Hodgkin's disease
Highlights
Drug Warning
Chemotherapy can cause anemia, a drop in red blood cell (hemoglobin) levels. Erythropoiesis-stimulating drugs, which boost the production of red blood cells, are administered to counteract this complication. However, these drugs, including epoietin alfa (Epogen, Procrit) and darbepoietin alfa (Aranesp), can also cause serious side effects and adversely affect survival when hemoglobin levels are raised too high.
In 2007, the U.S. Food and Drug Administration (FDA) made several changes to the prescribing labels for erythropoiesis-stimulating drugs. The new labels contain stronger warnings and updated dosing-related safety information.
The FDA advises that for treating anemia associated with chemotherapy, dosing should increase hemoglobin levels to no more than 12 g/dL. Treatment with these drugs should stop as soon as the chemotherapy course is completed. Erythropoiesis-stimulating drugs are not safe or appropriate for all patients undergoing chemotherapy. Patients should discuss the risks and benefits with their oncologists. The FDA is currently reviewing additional data concerning the safety of these drugs.
Preventing Infection after Cancer Treatment
Both chemotherapy and stem cell transplants increase the risk for serious infections. Patients must take precautions to avoid exposure to germs. Ways to prevent infection include:
- Practice good hygiene, including regular handwashing and dental care (brushing, flossing)
- Avoid crowds, especially during cold and flu season
- Eat only well-cooked foods (no raw fruits or vegetables)
- Boil tap water before drinking it
- Do not keep fresh flowers or plants in your house as they may carry mold
Introduction
Hodgkin's disease is a type of lymphoma. Lymphomas are cancers of the lymphatic system. They are generally subdivided into two groups: Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). NHL is discussed in another report. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas.]
HD is the major tumor in a group known as malignant lymphomas. Most often HD starts in B cell lymphocytes located in lymph nodes in the neck area, although any lymph node may be the site of initial disease.
Click the icon to see an image of the lymph nodes in the head and neck.
The following is a possible description of the process leading to HD:
- In early development, B cells normally undergo a series of genetic rearrangements until they create immunoglobulins, proteins that act as antibodies.
- Antibodies are produced by the immune system. They contain receptors that match and bind to a wide array of foreign substances (such as viral proteins) called antigens. Antibodies help launch an immune attack against antigens.
- B cells normally undergo limited cycles of genetic rearrangement that result in immunoglobulin production. In rare cases, however, the genetic arrangements create a mutation that does produce immunoglobulins. The results are large, abnormal cells referred to as Reed-Sternberg cells.
- Without immunoglobulin, Reed-Sternberg cells can be infected by certain viruses (notably the Epstein-Barr virus -- the cause of infectious mononucleosis). Genetic byproducts of these viruses appear to inhibit a natural process of self-destruction (called apoptosis) that would normally kill off these natural cells. Instead, the abnormal B cells grow non-stop, causing most forms of HD.
Click the icon to see an image of an antibody.
Only a very small percentage (about 1%) of cells found in the affected lymph tissues of HD are actually Reed-Sternberg cells. Researchers are unable to completely explain why so few cells can cause such severe symptoms. One explanation is that these cells trigger production of very powerful immune system proteins called cytokines (including those known as interleukin-1, interleukin-6, and tumor necrosis factor). These cytokines produce an inflammatory response that can cause local pain, fever, and other symptoms typical of HD. The dominance of different kinds of cytokines may also explain why HD takes different forms.
Classical Hodgkin's Lymphoma. Based on the variations and numbers of Reed-Sternberg cells, as well as other features, four major subtypes of classical HD have been identified:
- Nodular Sclerosis. Nodular sclerosis is the most common subtype, representing almost 60% of HD cases. Younger patients are more likely to have this type. The nodes first affected are often those located in the center of the chest (the mediastinum).
- Mixed Cellularity. Mixed cellularity is the next most common HD form, occurring in about 25% of patients, mostly in older patients, children, and those with immune disorders, such as AIDS. It usually indicates a more severe condition.
- Lymphocyte Depleted. Lymphocyte-depleted HD occurs in about 4% of patients, nearly always in elderly people. It indicates extensive disease and a poor outlook. It can easily be confused with non-Hodgkin's lymphoma.
- Lymphocyte-Rich Classical Hodgkin's Lymphoma. This form is similar to nodular lymphocyte predominant HD, but has more cell characteristics that conform to classical HD.
Nodular Lymphocyte-Predominant Hodgkin's Disease. Nodular lymphocyte-predominant Hodgkin's disease (LPHD) occurs in about 5% of patients. The cells in LPHD known as lymphocytic and histolytic cells are proving to be distinctly different from classic Reed-Sternberg B cells. Patients with lymphocyte predominance are usually young men, who often have no symptoms. LPDH is very slow growing and may be associated with long survival. There is a 3% risk, however, that LPDH will transform to non-Hodgkin's lymphoma. In fact, lymphocyte-predominant HD may eventually be defined as a non-Hodgkin's lymphoma.
Lymphomas represent tumors of the lymphatic system. This system is a network of organs, ducts, and nodes. The system interacts with the blood's circulatory system to transport a watery clear fluid called lymph throughout the body. The lymphatic system contains lymphocytes, which are important cells involved in defending the body against infections. This system also restores 60% of the fluid that leaks out from blood capillaries back into circulation. Its ducts provide transportation for fats, proteins, and other substances collected from the body's tissues.
Lymphocytes. The lymphatic system helps produce and transport lymphocytes, white blood cells that are a primary component of the immune system. Some lymphocytes produce antibodies that can target and attack specific foreign substances (antigens).
- Lymphocytes develop in the bone marrow or thymus gland. They are categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells).
- B cells complete their structural growth and definition (known as differentiation) and mature in the bone marrow.
- T cells also start out in the bone marrow, but differentiate and mature in the thymus gland, located beneath the breastbone (sternum). This small gland is active mostly in the fetal stage through the first 10 years of life, after which it shrinks.
- B-cell and T-cell lymphocytes leave these organs through the bloodstream, which eventually branches out into the tiny blood vessels called capillaries.
- Some lymphocytes, along with fluid, proteins, and other substances, move out of the capillaries into the surrounding tissues. Some enter the lymphatic vessels.
- Lymphatic vessels begin as tiny, blind-ended tubes. They lead to larger lymphatic ducts and branches, and drain into two ducts in the neck, where the fluid re-enters the bloodstream.
- Along the way, the fluid passes through lymph nodes, which are oval structures composed of lymph vessels, connective tissue, and white blood cells. Here, the lymphocytes are either filtered out or added to the contents of the node.
Lymph Nodes. In a lymph node, lymphocytes typically receive their initial exposure to foreign substances, such as bacteria. This exposure prompts the lymphocytes to perform their immune functions. The size of a lymph node varies generally from that of a pinhead to a bean. Most nodes are clustered throughout the body. Important node clusters are found in the neck, lower arm, armpit, and groin.
Other Structures in the Lymphatic System. The tonsils and adenoids are secondary lymphatic organs. They are composed of masses of lymph tissue that also play a role in the lymphatic system. The spleen is another important organ that processes lymphocytes from incoming blood.
Click the icon to see an animation about lymph nodes.
Click the icon to see an image of an antibody.
Click the icon to see an image of the immune system structures.
Risk Factors
Hodgkin’s disease accounts for about 11.5% of all types of lymphomas. According to the American Cancer Society, about 8,200 new cases of Hodgkin's disease (HD) were diagnosed in the United States in 2007 and about 1,000 people died of the disease. Experts believe that the malignant process leading to Hodgkin's disease is triggered by a combination of environmental and genetic factors along with a susceptible immune system. The exact triggers, however, are unknown.
Hodgkin's disease occurs most often in people between the ages of 15 - 40, (especially in the 20s), and in people over age 55. About 10 - 15% of Hodgkin’s disease cases are diagnosed in children and teenagers.
Hodgkin's disease is slightly more common among males than females. Women who get Hodgkin's disease appear to have a slightly lower risk for relapse after treatment than men.
Infectious mononucleosis (“mono”), which is caused by the Epstein-Barr virus (EBV), appears to increase the risk for Hodgkin’s disease. Research suggests that the virus activates some pathway within the lymphocyte cell that leads to cell proliferation. However, only 1 in 1,000 patients with mononucleosis develops Hodgkin's disease. The Epstein-Barr virus itself is present in 90% of the population and, in the great majority of these cases, causes a mild infection or none at all. Very few people who have had mononucleosis go on to develop HD. Other factors must be present to trigger the malignancy.
Hodgkin's disease runs in families in about 5% of cases. Siblings have three times more risk than the general population.
Symptoms
The onset of Hodgkin's disease symptoms is highest during late winter months, with lymph node enlargement usually being the first sign. Lymph nodes may be enlarged in the following regions:
- The most common first sign of Hodgkin's disease is painless enlargement of one or more lymph nodes above the diaphragm, most often those in the neck, chest, or armpits.
- Enlarged lymph nodes are often detected in the chest cavity between the lungs (the mediastinum), particularly in younger patients.
- Only about 15% of cases occur exclusively below the diaphragm.
Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site.
- If it spreads below the diaphragm, it usually reaches the spleen first; the disease may then spread to the liver and bone marrow.
- If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs.
Symptoms in or around the Lymph Nodes. Occasionally, patients may have a cough or chest pain if the disease is located in the middle of the chest, but usually the enlarged nodes produce no symptoms. Sometimes patients experience pain in the diseased lymph nodes after drinking alcohol.
Systemic (B) Symptoms. Between 20 - 40% of patients have systemic symptoms that affect the whole body rather than just the specific location of the disease. Some of systemic symptoms are referred to as B symptoms. Patients who have B symptoms have a more severe condition than asymptomatic patients with the same cancer stage or tumor location or size.
Systemic symptoms include:
- Drenching night sweats and weight loss (B symptoms)
- Fever -- may occur only at night in episodes that come and go (B symptoms)
- Itching all over the body -- caused by the release of histamines, substances ordinarily triggered by an allergic response. In the case of Hodgkin's disease, histamine release is due to abnormalities in the immune system. Although itching is a systemic symptom, it is not usually considered a B symptom if other systemic symptoms are not also present.
- Rash (late stages)
Many patients seek medical help for abnormally swollen lymph nodes (commonly referred to as “swollen glands”). Swollen glands can be caused by many conditions, most often infections, and are rarely serious.
Infections. In the great majority of cases, swollen glands are caused by an infection:
- For example, although Hodgkin's often first appears in the neck, enlarged lymph nodes in that location are much more likely to be a sign of strep throat, or other throat infections.
- Infectious mononucleosis (caused by the Epstein Barr virus) is a common cause of swollen lymph nodes in young people.
- Recent travel, particularly to countries with a high incidence of tropical diseases, can trigger similar symptoms.
- Other infections that cause similar symptoms include cat scratch fever, Lyme or other tick-borne disease, HIV, tularemia, tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, and hepatitis.
Non-Hodgkin's Lymphomas. Although both Hodgkin's disease and non-Hodgkin's lymphomas are malignancies of the lymph nodes, they can usually be distinguished by certain characteristics. It is extremely important to differentiate between Hodgkin's lymphomas and non-Hodgkin's lymphomas, since the treatments for these two conditions differ. In particular, a subtype of lymphoma called anaplastic large-cell lymphoma (ALCL) might be confused with Hodgkin’s disease under some circumstances. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas.]
Characteristics | Hodgkin's Disease | Non-Hodgkin's Lymphomas |
Age and Prevalence | Average age is 27.7 with two age peaks, the major one between 15 - 24 with a lesser peak after age 55. It is less common than NHL. | Average age is about 67. It is more common than HD. |
Location | In both malignancies, the disease occurs most often in lymph nodes above the collarbone. However, in HD it is also more likely to appear in the chest cavity between the lungs (the mediastinum), particularly in younger patients. Only about 15 - 20% of cases are found in areas below the diaphragm. Disease occurs outside the nodes in about 4% of cases. | In both malignancies, the disease occurs most often in lymph nodes above the collarbone. In NHL, however, it is also more likely to appear in the nodes in the abdomen (called the mesenteric nodes). The disease occurs in the chest cavity in less than 40% of patients. (An exception, lymphoblastic lymphoma, which is seen most often in young people, is likely to first appear in the chest.) Disease occurs outside the nodes in about 23% of patients. Slow-growing lymphomas are common in the liver and bone marrow. |
Symptoms | More likely than NHL (40%) to have systemic symptoms (such as fever and night sweats) at the time of diagnosis. | Less likely to have systemic symptoms (27%) at the time of diagnosis. |
Progression | Less likely than NHL to be diagnosed in stage IV (10%). Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site. If it spreads below the diaphragm, it usually reaches the spleen first; the disease then may spread to the liver and bone marrow. If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs. | More likely than HD to be diagnosed in stage IV (36%). The lymphomas are less predictable in their course than Hodgkin's disease and they are more apt to spread. |
Other Cancers or Serious Conditions in the Lymphatic System. Other cancers that can travel to lymph nodes include breast cancer and leukemia.
Very serious causes of enlarged lymph nodes include disorders of the lymph system that include Castleman's disease, lymphomatoid granulomatosis, and angioimmunoblastic lymphadenopathy. These lymph system disorders, although noncancerous, involve abnormal lymph cells. They are often fatal and can be very difficult to distinguish from lymphomas. Many of the other serious illnesses involving diseased lymph nodes develop simultaneously at multiple sites, while Hodgkin's nearly always starts at one location before spreading to nearby nodes. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas or Report #86: Acute lymphocytic leukemia.]
Exposure to Chemicals. Exposure to industrial chemicals or certain medications, such as phenytoin (Dilantin), may cause enlarged nodes. In addition, other drugs, such as cephalosporins, penicillins, or sulfonamides, can cause enlarged nodes and other symptoms, including fever and rash that may resemble Hodgkin's disease.
Diagnosis
The doctor will take a medical history and perform a physical examination. If these simple procedures point to Hodgkin's disease, a number of additional tests may be needed to either rule out other diseases or confirm HD and determine the extent of the cancer.
The doctor will examine not only the affected lymph nodes but also the surrounding tissues and other lymph node areas for signs of infection, skin injuries, or tumors. The consistency of the node is sometimes indicative of certain conditions. For example, a stony, hard node is often a sign of cancer, usually one that has metastasized (spread to another part of the body). A firm, rubbery node may indicate lymphoma (including Hodgkin's). Soft nodes suggest infection or inflammatory conditions.
Blood tests are performed to measure white and red blood cells, blood protein levels, the uric acid level, blood proteins, and the liver's function. Another blood test is the erythrocyte sedimentation rate (ESR), which is sometimes elevated in Hodgkin's disease (although it is not specific for this condition).
Click the icon to see an image of the formed elements of blood.
Chest X-Ray. A chest x-ray shows the lymph nodes in the chest and neck area, where Hodgkin's disease usually starts. It a useful step for detection of enlarged lymph nodes.
Click the icon to see an image of an x-ray machine.
Computer Tomography. Computed tomography (CT) scans are more accurate than x-rays. They can detect abnormalities in the chest and neck area, as well as revealing the extent of the cancer and whether it has spread. CT scans are used to evaluate symptoms and help diagnose lymphomas, help with staging of the disease, monitor response to treatment, and evaluate when the symptoms occur. A CT scan is also often used in detecting lymphomas in the abdominal and pelvic areas, the brain, and chest area.
Click the icon to see an image of a CT machine.
Positron Emission Tomography (PET). PET scans combined with CT scans can help doctors clarify the location of the cancer. PET scans can also provide information on whether or not an enlarged lymph node is benign or cancerous and are more accurate than CT scans or other imaging tests for staging lymphomas. PET scans may also help doctors determine how well a patient has responded to treatment, if any residual cancer exists, and if a patient has achieved remission.
A biopsy of the suspicious lymph node is the most definitive way to diagnose Hodgkin's disease. A biopsy has risks, and should be performed only by a qualified and experienced doctor. Sometimes a doctor may choose to wait and observe the involved lymph nodes, which will usually regress on their own if a temporary infection is causing the enlargement. However, some lymphomas may regress and appear to be benign, only to reappear at a later time.
The Procedure. During a biopsy, the doctor usually removes the node and checks the surrounding areas. The tissue in the node is then examined for signs of infection and blood cell or other abnormalities. Biopsies of bone marrow may also be performed in patients with existing Hodgkin's disease if the doctor suspects that it may have spread to the marrow.
Biologic markers, called biomarkers for short, are high levels of substances that are released by tumors and indicate the level of cancer activity. Biomarkers can be found in sputum, blood, and tissue samples. Biomarkers can be enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some under investigation include:
- CD44 is a molecule that binds to the surface of cells and may be involved in metastasis. High levels of this molecule may suggest a more aggressive disease.
- Interleukin (IL) 10 is another immune factor that may indicate a poor outlook when it occurs in high levels.
Outlook
Hodgkin’s disease is considered one of the most curable forms of cancer, especially if it is diagnosed and treated early. Unlike other cancers, Hodgkin's disease is even potentially curable in late stages. About 85% of patients with Hodgkin’s disease survive at least 5 years after cancer treatment. Five-year survival rates for patients diagnosed with stage I or II Hodgkin’s disease are 90 - 95%. Patients who survive 15 years after treatment are more likely to later die from other causes than Hodgkin’s disease.
Survival rates are poorest for:
- Those who relapse within a year of treatment
- Patients who do not respond to the first-line therapy and have signs of disease progression
The good news about Hodgkin's disease is that treatment can cure the disease. The bad news is that survivors face a higher than average risk for long-term complications of these treatments, some very serious.
Many patients may experience chronic fatigue that could persist for years. One study indicated that aerobic exercise may significantly improve fatigue; in doing so it could have a positive effect on mood as well.
The most serious complications are secondary cancers and heart disease, which occur over the 2 - 3 decades following treatments. Secondary cancers include non-Hodgkin's lymphoma, leukemia, melanoma, stomach and lung cancers, and breast and uterine cancers. Heart disease complications include coronary artery disease, stroke, heart valve problems, and cardiomyopathy (weakening of the heart muscle). Thyroid disorders are also a potential complication. Combinations of radiation and chemotherapies are especially associated with these problems.
A 2006 study in the New England Journal of Medicine evaluated the long-term health status of adult survivors of various childhood cancers. The study found that, 30 years after treatment, patients with Hodgkin’s disease had among the highest risk of developing serious health problems. Female survivors had a significantly greater risk than male survivors. In particular, women who received chest radiation are at very high risk for developing breast cancer. Still, in a 2000 study, 20 years after treatment, 90% of patients who had survived treatments were still living.
Patients with Hodgkin’s disease should get a written record of the treatments they received as children, and the potential risks of these treatments. These records can help the doctors who later oversee their care monitor for potential health problems. Survivors of Hodgkin’s disease should receive regular screening tests for cancer and heart disease. They may need to get these tests at a younger age than most patients. In particular, patients who were treated with chest radiation should get blood tests every 5 years to measure their cholesterol levels. Female patients who received chest radiation should get early and frequent mammograms.
Although HD is highly curable, it can have many psychologic consequences. Depression and anxiety are common in survivors, particularly those who suffer additional medical conditions. Fatigue persists in the majority of patients for years. Still, many survivors have an excellent quality of life.
Staging and Treatment Guidelines
Multiple treatment approaches are available for patients with Hodgkin's disease at nearly every stage, often resulting in similar rates of cure. Ultimately, the choice of treatment is based on a consideration of various prognostic factors as well as treatment side effects, both short and long term. Treatment decisions are individualized, and patients should discuss the pros and cons of various approaches with their doctors.
Staging the disease according to how far the cancer has spread (I through IV) is a primary method for determining both treatment options and prognosis. There are two levels of staging: Clinical staging and pathological staging.
- Clinical stages are determined by conducting a thorough examination, which may include blood tests and different kinds of x-rays.
- Pathologic staging is conducted after a laparotomy and biopsy of the tissue to help determine treatment options. It involves a much more detailed examination, but is not required as often as in the past for making treatment decisions.
In general, the prognosis according to stage is as follows:
- If the disease is treated in stages I or II, the cure rates are as high as 90%. (Slightly more than half of all patients are diagnosed in these stages.)
- Patients in stages III or IV are usually diagnosed with advanced Hodgkin's disease. (Even in such stages, survival at 5 years can be as high as 85%.)
The staging system can be further refined according to other features or factors that indicate a more or less severe condition and can help determine whether treatments should be more or less aggressive.
Presence or Absence of B Symptoms. For example, stages I through III are further categorized as either A or B according to whether certain widespread symptoms are absent (A) or present (B). The presence of B symptoms increases the risk of relapse.
- The patient is classified as B if they have unexplained weight loss of more than 10% within 6 months, unexplained fever, and drenching night sweats. Fever and weight loss are the most important indications of B symptoms; night sweats alone do not always mean that such symptoms are present. Itching by itself is not considered a reliable B symptom.
- If the patient has none of these symptoms, the disease is considered at A, which is less severe than the B form at any stage.
- Another letter used to further refine a stage is E, which indicates that the malignancy is still local but has gone beyond the lymph node into surrounding tissue.
Indicators for Aggressive Treatments. Certain factors are indicators of a more serious case at any stage and the need for aggressive treatment:
- The malignancy is "bulky" (a large mass)
- Blood tests show high levels of erythrocyte sedimentation rates
- Multiple tumors in the spleen
- Greater involvement in the abdomen
Even if a patient has stage II disease, the presence of a bulky tumor or multiple tumors in the spleen indicates the patient may be treated as if they had advanced Hodgkin's disease.
Cell Types. The cell type of Hodgkin's disease may also influence treatment. For example, those with mixed cellularity type might require more aggressive therapy in certain cases than those with a slower-growing form, such as lymphocyte-predominant Hodgkin's disease (LPHD). In fact, some studies suggest that LPHD is the mildest form of Hodgkin's disease and that patients with LPHD are more likely to die of treatment-related disease than from Hodgkin's itself. Some experts are investigating the role of limiting radiation doses in such patients, although the most optimal approach is not yet known.
Other Prognostic Risk Factors. The International Prognostic Factors Project on Advanced Hodgkin’s Disease has developed seven factors that help determine which patients with advanced Hodgkin's disease would benefit from more or less aggressive chemotherapy. They are also useful to help determine success in patients with relapsed or persistent HD who are undergoing stem cell transplantation. The score is determined by the number of yes answers to the following questions. The more yes answers, the more likely the patient needs to be treated aggressively:
- Is the patient male?
- Is the patient older than 45?
- Does the patient have stage IV disease?
- Does the patient have blood tests showing lower than normal albumin levels? (Albumin is a protein found throughout the body.)
- Does the patient have abnormally low hemoglobin levels? (Hemoglobin is the oxygen-carrying compound in red blood cells, so low levels suggest anemia.)
- Does the patient have an abnormally high white blood cell count (15,000 or more)?
- Does the patient have abnormally low levels of lymphocytes?
To avoid putting patients through unnecessary treatments that may actually be as or even more lethal than the disease itself over time, doctors are attempting to identify more specifically those patients who would or would not benefit from aggressive therapy.
Preventing Infection. Both the disease and some of the treatments suppress the immune system, increasing the risk for infections. Widespread, life-threatening infection is a particular danger if the spleen has been removed and both radiation and chemotherapy are administered. A week before any treatment, patients are often vaccinated against three bacteria: pneumococcus, meningococci, and Haemophilus influenza.
Measures for Infertility. People who wish to have children should discuss the possibility for receiving treatments that may lessen the risk for infertility. Examples include the following:
- Men with Hodgkin's disease may want to consider sperm freezing and assisted reproductive techniques. One encouraging study on male survivors of childhood Hodgkin's disease, reported that although treatments had reduced their sperm count and quality, the actual genetic material was healthy. Such men, then, would still be good candidates for assisted reproductive techniques.
- Women should ask their doctors about the possibility for preserving fertility by taking hormonal drugs called GnRH analogs before and during chemotherapy.
[For more information on fertility preservation treatments, see In-Depth Report #67: Male infertility and In-Depth Report #22: Female infertility.]
Considerations During Pregnancy. Women who are pregnant need special preparation and treatments.
Periodic examination for recurrent Hodgkin's disease is necessary for years after treatment, since relapse is not uncommon, even after treatment for early stages, and can occur a decade or more after treatment. Chest x-rays and CT scans of the abdomen are useful for detecting relapsed disease. Relapse is more likely to occur in early-stage disease, probably because limited radiation normally used in such cases did not destroy all malignancies. Patients who had large tumors in the chest are also at higher risk for recurrence. Patients also need to be monitored for long-term effects of the treatments themselves. Conditions to watch for include inflammation in the lungs and thyroid disease from radiation in the chest and heart disease and cancers from combined treatments, chemotherapy (particularly the use of MOPP), and blood stem cell transplantation.
Because Hodgkin's disease often occurs in young adults, treatment for pregnant women is of particular concern. Therapy must be effective enough to protect the mother without hurting the fetus. Treatment choice must be individualized, taking into consideration the mother's wishes, the severity and pace of the disease, and the length of the remaining pregnancy. The treatment plan may need to be changed as the pregnancy progresses.
Early in the Term. Unfortunately, an abortion may sometimes be the most prudent approach if the disease occurs in the first trimester. Chemotherapy is rarely used during that period, because it poses a risk for birth defects. Deciding on a course of action when Hodgkin's disease occurs in the first trimester is very difficult and emotionally wrenching. Prospective parents should not be shy about consulting with more than one doctor if they are uncertain about how to proceed.
Later in the Term. If the disease develops in the second half of the pregnancy, it may be possible to postpone therapy until after an early induced delivery. Alternatively, some evidence suggests that chemotherapy in pregnant women after the first trimester may be beneficial without harming the fetus. If full-dose standard chemotherapy is not deemed possible, vinblastine alone may be beneficial; this drug is not usually associated with fetal abnormalities in the second half of pregnancy.
Steroids may also be used late in the pregnancy both because of their antitumor effect and their effect in hastening fetal lung maturity. As an alternative, a short course of radiation (with extensive shielding of the fetus) can sometimes be considered prior to delivery if the mother is experiencing lung problems because of a rapidly enlarging mass in the chest. Combination chemotherapy may also be safe in the second half of pregnancy.
In one study, the 20-year survival rate of pregnant women with Hodgkin's disease was no different from that of nonpregnant women matched for similar stage of disease and age at diagnosis.
Treatment Options by Stage
Treatment is guided by the stage of the disease and usually relies on the location and extent of the disease. Treatment may vary within a stage, depending on whether it is categorized as either A or B. (Systemic symptoms are absent in "A" and present in "B.”) The presence of B symptoms increases the risk of relapse, and so may require more aggressive treatments for that stage.
Early Stages (I or II). For disease in stages I or II, the following treatments may be used:
- Treatment in Adults. Doctors usually recommend radiation first for adults with HD. It provides excellent remission rates, although studies have reported a number of serious long-term complications in some patients. Selected patients in early stages may also be candidates for radiation limited only to areas above the diaphragm (called the mantle field), which can also have excellent results although still pose a considerable risk for late serious complications.
- Treatment in Children. Chemotherapy and low-dose radiation is the standard treatment for most children and adolescents who have not reached full growth. Specific chemotherapy combinations have been developed to reduce the risks for infertility, leukemia, and toxic effects on the heart and lungs. Researchers are studying the use of chemotherapy alone in this group.
Later Stages. For stage III disease, chemotherapy, often with radiation, is a standard treatment. For stage IV disease, chemotherapy alone is generally recommended. The latest chemotherapy regimens are achieving survival rates that reach 90%.
Relapse. Relapse after treatment occurs in 20 - 35% of patients. Treatments for relapse include chemotherapy, radiation, and bone marrow or blood stem cell transplantation. Many patients respond favorably to such treatments, although another relapse is still possible.
Click the icon to see an illustrated series detailing bone marrow transplant surgery.
Disease is limited to a single node region (I) or has involved one neighboring area or a single nearby organ (IE). The standard treatment for stage I disease is usually radiation for adult patients who have determined the stage using pathologic staging with laparotomy. Chemotherapy with low-dose radiation is now the standard approach for children and adolescents. Cure rates can be greater than 90%.
Stage IA. Treatments depend on location. For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:
- Radiation therapy to the mantle field (chest, neck, and arm pits) and to the lymph nodes in the upper abdomen and spleen
- Radiation therapy to a mantle field in certain patients -- best candidates are females with nodular sclerosis or lymphocyte predominant cell types, who are no older than 40 years, have no "B" symptoms, and have erythrocyte sedimentation rate (ESR) levels less than 50
- Radiation therapy to a mantle field, the lymph nodes in the upper abdomen, and the spleen (subtotal node irradiation)
- Chemotherapy alone is under investigation
If the malignancy is bulky, above the diaphragm, and involves a large part of the chest, chemotherapy plus radiation therapy is commonly used.
If the malignancy is below the diaphragm, treatment includes chemotherapy with or without radiation. Radiation therapy may be directed to the lymph nodes in the upper abdomen and pelvis, and sometimes the spleen or groin. Total nodal irradiation is an option which includes these regions plus the mantle field.
Stage IB. Treatments depend on location. For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:
- Chemotherapy plus radiation therapy to a mantle field (in patients who have severe symptoms and did not undergo laparotomy to determine the extent of the disease below the diaphragm)
- Radiation therapy to the mantle field and to the lymph nodes in the upper abdomen is sometimes considered, but relapse rate can be high if significant B symptoms are present
- Chemotherapy alone under investigation for children
If the malignancy is bulky, above the diaphragm, and involves a large part of the chest, chemotherapy plus radiation therapy is commonly used.
If the malignancy is below the diaphragm, treatment includes chemotherapy with or without radiation to the upper abdomen and pelvis, to the areas that contain cancer, or to the spleen. Total nodal irradiation or radiation to lymph nodes in the upper abdomen and pelvis is another option.
Disease is limited to two or more lymph nodes on the same side of the diaphragm (II) or involvement of a single neighboring organ or area and one or more nearby lymph nodes; other lymph nodes on the same side of the diaphragm may be involved (IIE).
There are few differences between treatments for stage IIA and IIB, and the approach for both depends on the extent and location of the disease:
Non-bulky disease:
- Radiation alone for adult and possibly adolescent (especially male) patients
- Chemotherapy with low-dose radiation is used for children
For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:
- Radiation therapy to a mantle field and to the lymph nodes in the upper abdomen
- Radiation therapy to a mantle field only (See Stage I Hodgkin's Disease section above)
Chemotherapy alone or with radiation therapy (combined modality) is being evaluated for those with non-bulky stage IIA. Also under investigation is radiation therapy to a mantle field only in patients with lymphocyte predominant cell types, who are no older than 40 years.
If the malignancy is above the diaphragm and does involve a large part of the chest, chemotherapy plus radiation therapy to a mantle field is the common approach.
If the malignancy is below the diaphragm, treatment includes chemotherapy with or without radiation to the upper abdomen and pelvis, and possibly the spleen. Total nodal irradiation is another option.
Disease is in lymph nodes on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an associated organ or site outside the lymph node (IIIE), by involvement of the spleen (IIIS), or by both (IIIE+S). In addition, stage III may be further categorized by the extent of its spread into the spleen or where it has spread in the abdominal area. Survival rates in some cases can be as high as 90%.
Stage IIIA. Chemotherapy is the most common treatment approach for most adults and children. Radiation may be added under certain circumstances, especially to provide localized treatment of bulky areas. (Radiation does not appear to offer any survival advantage for patients whose disease is in complete remission after chemotherapy.)
For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:
- Chemotherapy alone
- Chemotherapy with radiation therapy (combined modality)
- Total or subtotal nodal radiation therapy alone -- for adults if disease is only in the upper abdomen and fewer than five nodes in the spleen are affected
If the malignancy involves a large part of the chest, the following may be used:
- Standard chemotherapy alone
- Chemotherapy plus radiation therapy (combined modality)
- Investigative treatments
Stage IIIB. Chemotherapy alone is the standard treatment for most adults and children. Radiation is often added to treat areas of bulky tumor.
Disease has spread to organs outside the lymph system, such as liver, lung, or bone marrow. Even in this population, high long-term survival rates of over 85% are possible, including in children.
Treatment may include:
- Chemotherapy alone
- Chemotherapy with limited radiation to places of bulky disease
- A clinical trial of investigational chemotherapy regimens or of stem-cell transplantation
Click the icon to see an image of liver involvement in Hodgkin's disease.
When disease recurs or persists after initial treatment either in the same area or in another part of the body, the next round of therapy depends on where the disease returns and the previous treatment used.
- If the previous treatment was radiation therapy without chemotherapy, salvage chemotherapy is the usual choice.
- If the patient was previously treated with chemotherapy, the choice may be radiation therapy to the lymph nodes with or without salvage chemotherapy.
- In some patients, if the disease has persisted or if relapse has occurred after chemotherapy with or without radiation, high-dose chemotherapy and stem cell transplantation may be given.
Radiation Treatments
High-dose radiation therapy, which shrinks the tumors, has been used for more than 50 years for treating Hodgkin's disease. High-dose radiation is generally reserved for adults. Radiation treatments are highly toxic for children and appear to add little benefit. In such young age groups radiation is mostly used if there are large areas of disease in the chest; otherwise, chemotherapy with possibly low-dose radiation is the best option with excellent survival rates.
Radiation is directed to specific areas depending on the location of the disease:
- If HD is above the diaphragm, “extended field radiation” is delivered to the neck, chest, and under arms (called the mantle field). Extended-field radiation is sometimes expanded to include lymph nodes in the upper abdomen.
- If cancer is below the diaphragm, an "inverted Y" field is sometimes used, in which radiation is directed at lymph nodes in the upper abdomen, spleen, and pelvis.
- Inverted Y-field radiation therapy combined with mantle-field radiation is called “total nodal radiation.”
- "Involved field radiation" targets only lymph node regions that are known to have cancer. By contrast, extended-field radiation targets lymph node regions with cancer as well as adjacent, uninvolved lymph node regions. Involved-field radiation is usually given after several rounds of chemotherapy.
A 2006 study indicated that radiation therapy alone, without chemotherapy, may help older patients with early-stage Hodgkin’s disease. If chemotherapy is given, another 2006 study suggested that involved-field is a better option than extended-field radiation for elderly adults with early-stage unfavorable Hodgkin’s lymphoma.
In general, recent research suggests that extended-field radiation adds little survival advantage and carries a greater risk of serious side effects. Involved-field radiation is now becoming the preferred method. Some researchers recommend that involved-field radiation therapy plus chemotherapy should become the standard treatment for patients with early-stage Hodgkin’s disease who have a good prognosis. More research is needed before standard practice guidelines can be implemented.
It is very important that radiation treatments cover the entire diseased area and that the radiation therapy be powerful enough to destroy the malignant cells' capacity to grow and divide. Unfortunately, this means that normal cells are also affected, which can cause serious side effects. Different approaches may be used to prevent complications.
- Devices called planning simulators allow doctors to plan x-ray treatments that accurately conform to the patient's anatomy so that protective shields can be created to precisely protect the regions outside the treatment areas.
- Long-term complications generally occur at higher radiation doses (over 35 Gy). Investigators are studying the doses as low as 20 Gy (in children). Studies indicate that radiation alone in doses under 35 Gy can control the disease as well as higher doses in most stage I and II patients, although some patients may require more aggressive treatment.
- To protect ovaries, a technique called ovarian transposition may sometimes be performed. The procedure uses a laparoscope (a thin tube containing tiny instruments and cameras) that is introduced through a small incision. The doctor uses the laparoscope to move the ovaries out of the range of areas being treated with radiation.
Infections. Infections may be a particular problem with radiation combined with chemotherapy. All patients should be vaccinated against pneumonia and influenza.
Inflammation in the Lungs. With carefully conducted therapy, the risks for lung complications are small. Lung impairment may not even be evident, and the lungs usually recover after 2 - 3 years.
Click the icon to see an image of the lungs.
Infertility. Radiation therapy to the pelvic area can adversely affect later fertility in women and men. Such negative effects may be worse in women; sperm usually recover within 5 years.
Heart Disease and Stroke. Radiation is associated with a future risk of heart disease, which includes atherosclerosis (hardening of the arteries) and diseases of the heart valves. Lower doses pose less risk. Recent research suggests that adults who survived childhood Hodgkin’s disease have a four times higher risk of having a stroke than healthy patients.
Fatigue. Fatigue is significant and chronic in many survivors. It is more highly associated with intensive chemotherapy, but it also may be a late response to radiation treatment.
Secondary Cancers. Second cancers (such as breast, stomach, lung, melanoma) may develop later in areas within or at the edge of the radiation area. Thyroid, respiratory tract, and digestive tract secondary cancers may affect patients who were treated as children. The risks are twice as high with treatments that are combined with chemotherapy.
Lung cancer in survivors is highly associated with smoking after treatment, and no survivor should smoke. The risk for breast cancer increases significantly in young women after treatment, particularly with high radiation doses and combined chemotherapy and radiation. The risk can persist for 25 years or more after radiotherapy, and lifetime monitoring (including frequent mammograms) is essential.
Thyroid Disorders. Hypothyroidism (underactive thyroid) occurs in a number of patients treated with radiation treatments. There is also a 5% chance for hyperthyroidism (overactive thyroid).
Click the icon to see an image of hypothyroidism.
Click the icon to see an image of hyperthyroidism.
Impaired Growth in Children. Children and adolescents are at special risk for impaired bone growth.
Chemotherapy
Chemotherapy uses drugs to kill cancer cells. The drugs are called cytotoxic medications. Chemotherapy is referred to as body-wide, or systemic, therapy because the drugs travel throughout the entire body.
Cytotoxic drugs may be taken by mouth or given by injection. Treatment may be administered at a medical center, doctor's office, or even a patient's home. Some patients receiving chemotherapy may need to remain in the hospital for several days so the effects of the drug can be monitored.
Patients may receive 4 - 8 cycles of chemotherapy, depending on the stage. A cycle is usually 28 days and consists of several doses of drug administration followed by a period of rest.
The standard chemotherapy regimens for Hodgkin’s disease are ABVD and Stanford V.
ABVD consists of a 4-drug combination:
- Doxorubicin (Adriamycin)
- Bleomycin
- Vinblastine
- Dacarbazine
Stanford V consists of a 7-drug combination:
- Doxorubicin (Adriamycin)
- Mechlorethamine (nitrogen mustard)
- Vincristine
- Vinblastine
- Bleomycin
- Etoposide
- Prednisone
BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) is a chemotherapy regimen reserved for high-risk patients. This regimen is proving to be extremely effective, particularly in advanced stages, with studies reporting remission rates of over 95% in patients with advanced Hodgkin's. However, this regimen also increases the risk for developing secondary cancers such as leukemia. Patients who are treated with BEACOPP should receive long-term follow-up care to monitor for side effects from this therapy.
Side effects and complications of any chemotherapeutic regimen are common, are more severe with higher doses, and increase over the course of treatment, though some trials suggest that toxicities can be reduced by administering the drugs for shorter duration without loss of cancer-killing effects.
Common Side Effects. Common side effects include the following:
- Nausea and vomiting -- drugs known as serotonin antagonists, including ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs.
- Diarrhea
- Hair loss
- Weight loss
- Depression
These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days a month.
Serious Side Effects. Serious side effects can also occur and may vary depending on the specific drugs used. They include:
- Neutropenia is a severe drop in white blood cells. Neutropenia increases the chance for infection from suppression of the immune system and is a potentially life-threatening condition. Drugs known as granulocyte colony stimulating factor (G-CSF) are used to help boost white blood cell count. These drugs, which include filgrastim (Neupogen) and pegfilgrastim (Neulasta) can help lessen the risk for neutropenia occurrence and, if neutropenia does occur, to reduce its length and severity.
- Anemia is a lack of red blood cells. Erythropoietin stimulates red blood cell (hemoglobin) production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). In 2007, the FDA released strict dosing guidelines for these drugs. In patients with cancer, they should be used to only treat anemia associated with chemotherapy and to increase hemoglobin levels to no more than 12 g/dL. Treatment should stop as soon as chemotherapy is complete. These drugs may not be safe or appropriate for all patients.
- Infection. Patients must take precautions against infections (see "Infection Prevention" in Transplant section).
- Liver and kidney damage
- Abnormal blood clotting (thrombocytopenia)
- Allergic reaction
Long-Term Complications.
- Fatigue and general aches and pains are called somatic symptoms. Fatigue is especially common after chemotherapy and can even last for years.
- Many women stop menstruating after chemotherapy. The risk for infertility is highest for women with advanced stage Hodgkin’s disease who are treated after age 30. Studies indicate that the risk for infertility is higher with BEACOPP than with ABVD. Researchers are studying whether taking oral contraceptives during chemotherapy can reduce the risk.
- Bone thinning (osteoporosis) may be related to steroid treatments such as prednisone.
- Heart failure may occur with the use of anthracyclines (such as doxorubicin).
- Bleomycin (Blenoxane), an antibiotic, is particularly toxic to the lungs. Vinblastine may also pose a risk when used in combination with radiation therapy.
In general, these serious late side effects are dependent on the cumulative drug dose and rate of administration.
Regimens. Chemotherapy (usually ABVD) plus radiation, referred to as combined modality, is a common treatment approach for patients with more advanced-stage disease and for those who have early-stage bulky (large mass) disease.
Chemotherapy with low-dose radiation is being used in children with excellent results, even for late stage cancer. In one study, 82% of the children were still disease free at 5 years. Some chemotherapy drugs or high doses of radiation may be more deleterious to a boy's future fertility than to a girl's. A gender-specific combined regimen for pediatric Hodgkin's reduces the amount of radiation given to boys and also substitutes etoposide for procarbazine in the chemotherapy mixture (procarbazine, vincristine, prednisone, and doxorubicin).
Side Effects and Long-Term Complications. Side effects of combination treatments can be very serious. Examples include:
- Combined modality poses a higher risk for secondary cancers than the use or radiation or chemotherapy alone. They include breast, lung, thyroid, melanoma, and gastrointestinal cancers, which usually develop in near or in the areas treated with radiation. Of note, the risk for breast cancer is lower when chemotherapies using alkylated drugs or radiation treatments damage the ovaries, suggesting that hormone stimulation plays a role in this higher risk. Newer drugs used in combined modalities may reduce the risk, at least for breast cancer.
- ABVD and other regimens containing bleomycin increase the risk for severe effects on the lungs when used before or after mantle-field radiation. EVA (etoposide, vinblastine, and doxorubicin) is considered to be an effective substitute in patients with lung disease for whom bleomycin and radiation present an unacceptable risk.
Transplantation
Patients with relapsed or progressive HD are often treated with high-dose chemotherapy followed by stem cell transplantation procedures. (Transplantation does not appear to offer an advantage compared to standard chemotherapy as initial treatment for patients with high-risk advanced HD.)
This treatment involves removal and replacement of stem cells, which are produced in the bone marrow. This allows the patient to receive high-dose chemotherapy without destroying these important cells. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments harm growing cells as well as cancer cells, and so the healthy stem cells must be replaced by transplanting them.
For Hodgkin’s disease, the most common type of transplant is an autologous procedure, using the patient’s own cells. An allogeneic transplant, using cells from a donor, is more risky for patients with Hodgkin’s disease and is generally used only when an autologous transplant has failed. (This section provides information pertinent to autologous procedures. Detailed information on allogeneic transplants, including such complications as graft-versus-host-disease, can be found in In-Depth Report #84: Non-Hodgkin’s Lymphoma.)
Stem cells must first be collected in one of the following ways:
- Directly from blood (peripheral blood stem cell transplantation)
- From bone marrow (bone marrow transplantation)
Click the icon to see an illustrated series detailing bone marrow transplant surgery.
Stem cells are collected several weeks before the procedure. They are frozen and stored while the patient undergoes high-dose chemotherapy. Some patients receive high-dose whole body radiation therapy along with chemotherapy.
After the patient completes the pre-transplant therapy, the frozen cells are thawed and then infused into the patient. Within a few weeks, these cells start to generate new white blood cells and then new red blood cells.
The risk for infection is greatest during the first 6 weeks following the transplant. During this period, a patient usually remains in isolation and receives antibiotics and intravenous nutrition. It takes 6 - 12 months post-transplant for a patient’s immune system to fully recover.
Many patients develop severe herpes zoster virus infections (shingles) or have a recurrence of herpes simplex virus infections (cold sores and genital herpes). Pneumonia, cytomegalovirus, aspergillus (a type of fungus), and Pneumocystis carinii (a protozoan) are among the most important life-threatening infections.
It is very important that patients take precautions to avoid infections. Guidelines for infection prevention include:
- Discuss with your doctor what vaccinations you need and when you should get them.
- Avoid crowds, especially during cold and flu season.
- Be diligent about handwashing, and make sure that visitors wash their hands.
- Avoid eating raw fruits and vegetables -- food should be well cooked. Do not eat foods purchased at salad bars or buffets. In the first few months after the transplant, be sure to eat protein-rich foods to help restore muscle mass and repair cell damage caused by chemotherapy and radiation.
- Boil tap water before drinking it.
- Dental hygiene is very important, including daily brushing and flossing. Schedule regular visits with your dentist.
- Do not sleep with pets. Avoid contact with pets’ excrement.
- Avoid fresh flowers and plants as they may carry mold. Do not garden.
- Swimming may increase exposure to infection. If you swim, do not submerge your face in water. Do not use hot tubs.
- Report to your doctor any symptoms of fever, chills, cough, difficulty breathing, rash or changes in skin, and severe diarrhea or vomiting. Fever is one of the first signs of infection.
- Report to your ophthalmologist any signs of eye discharge or changes in vision. Patients who undergo radiation or who are on long-term steroid therapy have an increased risk for cataracts.
Common side effects of stem cell transplants include nausea, vomiting, fatigue, mouth sores, and loss of appetite.
The procedures themselves are fairly dangerous and carry a small risk for death. When it was first used, transplantation procedures had 10 - 25% morality rates. Now mortality rates are below 5%.
There is a small long-term risk for leukemia after transplantation in young people. Chemotherapy itself increases the risk of secondary cancers. Recent studies suggest that transplantation after chemotherapy does not add any additional risks. In addition, use of newer chemotherapeutic drugs may not pose as high a danger as older treatments.
Other serious potential complications include:
- Bleeding because of reduced platelets (highest risk within the first 4 weeks); blood transfusions may be required
- Infertility
- Organ complications to the liver, heart, kidney, or lungs
- Failure of the transplant
- Muscle problems including stiffness, cramps, and joint pain
- Frequent urination and bladder control problems
- Older patients should be screened for osteoporosis (bone thinning) and hypothyroidism (underactive thyroid)
Immunotherapy
Investigational approaches to Hodgkin's disease include immunotherapies, which are drugs that take advantage of the patients' own immune factors to attack the disease.
One important approach uses genetically designed immune factors called monoclonal antibodies (MAb) that recognize and attack specific molecules found on the surface of cells associated with HD.
Rituximab (Rituxan) was the first monoclonal antibody to be approved for any cancer. It is an unconjugated MAb that targets the CD-20 antigen, which is found on most B-cell lymphomas and normal mature B cells (although not stem cells). It is used in non-Hodgkin's lymphomas, but it may have benefits for some patients with Hodgkin's disease as well.
Resources
- www.cancer.gov -- National Cancer Institute
- www.cancer.org -- American Cancer Society
- www.lymphoma.org -- Lymphoma Research Foundation
- www.leukemia.org -- Leukemia and Lymphoma Society
- www.canceradvocacy.org -- National Coalition for Cancer Survivorship
- www.asco.org -- American Society of Clinical Oncology
- www.plwc.org -- People Living with Cancer
- www.marrow.org -- National Marrow Donor Program
- www.oncolink.org -- Cancer information
- www.lymphomainfo.net -- Lymphoma Information Network
- www.cancer.gov/clinicaltrials -- Find clinical trials
References
Fermé C, Eghbali H, Meerwaldt JH, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27.
Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10;25(5):571-8. Epub 2007 Jan 22.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hodgkin Disease / Lymphoma. V.1.2007.
Reviewed By: A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz. Previously reviewed by Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (1/21/2008).
