Written by

Sue McCann, MSN, RN, DNC, Photopheresis Coordinator, University of Pittsburgh Medical Center

Extracorporeal photopheresis (ECP) was the first therapy approved by the Food and Drug Administration (FDA) specifically for the treatment of cutaneous T-cell lymphoma (CTCL). ECP is indicated for the palliative treatment of the skin manifestations of CTCL that have not responded to other types of therapy.

If you aren’t very familiar with ECP, you’re not alone. Despite its growing use in the United States and Europe since its FDA approval in March of 1988, there are still many health care practitioners and patients who have little or no knowledge of it. In early 1988, ECP was performed in only about five treatment centers in the United States. Today, ECP is in use in over 120 treatment centers within the United States and throughout Europe.


Some practitioners quickly and succinctly define ECP as PUVA to the blood. (PUVA, as you may know, is a skin directed therapy that involves using a combination of Psoralen, a photosensitizing medication, and ultraviolet A (UVA) light delivered in specific doses to the skin).

However, the more complicated definition is that ECP is a photoimmune therapy that uses the UVAR® Photopheresis System in conjunction with Psoralen to process and treat a patient’s blood. This system involves highly specialized equipment that separates white blood cells (WBCs) from the patient’s whole blood and then exposes the collected, photosensitized WBCs to UVA light within a photoactivation chamber. A novel aspect of this therapy is that the collected cells are treated outside of the patient’s body (extracorporeal). The treated WBCs are then returned to the patient.

How does ECP work?

Amazingly, the exact mechanism of action is not clearly understood. However, research is currently underway to determine this elusive mechanism of action.

It is known that the treated cells stimulate or modify the patient’s own immune system to fight the disease. The response observed could not be due to the anti-proliferative (prevention of cancer cell growth) effect since only 3-5% of the body’s total lymphocyte population are treated during one ECP therapy. As a result of the photosensitized WBC exposure to UVA light, cellular damage occurs, altering cellular DNA and resulting in apoptotic cell death (programmed cell death).

When these altered or damaged cells are returned to the patient, the immune system is alerted and becomes sensitized to the changed cells. The patient’s own immune system may also work to repair the cellular damage, further sensitizing the immune system to antigens (foreign material) now more visible to the immune system. As a result, a system-wide immune response may occur to the pathologic (disease-causing) cancer cell (clone).

What is the typical response rate?

The initial clinical trials done from 1984-1987 showed that 73% of the patients met response criteria of a 25% reduction in skin scores maintained for at least 4 weeks. 30% of patients had an excellent response to ECP demonstrating a 75-100% clearing of skin. This was remarkable given the average clinical trial entry score was 303 out of a possible 400 points, where a zero score meant no skin involvement and a 400 score meant maximal, severe skin involvement. Current literature continues to support this early work regarding response to treatment.

The response to treatment time varies for each person but the average time to response in the clinical trial was 100 days; however, 4-8 months of treatment is usually required to achieve significant benefit for most patients. If no response is obtained at that time, additional therapies may be added to enhance or encourage a response.

What happens during a photopheresis treatment?

ECP is accomplished in several steps.

After an intravenous line is inserted, the patient’s whole blood is separated via centrifugation into its component parts of plasma (serum), white blood cells, and red blood cells. For each cycle, all of the white blood cells, some of the plasma, and a few of the red blood cells are collected, saved, and ultimately circulated within a special UVA light chamber called a photoactivation module. This WBC enriched product is called a buffy coat. Unused portions of the plasma and red blood cells are immediately returned to the patient during each cycle via the same intravenous line. To keep the blood from clotting while inside the photopheresis machine, it is mixed with small amounts of an anticoagulant medicine, such as heparin.

Generally, each treatment consists of 3-6 cycles of cell collection. The cell collection phase is followed by a treatment phase. The treatment phase involves photosensitization and photoactivation of the collected cells.

Photosensitization is accomplished in one of two ways. Most treatment centers now utilize a liquid methoxsalen (UVADEX) that is added directly to the collected WBCs. Because UVADEX is added directly to the cells it is administered at 1/200 the dose of the oral formulation of 8 MOP. In some instances, however, oral methoxsalen (8-MOP) is given. (In this case, the 8-MOP is given 2 hours before the ECP is started to allow for adequate absorption into the bloodstream).

Once the photosensitized WBCs circulate through the Photoactivation chamber for a specified amount of time (usually 30-90 minutes), the treated cells are then returned via the IV line to the patient. Once the treated cells are returned, the IV line is removed and a pressure bandage is applied. The entire treatment takes about 2 to 4 hours to complete.

How frequently does treatment occur?

ECP is usually given on an every 4-5 week schedule over two consecutive days. This consecutive, two day treatment is considered one ECP cycle. In some instances, ECP is given on different schedules, such as every two weeks, or even every 2-3 months.

The treatment schedule selected depends on many factors, including the stage and severity of CTCL, response to treatment, patient circumstances, and the experience of the treating physician. ECP can be performed as either an outpatient or inpatient procedure, depending on the patient’s condition and the treating physician/institution preference.

What are potential side effects of ECP?

ECP is a very safe therapy.

To date, there have been no major adverse effects or reactions in over 200,000 treatments performed worldwide. An additional benefit is that ECP does not seem to suppress the immune system or increase the risk of infection for the patient. The most common side effects are relatively minor ones and may include:


If the oral form of methoxsalen is used, nausea commonly results from ingestion of the pills. This reaction is usually decreased or eliminated by taking the pills _ hour after a light, low-fat meal. Inadequate drug dose may also occur with oral 8 MOP since it is poorly absorbed in the intestinal tract. Clinical data indicate that 20% of the oral 8-MOP doses given result in inadequate patient drug levels. UVADEX insures proper drug dosing to the target cells and eliminates the nausea and vomiting complication because of the low dose and extracorporeal delivery of the drug.


Any time venous access is required, infection, bruising, or bleeding may result. If venous access is difficult, a central line catheter may need to be placed. In this event, the risks of infection greatly increase.

Increased itching, redness and low-grade fever

A mild fever, increased itching or redness may occur 4-8 hours post re-infusion of the treated cells. These symptoms are usually short-lived and tend to resolve spontaneously.


Methoxsalen produces a body-wide light sensitivity, therefore, UV light precautions are necessary to avoid side effects of light exposure such as glaucoma, cataracts, and sun burns. Patients are required to protect their eyes (with UVL protective, wrap-around goggles) and skin (with sunscreen and protective clothing) from UVL exposure for 24 hours after each ECP treatment. This risk is greatly reduced with UVADEX because of its extremely low dose versus the oral formulation of 8-MOP.

Blood Pressure Changes

Withdrawal of blood volume is usually limited to less than one pint at any one time, however, some patients are very sensitive to blood volume loss. In this case, the blood pressure may drop. This is usually easily managed through the administration of additional fluids and positioning of the patient.

Fluid Volume Changes

During ECP, additional fluid is given to the patient. This amounts to about one pint and is usually not a problem. However, if the patient is sensitive to the administration of additional fluids (as in heart failure), additional measures or precautions may need to be taken to prevent fluid volume overload.

Learn More

Skin-Directed Therapies

Individuals with disease limited to the skin (stages I and II) can often achieve a good response with one of the readily available skin-directed therapies. Learn more about skin-directed therapies.

Systemic Therapies

Individuals who have only partial or short responses to skin-directed therapies, or more advanced stages of disease, may benefit from systemic therapy. Learn more about available systemic therapies.

Clinical Trials: A Pathway to Treatment

Physician & Patient
Clinical trials are research studies that investigate new or experimental treatments in patients living with a specific disease. Clinical trials empower patients to play an active role in their own care, contribute to the understanding around a disease, and open them up to access new treatments before they are widely available.
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