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
Affiliations
Joerg Henes
University Hospital Tuebingen; Intenal Medicine II, Tuebingen, Germany;
Maria Carolina Oliveira
University of São Paulo, Ribeirão Preto, Brazil;
Myriam Labopin
Saint Antoine Hospital, Université Pierre et Marie Curie, Paris, France;
Manuela Badoglio
EBMT Paris Study Office, Hôpital St Antoine, Paris, France;
Hans Ulrich Scherer
Leiden University Medical Center, Department of Rheumatology; Leiden, Netherlands;
Nicoletta Del Papa
Scleroderma Clinic, Osp. G. Pini, Department of Rheumatology, Milan, Italy;
Thomas Daikeler
University and University Hospital of Basel, Department of Rheumatology, Basel, Switzerland;
Marc Schmalzing
University Hospital of Wuerzburg, Department of Rheumatology/Immunology, Wuerzburg, Germany;
Roland Schroers
University Hospital of Bochum, Med. Klinik, Bochum, Germany;
Thierry Martin
Service de Medecine Interne et Immunologie Clinique, Hopitaux Universitaires de Strasbourg, France;
Gregory Pugnet
CHU de Toulouse, Hopital Purpan, Service de Medecine Interne, Toulouse, France;
Belinda Simoes
Dept. of Hematology, Ribeirão Preto Medical School, University of São Paulo, Brazil;
David Michonneau
Dept. of Hematology, Hopital Saint Louis and Université Paris 7, Denis Diderot, Paris, France;
Erik W.A. Marijt
Leiden University Medical Center, Department of Hematology, Leiden, Netherlands;
Bruno Lioure
Strasbourg University Hospital, Department of Hematology, Strasbourg, France;
Jacques Olivier Bay
CHU de Clermont Ferrand, Department of Hematology, Clermont Ferrand, France;
John A. Snowden
Dept. of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK;
Montserrat Rovira
Department of Hematology, Hospital Clínic of Barcelona, Barcelona, Spain;
Anne Huynh
UCT Oncopole, Department of Haematology, Toulouse, France;
Francesco Onida
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milano Italy;
Lothar Kanz
University Hospital Tuebingen, Department of Internal Medicine II, Tuebingen, Germany;
Zora Marjanovic
Saint Antoine Hospital, Department of Haematology, Paris, France;
Dominique Farge
Assistance Publique-Hopitaux de Paris, Saint-Louis Hospital, Paris, France
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 (p24 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
