Extracorporeal Photopheresis (ECP) is a specialized medical procedure that treats certain diseases by modifying a patient’s immune cells outside of the body. The term “extracorporeal” means occurring outside the body, and “photopheresis” refers to the use of light to treat the blood. This treatment selectively targets and alters the function of problematic white blood cells, primarily lymphocytes, which are the main components of the immune system.
ECP is a type of apheresis, a process where blood is drawn, separated into components, treated, and then returned to the patient. The procedure combines this separation technique with a photosensitive drug and ultraviolet light exposure to achieve its therapeutic effect. It is a form of immunotherapy designed to regulate an overactive or misdirected immune response without broadly suppressing the entire system.
The Three Phases of the ECP Procedure
The entire ECP process is performed using a specialized machine and is divided into three distinct phases: collection, photoactivation, and reinfusion.
Collection (Leukapheresis)
The first phase involves drawing blood from the patient, typically through a large peripheral vein or a central venous catheter. The machine separates the whole blood into its components using centrifugation to isolate the white blood cells (leukocytes) from the red blood cells and plasma. The leukocytes are collected into a sterile chamber, while the red blood cells and plasma are immediately returned to the patient, minimizing volume loss.
Photoactivation
The collected white blood cells are mixed with a photosensitizing compound, most commonly 8-methoxypsoralen (8-MOP). This drug intercalates into the DNA of the immune cells, making them susceptible to light exposure. The mixture is then exposed to a specific wavelength of ultraviolet A (UVA) light. The UVA light activates the 8-MOP, causing it to form cross-links within the DNA of the white blood cells, particularly the lymphocytes. This process induces programmed cell death, or apoptosis.
Reinfusion
In the final phase, the treated, photoactivated white blood cells are returned to the patient intravenously. These cells, now containing damaged DNA and entering an apoptotic state, act as the therapeutic agent. The entire three-phase cycle takes approximately one and a half to three hours to complete, with the patient remaining connected to the machine throughout.
How ECP Modifies the Immune System
The therapeutic effect of ECP involves a sophisticated reprogramming of the body’s immune response, not just the destruction of immune cells. The procedure primarily affects T-lymphocytes, which are active in autoimmune diseases and transplant rejection.
When the treated, apoptotic cells are returned during reinfusion, the immune system’s antigen-presenting cells (APCs), such as dendritic cells and macrophages, engulf and process them. This ingestion of apoptotic material in a non-inflammatory environment signals the immune system to shift its response. This signal moves the immune response from an aggressive, pro-inflammatory state toward a more tolerogenic, or anti-inflammatory, state.
The processing of these apoptotic cells by APCs is believed to lead to the generation and proliferation of regulatory T-cells (Tregs). Tregs are specialized immune cells that actively suppress the activity of other T-cells, promoting immune tolerance. This mechanism helps calm misdirected immune attacks without causing global immunosuppression.
Key Diseases Treated with Photopheresis
ECP is primarily used for managing conditions driven by dysfunctional or overactive T-lymphocytes. The United States Food and Drug Administration (FDA) initially approved ECP for the treatment of advanced Cutaneous T-Cell Lymphoma (CTCL), a rare skin cancer. ECP is often utilized when CTCL is unresponsive to other therapies.
A major application is the treatment of Graft-versus-Host Disease (GvHD), a serious complication following allogeneic bone marrow or stem cell transplant. ECP is typically employed as a second-line therapy for patients with chronic or acute GvHD that is refractory to standard treatments. In GvHD, donor T-cells attack the recipient’s tissues, and ECP helps modulate these aggressive cells.
ECP has also been used for other immune-mediated conditions:
- Managing rejection following solid organ transplantation, particularly in heart and lung recipients.
- Systemic sclerosis.
- Crohn’s disease.
Patient Experience and Treatment Logistics
ECP is an outpatient procedure. A single treatment session usually ranges from two to four hours, similar to other apheresis procedures. A major logistical consideration is the need for reliable venous access to efficiently draw and return the blood components during the session.
The standard treatment schedule involves receiving ECP on two consecutive days. This two-day cycle is typically repeated every two to four weeks and maintained over several months. The frequency is adjusted based on the patient’s clinical response. Patients can generally resume normal activities immediately after the session.
Temporary fatigue is a common side effect, but it is usually mild. Because the photosensitizing drug 8-MOP increases sensitivity to ultraviolet light, patients must take precautions. This involves wearing UV-protective clothing and sunglasses and avoiding direct sunlight for at least 24 hours after treatment to prevent phototoxic reactions.