Hodgkin lymphoma will not respond to treatment or recur (come back) after treatment. It is used to plan initial treatment.

• Low-risk childhood Hodgkin lymphoma.
• Intermediate-risk childhood Hodgkin lymphoma.
• High-risk childhood Hodgkin lymphoma.

Low-risk Hodgkin lymphoma requires fewer cycles of treatment, fewer anticancer drugs, and lower doses of anticancer drugs than high-risk lymphoma.

Sometimes childhood Hodgkin lymphoma does not respond to treatment or comes back after treatment.

Primary refractory Hodgkin lymphoma is cancer that does not respond to initial treatment.

Recurrent Hodgkin lymphoma is cancer that has recurred (come back) after it has been treated. The lymphoma may come back in the lymph system or in other parts of the body, such as the lungs, liver, bones, or bone marrow.

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

Different types of treatment are available for children with Hodgkin lymphoma. Some treatments are standard 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 Hodgkin lymphoma should have their treatment planned by a team of health care providers who are experts 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 pediatric health care providers who are experts in treating children with Hodgkin lymphoma and who specialize in certain areas of medicine. These may include the following specialists:

• Pediatrician.
• Medical oncologist/hematologist.
• Radiation oncologist.
• Pediatric nurse specialist.
• Psychologist.
• Social worker.
• Child-life specialist.

The treatment of Hodgkin lymphoma in adolescents and young adults may be different than the treatment for children. Some adolescents and young adults are treated with an adult treatment regimen.

Six types of standard treatment are used:

Chemotherapy

Chemotherapy is a cancer treatment that uses one or more drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Cancer treatment using more than one chemotherapy drug is called combination chemotherapy. 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).

The way the chemotherapy is given depends on the risk group. For example, children with low-risk Hodgkin lymphoma receive fewer cycles of treatment, fewer anticancer drugs, and lower doses of anticancer drugs than children with high-risk lymphoma.

Radiation therapy

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. External radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer.

Certain ways of giving radiation therapy can help keep radiation from damaging nearby healthy tissue. These types of external radiation therapy include the following:

• Conformal radiation therapy: Conformal radiation therapy is a type of external radiation therapy that uses a computer to make a 3-dimensional (3-D) picture of the tumor and shapes the radiation beams to fit the tumor.
• Intensity-modulated radiation therapy (IMRT): IMRT is a type of 3-dimensional (3-D) radiation therapy that uses a computer to make pictures of the size and shape of the tumor. Thin beams of radiation of different intensities (strengths) are aimed at the tumor from many angles.

Radiation therapy may be given, based on the child’s risk group and chemotherapy regimen. The radiation is given only to the lymph nodes or other areas with cancer.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do. Types of targeted therapy include the following:

• Monoclonal antibody therapy: Monoclonal antibodies are immune system proteins made in the laboratory to treat many diseases, including cancer. As a cancer treatment, these antibodies can attach to a specific target on cancer cells or other cells that may help cancer cells grow. The antibodies are able to then 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 or brentuximab may be used to treat refractory or recurrent childhood Hodgkin lymphoma.

• Proteasome inhibitor therapy: Proteasome inhibitor therapy is a type of targeted therapy that blocks the action of proteasomes in cancer cells. Proteasomes remove proteins no longer needed by the cell. When the proteasomes are blocked, the proteins build up in the cell and may cause the cancer cell to die.

  Bortezomib is a proteasome inhibitor used to treat refractory or recurrent childhood Hodgkin lymphoma.

Immunotherapy

Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This cancer treatment is a type of biologic therapy. Types of immunotherapy include the following:

• PD-1 and PD-L1 inhibitor therapy: PD-1 is a protein on the surface of T cells that helps keep the body’s immune responses in check. PD-L1 is a protein found on some types of cancer cells. When PD-1 attaches to PD-L1, it stops the T cell from killing the cancer cell. PD-1 and PD-L1 inhibitors keep PD-1 and PD-L1 proteins from attaching to each other. This allows the T cells to kill cancer cells.

  Pembrolizumab is a type of PD-1 inhibitor that may be used in the treatment of childhood Hodgkin lymphoma that has come back after treatment.

• CAR T-cell therapy: This treatment changes the patient's T cells (a type of immune system cell) so they will attack certain proteins on the surface of cancer cells. T cells are taken from the patient and special receptors are added to their surface in the laboratory. The changed cells are called chimeric antigen receptor (CAR) T cells. The CAR T cells are grown in the laboratory and given to the patient by infusion. The CAR T cells multiply in the patient's blood and attack cancer cells. CAR T-cell therapy is being studied to treat refractory or recurrent childhood Hodgkin lymphoma.

Surgery

Surgery may be done to remove as much of the tumor as possible for localized nodular lymphocyte-predominant Hodgkin lymphoma in children.

High-dose chemotherapy with stem cell transplant

High doses of chemotherapy are given to kill cancer cells. Healthy cells, including blood-forming cells, are also destroyed by the cancer treatment. Stem cell transplant is a treatment to replace the blood-forming cells. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the patient completes chemotherapy, 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.

Treatment of newly diagnosed low-risk classic Hodgkin lymphoma in children may include the following:

• Combination chemotherapy.
• Radiation therapy may also be given to the areas with cancer.

Treatment of newly diagnosed intermediate-risk classic Hodgkin lymphoma in children may include the following:

• Combination chemotherapy.
• Radiation therapy may also be given to the areas with cancer.

Treatment of newly diagnosed high-risk classic Hodgkin lymphoma in children may include the following:

• Higher dose combination chemotherapy.
• Radiation therapy may also be given to the areas with cancer.

Treatment of newly diagnosed nodular lymphocyte-predominant Hodgkin lymphoma in children may include the following:

• Surgery, if the tumor can be completely removed.
• Chemotherapy with or without low-dose external radiation therapy.

Treatment of primary refractory or recurrent childhood Hodgkin lymphoma may include the following:

• Chemotherapy, targeted therapy (rituximab, brentuximab, or bortezomib), or both of these therapies.
• Immunotherapy (pembrolizumab).
• High-dose chemotherapy with stem cell transplant using the patient's own stem cells. Monoclonal antibody therapy (brentuximab) may also be given.
• Radiation therapy may be given after stem cell transplant using the patient's own stem cells or if the cancer has not responded to other treatments and the area with cancer has not been treated before.
• High-dose chemotherapy with stem cell transplant using a donor's stem cells.
• A clinical trial of CAR T-cell therapy.
• A clinical trial of immunotherapy (pembrolizumab).

Treatment for childhood Hodgkin lymphoma causes side effects and late effects.

Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects. Because late effects affect health and development, regular follow-up exams are important.

Late effects of cancer treatment may include the following:

• Physical problems that affect the following:
  • Development of sex and reproductive organs.
  • Fertility (ability to have children).
  • Bone and muscle growth and development.
  • Thyroid, heart, or lung function.
  • Teeth, gums, and salivary gland function.
  • Spleen function (increased risk of infection).
• Changes in mood, feelings, thinking, learning, or memory.
• Second cancers (new types of cancer), such as breast, thyroid, skin, lung, stomach, or colorectal.

For female survivors of Hodgkin lymphoma, there is an increased risk of breast cancer. This risk depends on the amount of radiation the breast received during treatment and the chemotherapy regimen used. The risk of breast cancer is decreased if radiation to the ovaries was also given.

It is suggested that female survivors who received radiation therapy to the breast have a mammogram and MRI once a year starting 8 years after treatment or at age 25 years, whichever is later. It is also suggested that female survivors do a breast self-exam every month beginning at puberty and have a breast exam done by a health professional every year beginning at puberty until age 25 years.

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the possible late effects caused by some treatments.

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.

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.

For patients who receive chemotherapy alone, a PET scan may be done 3 weeks or more after treatment ends. For patients who receive radiation therapy last, a PET scan should not be done until 8 to 12 weeks after treatment ends.

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.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis and treatment options dependon the following:

• The stage of the cancer (the size of the cancer and whether the cancer has spread below the diaphragm or to more than one group of lymph nodes).
• The size of the tumor.
• Whether there are B symptoms (fever for no known reason, weight loss for no known reason, or drenching night sweats) at diagnosis.
• The type of Hodgkin lymphoma.
• Certain features of the cancer cells.
• Having more than the usual number of white blood cells or anemia at the time of diagnosis.
• Whether there is fluid around the heart or lungs at diagnosis.
• The sedimentation rate or the albumin level in the blood.
• How well the cancer responds to initial treatment with chemotherapy.
• The child's sex.
• Whether the cancer is newly diagnosed or has recurred (come back).

The treatment options also dependon:

• Whether there is a low, medium, or high risk the cancer will come back after treatment.
• The child's age.
• The risk of long-term side effects.

Most children and adolescents with newly diagnosedHodgkin lymphoma can be cured.