Results from the international NISSC1-LTE study published in The Lancet Rheumatology demonstrate that autologous stem cell transplantation achieves a 60% progression-free survival rate and 71% overall survival at 10 years for severe systemic sclerosis patients. Led by Joerg Henes and Dominique Farge, the trial followed 80 patients across Europe and South America. While 43% maintained remission without immunosuppression, treatment risks persist, including a 13% non-relapse mortality rate.
Long-term clinical efficacy outcomes
- ▪Median modified Rodnan skin scores among NISSC1-LTE study participants decreased from 24 at baseline to 6 at five years and 5 at 10 years.
- ▪In the NISSC1-LTE cohort of 80 systemic sclerosis patients, 43% remained alive and maintained disease remission without requiring further immunosuppressive treatment at 10 years.
- ▪At 10 years post-transplantation, systemic sclerosis patients in the NISSC1-LTE study demonstrated an estimated overall survival rate of 71%.
- ▪The NISSC1-LTE study published in The Lancet Rheumatology showed that 60% of systemic sclerosis patients achieved progression-free survival 10 years after autologous stem cell transplantation.
Treatment safety and mortality risks
- ▪Estimated non-relapse mortality at 10 years following autologous hematopoietic stem-cell transplantation for systemic sclerosis was 13% in the NISSC1-LTE cohort.
- ▪In the NISSC1-LTE study, 10-year cumulative incidence rates reached 20% for late serious infections, 8% for post-transplant malignancies, and 5% for major adverse cardiovascular events.
- ▪Eighteen of 80 patients in the NISSC1-LTE study died during follow-up, with nine deaths caused by systemic sclerosis progression and five attributed directly to the transplant procedure.
- ▪The 10-year cumulative incidence of secondary autoimmune diseases among systemic sclerosis patients receiving autologous HSCT reached 14% in the NISSC1-LTE trial.
Trial design and patient cohort
- ▪The NISSC1-LTE study followed 80 severe systemic sclerosis patients across 13 medical centres in France, Germany, the Netherlands, Italy, Spain, Switzerland, and Brazil for a median of 9.2 years.
- ▪Led by Professors Joerg Henes and Dominique Farge on behalf of the EBMT Autoimmune Diseases Working Party, NISSC1-LTE tracked adults transplanted between December 2012 and January 2016.
Evidence and clinical guidelines
- ▪Autologous hematopoietic stem-cell transplantation holds grade A level evidence recommendations from EULAR and CIBMTR for treating early diffuse severe systemic sclerosis.
- ▪Three randomised controlled trials—ASSIST, ASTIS, and SCOT—comparing autologous stem-cell transplantation with intravenous cyclophosphamide provided evidence supporting transplantation as a routine treatment option in selected patients.
Approved pharmaceutical therapies
- ▪European regulators approved the antifibrotic agent nintedanib in 2020 for treating systemic sclerosis-associated interstitial lung disease.
- ▪The FDA approved nintedanib in 2019 and tocilizumab in 2021 for systemic sclerosis-associated interstitial lung disease, expanding therapeutic options prior to stem cell transplantation.
Disease mortality and severity
- ▪Early diffuse cutaneous systemic sclerosis carries 5-year and 10-year mortality rates between 30% and 50% depending on major organ involvement.
- ▪Systemic sclerosis carries the highest mortality rate of all rheumatic diseases.
Transplant protocols and safety
- ▪Pre-transplant cardiac screening protocols and reduced cyclophosphamide conditioning doses lowered early transplant-related mortality from 10% in the ASTIS trial to 6·25% in the NISSC1 study.
- ▪All participants in the NISSC1 study received conditioning with cyclophosphamide plus antithymocyte globulin, and 35 patients underwent CD34+ cell selection.
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