Disease-Specific Indications and Outcomes

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]

systemic sclerosis figure 1

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

systemic sclerosis figure 2

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)

Download as a slide (PPT)

View complete Referral Timing Guidelines

References

  1. 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.
  2. Asano Y. Systemic sclerosis. The Journal of Dermatology. 2018;45(2):128-138. doi:10.1111/1346-8138.14153.
  3. 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.
  4. Sullivan, K. Stem cell transplantation for scleroderma: results and research. Oral presentation at Vanderbilt Rheumatology Grand Rounds. September, 2021. Nashville, TN.
  5. 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.
  6. 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.