Hodgkin's Disease: Treatment

All of the available treatments for Hodgkin's disease have serious side effects, both short and long-term. However, with accurate staging, physicians and patients often can choose the minimum treatment that will cure the disease. The staging system for Hodgkin's disease is the Ann Arbor Staging Classification, also called the Cotswold System or the Revised Ann Arbor System.

Hodgkin's disease is divided into four stages, with additional substages:

• Stage I: The disease is confined to one lymph node area
• Stage IE: The disease extends from the one lymph node area to adjacent regions
• Stage II: The disease is in two or more lymph node areas on one side of the diaphragm (the muscle below the lungs)
• Stage IIE: The disease extends to adjacent regions of at least one of these nodes
• Stage III: The disease is in lymph node areas on both sides of the diaphragm
• Stage IIIE/IIISE: The disease extends into adjacent areas or organs (IIIE) and/or the spleen (IIISE)
• Stage IV: The disease has spread from the lymphatic system to one or more other organs, such as the bone marrow or liver

Treatment for Hodgkin's disease depends both on the stage of the disease and whether or not symptoms are present. Stages are labeled with an A if no symptoms are present. If symptoms are present, the stage is labeled with a B. These symptoms include:

• loss of more than 10% of body weight over the previous six months
• fevers above 100°F (37.7°C)
• drenching night sweats

Radiation therapy and/or chemotherapy (drug therapy) are the standard treatments for Hodgkin's disease. If the disease is confined to one area of the body, radiotherapy is usually used. This treatment, with x rays or other high-energy rays, also is used when the disease is in bulky areas such as the chest, where chemotherapeutic drugs cannot reach all of the cancer. External-beam radiation, a focused beam from an external machine, is used to irradiate only the affected lymph nodes. This procedure is called involved field radiation.

More advanced stages of Hodgkin's disease may be treated with mantle field radiation, in which the lymph nodes of the neck, chest, and underarms are irradiated. Inverted Y field radiation is used to irradiate the spleen and the lymph nodes in the upper abdomen and pelvis. Total nodal irradiation includes both mantle field and inverted Y field radiation.

Since external-beam radiation damages healthy tissue near the cancer cells, the temporary side effects of radiotherapy can include sunburn-like skin damage, fatigue, nausea, and diarrhea. Other temporary side effects may include a sore throat and difficulty swallowing. Longterm side effects depend on the dose and the location of the radiation and the age of the patient. Since radiation of the ovaries causes permanent sterility (the inability to have offspring), the ovaries of girls and young women are protected during radiotherapy. Sometimes the ovaries are surgically moved from the region to be irradiated.

If the Hodgkin's disease has progressed to additional lymph nodes or other organs, or if there is a recurrence of the disease within two years of radiation treatment, chemotherapy is used.

Chemotherapy utilizes a combination of drugs, each of which kills cancer cells in a different way. The most common chemotherapy regimens for Hodgkin's disease are MOPP (either mechlorethamine or methotrexate with Oncovin, procarbazine, prednisone) and ABVD (Adriamycin or doxorubicin, bleomycin, vincristine, dacarbazine). Each of these consists of four different drugs. ABVD is used more frequently than MOPP because it has fewer severe side effects. However MOPP is used for individuals who are at risk for heart failure. The chemotherapeutic drugs may be injected into a vein or muscle, or taken orally, as a pill or liquid.

Children who are sexually mature when they develop Hodgkin's disease, and whose muscle and bone mass are almost completely developed, usually receive the same treatment as adults. Younger children usually are treated with chemotherapy, since radiation will adversely affect bone and muscle growth. However, radiation may be used in low dosages, in combination with chemotherapy. The chemotherapy for children with Hodgkin's disease usually includes more drugs than ABVD and MOPP.

The side effects of chemotherapy for Hodgkin's disease depend on the dose of drugs and the length of time they are taken. Since these drugs target rapidly dividing cancer cells, they also affect normal cells that grow rapidly. These include the cells of the bone marrow, the linings of the mouth and intestines, and hair follicles. Damage to bone marrow leads to lower white blood cell counts and lower resistance to infection. It also leads to lower red blood cell counts, which can result in fatigue and easy bleeding and bruising. Damage to intestinal cells leads to a loss of appetite, nausea, and vomiting. Mouth sores and hair loss also are common side effects of chemotherapy. These side effects disappear when the chemotherapy is discontinued. Some drugs can reduce or prevent the nausea and vomiting.

Chemotherapy for Hodgkin's disease may lead to long-term complications. The drugs may damage the heart, lungs, kidneys, and liver. In children, growth may be impeded. Some chemotherapy can cause sterility, so men may choose to have their sperm frozen prior to treatment. Women may stop ovulating and menstruating during chemotherapy. This may or may not be permanent.

Treatment for higher-stage Hodgkin's disease often involves a combination of radiotherapy and chemotherapy. Following three or four chemotherapy regimens, involved field radiation may be directed at the most affected areas of the body. The long-term side effects often are more severe when radiation and chemotherapy are used in combination.

The development of a second type of cancer is the most serious risk from radiation and chemotherapy treatment for Hodgkin's disease. In particular, there is a risk of developing leukemia, breast cancer, bone cancer, or thyroid cancer. Chemotherapy, particularly MOPP, or chemotherapy in conjunction with radiotherapy, significantly increases the risk for leukemia.

RESISTANT, PROGRESSIVE, AND RECURRENT HODGKIN'S DISEASE. Following treatment, the original diagnostic tests for Hodgkin's disease are repeated, to determine whether all traces of the cancer have been eliminated and to check for long-term side effects of treatment. In resistant Hodgkin's disease, some cancer cells remain following treatment. If the cancer continues to spread during treatment, it is called progressive Hodgkin's disease. If the disease returns after treatment, it is known as recurrent Hodgkin's disease. It may recur in the area where it first started or elsewhere in the body. It may recur immediately after treatment or many years later.

Additional treatment is necessary with these types of Hodgkin's disease. If the initial treatment was radiation therapy alone, chemotherapy may be used, or vice versa. Chemotherapy with different drugs, or higher doses, may be used to treat recurrent Hodgkin's. However, radiation to the same area is never repeated.

BONE MARROW AND PERIPHERAL BLOOD STEM CELL TRANSPLANTATIONS. An autologous bone marrow and/or a peripheral blood stem cell transplantation

(PBSCT) often is recommended for treating resistant or recurrent Hodgkin's disease, particularly if the disease recurs within a few months of a chemotherapy-induced remission. These transplants are autologous because they utilize the individual's own cells. The patient's bone marrow cells or peripheral blood stem cells (immature bone marrow cells found in the blood) are collected and frozen prior to high-dosage chemotherapy, which destroys bone marrow cells. A procedure called leukapheresis is used to collect the stem cells. Following the high-dosage chemotherapy, and possibly radiation, the bone marrow cells or stem cells are reinjected into the individual.

— Rosalyn S. Carson-DeWitt, MD; Margaret Alic, Ph.D.