Extracorporeal photopheresis: A comprehensive review from a transfusion medicine perspective

Extracorporeal photopheresis is a unique immunomodulatory therapy that involves the ex vivo treatment of leukocytes with 8-methoxypsoralen and ultraviolet A light, followed by reinfusion into the patient. Initially developed for cutaneous T-cell lymphoma, extracorporeal photopheresis has gained recognition for its efficacy in treating various immune-mediated conditions such as graft-versus-host disease, systemic sclerosis, solid organ transplant rejection, and inflammatory bowel diseases. This review outlines the historical evolution, pharmacology of psoralens, mechanisms of action, clinical applications, equipment types, quality control methods and practical aspects for initiating extracorporeal photopheresis. The therapy's core mechanism, inducing apoptosis and modulating dendritic cell function, promotes immune tolerance and regulatory T-cell expansion. Different inline and offline systems are employed, each with distinct operational and safety considerations. Current evidence supports extracorporeal photopheresis in steroid-refractory graft-versus-host disease and cutaneous T-cell lymphoma, although its role in visceral and long-term disease remains underexplored. Quality control methods such as proliferation assays, flow cytometry, and surrogate markers are discussed in detail. Despite its promise, further randomized trials are necessary to clarify standardized protocols and long-term outcomes.