Table 2

Inclusion and exclusion criteria

Inclusion criteriaExclusion criteria
Age between 18 and 65 yearsPregnancy or unwillingness to use adequate contraception during study
Fulfilling the 2013 ACR-EULAR classification criteria for dcSScPoor compliance of the patient as assessed by the referring physician
Disease duration ≤2 years (from onset of first non-Raynaud’s symptoms)
  • mRSS ≥15 (diffuse skin pattern) and/or

  • Clinically significant organ involvement as defined by either:

    • Respiratory involvement =

      • DLco and/or (F)VC ≤85% (of predicted) and evidence of interstitial lung disease on HR-CT scan with clinically relevant obstructive disease and emphysema excluded

      • Patients with a DLco and/or FVC >85%, but with a progressive course of lung disease: defined as relative decline of >10% in FVC predicted and/or TLC predicted, or >15% in DLco predicted within 12 months. Intercurrent infections excluded

    • Renal involvement=any of the following criteria: hypertension (two successive BP readings of either systolic ≥160 mm Hg or diastolic >110 mm Hg, at least 12 hours apart), persistent urinalysis abnormalities (proteinuria, haematuria, casts), microangiopathic haemolytic anaemia, new renal insufficiency (serum creatinine>upper limit of normal); non-scleroderma-related causes (eg, medication, infection) must be reasonably excluded

    • Cardiac involvement=any of the following criteria: reversible congestive heart failure, atrial or ventricular rhythm disturbances such as atrial fibrillation or flutter, atrial paroxysmal tachycardia or ventricular tachycardia, second-degree or third-degree AV block, pericardial effusion (not leading to haemodynamic problems), myocarditis; non-scleroderma-related causes must have been reasonably excluded

Concomitant severe disease=
  • Respiratory: resting mPAP >20 mm Hg (by right heart catheterisation), DLco <40% predicted, respiratory failure as defined by the primary end point

  • Renal: creatinine clearance <40 mL/min (measured or estimated)

  • Cardiac: clinical evidence of refractory congestive heart failure; LVEF <45% by cardiac echo or cardiac MR; chronic atrial fibrillation necessitating oral anticoagulation; uncontrolled ventricular arrhythmia; pericardial effusion with haemodynamic consequences16

  • Liver failure as defined by a sustained threefold increase in serum transaminase or bilirubin, or Child-Pugh score C

  • Psychiatric disorders including active drug or alcohol abuse

  • Concurrent neoplasms or myelodysplasia

  • Bone marrow insufficiency defined as leukocytopenia <4.0×109/L, thrombocytopenia <50×109/L, anaemia <80 g/L, CD4+ T lymphopenia <200×106/L

  • Uncontrolled hypertension

  • Uncontrolled acute or chronic infection, including HIV and HTLV-1,2 positivity

  • Zubrod-ECOG-WHO Performance Status Scale >2

Written informed consent

Previous treatments with immunosuppressants >6 months, including mycophenolate mofetil, methotrexate, azathioprine, rituximab, tocilizumab and glucocorticoids
Previous treatments with TLI, TBI or alkylating agents including cyclophosphamide
Significant exposure to bleomycin, tainted rapeseed oil, vinyl chloride, trichlorethylene or silica
Eosinophilic myalgia syndrome, eosinophilic fasciitis, morphea
  • ACR-EULAR, American College of Rheumatology/European League Against Rheumatism; AV, atrioventricular; BP, blood pressure; dcSSC, diffuse cutaneous systemic sclerosis; DLco, diffusing capacity for carbon monoxide; ECOG, Eastern Cooperative Oncology Group; FVC, forced vital capacity; HR-CT, high-resolution CT; HTLV, human T-lymphotropic virus; LVEF, left ventricular ejection fraction; mPAP, mean pulmonary artery pressure; mRSS, modified Rodnan skin score; TBI, total body irradiation; TLC, total lung capacity; TLI, total lymphoid irradiation.