Photopheresis (also known as extracorporeal photochemotherapy, ECP) is a blood-filtering treatment that works with your body’s own immune system to treat disease. This immunotherapy was developed by a Yale Medicine dermatologist to treat cutaneous T-cell lymphomas, a rare group of cancers that usually affects the skin but sometimes can be found in the blood, lymph nodes and other internal organs.

Over time, the treatment has been used for other health issues like graft-versus-host disease (GVHD, in which donated bone marrow or blood stem cells attack the recipient’s body) and organ rejection. Today, photopheresis is being investigated as a potential treatment for other autoimmune diseases.

What’s unique about photopheresis is how it can be tailored to particular needs. Sometimes it is used as a kick-start, to strengthen an immune response, while in other situations it provides what amounts to a “reset,” halting a problematic immune response.

“People are surprised that you can have one therapy capable of turning on the immune system when you need a stronger reaction, like with cancer. Or turning it off, when the immune system is actually causing the problem, like with a reactive organ transplantation rejection,” says Richard Edelson, MD, chair of Yale Medicine Dermatology, who developed the treatment in 1987.

At Yale Medicine ECP (Photopheresis) Immunotherapy Program, our dermatology team treats patients with cutaneous T-cell lymphoma, GVHD and organ transplant rejection. Our physician-scientists are actively studying how Photopheresis may be used to treat a host of other immunologic disorders. 

Photopheresis is considered a cellular immunotherapy that recruits the body’s “fighter” white blood cells (T-cells) to wage (or calm) an immune response, as needed.

The treatment is performed on a patient's blood. Using either an IV or a catheter, blood is routed through a device which separates a portion of white blood cells (leukocytes) and treats them with naturally occurring photosensitizing chemicals called 8-methoxypsoralen (8-MOP), also called psoralen. (Psoralen is found in lemons, figs and celery, for instance.) Once chemically treated, the blood is then exposed to specific wavelengths of ultraviolet (UVA) light. 

The blood—with its immune cells either activated by the treatment to fight off cancer or slowed down to prevent organ rejection— is then returned to the patient’s body. Though somewhat time-consuming (it takes three to four hours, performed over a couple days, and repeated every few weeks for at least several months), the treatment is not painful and causes relatively few, if any, side effects. 

T-cell lymphoma is a rare form of lymphoma that can affect different parts of the body, including the blood, lymph system and internal organs. Usually, however, CTCL presents with skin symptoms, sometimes very mild ones such as small patches of redness or dryness that grow or spread very slowly, over long periods of time. Sometimes, however, CTCL is aggressive and moves quickly.

When CTCL is untreated, the cancerous lymphocytes of CTCL can spread to the blood and to other internal organs and distant skin sites. Two of the most common cutaneous T-cell lymphomas are mycosis fungoides and Sézary syndrome, described below. Photopheresis is a treatment option for both, although it is less commonly used in cases where the cancer has not spread to the patient’s blood.

• Mycosis fungoides: The most common form of CTCL, this cancer generally appears on the skin as a red rash, which is often barely noticeable. It can evolve into plaques—large, thick areas on the skin that can be scaly and itchy—and, if left untreated, tumors may develop on the skin, usually in the trunk or torso area.
• Sézary syndrome: This is one of the most advanced forms of CTCL. Although it can feature the skin-related symptoms of mycosis fungoides, this cancer can be found in the blood and in the lymph nodes.

Though cutaneous T-cell lymphoma is chronic, it is treatable. Patients who enter remission should be monitored closely for returning symptoms.

“In the spectrum of non-Hodgkin lymphoma, it’s one that has a better prognosis,” says Michael Girardi, MD, PhD, director of the ECP Immunotherapy Program.

GVHD is a complication of peripheral blood stem cell transplantation, where the donor's blood is actually reacting against the patient's body, Dr. Girardi says. This could involve the lungs, the liver, the skin, or other organs of the body.

One of the ways GVHD is treated is by giving the patient strong immune-suppressive medications. When those medications have unwanted side effects or fail, photopheresis may be a next step doctors will try.

“Photopheresis is another way to treat the disease in a more ‘gentle’ way,” Dr. Girardi says. “We can kind of ask the immune system to lighten its reactivity, and in this way, we can lessen the severity of GVHD and also hopefully decrease the patient's medications to avoid and lessen their side effects.”

Similary, photopheresis can be used to “down-regulate” the immune response involved with organ transplantation rejection.

“When patients receive an organ transplantation, like a heart, sometimes their immune systems react against the organ in a way that can progress to organ rejection,” says Dr. Girardi.

Photopheresis essentially calms the immune system’s over-reactivity to the transplanted organ, slowing down the body’s reaction against it. “The patient can then maintain the transplant, and hopefully live a long life,” Dr. Girardi says.

Photopheresis is considered a safe procedure that brings little, if any, discomfort. Although anemia (low iron in the blood) is a potential side effect, along with temporary hypotension, tachycardia and thrombocytopenia, the reported side effects are infrequent.

“In general, we don't see much in the way of any side effects for the patient,” says Dr. Girardi.

We are internationally recognized as the institution where photopheresis was developed. Our scientists at Yale School of Medicine Dermatology are investigating how at a cellular level exposing white blood cells to light alters the body’s immune response. And we are researching new uses for this immunotherapy treatment through ongoing observational studies and clinical trials.