What is the role of autologous (self-derived) Hematopoietic Stem Cell Transplantation (HSCT) in the treatment of Systemic Sclerosis (Scleroderma)?

From the Guidelines

Autologous hematopoietic stem cell transplantation (AHSCT) should be considered for the treatment of selected patients with early severe diffuse cutaneous systemic sclerosis (dcSSc) and poor prognosis, in the absence of advanced cardiorespiratory involvement, as it may improve morbidity, mortality, and quality of life outcomes. The procedure involves collecting the patient's own hematopoietic stem cells, administering high-dose chemotherapy to eliminate the dysfunctional immune system, and then reinfusing the previously collected stem cells to reconstitute a new, hopefully non-autoaggressive immune system. According to the most recent guidelines, AHSCT may be considered for patients with early severe dcSSc and poor prognosis, as stated in the 2023 EULAR recommendations update 1.

The typical regimen includes cyclophosphamide for mobilization, followed by stem cell collection via apheresis, and conditioning regimens commonly use cyclophosphamide with anti-thymocyte globulin (ATG). AHSCT has shown significant benefits in skin thickening, lung function stabilization, and quality of life improvements, with some studies demonstrating improved long-term survival compared to conventional treatment, as seen in the SCOT study, which reported a 54-month beneficial effect of autologous HSCT on a combined morbidity/mortality outcome 1.

However, the procedure carries substantial risks, including treatment-related mortality, infections, and secondary autoimmune diseases. Patient selection is crucial, with the best candidates being those with diffuse cutaneous systemic sclerosis of less than 5 years duration, with significant internal organ involvement (especially early lung disease), but without severe irreversible organ damage, as suggested by a review article in Nature Reviews Rheumatology 1. The procedure should be performed at experienced centers with expertise in both stem cell transplantation and scleroderma management to minimize complications and optimize outcomes.

Key considerations for AHSCT in scleroderma include:

• Patient selection: early severe dcSSc, poor prognosis, and absence of advanced cardiorespiratory involvement
• Procedure: high-dose chemotherapy, stem cell collection, and reinfusion
• Risks: treatment-related mortality, infections, and secondary autoimmune diseases
• Benefits: improved skin thickening, lung function stabilization, and quality of life outcomes
• Expertise: procedure should be performed at experienced centers with expertise in both stem cell transplantation and scleroderma management.

From the Research

Autologous Hematopoietic Stem Cell Transplantation in Sclerodermy

• Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a therapeutic modality for severe systemic sclerosis (SSc) 2.
• A systematic review and meta-analysis of randomized controlled trials (RCTs) and retrospective studies found that AHSCT reduced all-cause mortality and improved skin thickness, forced vital capacity, total lung capacity, and quality of life compared to standard immunosuppressive therapy 2.
• The risk of treatment-related mortality was higher with AHSCT, but the risk of bias for studies included in the analysis was low 2.
• A more recent study found that AHSCT has a significant impact on event-free survival, overall survival, cutaneous and pulmonary involvement, and quality of life in patients with recent severe diffuse cutaneous systemic scleroderma, compared to IV cyclophosphamid 3.
• French and international guidelines now position AHSCT as a level 1A evidence-based therapeutic alternative in severe early and rapidly progressive systemic scleroderma 3.
• Other studies have also shown that AHSCT can induce regression of fibrosis in skin and lung, and increase survival in patients with severe rapidly progressive SSc 4.
• Improvements in patient screening, treatment regimens, and center experience have improved the AHSCT safety profile for patients with scleroderma 4.

Key Findings

• AHSCT reduces all-cause mortality and improves skin thickness, forced vital capacity, total lung capacity, and quality of life in patients with SSc 2, 3.
• AHSCT has a significant impact on event-free survival, overall survival, cutaneous and pulmonary involvement, and quality of life in patients with recent severe diffuse cutaneous systemic scleroderma 3.
• The risk of treatment-related mortality is higher with AHSCT, but the risk of bias for studies included in the analysis is low 2.
• AHSCT is now considered a level 1A evidence-based therapeutic alternative in severe early and rapidly progressive systemic scleroderma 3.