SPECIAL REPORT Does ex vivo CD34+ positive selection influence outcome after autologous hematopoietic stem cell transplantation in systemic sclerosis patients? MC Oliveira 1 , M Labopin 2 , J Henes 3 , J Moore 4 , ND Papa 5 , A Cras 6,7 , I Sakellari 8 , R Schroers 9 , HU Scherer 10 , A Cuneo 11 , S Kyrcz-Krzemien 12 , T Daikeler 13 , T Alexander 14 , J Finke 15 , M Badoglio 16 , B Simões 17 , JA Snowden 18 and D Farge 19,20 , for the EBMT Autoimmune Diseases Working Party This EBMT Autoimmune Disease Working Party study aimed to evaluate the influence of CD34+ positive graft selection (CD34+) on the outcome of systemic sclerosis (SSc) patients after autologous hematopoietic stem cell transplantation (AHSCT). Clinical and laboratory data from 138 SSc patients at diagnosis, before and after AHSCT were retrospectively analyzed. CD34+ selection was performed in 47.1% (n = 65) patients. By multivariate analysis adjusting for all factors differing between the two groups (without or with CD34+), there was no statistically significant difference in terms of overall survival (hazard ratio (HR): 0.98, 95% confidence interval (CI) 0.40–2.39, P = 0.96), PFS (HR: 1.55, 95% CI 0.83–2.88, P = 0.17) and incidence of relapse or progression (HR: 1.70, 95% CI 0.85–3.38, P = 0.13). We demonstrate that CD34+ does not add benefit to the outcome of SSc patient treated with AHSCT. These findings should be further confirmed by prospective randomized trials. Bone Marrow Transplantation (2016) 51, 501–505; doi:10.1038/bmt.2015.299; published online 7 December 2015 INTRODUCTION Systemic sclerosis (SSc) is a chronic autoimmune disease (AD) that affects skin and internal organs. 1 Severe progressive cutaneous SSc with visceral involvement has a poor prognosis, with mortality rates that may reach 30% 5 years after diagnosis, despite standard therapies. 2,3 In the past 20 years, autologous hematopoietic stem cell transplantation (AHSCT) has been shown to be effective to treat severe or rapidly progressive SSc. Improved skin score and quality of life and at least stabilization of lung function were consistently reported in early phase II trials. 4–8 Recently, the phase II ASSIST 9 and the larger phase III ASTIS 10 prospective randomized trials showed better survival rates and improved skin, lung and functional status in patients treated with AHSCT as compared with monthly IV cyclophosphamide. Still, the transplant-related mortality reaching 10% and disease-progression rates of around 20–30% after AHSCT indicate that further improvements are still warranted. 6–12 Among current strategies to increase safety and efficacy of AHSCT, the benefit of ex vivo CD34+ positive selection of the graft remains debated. This study was therefore designed to evaluate the influence of ex vivo CD34+ selection on the outcome of SSc patients treated with AHSCT. PATIENTS AND METHODS This Autoimmune Disease Working Party (ADWP) multicenter retrospective study followed the European Society for Blood and Marrow Transplanta- tion (EBMT) guidelines (www.ebmt.org). All EBMT-affiliated centers with eligible SSc patients were invited to participate. The study was approved in each participating center, according to local institutional review board rules, and full informed consent was obtained from all patients before AHSCT. Patients with diagnosis of SSc according to the American College of Rheumatology criteria and having received a first AHSCT between 2000 and 2012 were included, while those having been treated with irradiation as part of the transplant conditioning regimen or enrolled in the former EBMT ASTIS trial 10 were excluded. For centers that agreed to participate, primary data were collected, when available, using a standardized SSc minimal essential data ‘B’ form. Data were collected by questionnaire or by the electronic EBMT data management system ProMISe. All EBMT participating centers were requested to report all consecutive transplants. Additional clinical and laboratory data at diagnosis, before and after AHSCT were 1 Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; 2 EBMT, Hôpital Saint Antoine, Paris, France; 3 Medizinische Universitätsklinik Abt. II, Tübingen, Germany; 4 Department of Haematology, St Vincent’s Hospital, Sydney, New South Wales, Australia; 5 Scleroderma Clinic, U.O.C. Day Hospital Rheumatology, Osp. G. Pini, Milan, Italy; 6 Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Cell Therapy Unit, Cord Blood Bank and CIC-BT501, Paris, France; 7 INSERM UMRS 1140, Paris Descartes, Faculté de Pharmacie, Paris, France; 8 Bone Marrow Transplantation Unit, George Papanicolaou General Hospital, Thessaloniki, Greece; 9 Ruhr-Universität Bochum, Medizinische Klinik Knappschaftskrankenhaus, Bochum, Germany; 10 Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands; 11 University of Ferrara—St Anna Hospital, Ferrara, Italy; 12 Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland; 13 Department of Rheumatology, University Hospital Basel, Basel, Switzerland; 14 Department of Rheumatology and Clinical Immunology, Charité— University Medicine Berlin, Berlin, Germany; 15 Department of Medicine—Hematology and Oncology, University of Freiburg, Freiburg, Germany; 16 EBMT Paris Office, Hôpital Saint Antoine, Paris, France; 17 Division of Hematology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; 18 Department of Hematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; 19 Paris 7 University, INSERM U1160, Paris, France and 20 Unité de Médecine Interne et Pathologie Vasculaire, Saint Louis Hospital, Assistance Publique des Hôpitaux de Paris, Paris 7 Denis Diderot University, Paris, France. Correspondence: Dr MC Oliveira, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Avenida dos Bandeirantes 3900, Ribeirão Preto, Sao Paulo 14048-900, Brazil. E-mail: mcarolor@usp.br or Professor D Farge, EBMT Autoimmune Diseases Working Party Chair, Unité Clinique de Médecine Interne UF 04: Maladies Auto-immunes et Pathologie Vasculaire, Hôpital Saint-Louis, AP-HP Assistance Publique des Hôpitaux de Paris, INSERM UMRS 1160, Paris 7 Denis Diderot Université, Paris, France. E-mail: dominique.farge-bancel@sls.aphp.fr Received 23 July 2015; revised 22 October 2015; accepted 23 October 2015; published online 7 December 2015 Bone Marrow Transplantation (2016) 51, 501 – 505 © 2016 Macmillan Publishers Limited All rights reserved 0268-3369/16 www.nature.com/bmt