Incidence, Risk Factors, and Long-Term Outcomes of Sclerotic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation Jieun Uhm 1 , Nada Hamad 1 , Elizabeth M. Shin 2 , Fotios V. Michelis 1 , Mohamed Shanavas 1 , Vikas Gupta 1 , John Kuruvilla 1 , Jeffrey H. Lipton 1 , Hans A. Messner 1 , Matthew Seftel 1 , Dennis (Dong Hwan) Kim 1 , * 1 Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Ontario, Canada 2 School of Medicine, University of Toronto, Toronto, Ontario, Canada Article history: Received 9 June 2014 Accepted 1 July 2014 Key Words: Chronic graft-versus-host disease Sclerosis Allogeneic hematopoietic stem cell transplantation abstract Sclerotic chronic graft-versus-host disease (sclGVHD) is associated with significant morbidity and a poor quality of life. We reviewed 502 patients diagnosed with chronic GVHD and analyzed the incidence and risk factors of sclGVHD and long-term outcomes and immunosuppressive therapy (IST) cessation in patients with sclGVHD. With a median onset at 18 months the cumulative incidence of sclGVHD was estimated at 22.6% at 5 years (95% confidence interval, 18.6% to 26.8%). Univariate and multivariate analysis identified 2 risk factors for sclGVHD: non-T cell depletion (hazard ratio [HR] 9.09, P < .001) and peripheral blood stem cell (HR 3.87, P < .001). Overall survival (OS) at 5 years was significantly better in the sclGVHD group (88.1%) compared with the non-sclGVHD group (62.7%; P < .001), as were nonrelapse mortality (7.3% versus 21.5% at 5 years) and relapse rates (9.1% versus 19.3% at 5 years). There was no difference in the rate of IST cessation at 5 years (44.8% versus 49.9%, P ¼ .312), but there was a trend of longer IST duration in the sclGVHD group compared with the non-sclGVHD group (median 71.6 months versus 62.9 months). In conclusion, T cell depletion and graft source affect the risk of sclGVHD. SclGVHD did not adversely affect long-term outcomes or IST duration. Ó 2014 American Society for Blood and Marrow Transplantation. INTRODUCTION Chronic graft-versus-host disease (cGVHD) is a significant cause of morbidity and mortality of allogeneic hematopoietic cell transplantation (allo-HCT), resulting in a higher risk of late nonrelapse mortality (NRM) and poor quality of life [1,2]. The National Institutes of Health (NIH) proposed consensus criteria for the diagnosis and staging of cGVHD based on clinical manifestations, which are now widely used in clinical practice [3]. These criteria identify sclerotic cGVHD (sclGVHD) as a distinctive phenotype of cGVHD with sclerotic features in the skin characterized by thickened, tight, and fragile skin [3]. SclGVHD includes several cutaneous pre- sentations resembling morphea, systemic sclerosis, or eosinophilic fasciitis [4]. SclGVHD may cause significant morbidity and disability because it is often associated with poor wound healing, inadequate lymphatic drainage, skin ulcers from minor trauma, and joint contractures, but there are only a few studies that described its clinicopathological features and risk factors [4-8]. The incidence of sclGVHD has been re- ported to be 15% to 20% among patients with cGVHD [5,7,8], and a large cross-sectional study of single-patient visits for the evaluation of severe cGVHD reported it to be as high as 53% [4]. Because sclGVHD usually occurs late in the course of cGVHD, it may result in the need for prolonged systemic immunosuppressive therapy (IST) with multiple agents [4,5,7] and consequently adversely affect long-term out- comes [4,8]. However, because long-term outcomes of sclGVHD have not been investigated recently, the question of whether sclGVHD patients have an adverse prognosis with higher mortality has not been answered. Therefore, we conducted an institutional retrospective study of patients who developed cGVHD to analyze the incidence, clinical risk factors of sclGVHD, long-term outcomes, IST treatment fail- ure, and IST cessation rates in patients who developed sclGVHD. Financial disclosure: See Acknowledgments on page 1757. * Correspondence and reprint request: Dennis (Dong Hwan) Kim, MD, PhD, Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Uni- versity of Toronto, 610 University Ave. Toronto, Ontario M5G2M9, Canada. E-mail address: dr.dennis.kim@uhn.ca (D.(D.H.) Kim). http://dx.doi.org/10.1016/j.bbmt.2014.07.001 1083-8791/Ó 2014 American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 20 (2014) 1751e1757 Biology of Blood and Marrow Transplantation journal homepage: www.bbmt.org