Photopheresis, Indications and Mechanisms of Action

Graft-versus-host disease (GvHD) is a frequent complication ofallogeneic hematopoietic stem cell transplantation (HCT). Its severityand frequency depend on many factors such as HLA compatibility, ageand gender of donor and patient, bone marrow or peripheral blood orcord blood stem cell origin and its dose, conditioning and prophylacticregimens. The acute GvHD (aGvHD) occurs in about 60-to 80%, andchronic GvHD (cGvHD) occurs in about 50% of patients under standardimmunosuppressive therapies and is responsible for the high rate ofmorbidity and mortality. The extracorporeal photochemotherapy (ECP),so-called photopheresis, is an immunomodulating cell therapy, wherethe own mononuclear cells of the patient are reinjected to the patientafter an ex vivo exposure to the UVA light in the presence of a DNAintercalating agent such as 8-methoxy psoralene (8-MOP). This treatmentmodality was first used in the treatment of cutaneous T-cell lymphoma(CTCL) successfully. Then, it was examined in a variety of T-cell dependingpathologies, including GvHD. Because of the efficacy and safety of ECP,the number of treated patients has been dramatically increased worldwidein three main indications, including acute graft rejection, GvHD, andCTCL. The other indications of ECP are the autoimmune diseases suchas rheumatoid arthritis, systemic sclerosis, SEL, Pemphigus vulgaris,multiple sclerosis, erosive lichen planus, generalized extensive lichenplanus, diabetes, and refractory Crohn’s disease. Numerous clinical trialsof GvHD treatment by ECP have already been published indicating itssafety and efficacy. Mechanisms of action of ECP are not well known.Induction of apoptosis is one of the major consequences of ECP and thereinjection of these apoptotic cells to the patient is the main factor ofimmunological changes and therapeutic effects of ECP and induction oftolerance by increase of the T regulatory cells (CD4 CD25hi), and shiftin the cytokine pattern (increase of IL10, IL4, TGF beta and decrease ofpro-inflammatory cytokines.

کلیدواژه ها:

Graft-versus-host disease ، Photopheresis ، Hematopoietic stem cell transplantation