Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis A Randomized Clinical Trial

作者：van Laar, Jacob M.^*; Farge, Dominique; Sont, Jacob K.; Naraghi, Kamran; Marjanovic, Zora; Larghero, Jerome; Schuerwegh, Annemie J.; Marijt, Erik W. A.; Vonk, Madelon C.; Schattenberg, Anton V.; Matucci-Cerinic, Marco; Voskuyl, Alexandre E.; van de Loosdrecht, Arjan A.; Daikeler, Thomas; Koetter, Ina; Schmalzing, Marc; Martin, Thierry; Lioure, Bruno; Weiner, Stefan M.; Kreuter, Alexander; Deligny, Christophe; Durand, Jean-Marc; Emery, Paul; Machold, Klaus R.

来源：JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2014, 311(24): 2490-2498.

DOI：10.1001/jama.2014.6368

• TERM-FOLLOW-UP
• MARROW-TRANSPLANTATION
• AUTOIMMUNE-DISEASES
• EUROPEAN GROUP
• CIGARETTE-SMOKING
• SCLERODERMA
• BLOOD
• INVOLVEMENT
• MORTALITY
• PREVALENCE

IMPORTANCE High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. @@@ OBJECTIVE To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. @@@ DESIGN, SETTING, AND PARTICIPANTS The 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. @@@ INTERVENTIONS HSCT vs intravenous pulse cyclophosphamide. @@@ MAIN OUTCOMES AND MEASURES The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. @@@ RESULTS A 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 x 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 RELEVANCE Among 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.

• 出版日期2014-6-25