Assessment of Durability of Response in Patients with Skin Graft Versus Host Disease beyond Six Months Treatment with Extracorporeal Photopheresis: Reduction of Steroid Resistance and Evaluation of Long-Term Therapy on Survival.

Background: Chronic graft versus host disease (GVHD) is one of the major limitations to successful allogeneic haemopoeitic stem cell transplantation (HSCT) with a substantial impact not only on survival but also on the quality of life of otherwise cancer free patients. Chronic GVHD has a negative impact on the morbidity and quality of life, as well as in nonrelapse mortality. Corticosteroids are considered the standard of care for initial treatment of chronic GVHD. Chronic GVHD is a complex disease, and its diagnosis, definition, staging and therefore criteria to evaluate response are particularly challenging. Extracorporeal photopheresis (ECP) is a cell based immuno-modulatory therapy involving the separation of leucocyte-rich plasma followed by ex-vivo administration of a photosensitiser and ultraviolet A radiation before re-infusion.

Aims: Quantification of durability of skin response to ECP beyond 28 weeks, its impact on steroid refractoriness together with overall survival (OS) in patients with chronic skin GVHD post allogeneic HSCT.

Methods: The ECP unit at Rotherham General Hospital acts as a supra-regional referral centre, accommodating approximately one half of all UK ECP referrals for treatment of chronic GVHD. In this study we retrospectively evaluated 51 patients referred between November 1996 and August 2008 to our ECP unit who completed at least 28 weeks of treatment. All patients had various degrees of skin GVHD following allogeneic HSCT for various haematological disorders. Skin response was measured at 28, 56 and 112 weeks of treatment. Steroid reduction was assessed in 33 patients who had reached 56 weeks of treatment. We also monitored patients’ quality of life using a patient satisfaction questionnaire at 3 monthly intervals.

Results: On completion of 28 weeks of ECP treatment 39 out of the total 51 patients were deemed to have achieved > 25% skin response. Three of the 39 responders were classified as possible responders as they had a steroid reduction >50% despite a skin response < 25%. All 39 responders continued to be treated with ECP beyond 28 weeks. We compared the degree of skin response of this group at 56 and 112 weeks to that achieved at 28 weeks of ECP treatment. At timescale 56 weeks 12 patients had to be discounted from evaluation, (3 having stopped, 2 having data missing and 7 still undergoing treatment but 56 weeks not reached), 2 patients had a worse response, 14 patients had no change in response and in 12 patients the response had improved. At timescale 112 weeks 33 patients had to be discounted from evaluation, (21 having stopped, and 12 still undergoing treatment but 112 weeks not reached), 2 patients had a worse response, 2 patients had no change in response and in 3 patients the response had improved. For the 39 responders the mean duration of further treatment post 28 weeks was 57 weeks and the mean further follow-up period was 157 weeks. Out of all 39 responders 26 had stopped ECP treatment reasons being that 17 improved not requiring further ECP treatment, 2 showed lack of response, 4 had disease relapse and 3 died. Overall survival in the group of skin responders that had completed 28 weeks of ECP treatment was 74%, compared to 67% in the non responders. Steroid reduction was assessed at 56 weeks of treatment, 26 (78%) patients had a prednisolone dose reduction > 50%, 2 (6%) had dose reduction > 25 < 50%, 5 (50%) had dose reduction < 25%. OS in this group of steroid responders was 73%, OS in prednisolone dose reduction > 50% was 73%. The cohort of patients (16) which had a prednisolone reduction of > 25% at 28 weeks and > 50% at 56 weeks as well as > 50% skin reduction at 56 weeks had an OS of 81%.

Conclusions: Chronic GVHD has a direct impact on survival following allogeneic HSCT and quality of life. Our study shows that ECP produces a durable GVHD response, improves OS especially in the group of patients that respond by both steroid reduction and decreased skin GVHD, as well as improvement of quality of life with alleviation of symptoms and reduction in immunosuppressive treatment.