Extracorporeal Photopheresis as Induction Therapy after Lung Transplantation for Cystic Fibrosis: Interim Analysis

Purpose Extracorporeal photopheresis has emerged as a promising treatment for chronic rejection. To date, there are no data on extracorporeal photopheresis as induction therapy. We are implementing a single-center, single blind, randomized controlled trial enrolling 24 recipients with cystic fibrosis (CF) who undergo lung transplantation (LTx) randomly allocated in 2 parallel arms: induction with extracorporeal photopheresis plus standard immunosuppressive therapy (ECP) vs. standard immunosuppressive therapy (CTR). We present the interim analysis focused on safety and immunomodulation effectiveness. Methods We recorded every adverse event, including acute rejection (AR), which occurred in the first year after lung transplantation. Immune parameters (activated T cells, Treg, Th17, Th1, NK, PD-1 and PD-L1 expression, IL-10, TNFα, IL-1β, and IFNγ production) were evaluated at different time points in the first year after LTx. Preliminary data on the first ten patients (6 ECP and 4 CTR) are reported. Results No AR episodes were observed and no adverse events due to extracorporeal photopheresis were recorded. In the control arm, one patient died of post-operative infection on 20th postoperative day. In ECP compared to CTR patients: 1) regulatory T cells (Treg) as well as IL10 production by Treg were increased; 2) IL17-secreting Th17 as well as Th1 T cells were reduced; 3) CD107+/CD8+ (perforin-releasing CTL) T lymphocytes were reduced, 4) IL10-producing NK cells were increased; 5) LPS-stimulated IL-10 production was augmented whereas that of TNFα and IL-1β was reduced. Conclusion In the setting of LTx for CF, extracorporeal photopheresis is well tolerated and it results in an overall modulation of immune responses. The positive result of this interim analysis led to the decision of continuing to enroll patients in this randomized trial with the aim of probing the possible positive effect of extracorporeal photopheresis as induction therapy in AR prevention.