Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations

Rheumatology (Oxford). 2014 May;53(5):919-22. doi: 10.1093/rheumatology/ket464. Epub 2014 Jan 22.


Objective: The aim of this study was to find a new and less cardiotoxic conditioning regimen for high-dose chemotherapy and autologous stem cell transplantation (aSCT) in patients with severe SSc and pre-existing cardiac involvement.

Methods: Six patients with cardiac involvement were treated for SSc with a conditioning regimen including reduced-dose CYC plus the non-cardiotoxic alkylant thiotepa. All patients received an implantable cardioverter defibrillator (ICD) before aSCT. The response at months 6 and 12 was measured according to reduction of the modified Rodnan skin score (mRSS). CT histography was used to monitor pulmonary manifestations, as were echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin for the cardiac involvement. Cardiac events were defined as death or hospitalisation due to heart failure or appropriate discharge of the ICD.

Results: Between December 2008 and May 2012, four male and two female patients with a median age of 41 years received aSCT. The median mRSS significantly decreased from 26.5 to 18 and 17.5 at month 6 and 12, respectively. The total lung volume also significantly improved. Within the median follow-up of 1.6 years (range 1-3.8) two patients experienced a relapse of SSc, which results in a progression-free survival rate of 66.6%. Three patients experienced ICD discharge.

Conclusion: For patients with SSc and cardiac involvement, the use of thiotepa and reduced-dose CYC is feasible and effective. The rate of ICD discharge underlines the need for protection in these endangered patients. This preliminary experience allowed us to use this regimen for our currently recruiting prospective trial (NCT01895244).

Keywords: CT histography; cyclophosphamide; heart; stem cell transplantation; systemic sclerosis; thiotepa; treatment.

MeSH terms

  • Adult
  • Autoimmune Diseases / epidemiology
  • Comorbidity
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use*
  • Defibrillators, Implantable
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Heart Diseases / blood
  • Heart Diseases / epidemiology*
  • Heart Diseases / therapy*
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Prevalence
  • Retrospective Studies
  • Risk Factors
  • Scleroderma, Systemic / epidemiology*
  • Scleroderma, Systemic / therapy*
  • Stem Cell Transplantation* / adverse effects
  • Thiotepa / adverse effects
  • Thiotepa / therapeutic use*
  • Treatment Outcome
  • Troponin / blood


  • Peptide Fragments
  • Troponin
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Cyclophosphamide
  • Thiotepa

Associated data