High-dose immunosuppressive therapy and autologous progenitor cell transplantation for systemic sclerosis

High-dose immunosuppressive therapy aimed at immunoablation, given together with autologous stem cell transplantation, has resulted in prolonged (>3 years) improvements of skin thickening and functional ability, together with a stabilization of pulmonary function in two-thirds of treated patients with severe systemic sclerosis. Transplant-related mortality occurred in 17% of the first cohort of 41 patients reported to the European Group for Blood and Marrow Transplantation, which included cases from the United States, but this figure has dropped to 8.7% in a recent retrospective analysis of 57 transplants performed in Europe. Similar outcomes were reported in multicentre studies from the United States of 19 patients, and from France of 12 patients, with improvements in skin scores and functional assessments, together with a stabilization of internal organ dysfunction. Based on the results of these phase I/II studies, multicentre prospective randomized trials are being planned or are in progress in Europe and the United States employing uniform patient entry criteria and outcome parameters. The aim of these studies is to compare the clinical benefits and safety of transplant regimens versus conventional chemotherapy in patients with severe systemic sclerosis who are at risk of life-threatening organ failure and premature mortality. Eligibility criteria include a diagnosis of diffuse systemic sclerosis of recent onset and major organ (heart, kidney, lungs) involvement according to predefined criteria. The prospective randomized trials address two issues related to the treatment of severe systemic sclerosis: is intensive immunosuppressive therapy superior to conventional therapy, and can self-tolerance be re-established?