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Updated: May 3, 2026
Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
Published on: November 8, 2016
Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac
Joerg C Henes1, Ina Koetter, Marius Horger
1University Hospital Tübingen, Department of Internal Medicine II, Otfried-Mueller-Str. 10, D-72076 Tübingen, Germany. joerg.henes@med.uni-tuebingen.de.
Insights
This study explored a gentler conditioning regimen for severe scleroderma patients undergoing stem cell transplants. The new method showed promising results in reducing skin and lung symptoms while managing cardiac risks.
Area of Science:
- Hematology
- Immunology
- Rheumatology
Background:
- Severe systemic sclerosis (SSc) often involves cardiac complications.
- High-dose chemotherapy and autologous stem cell transplantation (aSCT) can be cardiotoxic.
- A less cardiotoxic conditioning regimen is needed for SSc patients with cardiac involvement.
Purpose of the Study:
- To evaluate a novel, less cardiotoxic conditioning regimen for SSc patients with cardiac involvement undergoing aSCT.
- To assess the efficacy and safety of reduced-dose cyclophosphamide (CYC) combined with thiotepa.
Main Methods:
- Six SSc patients with cardiac involvement received a conditioning regimen of reduced-dose CYC and thiotepa.
- Patients were monitored with implantable cardioverter defibrillators (ICDs).
- Efficacy was assessed by modified Rodnan skin score (mRSS), CT histography, echocardiography, NT-proBNP, and troponin levels.
Main Results:
- Median mRSS significantly decreased from 26.5 to 18 at 6 months and 17.5 at 12 months.
- Total lung volume showed significant improvement.
- Progression-free survival was 66.6% after a median follow-up of 1.6 years.
- Three patients experienced ICD discharge, indicating ongoing cardiac risk.
Conclusions:
- Thiotepa and reduced-dose CYC are feasible and effective for SSc patients with cardiac involvement undergoing aSCT.
- The observed ICD discharge rate highlights the need for cardiac protection in this high-risk population.
- This regimen is being used in a prospective clinical trial (NCT01895244).
Objective:
The aim of this study was to find a new and less cardiotoxic conditioning regimen for high-dose chemotherapy and autologous stem cell transplantation (aSCT) in patients with severe SSc and pre-existing cardiac involvement.
Methods:
Six patients with cardiac involvement were treated for SSc with a conditioning regimen including reduced-dose CYC plus the non-cardiotoxic alkylant thiotepa. All patients received an implantable cardioverter defibrillator (ICD) before aSCT. The response at months 6 and 12 was measured according to reduction of the modified Rodnan skin score (mRSS). CT histography was used to monitor pulmonary manifestations, as were echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin for the cardiac involvement. Cardiac events were defined as death or hospitalisation due to heart failure or appropriate discharge of the ICD.
Results:
Between December 2008 and May 2012, four male and two female patients with a median age of 41 years received aSCT. The median mRSS significantly decreased from 26.5 to 18 and 17.5 at month 6 and 12, respectively. The total lung volume also significantly improved. Within the median follow-up of 1.6 years (range 1-3.8) two patients experienced a relapse of SSc, which results in a progression-free survival rate of 66.6%. Three patients experienced ICD discharge.
Conclusion:
For patients with SSc and cardiac involvement, the use of thiotepa and reduced-dose CYC is feasible and effective. The rate of ICD discharge underlines the need for protection in these endangered patients. This preliminary experience allowed us to use this regimen for our currently recruiting prospective trial (NCT01895244).
