Understanding Hodgkin Lymphoma

Hodgkin lymphoma (HL), also known as Hodgkin disease, represents about 10% of all lymphomas in the United States. It is estimated that 8,720 new cases of HL will be diagnosed in the United States in 2025. HL can occur in both children and adults, but it is most common in young adults between the ages of 20 and 29 years, with an average age of 39 years at diagnosis.

HL is often characterized by the presence of very large cells called Reed-Sternberg (RS) cells (Figure 1) and usually starts in the lymph nodes (small bean-shaped structures that help the body fight disease, Figure 2). It can spread to other lymph nodes and, rarely, to other organs.

The exact cause of HL is not fully understood, and most cases of HL are not explained by any clear cause. Certain factors may increase the risk of developing it, such as a weakened immune system, certain infections (like Epstein-Barr virus [EBV], also known as mononucleosis), genetic factors, or exposure to certain chemicals. Biological siblings of patients with HL have a slight increased risk of also developing HL.

Figure 1. Example of a normal lymphocyte (a type of white blood cell that fights infection and cancer) and a Reed- Sternberg cell found in HL. HL, Hodgkin lymphoma.

Figure 2. The lymphatic system and lymph nodes.

Symptoms, Staging, and Diagnostic Procedure

While most people who have these symptoms do not have HL, anyone with persistent symptoms should see a physician to make sure that lymphoma is not present.

For staging, the results of the different tests (such as biopsies and scans) are used to determine the severity of the disease and the appropriate treatment. The Lugano staging system is used for HL and is depicted in Figure 3 below. This system categorizes HL from Stage I (limited disease) to IV (advanced disease), based on whether the disease is restricted to a single group

Stage I:

Involvement of a single lymph node or group of adjacent nodes

Stage II:

Involvement of two or more groups of lymph nodes on the same side of the diaphragm (muscle that separates the chest from the abdomen)

Stage III:

Involvement of lymph nodes on both sides of the diaphragm, or Involvement of lymph nodes above the diaphragm plus spleen involvement

Stage IV:

Widespread disease in lymph nodes, bone marrow, and organ involvement, such as liver or lungs

Treatment is based on the severity of symptoms. When adult patients show no or few symptoms, doctors may decide to monitor the patient without treating the disease. This approach is called active surveillance, or watchful waiting. In this case, patients’ overall health and disease are monitored through regular check-up visits that may include laboratory tests (like a complete blood cell count) and physical examinations (like checking for any swelling). Sometimes, patients experience symptoms due to low red blood cell count (anemia). If patients begin to have symptoms or signs of disease progression, treatment is then prescribed. Children, however, always receive treatment for cHL.

First Treatment after Diagnosis

cHL

The majority of patients with newly diagnosed cHL can be cured. While the treatment depends on the type of cHL and the patient’s overall health, most patients receive as their first treatment:

Chemotherapy (drugs that stop the growth of or kill cancer cells).

• Common chemotherapy regimens used as initial treatment (frontline chemotherapy) for cHL are listed in Table 1.
• Some chemotherapy regimens include steroids (like dexamethasone or prednisone), which treat cancer and help to relieve inflammation (redness, swelling, pain, and/or a feeling of heat in an area of the body).

Radiation therapy (uses high-energy radiation to kill cancer cells) works very well against HL.

Immunotherapy (drugs that use the body’s immune system to fight cancer) with antibody- drug conjugates (ADC).

• An ADC is a monoclonal antibody (a protein made in the laboratory that binds to cancer cells and helps the immune system destroy them) attached to a chemotherapy drug. The monoclonal antibody in the ADC recognizes and binds to a protein on the cancer cell surface. Once the ADC is inside the cell, the chemotherapy drug separates from the ADC and kills the cancer cell by targeting cell multiplication. This targeting helps direct the chemotherapy to the cancer cells and prevent some of the killing of healthy cells in the body.
• The ADC brentuximab vedotin (Adcetris) can be used as frontline therapy for stage III orIV cHL in combination with other drugs such as doxorubicin, vinblastine, and dacarbazine (BV+AVD).

Chemoimmunotherapy is a combination of chemotherapy with immunotherapy. AVD chemotherapy combined with the checkpoint inhibitor nivolumab is used to treat patients with advanced disease.

For more information on ADCs and other types of immunotherapy, please view the Immunotherapy and Other Targeted Therapies fact sheet

Although many individuals diagnosed with HL are cured after treatment, researchers continue to develop new therapies that are more effective and have less side effects during therapy and for years after. New drugs being studied include immune checkpoint inhibitors (drugs that block proteins that help cancer cells evade immune response).

Investigators (experts who run clinical research) are also looking for ways to treat those patients who are not cured and in need of more treatment. These include new combinations of targeted therapies (drugs that target specific molecules that cancer cells use to survive and spread) or immunotherapies. Table 5 (below) lists some of these investigational drugs that can be accessed through a clinical trial. For more information on clinical trials, view the Understanding Clinical Trials publication on the Foundation’s website. It is also very important that patients with HL consult with their doctor to clear up any questions they may have.

Clinical trials are crucial in identifying effective drugs and optimal treatment doses for patients with lymphoma. They are not a “last resort” for patients. Every drug available today had to be tested in clinical trials before it was approved for general use, and all new and emerging treatments. There are four main types or phases of clinical trials. The phase is based on the study’s objective and the number of participants.

Phase I

• To identify a safe dose of a new drug
• To decide on a dosing schedule for the drug
• To see what side effects are related to the therapy

Phase II

• To see if a new treatment is effective against a certain type of cancer at the dose determined in Phase I
• To confirm and learn more about the side effects identified in Phase I

Phase III

• To compare the new treatment or new use of an existing treatment with the current standard treatments
• To obtain detailed information about how well the treatment works and the types and severity of side effects it causes

Phase IV

• To look at long-term safety and effectiveness that take place after a new treatment has been approved by the FDA and is available to the public.
  

Patients interested in participating in a clinical trial should view the Understanding Clinical Trials fact sheet on the Foundation’s website (visit lymphoma.org/publications), and the Clinical Trials Search Request Form, talk to their physician, or contact the Foundation’s Lymphoma Resource Center for an individualized clinical trial search by calling (800) 500-9976 or emailing [email protected].

Survivorship

As a cancer survivor, it is important that you practice self-care regularly to reset your physical and emotional well-being. Adopting routines of self-care will help you recharge your batteries and stay healthy. Talk with your healthcare team about developing a wellness plan to help you stay physically and emotionally healthy and improve your mood. Consider the following suggestions:

• Watch your health. Stay up-to-date with your own medical appointments and take any medications as prescribed.
• Exercise. Stay active with short periods of daily exercise (30 minutes of power walking, jogging or biking). If not possible, take the stairs instead of the elevator or park farther away than usual.
• Eat well. Include fruits and vegetables in your meals and maintain a balanced diet.
• Cut down on risk factors. Quit smoking and reduce alcohol intake.
• Sleep. Try to get 7 hours of sleep per night, or take naps when needed.
• Rest. Meditation, deep breathing and stretching can help you relax and reduce stress.
• Write it down. Keeping a journal with thoughts and feelings may help to let go of worries and fears.

View the Foundation’s Survivorship Series fact sheet on the Foundation’s website at lymphoma.org/publication for more info.

Care Partners

There are many ways you can help a loved one with lymphoma, as follows:

• Be present. The most important thing that a care partner can do is to “just show up.”
• Be prepared. Talk with the healthcare team so that you know what to expect throughout the treatment, how to manage symptoms and when to ask for help.
• Listen. Each person asks for help in different ways, verbally (through words) and nonverbally, and some may require more comfort while others are more action oriented.
• Avoid “cheerleading”. Do not disregard your love one’s negative feelings (sadness, anger or worry).
• Organize the help. A rush of sudden help upon diagnosis can make the situation harder to manage and create unproductive tension.
• Set up remote access with computer and/or phone access. This is helpful for regular communication with your loved one.
• Offer rides. This is important for people with decreased mobility or limited resources.
• Take notes. If you go into the appointments, write down notes with the doctor’s plan, medications, potential side effects and other relevant information.

Patients and their care partner are encouraged to keep copies of all medical records. This includes test results as well as information on the types, amounts, and duration of all treatments received. Medical records are important for keeping track of any side effects resulting from treatment or potential disease recurrences. The Foundation can help patients manage this documentation.

View the Care Partners fact sheet for more info.

• What is my exact diagnosis? What subtype of lymphoma do I have? May I have a copy of the report from the pathologist?
• What is the stage of my disease? In what area of the body is it specifically located?
• What are my treatment choices? Which do you recommend for me and why? Would choosing one treatment prevent me from getting a different kind of treatment later on? How are the different treatments administered?
• Do I need more than one type of treatment?
• What is the goal of treatment? What are the expected benefits of each type of treatment?
• How will we know if the treatment is working? What tests will I need to determine if treatment is working, and how often will I need to be tested?
• How long will the treatment last?
• What are the chances the treatment will be successful?
• What is a clinical trial? Are clinical trials available that are studying new treatments for my type of lymphoma? Would a clinical trial be appropriate for me? How would I benefit? Are there any drawbacks of participating in a clinical trial?
• Will I be able to work during treatment? Will I be able to drive or take public transportation during my treatment?
• Should I take care of other medical or dental issues before I start treatment?
• How much will the treatment cost? Will my insurance cover some or all of it? What will my out-of- pocket costs be?