Hodgkin’s lymphoma

What is Hodgkin’s lymphoma?

Hodgkin’s lymphoma, often known as Hodgkin’s disease, is an immune system cancer that affects the lymphatic system. It can affect persons of any age, although it is more common in people aged 20 to 40 and those aged 55 and up.

Cells in the lymphatic system grow improperly in Hodgkin’s lymphoma and can spread outside of it.

One of the two most frequent kinds of lymphatic cancer is Hodgkin’s lymphoma. Non-lymphoma, Hodgkin’s on the other hand, is significantly more prevalent.

Advances in Hodgkin’s lymphoma diagnosis and therapy have given persons with the disease a better chance of a full recovery. The prognosis for persons with Hodgkin’s lymphoma is improving.

Lymphomas are cancers that start in white blood cells called lymphocytes. There are 2 main types of lymphoma:

• Hodgkin lymphoma (HL)
• Non-Hodgkin lymphoma (NHL)

They behave, spread, and respond to treatment differently, so it’s important for you to know which one you have.

Types of Hodgkin’s lymphoma

Different types of Hodgkin lymphoma can grow and spread differently and may be treated differently. 

Classic Hodgkin lymphoma

Classic Hodgkin lymphoma (cHL) accounts for more than 9 in 10 cases of Hodgkin lymphoma in developed countries.

The cancer cells in cHL are called Reed-Sternberg cells. These cells are usually an abnormal type of B lymphocyte. Enlarged lymph nodes in people with cHL usually have a small number of Reed-Sternberg cells with a lot of normal immune cells around them. These other immune cells cause most of the swelling in the lymph nodes.

Classic HL has 4 subtypes:

• Nodular sclerosis Hodgkin lymphoma or NSCHL: This is the most common type of Hodgkin disease in developed countries. It accounts for about 7 out of 10 cases. It’s most common in teens and young adults, but it can occur in people of any age. It tends to start in lymph nodes in the neck or chest.
• Mixed cellularity Hodgkin lymphoma or MCCHL: This is the second most common type, found in about 4 out 10 cases. It’s seen mostly in people with HIV infection. It’s also found in children or the elderly . It can start in any lymph node but most often occurs in the upper half of the body.
• Lymphocyte-rich Hodgkin lymphoma: This sub-type isn’t common. It usually occurs in the upper half of the body and is rarely found in more than a few lymph nodes.
• Lymphocyte-depleted Hodgkin lymphoma: This is a rare form of Hodgkin disease. It’s seen mainly in older people and those with HIV infection. It’s more aggressive than other types of HL and likely to be advanced when first found. It’s most often in lymph nodes in the abdomen (belly) as well as in the spleen, liver, and bone marrow.

Nodular lymphocyte-predominant Hodgkin lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for about 5% of cases. The cancer cells in NLPHL are large cells called popcorn cells (because they look like popcorn), which are variants of Reed-Sternberg cells. You may also hear these cells called lymphocytic and histiocytic (L&H) cells.

NLPHL usually starts in lymph nodes in the neck and under the arm. It can occur in people of any age, and is more common in men than in women. This type of HL tends to grow more slowly and is treated differently from the classic types. 

Diagnosis of Hodgkin lymphoma

Your doctor will inquire about your medical history, both personal and familial. He or she may then have you undergo tests and procedures to determine whether you have Hodgkin’s lymphoma, such as:

Physical examination: Swollen lymph nodes, such as those in your neck, underarm, and groyne, as well as a swollen spleen or liver, are checked by your doctor.

Blood test: A lab examines a sample of your blood to check whether anything in it signals the risk of cancer.

Imaging tests: Imaging studies to search for symptoms of Hodgkin’s lymphoma in other parts of your body may be recommended by your doctor. X-rays, CT scans, and positron emission tomography are all possible tests.

Lymph node biopsy: A lymph node biopsy technique to remove a lymph node for laboratory testing may be recommended by your doctor. If Reed-Sternberg cells, which are aberrant cells, are identified within the lymph node, he or she will diagnosis classical Hodgkin’s lymphoma.
A sample of bone marrow is removed for examination. A needle is inserted into your hipbone to remove a sample of bone marrow during a bone marrow biopsy and aspiration operation. The sample is examined for the presence of Hodgkin’s lymphoma cells.

Depending on your situation, other tests and treatments may be used.

Stages of Hodgkin’s lymphoma

After your doctor has determined the extent of your Hodgkin’s lymphoma, your cancer will be assigned a stage. Knowing your cancer’s stage helps your doctor determine your prognosis and treatment options.

Stages of Hodgkin’s lymphoma include:

• Stage I. The cancer is limited to one lymph node region or a single organ.
• Stage II. In this stage, the cancer is in two lymph node regions or the cancer has invaded one organ and the nearby lymph nodes. But the cancer is still limited to a section of the body either above or below the diaphragm.
• Stage III. When the cancer moves to lymph nodes both above and below the diaphragm, it’s considered stage III. Cancer may also be in one portion of tissue or an organ near the lymph node groups or in the spleen.
• Stage IV. This is the most advanced stage of Hodgkin’s lymphoma. Cancer cells are in several portions of one or more organs and tissues. Stage IV Hodgkin’s lymphoma affects not only the lymph nodes but also other parts of the body, such as the liver, lungs or bones.

Treatment of Hodgkin’s lymphoma

The most common therapies for HL are chemotherapy and radiation therapy. One or all of these therapies may be used, depending on the circumstances.

Immunotherapy or a stem cell transplant may be used to treat certain patients who have failed to respond to prior treatments. Surgery is rarely utilized to treat HL, with the exception of biopsy and staging.

Chemotherapy drugs used in Hodgkin lymphoma

Chemo for classic Hodgkin lymphoma (cHL) combines several drugs because different drugs kill cancer cells in different ways. The combinations used to treat cHL are often referred to by abbreviations.

ABVD is the most common regimen used in the United States:

• Adriamycin (doxorubicin)
• Bleomycin
• Vinblastine
• Dacarbazine (DTIC)

Other common regimens include:

BEACOPP

• Bleomycin
• Etoposide (VP-16)
• Adriamycin (doxorubicin)
• Cyclophosphamide
• Oncovin (vincristine)
• Procarbazine
• Prednisone

Stanford V

• Doxorubicin (Adriamycin)
• Mechlorethamine (nitrogen mustard)
• Vincristine
• Vinblastine
• Bleomycin
• Etoposide
• Prednisone

Another drug that can be considered as chemo is brentuximab vedotin (Adcetris). This is an antibody-drug conjugate (ADC), which is a monoclonal antibody attached to a chemo drug.

Radiation therapy in Hodgkin lymphoma

Radiation therapy is frequently effective in destroying HL cells. Chemotherapy, on the other hand, has proven to be quite effective over time. Because of the potential for long-term negative effects, doctors today tend to employ less radiation and lower doses of radiation.

A machine delivers finely concentrated beams of radiation to treat HL. External beam radiation is the term for this type of radiation.

The radiation team takes precise measurements before beginning therapy to calculate the angles for focusing the radiation beams and the dose required. Simulation is a type of planning session that generally incorporates imaging tests like CT or PET scans. For each treatment, casts, body moulds, and head rests may be used to keep you in the same posture. Other areas of your body can be protected using blocks or shields. It’s possible that you’ll be asked to hold your breath for a brief period of time. The idea is to concentrate the radiation on the cancer in order to minimise the impact on healthy tissues.

Radiation treatments are usually administered five days a week for several weeks. The procedure is similar to receiving an x-ray, except the radiation is more powerful. Each treatment is only a few minutes long, but the setup period (getting you or your child into position) is frequently longer. Although the therapy is painless, some younger children may require sedation to ensure that they do not move throughout the procedure. Modern imaging techniques can detect the exact location of HL, allowing clinicians to focus radiation just on the lymphoma while preserving neighboring healthy tissues. This can assist to keep adverse effects to a minimum.

Involved site radiation therapy

When it comes to treating HL, many doctors prefer this newer method to radiation therapy. The radiation in ISRT is only directed towards the lymph nodes that originally contained the lymphoma, as well as any surrounding sites where the malignancy has spread. This reduces the size of the treatment region (or field) and helps to avoid radiation exposure to neighboring normal tissues and organs.

This is rarely done today, but radiation used to be given to the major lymph node areas that contained lymphoma, as well as the surrounding normal lymph node areas. This was done just in case the lymphoma had spread, even though the doctors could not actually detect it in these areas. This is called extended field radiation.

• If the lymphoma was in the upper body, radiation was given to the mantle field, which included lymph node areas in the neck, chest, and under the arms. Sometimes this was extended to also include lymph nodes in the upper abdomen (belly).
• Inverted Y field radiation therapy included the lymph nodes in the upper abdomen, the spleen, and the lymph nodes in the pelvis.
• When inverted Y field radiation was given together with mantle field radiation, the combination was called total nodal irradiation.

Because nearly all patients with HL are now treated with chemotherapy, extended field radiation is seldom used any more.

Total body irradiation

People who are getting a stem cell transplant may get radiation to the whole body along with high-dose chemotherapy, to try to kill lymphoma cells throughout the body

Immunotherapy

Immunotherapy is the use of medicines to help someone’s immune system better recognize and destroy cancer cells. Immunotherapy can be used to treat some people with Hodgkin lymphoma (HL).

Monoclonal antibodies
Antibodies are proteins made by your immune system to help fight infections. Man-made versions, called monoclonal antibodies (mAbs), can be designed to attack a specific target, such as a substance on the surface of lymphocytes (the cells in which HL starts).

Brentuximab vedotin (Adcetris)
Classic Hodgkin lymphoma (cHL) cells usually have the CD30 molecule on their surface. Brentuximab vedotin is an anti-CD30 antibody attached to a chemo drug. The antibody acts like a homing signal, bringing the chemo drug to the lymphoma cells with CD30 on them. The drug enters the cells and kills them when they try to divide into new cells.

This drug can be used:

As the first treatment for stage III or IV cHL (where it is given along with chemotherapy)
In people with cHL that has come back after other treatments, including after a stem cell transplant (or in people who can’t have a transplant for some reason). It can be given alone or along with chemo.
After a stem cell transplant for people at high risk of the cancer coming back after treatment. In this situation, it is usually given by itself for a year.
Brentuximab vedotin is infused into a vein (IV), usually every 3 weeks.

Common side effects include:

Nerve damage (neuropathy)
Low blood cell counts
Fatigue
Fever
Nausea and vomiting
Infections
Diarrhea
Rarely, serious side effects occur during IV infusions, such as trouble breathing and low blood pressure

Rituximab (Rituxan)
Rituximab may be used to treat nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). This mAb attaches to a substance called CD20 on some types of lymphoma cells. It’s often given along with chemotherapy and/or radiation therapy.

Rituximab is given as an IV infusion in the doctor’s office or clinic. When it’s used by itself, it’s usually given once a week for 4 weeks, which may then be repeated several months later. When it’s given along with chemotherapy, it’s most often given on the first day of each chemo cycle.

Common side effects are usually mild but can include:

Chills
Fever
Nausea
Rashes
Fatigue
Headaches
Rarely, more severe side effects occur during infusions, such as trouble breathing and low blood pressure. You will be given medicines before each treatment to help keep this from happening. But even if these symptoms do occur during the first infusion, it’s unusual for them to happen again with later doses.

Rituximab can cause prior hepatitis B infections to become active again, which sometimes leads to severe liver problems or even death. Your doctor will probably check your blood for signs of hepatitis before starting this drug.

Rituximab can also increase your risk of infection for several months after the drug is stopped.

Immune checkpoint inhibitors
An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoint” proteins, which act like switches on immune cells that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system.

Nivolumab (Opdivo) and pembrolizumab (Keytruda) are checkpoint inhibitors that can be used in people with classic Hodgkin lymphoma whose cancer has grown during treatment (called refractory cancer) or has returned after other treatments have been tried (called recurrent or relapsed cancer).

These drugs target PD-1, a protein on certain immune system cells (called T cells) that normally helps keep these cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

These drugs are given as an intravenous (IV) infusion, typically every 2, 3, or 6 weeks.

Possible side effects
Side effects of these drugs can include:

Fatigue
Fever
Cough
Nausea
Itching
Skin rash
Loss of appetite
Joint pain
Constipation
Diarrhea
Other, more serious side effects occur less often.

Infusion reactions: Some people might have an infusion reaction while getting one of these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting one of these drugs.

Autoimmune reactions: These drugs work by basically removing one of the safeguards on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.

If you notice any problems, you should tell your health care team about it right away. If serious side effects do occur, treatment may need to be stopped and you may get high doses of steroids to suppress your immune system.

Stem cell transplant in Hodgkin lymphoma

Stem cell transplants (SCTs) are occasionally used to treat Hodgkin lymphoma that is difficult to treat, such as illness that does not respond to chemotherapy (chemo) and/or radiation, or lymphoma that returns after treatment.

Chemotherapy drug doses are typically controlled by the negative effects that these treatments cause. Higher doses aren’t possible, even though they would kill more cancer cells, because they would harm the bone marrow, which produces new blood cells.

Doctors can use heavier chemo dosages after a stem cell transplant (sometimes along with radiation therapy). Because the patient receives a transplant of blood-forming stem cells to repair the bone marrow after high-dose chemo, this is the case.

Blood-forming stem cells can come from the blood or the bone marrow and be used in a transplant. The majority of transplants today are done with cells extracted from the blood, which are referred to as peripheral stem cell transplants.