Autologous stem cell therapy has been shown to be effective in patients with systemic sclerosis. Nevertheless treatment is associated with treatment related mortality and patients die during follow up despite successful transplantation.

Intention of this trial is to improve overall survival by modifying the existing protocol used for the ASTIS trial.

To reduce treatment toxicity we reduce the dose of Cyclophosphamide (CYC) for mobilisation to 2x1g.

Especially in patients with cardiac manifestations we also modify the conditioning regimen by adding thiotepa and reducing CYC; as CYC has known cardiotoxic side effects.

Inclusion Criteria:

• Diagnosis of progressive systemic sclerosis <7 years

• Progressive course despite cyclophosphamide pretreatment

• Cyclophosphamide i.v.: at least 3 x with 500-1000 mg/m² every 3-4 weeks or

• Cyclophosphamide p.o. with at least 100mg/day for at least 2 months or

• Contraindication to treatment with cyclophosphamide

• Progress defined as at least one of the following criteria:

  • Increase in the mRSS
  • Worsening of the lung function
  • Increase in fibrosis/alveolitis in thorax CT
  • Worsening kidney function through manifestation of systemic sclerosis

• Limited or diffuse cutaneous progressive form of Ssc with organ manifestation in the lungs/heart or kidneys

Exclusion Criteria:

• Age <18 years
• Pregnancy or inadequate contraception
• Severe heart failure with ejection fraction (EF) < 30% in echo
• Pulmonary arterial hypertension with systolic pulmonary arterial pressure (PAPsys) >50mm Hg
• Kidney insufficiency: creatinine clearance <30 ml/min
• Reduced lung function
• Inspiratory vital capacity (IVC) < 50% of normal
• Carbon monoxide (CO)-Diffusion capacity SB < 40%
• Previously damaged bone marrow
• Leukopenia < 2,000/µl
• Thrombopenia < 100,000/µl
• Previous myelotoxic treatment:
• Cyclophosphamide > 50g cumulative (relative)
• Infection (Hepatitis B/C, HIV, Salmonella carrier, syphilis, relative: history of tuberculosis)
• Severe concomitant psychiatric illness (depression, psychosis)
• Substance dependence
• Continued nicotine abuse
• Continued alcohol abuse
• Continued drug abuse
• Consent not given
• Poor compliance