What is the role of stem cell transplant in the therapy of Systemic Sclerosis?
Autologous HSCT is an effective therapy for skin thickening and ILD in patients with dcSSc and can favorably impact long-term survival. However, this approach is associated with 3% to 10% risk of treatment-related mortality. Two multicenter trials have been published regarding treatment response of autologous HSCT compared with CYC for severe dcSSc. The European trial (ASTIS) showed that those treated with HSCT had improved event-free survival and decreased mortality at a median follow-up of approximately 6 years. Clinically meaningful improvements in objective and patient-reported outcome measures were observed at 2 years. However, there was significant treatment-related mortality (10.1%) during the 1st year as well as more severe adverse events during the first 2 years of follow-up. In the North American trial (SCOT), event-free survival at 54 months was seen in 79% of the transplantation group and 50% of the CYC group. At 72 months, Kaplan–Meier estimates of event-free survival (74% versus 47%) and overall survival (86% versus 51%) also favored transplantation. Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the CYC group.
In light of these data, experts recommend that HSCT should be considered in patients with early dcSSc (within 5 years of disease onset) with mild-to-moderate internal organ involvement and should generally be restricted to patients who have failed to improve or have worsened on conventional immunosuppressive agents. In addition, active smokers should be excluded based on evidence of increased mortality risk. Patients with severe internal organ involvement are commonly ineligible for HSCT due to the higher risk associated with therapy in this setting. Cardiopulmonary involvement specifically is associated with higher mortality in HSCT; therefore, extensive invasive and noninvasive testing is required to evaluate for primary cardiac or pulmonary involvement, pericardial disease, or pulmonary hypertension (PH). Studies such as PFTs, HRCT, transthoracic echocardiogram, cardiac magnetic resonance imaging (MRI), and commonly right heart catheterization (RHC) are recommended before consideration of HSCT.