Positive Effect of Extracorporeal Photopheresis In Reducing Immunosuppression in Patients with Chronic Graft Versus Host Disease.
Authors: Dignan Fiona L , Greenblatt Danielle , Cox Michael , Shaw Bronwen E. , Scarisbrick Julia J 
Published: October 2019

Abstract
Abstract 3452
Extracorporeal photopheresis (ECP) has become a recognised treatment for steroid refractory chronic Graft versus Host Disease (cGvHD) but the optimal frequency and duration of treatment has yet to be established. We report on a large cohort of 75 patients who commenced ECP treatment for cGvHD from 01/01/2005 to 31/12/2009 at St Thomas' Hospital, London. Patients were initially treated with a bimonthly regimen of 2 ECP treatments on consecutive days (one cycle) which was subsequently tapered to a monthly regimen depending on response. Patients were reviewed pre-treatment and at 3 monthly intervals. Immunosuppression was tapered at the discretion of the referring transplant centre. Data were collected from the unit's GvHD database which had ethical approval. The median age of patients at time of commencing ECP was 43 years (16-67 years). 30 were female and 45 were male. Patients had undergone allogeneic transplant (22 – unrelated donor, 53 – sibling/related donor) at 13 referral centres. Underlying diagnoses were acute leukaemia (31), lymphoma (16), chronic leukaemias (16), myeloma (6) and other (6). The median time from transplant to commencing ECP was 2 years (6 months to 10 years). 16 patients had developed GvHD following donor lymphocyte infusion. 27 had denovo cGvHD and 18 had progressive disease. 72 patients had cutaneous disease. 38 had sclerodermoid disease and 32 had lichenoid disease (1 - both types, 1 - unknown). 37 patients had oral disease. Other organs involved included liver (17), eyes (12), gut (4), tongue (1), joint (1), genitalia (1). 29 had one organ involved, 26 had two, 17 had three and 3 had four organs involved. At the start of ECP, 64 patients were on immunosuppressive drugs (prednisolone – 56, cyclosporine – 36, mycophenolate mofetil – 26 and other (tacrolimus, rituximab, azathioprine, pentostatin, methotrexate) – 18). 10 patients were on a single agent, 38 were on 2, 14 were on 3 and 2 were on 4 agents. The median dose of prednisolone was 25mg (5mg-135mg). 52 patients had completed ECP at time of analysis. 23 were receiving ongoing treatment but had received at least 6 months of ECP. The median duration of treatment in those that had completed ECP was 330 days (42-987). The median number of ECP cycles received was 15 (1.5-32 cycles). 46 patients had reduced the frequency of ECP to monthly. The median time to reduction in treatment was 206 days (74-571 days). Reduction of immunosuppression at 6 months was used as a global measure of response to ECP as many patients had multiorgan involvement and response in organs may vary. Assessment of cGVHD symptoms and signs was also documented in 62/75 patients. 51 patients had a partial improvement, 8 patients had a complete improvement and 3 patients had no improvement. 49/64 patients on immunosuppression were reassessed and 37/49 (76%) had a dose reduction. 37/45 (82%) had decreased their steroid dose (10 stopped completely and 18 had ≥ 50% reduction). 3 patients' doses were stable and 5 had increased. The median dose was 10mg (3-30mg). 4 patients on other immunosuppressive drugs remained on a stable dose. The remaining patients had died (5), completed < 6 months treatment (6) or dosage data were missing (4). Of the 11 patients not on immunosuppression at start of ECP, 3 had recommenced steroids and 8 remained on no systemic immunosuppression. All patients were included in the survival analysis including those who had completed < 6 months of treatment. Overall survival at 2.5 years from the start of ECP was 73%. This study reports the largest series of patients receiving bimonthly ECP treatment for cGvHD. We confirm that ECP is highly effective in steroid refractory chronic cGvHD with 76% of patients successfully reducing immunosuppression within 6 months. Further randomised studies are required to assess the optimal ECP treatment schedule and to rationalise the reduction in immunosuppression.

Disclosures:
Dignan: Therakos (Johnson and Johnson): Honoraria, Research Funding. Off Label Use: The extracorporeal administration of UVADEX (methoxsalen) sterile solution was used with the THERAKOS UVARXTS system in this study for the treatment of patients with chronic graft versus host disease. Scarisbrick:Therakos (Johnson and Johnson): Honoraria, Speakers Bureau.