Extracorporeal photopheresis as first-line treatment in high-risk graft-versus-host disease

Background: Chronic graft versus host disease (cGVHD) is the major late complication after allogeneic stem cell transplantation. Standard therapy is steroid and Cyclosporine- A (CyA); however, immune suppression (ISS) related infections or unresponsiveness to ISS, are major mortality causes. Extracorporeal photopheresis (ECP) has shown activity in treatment of cGVHD, but its use has been limited to first-line-unresponsive cGVHD. Aim of the study. This is a single center pilot study testing feasibility of a programme of photopheresis in association with standard therapy as first line treatment in high risk cGVHD. High risk was defined as the presence of parameters predicting high cGVHD-related mortality. Secondary objectives were response and complications incidence. Patients: Among 9 pts fitting enrolling criteria, 2 refused due to logistic problem or low compliance with the procedure, 7 were enrolled. Median age was 40. Donor was HLA identical sibling in 6 cases and MUD in 1. All cases presented with extensive/moderate-severe cGVHD; Akpek score was > 0 in 3/7 pts. Treatment plan. Pts started with Prednison (PDN) 1 mg/kg and CyA at cGVHD diagnosis; ECP was started with a frequency of 4 application/month in the first 3 months and 2/month for the subsequent 9 months; PDN and CyA were slowly reduced until suspension, or otherwise modulated. Study duration was 1 year. Pts were ruled out the study in case of ECP suspension; requirement of other ISS drugs in case of GVHD progression unresponsive to standard therapy, or severe infections. Response was evaluated with standard criteria, as progression, partial response (PR), very good PR (vgPR) or complete response (CR). Results: Adherence to protocol was: 5/7 pts at 3 months, 4/7 at 6 and 9 months, 3/7 at 12 mm; exit from the study was due to infectious complications (2), ECP suspension due to venous access related thrombosis (1) and clear cGVHD progression (1). In evaluable pts, response (CR+very good PR / ≤PR) per trimester was 4/5, 2/4 and 3/4 at I, II and III respectively; at the IV trimester, 1 very good PR, 2 PR and 1 progression were observed. Complications were evaluated in 4 pts and are reported on the table. At 1 year, 2/7 pts died (1 TRM, 1 relapse). Conclusion: ECP in association with standard therapy is feasible; complications incidence seems to be similar to those observed in patients not treated with ECP; a larger group of patients is needed to evaluate response in this setting