Peter M Mauch, MD
Arnold S Freedman, MD
Rebecca F Connor, MD
INTRODUCTION — Hodgkin lymphoma (formerly called Hodgkin’s disease) is a cancer of the body’s lymphatic system. Lymphomas are cancers of lymphocytes, a type of white blood cell that is important in the immune system.
The lymphatic system is a network of lymph nodes and interconnecting lymph vessels (figure 1). Lymph nodes are small, pea-shaped organs that make and store lymphocytes, a type of white blood cell that fights infection. Lymph vessels are similar to blood vessels and carry a watery fluid (lymphatic fluid) that contains lymphocytes.
In Hodgkin lymphoma, a cancerous tumor develops in a lymph node, usually in the neck or chest. If Hodgkin lymphoma spreads, it usually spreads first to nearby lymph nodes, and then to the spleen, liver, or bone marrow. As it progresses, Hodgkin lymphoma can affect the body’s ability to fight infection. The exact cause of Hodgkin lymphoma is not known in most cases.
Fortunately, Hodgkin lymphoma is one of the most treatable forms of cancer. About 75 percent of people diagnosed with Hodgkin lymphoma can be cured with treatment. Over 90 percent of people live at least 10 years after treatment.
More detailed information about Hodgkin lymphoma is available by subscription. (See “Staging of Hodgkin lymphoma” and “Treatment of favorable prognosis early (stage I-II) classical Hodgkin lymphoma” and “Treatment of unfavorable prognosis early (stage I-II) classical Hodgkin lymphoma” and “Initial treatment of advanced (stage III-IV) classical Hodgkin lymphoma”.)
HODGKIN LYMPHOMA SYMPTOMS — Most people with Hodgkin lymphoma are diagnosed because of a painless, enlarged lymph node in the neck. Enlarged nodes may also be found above the collar bone, in the armpit (axilla), or the groin (inguinal) area (figure 1).
Some people are diagnosed with a mass in the chest, which causes a cough, chest discomfort, or shortness of breath. There may also be symptoms of fever, night sweats, and weight loss. (See “Clinical presentation and patterns of disease distribution in classical Hodgkin lymphoma in adults”.)
If your doctor or nurse is concerned that you could have Hodgkin lymphoma, you should see a physician who specializes in cancer treatment (called a hematologist/oncologist) for further testing.
HODGKIN LYMPHOMA DIAGNOSIS
Tissue biopsy — If you have symptoms of Hodgkin lymphoma, you will need surgery to remove an enlarged lymph node. This is usually done as a day surgery procedure. After removal, the lymph node is examined to see whether it contains any signs of lymphoma. (See “Initial evaluation and diagnosis of Hodgkin lymphoma in adults”.)
Bone marrow biopsy — A bone marrow biopsy might be recommended if your doctor suspects that Hodgkin lymphoma is advanced, if you have fever, weight loss, and/or night sweats, or if you have an abnormal blood count. This test determines whether there are lymphoma cells in the bone marrow, which indicates an advanced stage of Hodgkin lymphoma.
A bone marrow biopsy involves removing a sample of bone marrow fluid, usually from the pelvic or hip bone. You will be given medicine to reduce pain during the procedure. The bone marrow fluid is then examined under a microscope to determine whether it is involved with Hodgkin lymphoma.
HODGKIN LYMPHOMA STAGING — Staging involves dividing people with Hodgkin lymphoma into groups (stages) based upon certain criteria at the time of diagnosis. Treatment decisions are based in large part on the stage of disease that is found. (See “Staging of Hodgkin lymphoma”.)
The following are terms used in the staging criteria:
- Lymph node regions: An area of lymph nodes and the surrounding tissue. Examples include the cervical nodes in the neck, the axillary nodes in the armpit, the inguinal nodes in the groin, or the mediastinal nodes in the chest (figure 1).
- Lymph structures: Organs or structures that are part of the lymphatic system, such as the lymph nodes, spleen, and thymus gland (figure 1). These organs or structures play a role in the body’s immune system.
- Diaphragm: A large muscle that separates the chest from the abdomen
The stage of Hodgkin lymphoma is based upon:
- The number of lymph node regions or structures that are involved
- The location of the affected lymph node regions or structure (one or both sides of the diaphragm)
- Whether there are signs of cancer outside the lymphatic system (eg, in the liver, lung, or bone marrow)
- Whether you have unexplained fever, night sweats, or weight loss (called “B symptoms”)
Hodgkin lymphoma stages range from stage I (only one lymph node region or structure is involved) to stage IV (the cancer has spread beyond the lymphatic system) (table 1).
In general, lower-stage cancers are more likely to be cured and less likely to come back after treatment compared with higher-stage cancers. Stage I and II Hodgkin lymphoma are referred to as early stage, while stage III and IV Hodgkin lymphoma are referred to as advanced.
Subclassifications — Additional criteria help to further identify subgroups within each stage, as follows:
- A or B — The letter “A,” as in stage IIA, means that symptoms of unexplained fever, night sweats, or weight loss (at least 10 percent of the body weight) were NOT present during the six months prior to diagnosis. The letter “B,” as in stage IIIB, means that these symptoms were present. These symptoms are therefore referred to as “B symptoms.”
For example, a person with Hodgkin lymphoma involving lymph nodes in the neck, mediastinum, and groin (ie, involvement above and below the diaphragm) who also has symptoms of fever, night sweats, and weight loss has stage IIIB disease.
Tests used in staging — A number of tests are used in the process of staging. These tests help determine which areas of the body have been affected by Hodgkin lymphoma. However, not all patients will require every test. Tests that may be done include:
- Blood tests
- CT or PET scan of the chest, abdomen, and pelvic area
- Bone marrow biopsy: removal of tissue from the bone marrow, the spongy area in the middle of large bones
HODGKIN LYMPHOMA TREATMENT — The main treatments for Hodgkin lymphoma are chemotherapy and radiation.
Chemotherapy — Chemotherapy is a treatment given to stop the growth of cancer cells. Most treatments involve a combination of several chemotherapy drugs (called regimens). Most of the drugs are given into the vein (intravenous, IV).
Chemotherapy is not typically given every day but instead is given in cycles. A cycle of chemotherapy (which is typically 21 or 28 days) refers to the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines.
For example, two doses of ABVD chemotherapy (see below) are given 14 days apart to make up one cycle of treatment. If this regimen were repeated for a total of four cycles, it would take up to four months to complete.
Chemotherapy regimens for Hodgkin lymphoma include:
- ABVD — ABVD includes Adriamycin® (doxorubicin), bleomycin, vinblastine, and dacarbazine. ABVD is the most commonly used chemotherapy regimen.
- Stanford V — Stanford V includes Adriamycin®, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, and prednisone.
- BEACOPP — BEACOPP includes bleomycin, etoposide, Adriamycin, cyclophosphamide, Oncovin®, procarbazine, and prednisone. This regimen is more commonly used in Europe. Some experts feel that BEACOPP is more effective than other regimens, especially in people with more advanced disease. However, it has more toxic side effects, which some people cannot tolerate.
Side effects — The type and severity of chemotherapy side effects depend upon the combination and dose of chemotherapy medicines given. The most common treatment-related side effects include temporary hair loss, nausea, vomiting, fatigue, loss of appetite, increased risk of infections, and becoming bruised or bleeding easily. Many of these side effects can be prevented or treated.
Long-term side effects of chemotherapy include:
- Infertility — Some types of chemotherapy can damage a woman’s oocytes (eggs). If most or all of the eggs are damaged or destroyed, a woman will go through an early menopause. This means that her periods will stop permanently, and she will have infertility because her eggs are damaged or gone.
Early menopause, sometimes called “premature ovarian failure” or “primary ovarian insufficiency,” is most common with BEACOPP chemotherapy. About 50 percent of women lose their periods permanently after receiving BEACOPP. In contrast, ABVD chemotherapy does not seem to damage the ovaries.
The pattern is similar in men. BEACOPP chemotherapy causes very low sperm counts and infertility, but ABVD treatment does not.
- Lung damage — Bleomycin, which is used in all treatment regimens, can damage the lungs; this risk is highest in people who have radiation therapy to the chest.
- Secondary cancer — There is a risk of developing a second cancer years after the first treatment for Hodgkin lymphoma. The most common secondary cancers include those of the breast, lung, or gastrointestinal system. (See “Second malignancies after treatment of classical Hodgkin lymphoma”.)
Some forms of radiation therapy increase the risk of developing cancer in areas that were treated (such as to the lungs and breast tissue) years after therapy is finished. Women under 30 are at increased risk of breast cancer, and smokers have an increased risk of lung cancer (beyond the already increased risk of lung cancer from smoking). It is also possible to develop leukemia or other types of lymphoma.
Radiation therapy — Radiation therapy (RT) involves using high-energy X-rays to stop the growth of cancer cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to X-rays over several days. This prevents the cancer cells from growing further and causes them to eventually die.
Radiation therapy is sometimes recommended to treat Hodgkin lymphoma, usually after finishing chemotherapy. The radiation is directed to the area of affected lymph nodes with a carefully focused beam of radiation; this is called involved field radiation. Radiation therapy must be given in small daily doses over a period of weeks to minimize the side effects.
Side effects — During radiation treatment, some people develop skin changes in the area that was treated, similar to a sunburn. These changes fade over time. Other side effects can include fatigue and nausea.
You and your healthcare provider should discuss the risks and benefits of radiation therapy when deciding on a treatment plan. Limiting the radiation dose and area treated can reduce, but not totally eliminate, these risks. (See “Second malignancies after treatment of classical Hodgkin lymphoma”.)
Stage I or II — People with stage I or II disease are usually treated with chemotherapy with radiation or, in some cases, chemotherapy alone. (See “Treatment of relapse of classical Hodgkin lymphoma after initial chemotherapy” and “Treatment of unfavorable prognosis early (stage I-II) classical Hodgkin lymphoma”.)
Using chemotherapy along with radiation has a lower relapse rate than using chemotherapy alone, and it might improve survival. However, having chemotherapy and radiation therapy can have more late side effects. Discuss the risks and benefits of these options with your doctor or nurse; your understanding and involvement are an important part of your cancer care.
The challenge of managing Hodgkin lymphoma is that there are risks of long-term complications related to the treatment, which can affect survival. After finishing treatment for Hodgkin lymphoma, you should work with your doctor to monitor for and prevent new cancers.
Stage III and IV — The most common treatment for people with stage III and IV Hodgkin lymphoma is chemotherapy. Radiation therapy may be added if the tumor was large at the time of diagnosis or if there are areas of tumor that have not completely responded to chemotherapy. (See “Initial treatment of advanced (stage III-IV) classical Hodgkin lymphoma”.)
Most people with stage III and IV disease will be given the ABVD regimen. With this, 60 to 70 percent of patients will be alive and free of disease at five years. ABVD alone is the treatment of choice for most patients with advanced disease, although Stanford V and BEACOPP, combined with radiation, are reasonable alternatives for some people.
Hematopoietic stem cell transplantation — Hematopoietic stem cell transplantation (also known as bone marrow transplantation) might be offered to people who have:
- Recurrent Hodgkin lymphoma
- Hodgkin lymphoma that is resistant to other forms of treatment. This includes people whose disease relapses after the first round of treatment.
A separate article discusses bone marrow transplantation. (See “Patient information: Bone marrow transplantation (stem cell transplantation)” and “Hematopoietic cell transplantation in classical Hodgkin lymphoma”.)
CLINICAL TRIALS — Many people with Hodgkin lymphoma will be asked about enrolling in a clinical (research) trial. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask your doctor or nurse for more information, or read about clinical trials at:
- National Cancer Institute
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed every four months on our Web site (www.uptodate.com/patients).
Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient Level Information:
Patient information: Bone marrow transplantation (stem cell transplantation)
Professional Level Information:
Clinical features of and prognostic factors for relapse of classical Hodgkin lymphoma after initial chemotherapy
Clinical manifestations, pathologic features, and diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma
Clinical presentation and patterns of disease distribution in classical Hodgkin lymphoma in adults
Definition of favorable and unfavorable prognosis early (stage I-II) classical Hodgkin lymphoma
Epidemiology, pathologic features, and diagnosis of classical Hodgkin lymphoma
Hematopoietic cell transplantation in classical Hodgkin lymphoma
Initial evaluation and diagnosis of Hodgkin lymphoma in adults
Initial treatment of advanced (stage III-IV) classical Hodgkin lymphoma
Management of classical Hodgkin lymphoma during pregnancy
Monitoring of the patient with classical Hodgkin lymphoma during and after treatment
Overview of Hodgkin lymphoma in children and adolescents
Pathology of mediastinal tumors
Relapse of classical Hodgkin lymphoma after initial radiotherapy
Second and third line agents for relapsing or resistant classical Hodgkin lymphoma
Second malignancies after treatment of classical Hodgkin lymphoma
Overview of the treatment of classical Hodgkin lymphoma in adults
Staging of Hodgkin lymphoma
The Reed-Sternberg cell and the pathogenesis of Hodgkin lymphoma
The role of Epstein-Barr virus in Hodgkin lymphoma
Treatment of favorable prognosis early (stage I-II) classical Hodgkin lymphoma
Treatment of nodular lymphocyte-predominant Hodgkin lymphoma
Treatment of relapse of classical Hodgkin lymphoma after initial chemotherapy
Treatment of unfavorable prognosis early (stage I-II) classical Hodgkin lymphoma
The following organizations also provide reliable health information:
- National Cancer Institute
- American Society of Clinical Oncology