ECP therapy has been studied in two well-defined minor MHC incompatible murine models of CD8+ or CD4+ T cell mediated GVHD. These studies showed that ECP treated cells could successfully reverse established GVHD by reducing allogeneic responses of donor effector T cells and generating FOXP3+ Tregs from donor cells that had not been directly exposed to PUVA, thereby ruling out a mechanistic role for direct apoptosis of effector cells. The increase in Tregs occurred early after the infusion of ECP treated cells, remained stable for several weeks, and was required to reduce GVHD and mortality after BMT. Correlative data in humans is preliminary, but one small case series has shown an increase in the percentage of functional Tregs after 6 ECP procedures from 8.9% to 29% of the total circulating CD4+ cells (p = .05). UVAR Photopheresis System (Therakos, Inc., Exton, PA, USA) was approved for ECP treatment of advanced cutaneous T cell lymphoma in 1988 by the Food and Drug Administration. In 2009 FDA approval was granted for this indication for the new Cellex machine.