Systemic Sclerosis
Systemic sclerosis (SS) or scleroderma is a rare autoimmune disease affecting approximately 50 per 100,000 people in the United States. [1] It is characterized by debilitating effects on the connective tissue and various internal organs, caused by genetic and environmental predispositions. [2]
The use of autologous or allogeneic hematopoietic cell transplantation (HCT) is being considered for the treatment of SS. Preclinical and clinical studies suggest that high-dose immunotherapy alongside allogeneic HCT may improve outcomes. [3]
Risks related to the treatment regimen, graft-versus-host disease (GVHD), relapse and overall transplant eligibility must be weighed when choosing the best option and stem cell source for transplant. [3]
Advances
Risks for specific autoimmune, rheumatic diseases prove challenging due to the nature of the treatment. Research continues to expand the scope of HCT with a focus on:
Clinical trials specifically for SS focusing on the long-term effects of HCT, pharmacokinetics of cyclophosphamide, genetic expression and signatures, immunophenotypes, antibody repertoire, autoantibody profiles, and proteomics of SS [4]
Post-transplant cyclophosphamide (PTCy) as treatment for GVHD [4]
Allogeneic HCT versus autologous HCT [4]
Outcomes
Review outcomes for HCT in patients with SS below.
Figure 1. Event-free and Overall Survival from ASTIS Trial, 2001 – 2009 [5]

Figure 2. Outcomes Following HCT for Multiple Sclerosis (MS), Systemic Sclerosis (SS) and Crohn’s Disease (CD), Blood Advances, 1994-2015 [6]

Referral Timing Guidelines
These guidelines highlight disease categories that include patients at risk for disease progression and who should be referred for a consultation for autologous or allogeneic transplantation.
Transplant Consultation Guidelines: Systemic Sclerosis
HCT consultation should take place:
At the time of diagnosis or with diffuse disease
With increasing skin tightness score (modified Rodnan skin score, [mRSS])
Evidence of decrease ( < 80%) in % predicted pulmonary function tests: forced vital capacity (FVC) or/and diffusion capacity (DLCO)
View complete Referral Timing Guidelines
References
- Zhong L, Pope M, Shen Y, Hernandez JJ, Wu L. Prevalence and incidence of systemic sclerosis: A systematic review and meta-analysis. Int J Rheum Dis. 2019;22(12):2096-2107. doi:10.1111/1756-185X.13716.
- Asano Y. Systemic sclerosis. The Journal of Dermatology. 2018;45(2):128-138. doi:10.1111/1346-8138.14153.
- Sullivan KM, Sarantopoulos S. Allogeneic HSCT for autoimmune disease: a shared decision. Nature reviews Rheumatology. 2019;15(12):701-702. doi:10.1038/s41584-019-0306-7.
- Sullivan, K. Stem cell transplantation for scleroderma: results and research. Oral presentation at Vanderbilt Rheumatology Grand Rounds. September, 2021. Nashville, TN.
- van Laar JM, Farge D, Sont JK, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014;311(24):2490-2498. doi:10.1001/jama.2014.6368.
- Snowden JA, Badoglio M, Labopin M, et al. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Advances. 2017;1(27):2742-2755. doi:10.1182/bloodadvances.2017010041.