What are the indications for stem cell transplantation in patients with scleroderma?

Indications for Stem Cell Transplantation in Scleroderma

High-intensity immunosuppression followed by autologous hematopoietic stem cell transplantation (HSCT) may be considered for the treatment of selected patients with early severe diffuse cutaneous SSc and poor prognosis, in the absence of advanced cardiorespiratory involvement. 1

Patient Selection Criteria

• HSCT should be considered specifically for patients with early severe diffuse cutaneous SSc (dcSSc) who demonstrate:

  • Rapidly progressive disease 1, 2
  • Poor prognostic features such as high skin scores 2, 3
  • Risk of mortality from disease progression 3

• Key considerations for patient eligibility include:

  • Disease duration: Early disease (typically within first few years of onset) 3
  • Absence of advanced cardiorespiratory involvement which increases treatment-related mortality 1
  • Failure or inadequate response to standard immunosuppressive therapies 2, 4

Evidence Supporting HSCT in Scleroderma

• The SCOT study (Scleroderma Cyclophosphamide or Transplantation) demonstrated significant benefits of HSCT:

  • 67% of patients in the transplant arm had favorable outcomes compared to 33% in the cyclophosphamide arm (p=0.01) 1
  • 74% of patients in the transplant arm remained event-free at 72 months versus 47% in the cyclophosphamide arm 1
  • Improved overall survival at 72 months (86% vs. 51%) compared to cyclophosphamide 3

• Long-term benefits of HSCT include:

  • Regression of fibrosis in skin and lung 4
  • Sustained improvement in skin thickening 5
  • Stabilization of organ function for up to 7 years post-transplantation 5
  • Reduced need for disease-modifying antirheumatic drugs (9% vs. 44% in cyclophosphamide group) 3

Risks and Considerations

• Treatment-related mortality must be carefully evaluated:

  • 3-6% treatment-related mortality in the SCOT trial 3
  • Higher risk in patients with suboptimal cardiac function 1
  • Mortality rates have improved with better patient screening and center experience 4

• Standard HSCT protocol typically includes:

  • Cyclophosphamide for mobilization 6, 5
  • Granulocyte colony-stimulating factor (G-CSF) 6, 5
  • Conditioning with cyclophosphamide and anti-thymocyte globulin 6
  • Reinfusion of CD34+ selected stem cells 6, 5

Clinical Approach to Patient Selection

• Perform comprehensive cardiac evaluation to exclude patients with:

  • Pulmonary arterial hypertension 6
  • Significant cardiac dysfunction 1
  • Advanced pulmonary fibrosis 2

• Consider HSCT earlier rather than later in disease course:

  • Earlier intervention shows better outcomes 2, 4
  • Patients with established organ damage have poorer outcomes 6

• HSCT should be performed in specialized centers with experience in both scleroderma management and stem cell transplantation 4

Monitoring After Transplantation

• Regular follow-up to assess:

  • Skin improvement (using modified Rodnan skin score) 6, 5
  • Pulmonary function 5
  • Quality of life measures 3
  • Disease relapse (occurs in approximately 25-30% of patients) 5

• Long-term monitoring for potential late complications:

  • Secondary autoimmune diseases 4
  • Infections 6
  • Malignancies 4

HSCT represents the first treatment shown to modify disease course and improve survival in rapidly progressive scleroderma, though it carries significant risks that must be carefully weighed against potential benefits for each patient 4, 3.