After a stem cell or bone marrow transplant, some individuals may experience a serious complication called Graft-versus-Host Disease (GVHD). This condition arises when transplanted immune cells recognize the recipient’s body as foreign and initiate an immune response against it. Extracorporeal Photopheresis (ECP) offers a specialized treatment approach. ECP modulates the immune system, providing a targeted intervention for GVHD.
Understanding Graft-versus-Host Disease
Graft-versus-Host Disease (GVHD) is an immune reaction that can occur after an allogeneic hematopoietic stem cell transplant. The donor’s T-cells, a type of white blood cell, may perceive the recipient’s tissues as foreign. This triggers an immune attack on the recipient’s body, leading to various symptoms.
GVHD can manifest in two forms: acute and chronic. Acute GVHD typically develops within the first 100 days post-transplant and commonly affects the skin, liver, and gastrointestinal tract. Chronic GVHD can emerge after 100 days and may involve a broader range of organs, including the mouth, eyes, lungs, and musculoskeletal system. The severity of GVHD symptoms can vary widely, from mild to life-threatening.
What is Extracorporeal Photopheresis
Extracorporeal Photopheresis (ECP) is a medical procedure that involves treating a patient’s own white blood cells outside the body. The process begins with drawing blood from the patient, often through a central venous catheter or a peripheral vein. A specialized machine then separates the white blood cells, or leukocytes, from other blood components.
The collected white blood cells are then mixed with a photosensitizing agent, 8-methoxypsoralen (8-MOP). This compound makes the cells sensitive to light. The treated white blood cells are then exposed to ultraviolet A (UVA) light. After light exposure, these modified white blood cells are returned to the patient’s bloodstream.
How ECP Treats GVHD
ECP’s mechanism for treating GVHD involves immune modulation rather than broad immunosuppression. When white blood cells are treated with psoralen and UVA light, it leads to programmed cell death (apoptosis) in some cells. These apoptotic cells, when reinfused, are believed to be engulfed by the body’s antigen-presenting cells (APCs).
This interaction with APCs is thought to re-educate the immune system. It promotes a shift in APC activity, favoring anti-inflammatory cytokines over pro-inflammatory ones. This re-education also helps in the generation of regulatory T-cells (Tregs), which are a type of immune cell that suppresses immune responses and promotes immune tolerance. The increase in Tregs and the modulation of cytokine balance help to reduce the aggressive immune attack by donor T-cells on the recipient’s healthy tissues, thereby alleviating GVHD symptoms.
The ECP Treatment Process
An ECP session involves connecting the patient to an apheresis machine, similar to a dialysis setup. Blood is continuously withdrawn from one arm or a central line, processed by the machine, and then returned to the other arm or the same central line. The machine separates white blood cells, treats them with psoralen, exposes them to UVA light, and then reinfuses them.
Each ECP session usually lasts between two to three and a half hours. The frequency of treatments can vary, but a common schedule involves two consecutive days of treatment, repeated every two to four weeks initially. As the patient’s condition improves, the frequency may be gradually reduced, for instance, from weekly to every two weeks, and eventually stopped. ECP is typically performed as an outpatient procedure, allowing patients to return home after each session.
Outcomes and Considerations
ECP is used for GVHD that has not responded adequately to initial steroid treatment. While individual responses can vary, ECP has shown effectiveness in improving symptoms and quality of life for many patients. For acute GVHD, particularly involving the skin, reported response rates can be 60% or higher, with some studies showing an 82% complete response for cutaneous involvement. Chronic GVHD response rates are more variable, ranging from 33% to 75%, with better outcomes often seen in skin, mouth, gastrointestinal, or liver involvement.
The procedure has a favorable safety profile compared to other immunosuppressive treatments, with a lower risk of increasing infections. Common, usually mild, side effects can include temporary low blood pressure during the procedure, fatigue after treatment, or increased sensitivity to sunlight for about 24 hours due to the photosensitizing agent. Patients are advised to protect their skin and eyes from sun exposure during this period. ECP is part of a broader, individualized treatment plan managed by a medical team, and full benefits may take several weeks or months to become apparent.