Whole-Body (Systemic) Treatments for Skin Lymphomas

Systemic treatments can affect the whole body. They are most useful for more advanced or quickly growing skin lymphomas. In some cases, a systemic treatment is 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 minor. The most significant side effect 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 if the disease in the skin is more advanced and no longer getting better with other treatments. It can also be helpful if the lymphoma has spread to lymph nodes, blood, or distant organs and tissues.

Many chemo drugs are useful in treating patients with skin lymphoma, including:

  • Gemcitabine
  • Liposomal doxorubicin (Doxil)
  • Methotrexate
  • Chlorambucil
  • Cyclophosphamide
  • Pentostatin
  • Etoposide
  • Temozolomide
  • Pralatrexate

Often a single drug is tried first, but sometimes patients are treated with drug combinations like those 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.

Chemo treatments are given on different schedules, but usually they are 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 a hospital stay.

Patients often get chemo for 2 or 3 cycles and then have tests (such as PET or CT scans) to see if it is working. If the first chemo regimen doesn’t seem to be working, different drugs may be tried.

More information about chemo for non-Hodgkin lymphoma can be found in 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, 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 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 temporary and go away after treatment is finished. If serious side effects occur, the chemo may have to be delayed or the doses reduced. There are often ways to lessen 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.

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.

Although most side effects go away after chemo is stopped, some can be long-lasting or might not occur until months or years after treatment has ended. For example, drugs like doxorubicin can damage the heart. Other drugs can sometimes damage the kidneys, nerves, or other organs. In rare cases, people develop leukemia several years later. Before you start chemo, ask your doctor or nurse what drugs will be used and what the side effects might be.

To learn more about chemo, see the Chemotherapy section of our website.

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 lymphoma cells. Others work by boosting the body’s immune system to attack lymphoma cells.

These drugs work differently from standard chemo drugs, which generally affect all fast-growing cells. 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 is a cancer-fighting drug known as a histone deacetylase (HDAC) inhibitor. It is given as a pill, once a day. It is used to treat T-cell skin 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 T-cell skin 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.

Denileukin diftitox (Ontak): This drug combines part of an interleukin-2 (IL-2) molecule with diphtheria toxin. The drug attaches to the IL-2 receptor on certain lymphocytes and lymphoma cells, where the diphtheria toxin can kill these cells. 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. Vision problems that might not go away even after treatment is stopped are a rare side effect of this drug.

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 CD20, a substance on the surface of most B lymphocytes, which causes 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 can include chills, fever, nausea, rashes, fatigue, and headaches, especially during the first infusion. Side effects are less likely with later doses. Rituximab can also increase a person’s risk of infections. It can cause prior hepatitis B infections to become active again, sometimes leading to severe liver problems or even death. Your doctor will probably test you for hepatitis before giving you 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. This drug is given by injection either under the skin (subcutaneous) or into a vein (IV), usually several times a week.

Alemtuzumab works well against some types of skin lymphoma, but it can have serious side effects, especially when given IV. 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.

Brentuximab vedotin (Adcetris): This is an anti-CD30 antibody attached to a chemotherapy drug. Some skin lymphoma cells have the CD30 protein. The antibody acts like a homing signal, bringing the chemo drug to lymphoma cells, where it enters the cells and kills them. 

Brentuximab can be used to treat some types of skin lymphoma, especially after other treatments have been tried. This drug is infused into a vein (IV), typically every 3 weeks.

Common side effects can include nerve damage (neuropathy), low blood counts, fatigue, fever, nausea and vomiting, infections, diarrhea, and cough. 

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. Usually they are injected 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.

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 widespread.

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 can 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. Doctors aren’t yet sure exactly how well this type of treatment works for patients with skin lymphoma, but studies are now being done to find out, and it may become more common in the future.

Stem cell transplants let doctors give higher doses of chemotherapy (and sometimes radiation) than could normally be given. High-dose chemo destroys the bone marrow, where new blood cells are made. 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 the patient 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 blood cells.

The blood-forming stem cells used for a transplant come 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 having serious problems with the transplant.

This is often the preferred type of transplant if it can be done, but it is often hard to find a matched donor. Another drawback is that side effects of this treatment might be too severe for most older patients.

Non-myeloablative (mini) transplant: In this type of allogeneic transplant, lower doses of chemo and radiation are used than in a standard SCT. This may be an option for some patients who couldn’t tolerate a regular allogeneic transplant because of its side effects.

The lower dose treatment doses do not completely destroy the cells in the bone marrow. When the donor stem cells are given, they establish a new immune system, which sees the lymphoma cells as foreign and attacks them.

Autologous stem cell transplant

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

Autologous transplants are not used much for skin lymphomas.

Practical points

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 yours.

SCT often requires a long hospital stay and can be very expensive (often costing well over $100,000). 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 many thousands of dollars. Find out what your insurer will cover before the 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 (short-term) and late (long-term) effects.

Early or short-term effects: The early complications and side effects are basically those caused by high-dose chemo, and can be severe. They can include:

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

One of the most common and serious short-term effects is the increased risk of serious infections. Patients often stay in a special hospital room right after the transplant to help protect them from germs, and antibiotics are often given to try to prevent infections. Other side effects, like low red blood cell and platelet counts, might 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 (GVHD), a serious side effect in which the new immune system attacks the patient’s own body tissues. This can cause skin rashes, itching, mouth sores (which can affect eating), nausea, severe diarrhea, liver damage, and other problems. GVHD occurs only in allogeneic (donor) transplants.
  • 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 might need to have part of the affected bone and the joint replaced.
  • Damage to the lungs, causing shortness of breath
  • Development of another cancer (such as leukemia) years later

For more on stem cell transplants, see Stem Cell Transplant for Cancer.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: August 4, 2014 Last Revised: November 10, 2017

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