Lymphoma of the Skin

+ -Text Size

Treating Lymphoma of the Skin TOPICS

Whole-body (systemic) treatments for skin lymphomas

Systemic treatments have the potential to affect the whole body. They are most useful for more advanced or quickly growing skin lymphomas. In some cases, a systemic treatment may be combined with a skin-directed treatment or with another systemic treatment.

Photopheresis (photoimmune therapy)

This treatment is also called extracorporeal photopheresis, or ECP. It is sometimes used for T-cell skin lymphomas, especially Sezary syndrome. It is thought to work by killing some lymphoma cells directly and by boosting the body’s immune response against other lymphoma cells.

The procedure is similar to donating blood, but instead of going into a collecting bag, the blood goes into a special machine that separates out the lymphocytes (including lymphoma cells). They are then treated with a psoralen (a light-sensitizing drug) and UVA light before they are mixed back in with the rest of the blood and infused back into the patient. Each procedure usually takes a few hours. Treatments are typically given for 2 days in a row, and then repeated every 4 weeks or so.

Side effects are usually minimal. The most significant side effect from this procedure is sensitivity to sunlight for about a day after each treatment, which might result in sunburn or other problems. It is very important to protect yourself from sunlight as much as possible during this time.

Systemic chemotherapy

Chemotherapy (chemo) uses strong drugs to treat cancer. When the drugs are injected into a vein or a muscle or taken by mouth, they enter the bloodstream and reach all areas of the body.

Systemic chemo is not often used for early skin lymphoma, but it may be used when the disease in the skin is more advanced and no longer getting better with other treatments. It can also be helpful when the lymphoma has spread to lymph nodes, blood, or distant organs and tissues.

Many drugs are useful in the treatment of patients with skin lymphoma, including:

Often a single drug is tried first, but sometimes patients are treated with drug combinations more often used for lymphoma not involving the skin. For example, a chemo regimen called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) may be used, often along with the monoclonal antibody rituximab (Rituxan), which is described below.

The treatments all have different schedules, but they are usually repeated several times in cycles given 3 or 4 weeks apart. Most chemo treatments are given on an outpatient basis (in the doctor’s office, clinic, or hospital outpatient department), but some require hospital admission.

Patients often receive chemo for 2 or 3 cycles and then have tests to see if it is working. If the first regimen doesn’t seem to be working, different drugs may be tried.

More information about chemo for non-Hodgkin lymphoma can be found in our document Non-Hodgkin Lymphoma.

Possible side effects

Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow (where new blood cells are made), the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemo, which can lead to side effects. Side effects depend on the specific drugs used, their dose, and the length of treatment. Some common side effects include:

  • Hair loss
  • Mouth sores
  • Loss of appetite
  • Nausea and vomiting
  • Diarrhea
  • Increased chance of infection (from a shortage of white blood cells)
  • Bleeding or bruising after minor cuts or injuries (from a shortage of platelets)
  • Fatigue or shortness of breath (from 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 can be given to help prevent and reduce nausea and vomiting.

A major concern with chemo is its effect on the patient’s immune system, which is often already damaged by the lymphoma itself. This sometimes limits how intense the chemo treatment can be. Drugs known as growth factors (G-CSF or GM-CSF, for example) are sometimes given after chemo to help the body make new white blood cells to reduce the chance of a serious infection. Antibiotics may also be given at the earliest sign of an infection, such as a fever.

If your white blood cell counts are very low during treatment, you can help reduce your risk of infection by limiting your 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).

If your platelet counts are very low, you may be given drugs or platelet transfusions to help protect against bleeding. Fatigue caused by anemia (very low red blood cell counts) can be treated with drugs or with red blood cell transfusions.

Some possible side effects are more common with certain drugs. For example, drugs like doxorubicin can damage the heart. Other drugs can sometimes cause damage to the kidneys, nerves, or other organs. Your doctor or nurse can tell you about the possible side effects of specific drugs you may be getting.

If serious side effects occur, the chemotherapy may have to be reduced or stopped, at least for a while. Although most side effects go away after chemo is stopped, some can be permanent. Before you start chemo, discuss with your cancer team what drugs will be used and what side effects to expect.

Chemotherapy can also cause side effects that might not occur until years after treatment. For example, in rare cases, people may develop leukemia several years later.

You can find more information on chemotherapy in the “Chemotherapy” section of our website, or in our document Understanding Chemotherapy: A Guide for Patients and Families.

Targeted and biologic therapies

In recent years, many newer drugs have been developed to treat skin lymphomas. Some of these drugs target specific parts of cancer cells. Others work by boosting the body’s immune system to attack lymphoma cells.

These drugs work differently from standard chemotherapy drugs, which generally affect all quickly growing cells in the body. They sometimes work when chemo drugs don’t. They also tend to have different (and often milder) side effects than standard chemo drugs.

Vorinostat (Zolinza): This drug is in a class of cancer-fighting drugs called histone deacetylase (HDAC) inhibitors. It is given as a pill, once a day. It is used to treat cutaneous T-cell lymphomas, usually after other treatments have been tried. Side effects tend to be mild, but can include nausea, diarrhea, lowered blood cell counts, and effects on the rhythm of the heart.

Romidepsin (Istodax): Romidepsin is another HDAC inhibitor. It is also used to treat cutaneous T-cell lymphomas, usually after at other treatments have been tried. This drug is given as an infusion into a vein (IV), usually once a week. Side effects are similar to those of vorinostat.

Bortezomib (Velcade): This is a type of drug known as a proteasome inhibitor. It is usually used to treat other cancers of lymphocytes. But it can also be used to treat some skin lymphomas, usually after other treatments have been tried. Bortezomib is given as an IV infusion, typically twice a week for 2 weeks, followed by a rest period. Side effects can be similar to those of standard chemotherapy drugs, including low blood counts, nausea, loss of appetite, and nerve damage.

Denileukin diftitox (Ontak): This drug combines part of an interleukin-2 (IL-2) molecule with diphtheria toxin. The receptor for IL-2 is only found on certain lymphocytes and lymphoma cells. When the drug attaches to that receptor, the diphtheria toxin can kill the lymphoma cell. The drug is given as an IV infusion daily for 5 days in a row. It is used mainly in patients whose skin lymphoma has gotten worse (or come back) after another treatment.

Common side effects during the first day of treatment can include low blood pressure, shortness of breath, back pain, and rash. Patients getting this drug may also feel like they have the flu within the first few days of treatment. This improves with treatment and time. A rare side effect of this drug is problems with vision that may not go away even after treatment is stopped.

Rituximab (Rituxan): This drug is a monoclonal antibody – a man-made version of an immune system protein that has a very specific target. This antibody attaches to a substance called CD20 found on the surface of most B lymphocytes, causing the cells to die.

Rituximab can be used alone or with other drugs to treat B-cell skin lymphomas. Treatments are usually given as IV infusions weekly or at longer intervals.

Common side effects are often mild but may include chills, fever, nausea, rashes, fatigue, and headaches, especially during the first infusion. Side effects are less likely with later doses. Rituximab may also increase a person’s risk of infections. It can cause dormant (inactive) hepatitis B infections to become active again, sometimes leading to severe liver problems or even death. Your doctor may check your blood for signs of hepatitis before starting this drug.

Alemtuzumab (Campath): This monoclonal antibody targets the CD52 protein found on some types of lymphocytes and lymphoma cells. When the antibody binds to this protein, it triggers the immune system to destroy the cell. It is given by injection either under the skin (subcutaneous) or into a vein (IV), usually several times a week.

Alemtuzumab works well against skin lymphoma, but this drug can have serious side effects. Some people have allergic reactions during the first few infusions, which can sometimes be serious. Doctors usually give a low dose at first and gradually increase it to try to prevent this.

In some people, alemtuzumab can severely weaken the immune system. This can lead to serious or even life-threatening infections with germs that aren’t usually a problem for healthy people.

Because of these risks, alemtuzumab is not often used as a first treatment. It may be an option for people with skin lymphoma that has come back after other treatments.

Interferons: The interferons are hormone-like proteins normally made by white blood cells to help the immune system fight infections. Certain types of interferon can be made in the lab and given as medicine. Interferons can cause some types of skin lymphomas to shrink or stop growing. They are given as injections, usually under the skin several times a week.

People getting this treatment often have flu-like side effects, such as fatigue (which can be severe), fever, chills, headaches, muscle and joint aches, and mood changes. The side effects tend to be worse when higher doses are used.

More information about these treatments can be found in our documents Targeted Therapy and Immunotherapy.

Systemic retinoids

Retinoids are drugs related to vitamin A. Retinoids such as all-trans retinoic acid (ATRA), acitretin, isotretinoin (Accutane), and bexarotene (Targretin) can be used to treat some skin lymphomas, especially mycosis fungoides and Sezary syndrome. Bexarotene can be used as a topical treatment when only a few small skin lesions are present, but retinoids are often taken in pill form for skin lymphomas that are more extensive.

Side effects of systemic retinoids can include headache, nausea, fever, increased blood levels of triglycerides (fats), thyroid problems, and eye problems. Some retinoids can cause more serious side effects, like fluid buildup in the body. These drugs should never be given to a woman who is pregnant or who might become pregnant, as they may cause serious birth defects.

High-dose chemotherapy with stem cell transplant (SCT)

Stem cell transplants are sometimes used to treat lymphoma when standard treatments are no longer working. This type of therapy is used only rarely in patients with skin lymphoma, but it may become more common in the future.

Stem cell transplants allow doctors to give higher doses of chemotherapy (and sometimes radiation) than would normally be tolerated. High-dose chemotherapy destroys the bone marrow, which prevents new blood cells from being formed. This could lead to life-threatening infections, bleeding, and other problems due to low blood cell counts.

Doctors try to get around this problem by giving an infusion of blood-forming stem cells after treatment. Stem cells are very early forms of cells that can create new blood cells. They travel to the bone marrow and start making new cells.

The blood-forming stem cells used for a transplant are obtained either from the blood (for a peripheral blood stem cell transplant, or PBSCT) or from the bone marrow (for a bone marrow transplant, or BMT). Peripheral blood stem cells are collected in a procedure similar to a blood donation, while bone marrow donation is usually done in an operating room with the donor under general anesthesia (in a deep sleep). Bone marrow transplants were more common in the past, but they have largely been replaced by PBSCTs.

Allogeneic stem cell transplant

In an allogeneic stem cell transplant, the blood-forming stem cells come from another person (instead of using the patient’s own stem cells). The ideal donor is a relative (often a brother or sister) whose tissue type (HLA type) matches the patient’s. This lowers the chance of a serious side effect called graft vs. host disease, which is discussed later in this section. If the donor is someone who is a tissue type match to the patient but is not related, the transplant carries more risks.

Allogeneic transplants are often the preferred type of transplant if they can be done, but it is often hard to find a matched donor. Another drawback is that side effects of this treatment may be too severe for most people over 55 years old.

Non-myeloablative (mini) transplant: This is a type of allogeneic transplant in which lower doses of chemotherapy and radiation are used than in a standard SCT. This type of transplant may be an option for some patients who couldn’t tolerate a regular allogeneic transplant because of its side effects. In fact, a patient can receive a non-myeloablative transplant as an outpatient.

The lower dose treatment doses do not completely destroy the cells in the bone marrow. When the donor stem cells are given, they enter the body and establish a new immune system, which sees the lymphoma cells as foreign and attacks them (known as a graft-versus-lymphoma effect).

The major side effect is graft-versus-host disease (discussed later in this section), which can be serious.

Doctors aren’t yet sure exactly how effective these types of transplants are for patients with lymphoma, but studies are now being done to find out.

Autologous stem cell transplant

In this type of transplant, a patient’s own stem cells are removed from his or her bone marrow or peripheral blood. They are collected on several occasions in the weeks before treatment. The cells are frozen and stored while the person gets treatment (high-dose chemotherapy and/or radiation) and are then are reinfused into the patient’s blood.

With some types of lymphoma that tend to spread to the bone marrow or blood, an autologous transplant may not be possible because it might be hard to get a stem cell sample that is free of lymphoma cells. Even after purging (treating the stem cells in the lab to kill or remove lymphoma cells), returning some lymphoma cells with the stem cell transplant is possible.

Practical points

With either type of transplant, blood-forming stem cells collected from the donor or the patient are carefully frozen and stored. The patient then receives high-dose chemotherapy and sometimes whole body radiation treatment as well. This destroys remaining cancer cells, but it also kills all or most normal cells in the bone marrow. After therapy, the frozen stem cells are thawed and returned to the body by infusion into a vein, just like a blood transfusion.

For the next several weeks the patient will likely have very low blood cell counts, so they are given as much supportive therapy as needed. This may include antibiotics, red blood cell or platelet transfusions, other medicines, and help with nutrition. Because of the high risk of serious infections, patients stay in protective isolation (where exposure to germs is kept to a minimum) until their white blood cell counts are at a safe level. In an allogeneic SCT, the patient may be given drugs to keep the new immune system from attacking the body (known as graft-versus-host disease).

A stem cell transplant is a complex treatment that can cause life-threatening side effects. If doctors think a patient might benefit from a transplant, the best place to have it done is at a cancer center where the staff has experience with the procedure and with managing the recovery period. Ask the doctor about the number of times he or she has done this procedure, the number done at their facility, and their results with cases such as theirs.

SCT is very expensive (often costing well over $100,000) and often requires a long hospital stay. Some insurance companies may view SCT as an experimental treatment and may not pay for it. Even if the transplant is covered by your insurance, your co-pays or other costs could easily amount to tens of thousands of dollars. Find out what your insurer will cover before deciding on a transplant so you will have an idea of what you might have to pay.

Possible side effects

Side effects from a stem cell transplant are generally divided into early and long-term effects.

Early or short-term effects: The early complications and side effects are basically the same as those caused by any other type of high-dose chemotherapy and can be severe. They are caused by damage to the bone marrow and other rapidly growing tissues of the body and can include:

  • Hair loss
  • Mouth sores
  • Loss of appetite
  • Nausea and vomiting
  • Diarrhea
  • Low blood cell counts (with fatigue and increased risks of infection and bleeding)

One of the most common and serious short-term effects is the increased risk for infection. Antibiotics are often given to try to keep this from happening. Other side effects, like low red blood cell and platelet counts, may require blood product transfusions or other treatments.

Late or long-term side effects: Complications and side effects that can last for a long time or that may occur many years after the transplant include:

  • Graft-versus-host disease, which occurs only in allogeneic (donor) transplants (see below)
  • Menstrual changes, early menopause, and loss of fertility in female patients (caused by damage to the ovaries)
  • Loss of fertility in male patients
  • Damage to the thyroid gland, causing problems with metabolism
  • Cataracts (damage to the lens of the eye that can affect vision)
  • Bone damage called aseptic necrosis. If damage is severe, the patient will need to have part of the affected bone and the joint replaced.
  • Damage to the lungs, causing shortness of breath
  • Development of leukemia or another cancer years later

Graft-versus-host disease (GVHD): This is one of the most serious complications of allogeneic (donor) stem cell transplants. It occurs because the donor cells establish a new immune system in the patient. The new immune system then may “see” the patient’s own body tissues as foreign and attack them.

Symptoms can include severe skin rashes, itching, mouth sores (which can affect eating), nausea, severe diarrhea, and damage to the liver and lungs. The patient may also become easily fatigued and develop muscle aches.

GVHD is either acute or chronic, based on how soon after the transplant it begins. Sometimes GVHD can become disabling and, if it is severe enough, can be life-threatening. Usually drugs can be used to help control GVHD, although they can have their own side effects.

However, in some cases mild graft-versus-host disease can be a good thing, because it also leads to graft-versus-lymphoma activity. Since the donor’s immune system also sees the lymphoma cells as foreign, it often kills any lymphoma cells remaining after the chemotherapy and radiation therapy.

For more information on these procedures, see our document Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants).

Last Medical Review: 03/14/2013
Last Revised: 02/11/2014