title: Stem cell transplantation in systemic sclerosis.
abstract: OBJECTIVE
  The purpose of this review is to discuss recent published clinical and mechanistic studies on stem cell transplantation for systemic sclerosis and their implications for clinical practice.
  
  
  RESULTS
  Retrospective analyses of independent cohorts of systemic sclerosis patients treated with autologous stem cell transplantation showed significant improvement of skin thickening, lung function and quality of life, but at the expense of 6-17% treatment-related mortality. Right heart catheterization was employed in one study to identify and exclude patients at risk of serious cardiopulmonary toxicity. The superior efficacy of stem cell transplantation versus intravenous pulses cyclophosphamide was demonstrated in a small randomized, controlled phase 2 trial in 19 systemic sclerosis patients and a large randomized phase 3 trial in 156 patients with severe diffuse cutaneous systemic sclerosis. The latter also showed a survival benefit of transplanted patients despite a 10% transplant-related mortality. Mechanistic studies in transplanted patients have shown major shifts in circulating natural killer cells, T and B lymphocytes immediately after stem cell transplantation, similar to those observed in other autoimmune conditions. Stem cell transplantation of systemic sclerosis patients with lung involvement resulted in demonstrable attenuation of thoracic high-resolution CT (HRCT) abnormalities and serum markers of lung fibrosis.
  
  
  CONCLUSIONS
  Stem cell transplantation is an effective treatment option for patients with severe systemic sclerosis, but is associated with toxicity and treatment-related mortality. The available data suggest that patient selection and comprehensive cardiopulmonary screening are critical factors in determining outcome.
  
  
  BACKGROUND
  See the Supplementary Digital content 1 (http://links.lww.com/COR/A7).
authors.affiliation: aInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK bDivision of Cellular Therapy, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.forename: Keith
authors.initials: K
authors.lastname: Sullivan
mesh_terms: D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D018579:Patient Selection; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012595:Scleroderma, Systemic / Q000628:therapy*; D016896:Treatment Outcome