Childhood Hodgkin Lymphoma

Childhood Hodgkin lymphoma is a type of cancer that develops in the lymph system, part of the body's immune system. The lymph system 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 are located 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.

Lymph system; drawing shows the lymph vessels and lymph organs including the lymph nodes, tonsils, thymus, spleen, and bone marrow. One inset shows the inside structure of a lymph node and the attached lymph vessels with arrows showing how the lymph (clear fluid) moves into and out of the lymph node. Another inset shows a close up of bone marrow with blood cells. Source:NCI, ^[1]

Anatomy of the lymph system, showing the lymph vessels and lymph organs including lymph nodes, tonsils, thymus, spleen, and bone marrow. Lymph (clear fluid) and lymphocytes travel through the lymph vessels and into the lymph nodes where they destroy harmful substances. The lymph enters the blood through a large vein near the heart.

Because lymph tissue is found throughout the body, Hodgkin lymphoma can start anywhere and spread to almost any tissue or organ in the body.

Lymphomas are divided into two general types: Hodgkin lymphoma and non-Hodgkin lymphoma.

Hodgkin lymphoma can occur in both children and adults; however, treatment for children may be different than treatment for adults. There are two types of childhood Hodgkin lymphoma.

Types

• Classical Hodgkin lymphoma
• Nodular lymphocyte-predominant Hodgkin lymphoma

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

• Lymphocyte-rich classical Hodgkin lymphoma
• Nodular sclerosis Hodgkin lymphoma
• Mixed cellularity Hodgkin lymphoma
• Lymphocyte-depleted Hodgkin lymphoma

Stages of childhood Hodgkin 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. Treatment is based on the stage and other factors that affect prognosis. The following tests and procedures may be used in the staging process:

• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI). An MRI of the abdomen and pelvis may be done.
• 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 the glucose is being used. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
• Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for abnormal cells.

The letters "E" and "S" may be used to describe the stages of childhood Hodgkin lymphoma.

• E: Cancer is found in an organ or tissue that is not part of the lymph system but which may be next to an involved area of the lymph system.
• S: Cancer is found in the spleen.

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 group of lymph nodes.
• Stage IE: Cancer is found in one group of lymph nodes and has spread to a nearby organ or tissue that is not part of the lymph system.

Stage II

Stage II is divided into stage II and stage IIE.

• Stage II: Cancer is found in two or more lymph node groups on the same side of the diaphragm.
• Stage IIE: Cancer is found in two or more lymph node groups on the same side of the diaphragm and has spread from one of those lymph nodes to a nearby organ or tissue that is not part of the lymph system.

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 on both sides of the diaphragm.
• Stage IIIE: Cancer is found in lymph node groups on both sides of the diaphragm and has spread from one of these lymph nodes to a nearby organ or tissue that is not part of the lymph system.
• Stage IIIS: Cancer is found in lymph node groups on both sides of the diaphragm and in the spleen.
• Stage IIIE+S: Cancer is found in lymph node groups on both sides of the diaphragm and in the spleen, and has spread from one of these lymph node groups to a nearby organ or tissue that is not part of the lymph system.

Stage IV

In stage IV, cancer is found throughout one or more organs that are not part of the lymph system and may be in lymph nodes that are near or far away from those organs.

Untreated, classical childhood Hodgkin lymphoma is divided into risk groups based on the bulk of the tumor (tumors that are 5 centimeters or larger are considered "bulky") and whether the patient has "b" symptoms (fever, weight loss, or night sweats). Treatment is based on the risk group.

• Low-risk disease:
  • Patients with stage I or stage II disease; and
  • No bulky tumors or "b" symptoms.
• Intermediate-risk disease:
  • Patients with stage I or stage II disease, with bulky tumors, or with "b" symptoms; or
  • Patients with stage III or stage IV disease without "b" symptoms.
• High-risk disease: Patients with stage III or stage IV disease with "b" symptoms.

Childhood Hodgkin lymphoma is staged again after initial chemotherapy.

A PET or gallium scan is done after chemotherapy ends to find out how well the chemotherapy worked.

Primary progressive/recurrent Hodgkin lymphoma in children and Adolescents

Primary progressive Hodgkin lymphoma is lymphoma that continues to grow or spread during 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.

Signs and Symptoms

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

These and other symptoms may be caused by childhood Hodgkin lymphoma or by other conditions:

• Painless, swollen lymph nodes in the neck, chest, underarm, or groin
• Fever
• Night sweats
• Weight loss for no known reason
• Itchy skin

Diagnosis

Physical exams and medical histories, medical imaging, and laboratory tests are all used in the diagnosis of childhood Hodgkin lymphoma.

Physical exam and history

Doctors perform physical exams to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A medical history of health habits and past illnesses and treatments are also used to make a diagnosis.

Medical imaging

Medical imaging is used to find areas of rapidly dividing cells and tumor formation. Bone and gallium scans both employ radioactive markers that collect in rapidly growing cells. The former scan is specifically used to detect cancer in bone. Chest x-rays are used to image 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. A CT scan (CAT scan) makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

Laboratory tests

Lymph node biopsies partially or completely remove lymph node tissue. These biopsies are done in ne of several ways:

• Excisional biopsy: The removal of an entire lymph node.
• Incisional biopsy: The removal of part of a lymph node.
• Core biopsy: The removal of tissue from a lymph node using a wide needle.
• Fine-needle aspiration (FNA) biopsy: The removal of tissue from a lymph node using a thin needle.

A pathologist views the tissue under a microscope to look for cancer cells, especially Reed-Sternberg cells. Reed-Sternberg cells are common in classical Hodgkin lymphoma.

Reed-Sternberg cell; photograph shows normal lymphocytes compared with a Reed-Sternberg cell. Source:NCI ^[2]

Reed-Sternberg cell. Reed-Sternberg cells are large, abnormal lymphocytes that may contain more than one nucleus. These cells are found in Hodgkin lymphoma.

Another laboratory test used to diagnose Hodgkin lymphoma is the complete blood count (CBC). In this procedure, 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 (hematocrit).

Complete blood count (CBC); left panel shows blood being drawn from a vein on the inside of the elbow using a tube attached to a syringe; right panel shows a laboratory test tube with blood cells separated into layers: plasma, white blood cells, platelets, and red blood cells. Souce:NCI ^[3]

Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.

Blood is also drawn to determine the sedimentation rate and blood chemistry. In the former, 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. In the latter, the amounts of certain substances released into the blood by organs and tissues in the body are measured. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.

The type of malignant lymphocytes are identified by using immunophenotyping. This procedure involves examination of cells taken from the blood or bone marrow. The cells are examined under a microscope to identify changes in structure and composition that are characteristic of specific cancer types.

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

Treatment

Treatment options depend on the following:

• stage of the cancer
• tumor size and how quickly it shrinks after initial treatment
• symptoms when diagnosed
• certain features of the cancer cells
• whether the cancer is newly diagnosed, does not respond to initial treatment, or has recurred
• age and gender
• risk of long-term side effects

Most children and adolescents with newly diagnosed Hodgkin lymphoma can be cured.

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.

Treatment is 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:

• Medical oncologist /hematologist
• Pediatric surgeon
• Radiation oncologist
• Endocrinologist
• Pediatric nurse specialist
• Rehabilitation specialist
• Psychologist
• Social worker

Two types of standard treatment are used:

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type and stage of the cancer being treated.

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. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

New types of treatment are being tested in clinical trials. These include the following:

High-dose chemotherapy with stem cell transplant

High-dose chemotherapy with stem cell transplant is a way of giving high doses of chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. 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 chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These re-infused stem cells grow into (and restore) the body's blood cells.

Surgery

Surgery may be done to remove as much of the tumor as possible.

Low risk lymphoma

Treatment of low-risk childhood Hodgkin lymphoma may include the following:

• Combination chemotherapy with low- dose radiation therapy to involved areas.
• A clinical trial of combination chemotherapy with or without low-dose radiation therapy to involved areas.

Intermediate risk lymphoma

Treatment of intermediate-risk childhood Hodgkin lymphoma may include the following:

• Combination chemotherapy with low- dose radiation therapy to involved areas.
• A clinical trial of combination chemotherapy with or without low-dose radiation therapy to involved areas.
• A clinical trial of new combinations of chemotherapy before low-dose radiation therapy to involved areas.

High-Risk Lymphoma

Treatment of high-risk childhood Hodgkin lymphoma may include intensive or high-dose combination chemotherapy with low- dose radiation therapy to involved areas.

Nodular lymphocyte predominant lymphoma

Treatment of nodular lymphocyte predominant childhood Hodgkin lymphoma may include the following:

• Combination chemotherapy with low- dose radiation therapy to involved areas.
• Combination chemotherapy.
• Surgery.
• A clinical trial of surgery to remove a single lymph node.

Options for primary progressive/Recurrent Hodgkin lymphoma

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

• Chemotherapy with low- dose radiation therapy to involved areas for stage I or stage II non-bulky disease. Adolescent patients who have reached full growth may be treated with standard-dose radiation therapy.

Late effects from lymphoma treatment

Children and adolescents may have treatment-related side effects that appear months or years after treatment for Hodgkin lymphoma. Late effects may include problems with the following:

• Development of sex organs in males.
• Fertility (ability to have children)
• Thyroid, heart, or lungs
• An increased risk of developing a second primary cancer
• Bone growth and development

Outcome

The prognosis (chance of recovery) depends on the size and stage of the tumor, response to treatment, symptoms, characteristics of the tumor cells, and whether the cancer was newly diagnosed or recurred.

Treatment of childhood Hodgkin lymphoma is very effective, especially if detected early. Approximately 2% of children with Hodgkin lymphoma had died from 2001 to 2005.<rer name=nci> Natinal Cancer Institute Web site. [http://seer.cancer.gov/statfacts/html/hodg.html Hodgkin Lymphoma Fact Sheet.</ref>

Chances of Developing

According to the U.S. National Cancer Institute, 12% of Hodgkin lymphoma diagnoses from 2001 to 2005 had been made in people under the age of 20 years.</ref>ref name=nci />

Risk factors

Anything that increases the risk of getting a disease is called a risk factor. Having a risk factor does not mean that the disease will develop; not having risk factors does not mean that a disease will not develop. Below are some risk factors for childhood Hodgkin lymphoma:

• Being between the ages of 5 and 14. In children younger than 14 years, it is more common in boys than in girls.
• Being infected with the Epstein-Barr virus
• Having a brother or sister with Hodgkin lymphoma

Research

The influence of race on the outcome of treatment was examined in 327 Caucasian and African American children and teenagers with Hodgkin lymphoma. African American children were 3.7 times more likely to have a relapse of the cancer one year or more after treatment.^[4] However, 94.7% of Caucasian and 94.4% of African American children had been alive at the five-year endpoint of the analysis.

Other Resources

• National Cancer Institute

References

1. ↑ http://www.cancer.gov/cancertopics/pdq/treatment/childhodgkins/patient/
2. ↑ http://www.cancer.gov/cancertopics/pdq/treatment/childhodgkins/patient/
3. ↑ http://www.cancer.gov/cancertopics/pdq/treatment/childhodgkins/patient/
4. ↑ Metzger ML, Castellino SM, Hudson MM, et al. Effect of race on the outcome of pediatric patients with Hodgkin's lymphoma. J Clin Oncol. 2008 Mar 10;26(8):1282-8. ]Abstract

• Goldsby RE, Carroll WL. The molecular biology of pediatric lymphomas. J Pediatr Hematol Oncol. Jul-Aug 1998;20(4):282-96
• Hodgkin's Disease, Peter M. Mauch (Editor), James O. Armitage (Editor), Volker Diehl (Editor), June 1999.