title: Optimization of autologous stem cell transplantation for systemic sclerosis -- a single-center longterm experience in 26 patients with severe organ manifestations.
abstract: OBJECTIVE
  Autologous stem cell transplantation (aSCT) for systemic sclerosis (SSc) has been shown to be effective in recent reports. This aggressive approach and the disease itself are associated with a high mortality. We report our experiences in 26 consecutive patients.
  
  
  METHODS
  Between 1997 and 2009, 26 patients were scheduled for aSCT. Our standard transplant regimen consists of cyclophosphamide (CYC) and granulocyte colony-stimulating factor (GCSF) for mobilization and CYC plus antithymocyte globulin for conditioning before the retransfusion of CD34 selected stem cells. The major outcome variable was the response to treatment [reduction of modified Rodnan skin score (mRSS) by 25%] at Month 6. Secondary endpoints were the transplant-related mortality and the progression-free survival.
  
  
  RESULTS
  Significant skin and lung function improvement of the mRSS was achieved in 78.3% of patients at Month 6. The overall response rate was 91%, as some patients improved even after Month 6. Three patients died between mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was considered treatment-related (i.e., GCSF or CYC toxicity). Depending on definitions, transplant-related mortality was 4% and treatment-related mortality 11%. Seven patients experienced a relapse during the 4.4 years of followup. The progression-free survival was 74%. Four patients died during followup and the most frequent causes of death were pulmonary and cardiac complications of SSc.
  
  
  CONCLUSIONS
  aSCT led to significant improvement in most patients with SSc. The procedure requires further optimization; hence we are modifying our screening and treatment strategy. To minimize infectious complications, CYC for mobilization and GCSF were reduced. We intensified our screening for cardiac involvement and modified our conditioning regimen in case of cardiac involvement.
authors.affiliation: Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases and Department of Internal Medicine II, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Joerg C
authors.initials: JC
authors.lastname: Henes
authors.forename: Marc
authors.initials: M
authors.lastname: Schmalzing
authors.forename: Wichard
authors.initials: W
authors.lastname: Vogel
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Ina
authors.initials: I
authors.lastname: Koetter
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D012720:Severity of Illness Index; D013234:Stem Cells / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide