1. Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis A Randomized Clinical Trial
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Laar, J.M. van, Farge, D., Sont, J.K., Naraghi, K., Marjanovic, Z., Larghero, J., Schuerwegh, A.J., Marijt, E.W.A., Vonk, M.C., Schattenberg, A.V., Matucci-Cerinic, M., Voskuyl, A.E., Loosdrecht, A.A. van de, Daikeler, T., Kotter, I., Schmalzing, M., Martin, T., Lioure, B., Weiner, S.M., Kreuter, A., Deligny, C., Durand, J.M., Emery, P., Machold, K.R., Sarrot-Reynauld, F., Warnatz, K., Adoue, D.F.P., Constans, J., Tony, H.P., Papa, N. del, Fassas, A., Himsel, A., Launay, D., Monaco, A. lo, Philippe, P., Quere, I., Rich, E., Westhovens, R., Griffiths, B., Saccardi, R., Hoogen, F.H. van den, Fibbe, W.E., Socie, G., Gratwohl, A., Tyndall, A., EBMT EULAR Scleroderma Study Grp, Rheumatology, Hematology, and CCA - Innovative therapy
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medicine.medical_specialty ,Cyclophosphamide ,business.industry ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Hazard ratio ,General Medicine ,Hematopoietic stem cell transplantation ,3. Good health ,Surgery ,law.invention ,Clinical trial ,Transplantation ,Autologous stem-cell transplantation ,Randomized controlled trial ,law ,Internal medicine ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,medicine ,Clinical endpoint ,business ,medicine.drug - Abstract
Contains fulltext : 136804.pdf (Publisher’s version ) (Open Access) 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. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN54371254.
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- 2014