• Jacob M van Laar, Dominique Farge, Jacob K Sont, Kamran Naraghi, Zora Marjanovic, Jérôme Larghero, Annemie J Schuerwegh, Erik W A Marijt, Madelon C Vonk, Anton V Schattenberg, Marco Matucci-Cerinic, Alexandre E Voskuyl, Arjan A van de Loosdrecht, Thomas Daikeler, Ina Kötter, Marc Schmalzing, Thierry Martin, Bruno Lioure, Stefan M Weiner, Alexander Kreuter, Christophe Deligny, Jean-Marc Durand, Paul Emery, Klaus P Machold, Francoise Sarrot-Reynauld, Klaus Warnatz, Daniel F P Adoue, Joël Constans, Hans-Peter Tony, Nicoletta Del Papa, Athanasios Fassas, Andrea Himsel, David Launay, Andrea Lo Monaco, Pierre Philippe, Isabelle Quéré, Éric Rich, Rene Westhovens, Bridget Griffiths, Riccardo Saccardi, Frank H van den Hoogen, Willem E Fibbe, Gérard Socié, Alois Gratwohl, Alan Tyndall, and EBMT/EULAR Scleroderma Study Group.
• Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
• JAMA. 2014 Jun 25; 311 (24): 2490-8.

ImportanceHigh-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials.ObjectiveTo compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide.Design, Setting, And ParticipantsThe Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013.InterventionsHSCT vs intravenous pulse cyclophosphamide.Main Outcomes And MeasuresThe primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure.ResultsA total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years.Conclusions And RelevanceAmong patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit.Trial Registrationisrctn.org Identifier: ISRCTN54371254.

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