ArticlesAutologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial
Introduction
Systemic sclerosis is a chronic disease that starts as a diffuse vasculopathy, followed by immune activation and subsequent tissue fibrosis.1 Haemopoietic stem-cell transplantation (HSCT) is a potential treatment for systemic sclerosis2, 3, 4, 5, 6, 7, 8 and relies on early intervention during immune activation. However, there have been no randomised trials published about outcomes of such transplantation for autoimmune diseases in general or systemic sclerosis in particular. Previous studies of HSCT for systemic sclerosis showed significant improvements in skin flexibility, as measured by modified Rodnan skin score (mRSS),9 and two small non-randomised studies suggested that HSCT improves lung function.10, 11 However, positive efficacy outcomes were tempered by initial reports of high treatment-related mortality, albeit which diminished with increased experience, and absence of a randomised control group.12 In our phase 2 American Scleroderma Stem Cell versus Immune Suppression Trial (ASSIST), we aimed to assess safety and efficacy of autologous non-myeloablative HSCT compared with a control group who received one dose of intravenous cyclophosphamide every month for 6 months.
Section snippets
Study design and patients
In our randomised phase 2 trial, we screened consecutive patients at Northwestern Memorial Hospital (Chicago, IL, USA). Patients were eligible if they were aged younger than 60 years and had diffuse systemic sclerosis (defined as cutaneous involvement proximal to the elbow or knee with an mRSS of more than 14), and internal-organ involvement, which was defined as at least one of the following features: diffusing capacity of carbon monoxide (DLCO) of less than 80% or decline in forced vital
Results
We enrolled 19 patients between Jan 18, 2006, and Nov 10, 2009 (table 1, figure 2). No deaths occurred in either treatment group during follow-up. For patients treated with HSCT, engraftment of white blood cells (absolute neutrophil count >500 cells per μL) occurred at a mean of 10 days (SD 1·4) and platelets (transfusion independent >20 000 cells per μL) occurred at a mean of 11 days (2·4). Patients received a mean of 5·3 units (5·5) of single donor platelet transfusion and 4·4 units (2·3) of
Discussion
In our study, non-myeloablative HSCT significantly improved forced vital capacity, decreased diseased-lung volume, and showed that systemic sclerosis interstitial lung disease might be at least partially reversed with continued improvement in lung function for at least 2 years after transplantation. The improvement that we noted in lung function after HSCT was associated with improved high-resolution chest CT, skin score, and quality of life. Non-myeloablative autologous HSCT is the first
References (35)
- et al.
High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study
Blood
(2007) Will hematopoietic stem cell transplantation cure human autoimmune diseases?
J Autoimmun
(2008)- et al.
Association of transplant center and physician factors on mortality after hematopoietic stem cell transplantation in the United States
Blood
(2005) - et al.
Mortality in systemic sclerosis: an international meta-analysis of individual patient data
Am J Med
(2005) - et al.
Autologous hematopoietic stem cell transplantation for systemic sclerosis
Curr Stem Cell Res Ther
(2011) - et al.
Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I-II study
Br J Haematol
(2002) - et al.
Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR registry
Ann Rheum Dis
(2004) - et al.
Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis
Bone Marrow Transplant
(2007) - et al.
Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis
Ann Rheum Dis
(2008) - et al.
Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial: hope on the horizon for patients with severe systemic sclerosis
Ann Rheum Dis
(2005)
Autologous stem cell transplantation in diffuse scleroderma: impact on hand structure and function
Intern Med J
Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies
J Rheumatol
Autologous hematopoietic stem cell transplant in systemic sclerosis: quantitative high resolution computed tomography of the chest scoring
J Rheumatol
A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease
Ann Rheum Dis
Tricuspid annular displacement predicts survival in pulmonary hypertension
Am J Respir Crit Care Med
Computer-aided volumetry of pulmonary nodules exhibiting ground-glass opacity at MDCT
AJR Am J Roentgenol
Quantitative computerized analysis of diffuse lung disease in high-resolution computed tomography
Med Phys
Cited by (434)
The arguments favoring autologous haematopoietic stem cell transplantation in systemic scleroderma
2024, Revue de Medecine InterneFrench protocol for the diagnosis and management of hematopoietic stem cell transplantation in autoimmune diseases
2024, Revue de Medecine InterneSystemic sclerosis, silica exposure and cellular therapies: The sand in the gears?
2024, Revue de Medecine InterneIs cyclophosphamide still the gold standard in early severe rapidly progressive systemic sclerosis?
2024, Autoimmunity ReviewsNovel therapeutic strategies for autoimmune and inflammatory rheumatic diseases
2023, Drug Discovery Today
- ‡
Walter Barr died in December, 2008