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Childhood Cancer: Lymphoma

The term lymphoma refers to cancers that originate in the body's lymphatic tissues. Lymphatic tissues include the lymph nodes (also called lymph glands), thymus, spleen, tonsils, adenoids, and bone marrow, as well as the channels (called lymphatics or lymph vessels) that connect them. Although many types of cancer eventually spread to parts of the lymphatic system, lymphomas are distinct because they actually originate there.

About 1,700 children younger than 20 years old are diagnosed with lymphoma each year in the United States. Lymphomas are divided into two broad categories, depending on the appearance of their cancerous (malignant) cells. These are known as Hodgkin's disease and non-Hodgkin's lymphoma (NHL). Together, they are the third most common type of cancer in children.

Hodgkin's Disease
This type of lymphoma is defined by the presence of specific malignant cells, called Reed-Sternberg cells, in the lymph nodes or in some other lymphatic tissue. Hodgkin's disease affects about three out of every 100,000 Americans, most commonly during early and late adulthood (between ages 15 and 40 and after age 55).

The most common first symptom of Hodgkin's disease is a painless enlargement of the lymph nodes (a condition known as swollen glands) located in the neck, above the collarbone, in the underarm area, or in the groin. If cancer involves the thymus (a gland of the immune system that is larger in children and located in the middle of the chest), pressure from this gland may trigger an unexplained cough, shortness of breath, or problems in blood flow to and from the heart. About a third of patients have other nonspecific symptoms, including fatigue, poor appetite, itching, or hives. Unexplained fever, night sweats, and weight loss are also common.

Non-Hodgkin's Lymphoma (NHL)
There are about 500 new cases of non-Hodgkin's lymphoma diagnosed each year in children in the United States. It may occur at any age during childhood, but is usually rare before age 3. NHL is slightly more common than Hodgkin's disease in children younger than 15 years of age.

In non-Hodgkin's lymphoma, there is malignant growth of specific types of lymphocytes (a kind of white blood cell that collects in the lymph nodes). Malignant growth of lymphocytes is also seen in one of the forms of leukemia (acute lymphoblastic leukemia, or ALL), which sometimes makes it difficult to distinguish between lymphoma and leukemia in children. In general, people with lymphoma have no or only minimal bone marrow involvement, whereas those with leukemia have extensive bone marrow involvement.

The development of some types of NHL, such as Burkitt's lymphoma, may have some link to the Epstein-Barr virus (the cause of infectious mononucleosis, or mono). Pieces of viral genetic material have been detected in some cells taken from patients with NHL.

Risk for Childhood Lymphoma
Both Hodgkin's disease and NHL tend to occur more often in white males and in people with certain severe immune deficiencies - including people with inherited immune defects, adults with human immunodeficiency virus (HIV) infection, or those who have been treated with immunosuppressive drugs after organ transplants.

Although no lifestyle factors have been definitely linked to childhood lymphomas, children who have received either radiation treatments or chemotherapy for other types of cancer seem to have a higher risk of developing lymphoma later in life.

In most cases, neither parents nor children have control over the factors that cause lymphomas to arise. Most lymphomas come from noninherited mutations (errors) in the genes of growing blood cells. Regular pediatric checkups can sometimes spot early symptoms of lymphoma in the relatively rare cases where this cancer is linked to an inherited immune problem, HIV infection, prior cancer treatment, or to treatment of immunosuppressive drugs for organ transplants.

Diagnosis
Your child's doctor will check your child's weight and perform a physical examination to look for enlarged lymph nodes and signs of local infection. He or she will also examine your child's chest using a stethoscope and will feel your child's abdomen to check for pain, organ enlargement, or fluid accumulation.

Sometimes, when a child is found to have an enlarged lymph node for no apparent reason, the doctor will watch the node closely to see if it continues to grow. The doctor may prescribe antibiotics if the gland is believed to be infected by bacteria. If the lymph node remains enlarged, the next step is a biopsy (the removal and examination of tissue, cells, or fluids from the body). Biopsies are also necessary for lymphomas that involve the bone marrow or structures within the chest or abdomen.

Depending on the location of the tissue to be sampled, the biopsy may be done using a thin hollow needle (known as needle aspiration) or a small surgical incision made under local anesthesia (the skin around the biopsy site will be numbed with medication). Sometimes, a biopsy may require a larger surgical incision under general anesthesia. This is the case in an excisional biopsy, where the entire enlarged lymph node or a chain of lymph nodes is removed.

In the laboratory, tissue samples obtained from the biopsy are examined to determine the specific type of lymphoma. In addition to these basic lab tests, more sophisticated tests are also generally done, including genetic studies, to distinguish between specific types of lymphoma.

To identify which areas of the body are affected by lymphoma, the following tests are also commonly used:

• blood tests, including complete blood count (CBC)
• blood chemistry, including tests of liver and kidney function
• bone marrow biopsy or aspiration
• lumbar puncture (spinal tap) to check for cancer spread to the central nervous system (brain and spinal cord)
• ultrasound
• computed tomography (CT) of the chest and abdomen or sometimes X-rays
• magnetic resonance imaging (MRI)
• bone scan or gallium scan (when a radioactive material is injected into the bloodstream to look for evidence of inflammation or bone tumors)

These tests are important for determining the spread of the lymphoma within the body and in deciding which type of treatment should be used.

Treatment

Treatment of childhood lymphoma is largely determined by staging. Staging is a way to categorize or classify patients according to how extensive the disease is at the time of diagnosis.

There are four stages of lymphoma, ranging from Stage I (cancer involving only one area of lymph nodes or only one organ outside the lymph nodes) to Stage IV (cancer has spread, or metastasized, to one or more tissues or organs outside the lymphatic system). The stage at diagnosis can guide medical professionals in the decision of therapy and helps doctors predict how someone with lymphoma will do in the long term.

Treatment will likely involve radiation (the use of high-energy rays to shrink tumors and keep cancer cells from growing), chemotherapy (the use of highly potent medical drugs to kill cancer cells), or both, depending on the type and stage of the cancer as well as the age and overall health of the child.

Children with Stage I Hodgkin's disease or NHL, for example, may be treated with radiation alone. For children with more advanced stages of at the time of diagnosis, chemotherapy is used, sometimes together with radiation.

Short-Term and Long-Term Side Effects

Intensive lymphoma chemotherapy affects the bone marrow, causing anemia and bleeding problems, and increasing the child's risk for serious infections. Chemotherapy treatments have side effects - some short-term, such as hair loss, changes in skin color, increased risk of infection, and nausea and vomiting, and some long-term, such heart and kidney damage, reproductive problems, or the development of another cancer later in life - that parents should discuss with their child's doctor.

Side effects of radiation include fatigue, loss of appetite, and skin reactions. When total-body irradiation is used prior to bone marrow transplant, there is an increased risk that the child will have slowed growth, thyroid problems, abnormal function of the ovaries or testicles, or cataracts.

Chances for a Cure

The majority of children with either Hodgkin's disease or NHL are cured, meaning they will have cancer-free survival for more than 5 years.

About 90% of children with Hodgkin's disease go into remission (where there is no longer evidence of cancer cells in the body) following initial chemotherapy. A long-term cure (5 years disease-free or longer) is achieved in almost all Stage I or Stage II patients, in up to 90% of Stage III patients, and more than 60% of those with Stage IV.

In children with NHL, 5-year survival is about 90% for those with Stage I or Stage II at the time of diagnosis, and close to 70% for those with more advanced Stage III or IV disease.

New Treatments

Although most children do recover from lymphoma, some children with severe disease will have a relapse (reoccurrence of the cancer) that doesn't respond to conventional treatments. For these children, bone marrow transplants and stem cell transplants are among the newest treatment options. During a bone marrow transplant, healthy bone marrow is introduced into a child's body in the hopes that it will begin producing white blood cells that will help the child fight infections. Stem cell transplants have the same goal, except they use stem cells (primitive cells found mainly in bone marrow and umbilical cord blood that are capable of developing into mature blood cells) to boost the child's immune system after high doses of radiation and chemotherapy.

Promising new treatments being developed for childhood lymphomas include several different types of immune therapy, specifically the use of antibodies to deliver chemotherapy medicines or radioactive chemicals directly to lymphoma cells. This direct targeting of lymphoma cells may prevent the toxic side effects that occur when today's chemotherapy and radiation treatments damage normal, noncancerous body tissues.