Hodgkin Disease

What Is Hodgkin Disease?

Hodgkin disease (or Hodgkin lymphoma) is a type of lymphoma. There are 2 kinds of lymphoma:

• Hodgkin disease (named after Dr. Thomas Hodgkin, who recognized it in 1832)


• non-Hodgkin lymphoma

Non-Hodgkin lymphoma is covered in a separate American Cancer Society document.


The Lymph System and Lymphoid Tissue

To better understand Hodgkin disease, it helps to know about the body's lymph (pronounced "limf") system. The lymph system is made up of lymphoid tissue, lymph vessels, and a clear fluid called lymph.

Lymphatic tissue includes the lymph nodes and other organs that are part of the body�s immune and blood-forming systems. Lymph nodes are small, bean-shaped organs found in many places throughout the body. Other parts of the lymphatic system include the spleen, the bone marrow, and the thymus gland.

The lymph nodes make and store lymphocytes, which are special white blood cells that fight infection. There are 2 types of lymphocytes: B lymphocytes (or B cells) and T lymphocytes (or T cells). Most cases of Hodgkin disease start in B lymphocytes.


Start and Spread of Hodgkin Disease

Because lymphatic tissue is found in many parts of the body, Hodgkin disease can start almost anywhere. Most often it starts in lymph nodes in the upper part of the body. (Those in the chest, neck, or under the arms.) This disease causes the lymphatic tissue to become enlarged and press on nearby structures. But lymph nodes can become swollen for many reasons. Most often it happens when the body is fighting an infection.

Hodgkin disease can spread through the lymphatic vessels in a stepwise fashion from lymph node to lymph node. Rarely, and late in the disease, it gets into the blood vessels and can then spread to almost any other place in the body.


The Hodgkin Disease Cell

The cancer cells in Hodgkin disease are unique. They are called Reed-Sternberg cells (or Hodgkin cells). They are an abnormal type of B lymphocyte that is much larger than normal lymphocytes.

The 2 main types are classical Hodgkin disease (which has several subtypes) and nodular lymphocyte predominance Hodgkin disease. The types differ in the way the cancer cells look under a microscope. The types are important because each grows and spreads in a different way. Often they are treated differently. Ask your doctor about the exact type of Hodgkin disease you (or your loved one) has.


Classical Hodgkin Disease

Classical Hodgkin disease (HD) accounts for about 95% of all cases of Hodgkin disease in developed countries. It has 4 subtypes, all of which have Reed-Sternberg cells that can be seen under the microscope.


Nodular Lymphocyte Predominant Hodgkin Disease

Nodular lymphocyte predominant Hodgkin disease (NLPHD) accounts for about 5% of Hodgkin disease. This type mostly involves lymph nodes in the neck and under the arm.

All types of Hodgkin disease are cancerous (malignant) because as they grow they may compress, invade, and destroy normal tissue and spread to other tissues. Hodgkin disease occurs in both children and adults. Because Hodgkin disease is similar in both children and adults, this document covers treatment in both groups.

What Causes Hodgkin Disease?

We do not yet know exactly what causes Hodgkin disease, but we do know that certain risk factors are linked to the disease. A risk factor is something that affects a person's chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, such as smoking, can be controlled. Others, like a person's age or family history, can't be changed. But having a risk factor, or even many, doesn't mean that a person will get the disease. Likewise, not having any risk factors doesn't mean a person won't get the disease.

Scientists have found a few risk factors that may make a person more likely to get Hodgkin disease, although it's not always clear why these factors increase risk.


Epstein-Barr Virus (EBV) Infection/Mononucleosis

There is a higher risk of Hodgkin disease among people who have had "mono" (infectious mononucleosis), caused by the Epstein-Barr virus. The risk is a few times higher in people who have had this disease, although the overall risk is still very small.


Age

Hodgkin disease is most common in early adulthood (age 15 to 40, especially in a person's 20s) and in late adulthood (after age 55).


Gender

Hodgkin disease occurs slightly more often in males than in females.


Geography

Hodgkin disease is most common in the United States, Canada, and northern Europe, and is least common in Asian countries.


Family History

There is a higher risk for Hodgkin disease in brothers and sisters of young people with this disease. The risk is very high for an identical twin of a person with Hodgkin disease.


Socioeconomic Status

The risk of Hodgkin disease is greater in people with a higher socioeconomic background.

Can Hodgkin Disease Be Prevented?

Since we do not know what causes Hodgkin disease, it is not possible at this time to prevent the disease.

How Is Hodgkin Disease Found?

There are no tests to find Hodgkin disease early, and some people with the disease have no symptoms at all. Most people with Hodgkin disease see their doctor because they have felt a lump that hasn't gone away or they just don't feel well and go in for a check-up. They may have a swollen lymph node in the neck, arm pit, or groin area. Sometimes it will go away only to come back. Eventually, it doesn't go away, and though it doesn't hurt, it will get larger and cause the person to go to the doctor.

But in most people, especially children, enlarged lymph nodes are caused by an infection or other illness and not cancer. If you (or your child) have lymph nodes over an inch in size and no recent infection, it is best to have them checked by the doctor.


Signs and Symptoms of Hodgkin Disease

You or your child can have Hodgkin disease and feel perfectly well. However, there are some symptoms that this disease may cause.


Lumps Under the Skin

You may notice a lump in the neck, under the arm, or in the groin. Sometimes this may go away, only to come back. Although it doesn't hurt, it may finally not go away, and lead you to see a doctor.


General Symptoms

Some patients with Hodgkin disease have fever, drenching night sweats, or weight loss. The fever can come and go over many days or weeks. Itching, tiredness, and poor appetite are other symptoms that may occur. Sometimes the only symptom may be feeling tired all the time. However, infections, other types of cancer, or other conditions can also cause these symptoms.


Cough or Trouble Breathing

When Hodgkin disease affects lymph nodes inside the chest, the swelling of these nodes may press on the windpipe. This can make you cough or even have trouble breathing, especially when lying down.

If you or your child has any of these symptoms, discuss them with your doctor right away. The sooner a correct diagnosis is made, the sooner treatment can be started and the better the treatment will work.


Medical History and Physical Exam

If symptoms suggest that you might have Hodgkin disease, the doctor will want to get a complete medical history, including how long you have had the symptoms. The doctor will ask questions about your health now and in the past and to do a physical exam to see whether there is an infection. During the exam, the doctor will pay special attention to the lymph nodes. Because it is common for people, especially children, to have swollen lymph nodes, the doctor will look for infection first. If the doctor thinks that Hodgkin disease might be causing the symptoms, he or she will want to do a biopsy.

Biopsy

A biopsy involves removing a sample of the lymph node and looking at it under a microscope. This is the only way to know for sure if the swelling is caused by cancer. There are many different kinds of biopsies, and the doctor will choose the one best suited for you or your child. The goal is to get enough tissue to be sure of the diagnosis.

Some biopsies involve cutting through the skin to remove an entire node or a small part of a larger tumor. If the node is near the surface of the skin, the skin can be numbed and the sample taken. But if the node is deeper inside the body, the patient may need to be asleep first.

In a less common type of biopsy, the doctor uses a thin needle to remove a small amount of fluid and tiny bits of tissue from the tumor.

Lab Tests

A doctor with special training in blood and lymph tissue disease (called a pathologist) looks at all biopsy samples under a microscope. The doctor looks at the appearance, as well as the size and shape of the cells to find out whether any of them are Reed-Sternberg cells. Sometimes the first biopsy does not provide a definite answer and more biopsies are needed.

Looking at the tissue under the microscope can often tell whether you have Hodgkin disease and what type it is, but sometimes special stains are used on the sample to provide more information.

How Is Hodgkin Disease Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.


This section first describes the types of treatments used for Hodgkin disease. Then the treatment options based on the stage of the disease (as well as other factors) are explained.

In recent years, much progress has been made in treating Hodgkin disease. Most people can be cured with chemotherapy and radiation therapy. Treatment is based on the stage and type of the disease, but a person�s age, overall health and other factors may be taken into account as well.


Making Treatment Decisions

After Hodgkin disease is staged, the doctor will discuss treatment choices with you. It is important to take time and think about all the choices. Be sure that you understand all the risks and side effects before making a decision. Getting a second opinion can give you more information and help you feel more confident in the treatment you choose.

For nearly all people with Hodgkin disease, complete cure is the main goal. The two main methods of treating Hodgkin disease are chemotherapy and radiation therapy. Sometimes both treatments are used. High dose chemotherapy with blood-forming stem cell transplants, discussed later, is used for certain people. For the most part, surgery (except for biopsy and staging) is not part of the treatment of Hodgkin disease.


Chemotherapy

Chemotherapy (often called simply "chemo") refers to the use of drugs to kill cancer cells. Usually the drugs are given into a vein or by mouth (as pills). Once the drugs enter the bloodstream, they spread throughout the body. Several drugs are given at the same time to treat Hodgkin disease.

Although the chemo kills cancer cells, the drugs also damage normal cells. This can lead to side effects. The exact side effects depend on the type and dose of drugs used and the length of time they are taken. Side effects could include the following:

• hair loss
• mouth sores
• loss of appetite
• nausea and vomiting
• increased chance of infections (due to low white blood cell counts)
• easy bruising or bleeding (due to low blood platelet counts)
• fatigue (due to low red blood cell counts)

These side effects are usually short-term and go away after treatment is finished. There are often ways to lessen these side effects. For example, drugs are usually given to help prevent or reduce nausea and vomiting. If you or your child has side effects, talk to your cancer care team. They can suggest steps to ease them.

If white blood cell counts are very low during treatment, you can help reduce the risk of infection by carefully avoiding exposure to germs. During this time, your doctor may advise you to:

• Wash your hands often.
• Avoid fresh, uncooked fruits and vegetables and other foods that might carry germs.
• Avoid fresh flowers and plants because they may carry mold.
• Make sure other people wash their hands before they come in contact with you.
• Avoid large crowds and people who are sick (wearing a surgical mask offers some protection in these situations).

Some chemo drugs can have side effects that occur long after treatment has ended. These can affect a person's heart, lungs, growth, and ability to have children. There is also an increased risk of developing a second type of cancer, especially if chemo and radiation are given at the same time. It's important to discuss these possible side effects with the doctor before treatment begins. If the patient is old enough and is going to receive drugs that cause sterility, sperm banking should be discussed before treatment is started.


Radiation Therapy

Radiation therapy is the use of high-energy x-rays to destroy cancer cells. When radiation therapy is given for Hodgkin disease, it usually involves a focused beam of radiation, given from a machine outside the body. This is known as external beam radiation. Radiation is used along with chemotherapy when the Hodgkin disease involves a large or bulky tumor mass, usually in the chest

Doctors have found that in some cases, treating only the known areas of disease with radiation may also produce a cure. This is called involved field radiation and is now the preferred form of radiation therapy when used along with chemo, although they are not given at the same time. Chemo is given first, followed by involved field radiation given to areas that showed cancer.

Radiation therapy can cause some serious side effects including damage to nearby healthy tissue. Other problems can include skin changes similar to sunburn, tiredness, upset stomach, and diarrhea.

In the past, radiation was thought to have fewer side effects than chemo. But as more patients have been able to live out their normal life spans after successful treatment for Hodgkin disease, more long-term problems from radiation have been seen. Radiation to the chest leads to an increased risk of heart disease (such as heart attacks). Radiation to the neck may increase the risk of stroke many years later. Because of these problems, doctors are slowly moving away from using radiation, or at least limiting the dose and areas of the body that are treated.


High-Dose Chemotherapy and Bone Marrow or Peripheral Blood Stem Cell Transplant

Standard doses of chemo drugs can cause serious side effects to quickly dividing tissues such as the bone marrow. Although even higher doses of these drugs might work better to treat Hodgkin disease, they are not given because the severe damage to bone marrow cells would cause lethal shortages of blood cells, and other vital organs would likely be damaged too.

But sometimes Hodgkin disease does not respond well to standard treatment, or the disease comes back later. In these cases, a stem cell transplant (SCT) allows doctors to use higher doses of chemo. After treatment is finished, the patient receives a transplant of blood-forming stem cells to restore the bone marrow.


Autologous Stem Cell Transplant

For this type of transplant, blood-forming stem cells from the patient�s own blood (or, less often, from the bone marrow) are removed, frozen, and stored. Then very high doses of chemotherapy (with or without radiation therapy) are given in order to kill the cancer. These high doses destroy bone marrow, too. When that happens, the body is no longer able to make new blood cells. So, after the treatment, the stored stem cells are thawed and given back to the patient through a vein. The cells enter the bloodstream and return to the bone, replacing the marrow and making new blood cells.

(If this type of transplant fails, then a matched donor might supply the stem cells. When the stem cells come from someone else it is called an allogenic stem cell transplant.)


The Transplant Process

The treatment works like this: stem cells are collected from the bloodstream in a process called apheresis. The cells are frozen and stored. Patients are then given very high doses of chemo to kill the cancer cells. The patient might also receive total body radiation to kill any remaining cancer cells. After treatment, the stored stem cells are given to the patient like a blood transfusion. The stem cells settle into the patient's bone marrow over the next several days and start to grow and make new blood cells.

People who receive a donor's stem cells are given drugs to prevent rejection. Usually within a couple of weeks after the stem cells are given, they start making new white blood cells. Then they begin making platelets, and finally, red blood cells.

Patients having SCT have to be kept away from germs as much as possible until their white blood cell count is at a safe level. They are kept in the hospital until the white cell count reaches a certain number, usually around 1,000. After they go home, they will be seen as an outpatient regularly for about 6 months.


Some Things to Keep in Mind

Stem cell transplantation is a complex treatment. If the doctors think that a patient might be helped by this treatment, it is important that it be done at a hospital where the staff has experience with the procedure. Some transplant programs may not have experience in certain transplants, especially those from unrelated donors.

Stem cell transplant is very expensive (more than $100,000) and often involves a long hospital stay. Because some insurance companies see it as an experimental treatment, they might not pay for it. It is important to find out what your insurance will cover and what you might have to pay before deciding on a transplant.


"Mini Transplant"

Most patients over the age of 55 can't have a regular transplant that uses high doses of chemo. Some may be able to have what is called a "mini-transplant" (a non-myeloablative transplant or reduced-intensity transplant), where they get lower doses of chemo and radiation which do not destroy all the cells in their bone marrow. They then are given the donor stem cells. These cells enter the body and form a new immune system, which sees the cancer cells as foreign and attacks them (a "graft-versus-lymphoma" effect). To learn more about stem cell transplants, see the American Cancer Society document, Bone Marrow & Peripheral Blood Stem Cell Transplants.


Side Effects of Stem Cell Transplant

Side effects from stem cell transplant can be divided into short- and long-term effects. The short-term or early side effects are about the same as those caused by any other type of high-dose chemo. One of the most common and serious short-term effects is the greater risk of infection. Other side effects include low red blood cell counts, nausea, vomiting, loss of appetite, mouth sores, and hair loss.


Long-term Side Effects

Some side effects can last for a long time, or may not happen until years after the transplant. These long-term side effects can include the following:

• graft-versus-host disease (GVHD), which occurs only in a donor (allogeneic) transplant (see below)
• infertility
• early menopause
• radiation damage to the lungs, causing shortness of breath
• damage to the thyroid gland that causes problems with changing food into energy
• cataracts (damage to the eye that can affect vision)
• damage to the lungs, causing shortness of breath
• bone damage (if damage is severe, the patient will need to have part of the bone and joint replaced)
• getting leukemia several years later

Graft-versus-host disease is the main problem of a donor stem cell transplant. It happens when the immune system of the patient is taken over by that of the donor. The donor immune system then starts to attack the patient�s other tissues and organs.

Symptoms can include severe skin rashes with itching and severe diarrhea. The liver and lungs may also be damaged. The patient may also become tired and have aching muscles. If severe enough, the disease can be fatal. Drugs that weaken the immune system may be given to try to control it. On the plus side, this disease also causes any remaining lymphoma cells to be killed by the donor immune system. Mild graft-versus-host disease can be a good thing.



Hodgkin Disease in Children

The types of Hodgkin disease that develop in children are generally different from the types that are found in adults. In most cases, childhood cancers tend to respond better to chemo. Children's bodies also tend to tolerate chemo better than adults. But because chemotherapy can have some long-term side effects, children who survive their cancer need careful attention for the rest of their lives.


Treatment Differences

Although the treatment for Hodgkin disease is generally the same for adults and children, there are some differences. If the child is older, the treatment is often the same as that given to adults. But if the child's body is still growing, then the doctor is more likely to use chemo instead of radiation because radiation can affect bone and muscle growth. The goal of treatment for children is to cure the cancer without causing long-term problems.

Since radiation treatment in large doses can keep children from reaching their normal size, when children with Hodgkin disease are treated with radiation the dose is kept low. In order to cure children, doctors often combine radiation in low doses with chemotherapy. The success of this approach has been very good. Cure rates for children can reach 85% to 100%, even with more advanced disease.


Childhood Cancers Are Treated at Special Centers

Children (and teenagers) with cancer and their families have special needs that are best met by children�s cancer centers that work closely with the child�s main doctor. These centers offer the advantage of a team of experts with experience in treating children. They know the unique needs of children with cancer. The team can include (besides doctors and nurses) psychologists, social workers, child life specialists, educators, and others.

Since the 1960s most children with cancer in the United States have been treated at these special centers. Most children with cancer are treated at a children�s cancer center that is a member of the Children�s Oncology Group (COG). These centers are linked to either a medical college or a children�s hospital.


Resistant Hodgkin Disease

Treatment for Hodgkin disease should get rid of all traces of the cancer. If tests still show some disease after treatment, many experts think that more of the same treatment will not cure the disease. Sometimes, radiation to a single area of disease that remains after chemo might work. Sometimes if radiation has failed, using chemo might be an option. But if both have failed, most doctors would recommend a stem cell transplant, if possible.


Recurrent Hodgkin Disease

The treatment for Hodgkin disease that comes back (recurs) depends on where the disease shows up and which treatment was used before. If the first treatment was just radiation therapy, then chemo would usually be given. If chemo had been used first, and the cancer came back only in the lymph nodes, then radiation therapy, with or without more chemo, could be given to the lymph nodes.

Although chemo with different drugs can be used for people with recurrent disease, radiation usually cannot be given again in the same area. For example, if someone had Hodgkin disease in the chest that had been treated with radiation, more radiation could not be used if the disease came back there. This is the case no matter how much time has gone by.

If the Hodgkin disease has returned within a few months of the first treatment, high-dose chemo with stem cell transplantation might be an option. On the other hand, if the disease has returned after a long time, then giving different chemo drugs might work. These are decisions that need to be made by you and your doctor.


Hodgkin Disease in Pregnancy

If a pregnant woman has Hodgkin disease, there are many options. In about half of all cases, a woman can wait until the baby is born and then begin treatment. This approach is safest for the baby.

If treatment needs to begin right away, one (or many) chemotherapy drugs may be given, depending upon the situation. Radiation is often not given, because of concerns about the long-term effects to the unborn baby. However, there have been a few studies of radiation as a treatment for pregnant women with Hodgkin disease. These studies suggest that as long as very careful measures are taken to aim the radiation precisely and limit the doses used, pregnant women with Hodgkin disease in the lymph nodes in the neck, arm pit, or inside the chest may be able to have this treatment with little or no risk of birth defects or childhood cancer.