Autologous stem cell transplantation for progressive systemic sclerosis: a prospective non-interventional study from the European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party

Joerg Henes, Maria Carolina Oliveira, Myriam Labopin, Manuela Badoglio, Hans Ulrich Scherer, Nicoletta Del Papa, Thomas Daikeler, Marc Schmalzing, Roland Schroers, Thierry Martin, Gregory Pugnet, Belinda Simoes, David Michonneau, Erik W A Marijt, Bruno Lioure, Jacques Olivier Bay, John A Snowden, Montserrat Rovira, Anne Huynh, Francesco Onida, Lothar Kanz, Zora Marjanovic, Dominique Farge, Joerg Henes, Maria Carolina Oliveira, Myriam Labopin, Manuela Badoglio, Hans Ulrich Scherer, Nicoletta Del Papa, Thomas Daikeler, Marc Schmalzing, Roland Schroers, Thierry Martin, Gregory Pugnet, Belinda Simoes, David Michonneau, Erik W A Marijt, Bruno Lioure, Jacques Olivier Bay, John A Snowden, Montserrat Rovira, Anne Huynh, Francesco Onida, Lothar Kanz, Zora Marjanovic, Dominique Farge

Abstract

Three randomized controlled trials in early severe systemic sclerosis demonstrated that autologous hematopoietic stem cell transplantation was superior to standard cyclophosphamide therapy. This European Society for Blood and Marrow Transplantation multi-center prospective non-interventional study was designed to further decipher efficacy and safety of this procedure for severe systemic sclerosis patients in real-life practice and to search for prognostic factors. All consecutive adult systemic sclerosis patients undergoing a first autologous hematopoietic stem cell transplantation between December 2012 and February 2016 were prospectively included in the study. Primary endpoint was progression free survival. Secondary endpoints were overall survival, non-relapse mortality, response and incidence of progression. Eighty systemic sclerosis patients were included. Median follow-up duration was 24 (6-57) months after stem cell transplantation using cyclophosphamide plus antithymocyte globulins conditioning for all, with CD34+ selection in 35 patients. At 2 years, progression free survival was 81.8%, overall survival was 90%, response was 88.7% and incidence of progression was 11.9%. The 100 days non-relapse mortality was 6.25% (n=5) with four deaths from cardiac event, including three due to cyclophosphamide toxicity. Modified Rodnan skin score and forced vital capacity improved with time (p< 0.001). By multivariate analysis, baseline skin score >24 and older age at transplant were associated with lower progression free survival (Hazard ration 3.32) and 1.77, respectively). CD34+-selection was associated with better response (Hazard ration: 0.46). This study confirms the efficacy of autologous stem cell transplantation in real-life practice for severe systemic sclerosis using non myeloablative conditioning. Careful cardio-pulmonary assessment to identify organ involvement at patient referral, reduced cyclophosphamide doses and CD34+ selection may improve outcomes. The study was registered at ClinicalTrials.gov: NCT02516124.

Figures

Figure 1.
Figure 1.
Kaplan-Meier curves of outcomes of patients undergoing autologous hematopoietic stem cell transplantation for severe systemic sclerosis. Overall survival (OS), progression-free survival (PFS), progression and non-relapse (treatment)- related mortality (NRM) over time.
Figure 2.
Figure 2.
Boxplots of the four most important efficacy parameters in the 24 months following autologous hematopoietic stem cell transplantation for severe systemic sclerosis. (A) Improvement of the modified Rodnan skin score (mRSS) (n=55; P<0.001). (B) Improvement of forced vital capacity (FVC) (n=37; P=0.001. (C) Stabilization of diffusion capacity of carbon monoxide (DLCO) (n=35; P=0.01). (D) Improvement of Scleroderma Health Assessment Questionnaire (sHAQ) score (n=15, P=0.001).

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Source: PubMed

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