Background: Autologous hematopoietic stem cell transplantation (aHSCT) for systemic sclerosis (SSc) has been proven the most effective treatment strategy with regard to overall and event free survival in selected patients [1]. Limitation is its toxicity.

Objectives: To evaluate feasibility of aHSCT in patients with impaired lung or heart function. Second, to assess efficacy of aHSCT with a regimen with reduced toxicity.

Methods: AST MOMA was a prospective, open-label, monocentric phase II study. We stratified patients according to their clinical manifestations. Patients were eligible if they were between 18 -65 years old, had a limited (lc) or diffuse cutaneous (dc)SSc with a disease duration of ≤ 6 years and a progressive disease despite cyclophosphamide (CYC) pre-treatment. We excluded patients with a LVEF <30%, systolic pulmonal arterial pressure >50mmHg or severely impaired lung function (FVC <50% or DLCO <30%). Mobilization was conducted with 2x1000mg/m² CYC + lenograstim. For those patients with active alveolitis CYC was increased to 2x1500mg/m². CD34+ selection was performed. We used the ASTIS protocol [1] for patients without functional heart involvement. Patients with functional heart involvement received a conditioning regimen with thiotepa (2x5mg/kg), half dose of CYC (2x50mg/kg) and rATG (4x10mg/kg) before reinfusion of the CD34+ selected stem cells. The primary endpoint was overall survival. For secondary endpoints we decided for transplant related mortality, time to engraftment, response to treatment and the number of relapses.

Results: Between 09/2012 and 07/2020 44 patients were included. During the screening procedure for aHSCT we had to exclude 9 patients. In total we transplanted 35 patients.

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Figure 1.

Modified Rodnan skin score over time

A total of 8 patients died during the follow-up period of 3 years. Four patients (11.4%) died during the first 100 days and were counted as TRM, whereas 4 more patients died during follow-up due to disease progression. The overall response rate was 71.4% after 12 months and 60% after 36 months. Four patients had progressive disease and 1 relapsed during the first year, whereas 4 others had a relapse at a later time point. Of those relapsed patients 2 died during the 36 months follow-up. The median mRSS improved significantly from 30.5 at baseline to 18, 16 and 10.5 after 12, 24 and 36 months, respectively. For lung function tests improvement over time were found for FVC and DLCO.

Conclusion: The COVID pandemic led to a prolonged recruitment period with many screening failures or late drop outs. The primary endpoint was reached and the overall survival rate after 3 years was comparable to available data [2]. The TRM rate of 11.4% is higher than we expected, but probably attributed to a high-risk population, as >50% were male, >50% had functional cardiac involvement, and >90% were anti-Scl70 positive and >90% dcSSc patients. To our knowledge this is the first prospective study using a reduced CYC mobilizing and conditioning regimen in patients with cardiac involvement in a larger cohort and showed a comparable outcome regarding the OS.

REFERENCES: [1] van Laar JM et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014;311(24):2490-8.

[2] Farge D et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica. 2010;95(2):284-92.

Acknowledgements: NIL.

Disclosure of Interests: Ann-Christin Pecher: None declared, Ina Kötter: None declared, Reinhild Klein: None declared, Claudia Lengerke: None declared, Kathrin Peis: None declared, Wichard Vogel: None declared, Marc Schmalzing: None declared, Stefan Wirths: None declared, Jörg Henes NEOVII.