Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial
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BORIS DOI
Date of Publication
June 25, 2014
Publication Type
Article
Division/Institute
Author
van Laar, Jacob M | |
Farge, Dominique | |
Sont, Jacob K | |
Naraghi, Kamran | |
Marjanovic, Zora | |
Larghero, Jérôme | |
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 | |
Kötter, Ina | |
Schmalzing, Marc | |
Martin, Thierry | |
Lioure, Bruno | |
Weiner, Stefan M | |
Kreuter, Alexander | |
Deligny, Christophe | |
Durand, Jean-Marc | |
Emery, Paul | |
Machold, Klaus P | |
Sarrot-Reynauld, Francoise | |
Warnatz, Klaus | |
Adoue, Daniel F P | |
Constans, Joël | |
Tony, Hans-Peter | |
Del Papa, Nicoletta | |
Fassas, Athanasios | |
Himsel, Andrea | |
Launay, David | |
Lo Monaco, Andrea | |
Philippe, Pierre | |
Quéré, Isabelle | |
Rich, Éric | |
Westhovens, Rene | |
Griffiths, Bridget | |
Saccardi, Riccardo | |
van den Hoogen, Frank H | |
Fibbe, Willem E | |
Socié, Gérard | |
Gratwohl, Alois | |
Tyndall, Alan | |
EBMT/EULAR Scleroderma Study Group | |
Subject(s)
Series
JAMA : the journal of the American Medical Association
ISSN or ISBN (if monograph)
1538-3598
Publisher
American Medical Association
Language
English
Publisher DOI
PubMed ID
25058083
Description
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
isrctn.org Identifier: ISRCTN54371254.
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
isrctn.org Identifier: ISRCTN54371254.
File(s)
| File | File Type | Format | Size | License | Publisher/Copright statement | Content | |
|---|---|---|---|---|---|---|---|
| joi140072.pdf | text | Adobe PDF | 392.19 KB | publisher | published |