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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 (ECP). It is sometimes used for T-cell skin lymphomas, especially Sezary syndrome. It is thought to work by killing some lymphoma cells directly, as well as by boosting the body’s immune response against 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 ultraviolet A (UVA) light before they are mixed back in with the rest of the blood and infused back into the person. Each procedure usually takes a few hours. Treatments are typically given for 2 days in a row, and then repeated every few 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's 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 lymphomas, 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 the lymph nodes, blood, or to other parts of the body.

Many chemo drugs can be useful in treating people with skin lymphoma, including:

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

Often a single drug is tried first, but sometimes combinations of drugs are used, like those used for non-Hodgkin lymphoma not involving the skin.

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.

People 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.

For more information about chemo for non-Hodgkin lymphoma, see Non-Hodgkin Lymphoma.

Possible side effects of chemotherapy

Chemo drugs can cause side effects. These 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 a shortage of red blood cells)

These side effects usually 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.

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, see Chemotherapy.

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) and romidepsin (Istodax): These drugs are histone deacetylase (HDAC) inhibitors. They are 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. Vorinostat is a pill, typically taken once a day, whereas romidepsin is given as an infusion into a vein (IV), usually once a week.

Rituximab (Rituxan, other brand names): 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 protein 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 given as IV infusions or injections under the skin, usually 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 virus (HBV) infections to become active again, sometimes leading to severe liver problems or even death. Your doctor will probably test you for HBV before giving you this drug.

Brentuximab vedotin (Adcetris): Some skin lymphoma cells have the CD30 protein. This drug is an anti-CD30 antibody attached to a chemotherapy drug. The antibody acts like a homing device, 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.

Mogamulizumab (Poteligeo): This is a monoclonal antibody that binds to CCR4, a protein often found in high amounts on T-cell lymphoma cells. Binding to these cells may slow their growth, as well as mark them for attack by the immune system.

Mogamulizumab can be used to treat mycosis fungoides or Sezary syndrome that has come back or is no longer responding to at least one other systemic treatment. This drug is given by infusion into a vein (IV), typically once a week or once every other week.

Common side effects can include rash, allergic-like reactions during infusions, fever, fatigue, diarrhea, muscle or bone pain, and upper respiratory infections. Less common but more serious problems can include severe skin reactions, infections, and autoimmune problems (in which the immune cells in the body attack other cells or organs).

Alemtuzumab: This monoclonal antibody targets the CD52 protein found on some lymphoma cells. When the antibody binds to this protein, it triggers the immune system to destroy the cell. This drug is given by either as an injection 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. Some people have allergic reactions to it, which can sometimes be serious. It can also severely weaken the immune system, which 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 to treat skin lymphomas, although it may be an option if the lymphoma comes 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. 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.

Pembrolizumab (Keytruda): This is a type of immunotherapy drug known as an immune checkpoint inhibitor. It works by blocking a "checkpoint" protein on immune cells that keeps them from attacking cancer cells.

Pembrolizumab might be an option to treat some types of advanced skin lymphomas, often after other systemic treatments have been tried. This drug is given by infusion into a vein (IV), typically once every 3 to 6 weeks.

Side effects from this drug are usually mild, but some people might have serious side effects, such as an infusion reaction while getting the drug or a serious autoimmune reaction (in which the immune system attacks other organs in the body).

Systemic retinoids

Retinoids are drugs related to vitamin A. Retinoids such as 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)

A stem cell transplant (SCT) is sometimes an option to treat lymphoma when standard treatments are no longer working.

The doses of chemotherapy (chemo) drugs normally are limited by the side effects these drugs can cause. Higher doses can’t be used, even if they might kill more cancer cells, because they would severely damage the bone marrow, where new blood cells are made.

A stem cell transplant (also known as a bone marrow transplant) lets doctors give higher doses of chemo (sometimes along with radiation therapy). This is because after getting high-dose chemo treatment, the patient receives a transplant of blood-forming stem cells to restore the bone marrow. The blood-forming stem cells used for a transplant can come either from the blood or from the bone marrow.

The main types of transplants, based on the source of the stem cells are:

Allogeneic SCT: For this type of 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 individual’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 many older patients.

Autologous SCT: In this type of transplant, a patient’s own stem cells are removed from their 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 (put back) into the patient’s blood. Autologous transplants are not used much for skin lymphomas.

A stem cell transplant is a complex treatment that can cause life-threatening side effects. It should be done at a cancer center where the staff has experience with the procedure and with managing the recovery phase.

To learn more about stem cell transplants, including how they are done and their potential side effects, see Stem Cell or Bone Marrow Transplant.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.


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National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Primary Cutaneous Lymphomas. Version 2.2024. Accessed at on May 29, 2024.

Querfeld C, Rosen ST, Duvic M. Chapter 104: Cutaneous T-cell lymphoma and cutaneous B-cell lymphoma. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa. Elsevier: 2020.


Last Revised: June 3, 2024

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