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Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis

Jacob van Laar Dominique Farge 1 Jacob Sont Kamran Naraghi Zora Marjanovic 2 Jérôme Larghero 3 Annemie Schuerwegh Erik Marijt Madelon Vonk Anton Schattenberg Marco Matucci-Cerinic Alexandre Voskuyl Arjan van de Loosdrecht Thomas Daikeler Ina Kötter Marc Schmalzing Thierry Martin 4 Bruno Lioure 5 Stefan Weiner Alexander Kreuter Christophe Deligny 6 Jean-Marc Durand 7 Paul Emery Klaus Machold Françoise Sarrot-Reynauld 8 Klaus Warnatz Daniel Adoue 9 Joël Constans 10 Hans-Peter Tony Nicoletta del Papa Athanasios Fassas Andrea Himsel David Launay 11 Andrea Lo Monaco Pierre Philippe 12 Isabelle Quere 13, 14 Éric Rich Rene Westhovens Bridget Griffiths Riccardo Saccardi Frank van den Hoogen Willem Fibbe Gérard Socie 15 Alois Gratwohl Alan Tyndall Ebmt/eular Scleroderma Study Group
Abstract : 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 × 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. TRIAL REGISTRATION: Identifier: ISRCTN54371254.
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Soumis le : mercredi 5 décembre 2018 - 15:24:46
Dernière modification le : vendredi 11 décembre 2020 - 03:50:02

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Jacob van Laar, Dominique Farge, Jacob Sont, Kamran Naraghi, Zora Marjanovic, et al.. Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis. JAMA Ophthalmology, American Medical Association 2014, 311 (24), pp.2490-8. ⟨10.1001/jama.2014.6368⟩. ⟨hal-01945807⟩



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