Baseline Skin Score, Older Age and CD34-selection Influence the Outcome of Autologous Stem Cell Transplantation for Systemic Sclerosis – Results of a Prospective Non-interventional Study from the European Society for Blood & Marrow Transplantation (EBMT)

Joerg Henes¹, Maria Carolina Oliveira ², Myriam Labopin ³, Manuela Badoglio ⁴, Hans Ulrich Scherer ⁵, Nicoletta Del Papa ⁶, Thomas Daikeler ⁷, Marc Schmalzing ⁸, Roland Schroers ⁹, Thierry Martin ¹⁰, Grégory Pugnet ¹¹, Belinda Simoes ¹², David Michonneau ¹³, Erik Marijt ¹⁴, Bruno Lioure ¹⁵, Jacques Olivier Bay ¹⁶, John Snowden ¹⁷, Montserrat Rovira ¹⁸, Anne Huynh ¹⁹, Francesco Onida ²⁰, Lothar Kanz ¹, Zora Marjanovic ²¹ and Dominique Farge ²², ¹University Hospital Tuebingen, Department of Internal Medicine II (Oncology, Haematology, Immunology and Rheumatology), Tuebingen, Germany, ²Ribeirão Preto Medical School, University of São Paulo, Sao Paulo, Brazil, ³EBMT Paris Study Office, Saint Antoine Hospital, Université Pierre et Marie Curie, Paris, France, ⁴EBMT Paris Study Office, Hôpital St Antoine, Paris, France, ⁵Leiden University Medical Center, Department of Rheumatology, Leiden, Netherlands, ⁶Scleroderma Clinic, Osp. G. Pini, Department of Rheumatology, Milan, Italy, ⁷University and University Hospital of Basel, Department of Rheumatology, Basel, Switzerland, ⁸Universitätsklinikum Würzburg, Department of Rheumatology/ Clinical Immunology, Wuerzburg, Germany, ⁹University Hospital of Bochum, Med. Klinik, Bochum, Germany, ¹⁰Hôpitaux Universitaires de Strasbourg Service de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes Systémiques Rares Est-Sud-Ouest (RESO), Strasbourg, France, ¹¹CHU de Toulouse, Hôpital Purpan, Service de Médecine Interne, Toulouse, France, ¹²Ribeirão Preto Medical School, University of São Paulo, Division of Hematology, Sao Paulo, Brazil, ¹³Hôpital Saint Louis & Université Paris 7, Denis Diderot, Department of Hematology, Paris, France, ¹⁴Leiden University Medical Center, Department of Hematology, Leiden, Netherlands, ¹⁵Strasbourg University Hospital, Department of Hematology, Strasbourg, France, ¹⁶CHU de Clermont Ferrand, Department of Hematology, Clermont Ferrand, France, ¹⁷Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom, ¹⁸Hospital Clínic of Barcelona, Department of Haematology, Barcelona, Spain, ¹⁹UCT Oncopole, Department of Haematology, Toulouse, France, ²⁰Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy, ²¹Saint Antoine Hospital, Department of Haematology, Paris, France, ²²Hôpital Saint-Louis, AP-HP Assistance Publique des Hôpitaux de Paris, Centre de Référence des Maladies Auto-Immunes Systémiques Rares d’Ile-de-France, Filière ‘FAI2R’, Unité de Médecine Interne: Maladies Auto-immunes et Pathologie Vasculaire (UF 04), Université de Paris, EA 3518, Paris, France; Department of Medicine, McGill University, Montreal, QC, Canada, Paris, France

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: autoimmune diseases, Scleredema and transplantation

Session Information

Date: Monday, November 11, 2019

Title: Systemic Sclerosis & Related Disorders – Clinical Poster II

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: T

Three randomized controlled trials in systemic sclerosis (SSc) demonstrated that autologous hematopoietic stem cell transplantation (aHSCT) is superior to standard cyclophosphamide therapy. This EBMT trial was a multi-center, prospective non-interventional study (NISCC1), designed to further decipher aHSCT efficacy and safety in real-life practice and to search for prognostic factors.

Methods: All consecutive adult patients, fulfilling the 2013 ACR/EULAR classification criteria for SSc, and undergoing a first aHSCT between December 2012 and February 2016 were included in the study. Primary endpoint was progression free survival (PFS) after two years. Secondary endpoints were overall survival (OS), non-relapse mortality (NRM) and response (RESP) to treatment, defined as >25% improvement in modified Rodnan skin score (mRSS) and/or ≥10% improvement in lung function test for Forced vital capacity (FVC) or diffusion capacity for carbon monoxide (DLCO) and with no need for further immunosuppression.

Results: Eighty SSc patients were included. Median follow-up was 24 (6-57) months after aHSCT using cyclophosphamide plus antithymocyte globulin conditioning for all, with CD34+ selection in 35 (44%) patients. Following aHSCT, G-CSF was administered to 34 (43%) patients for a median duration of five (1-13) days. Median time following aHSCT to neutrophil engraftment was 11 (8-24) days and nine (1-25) days to platelet engraftment. There was an inverse correlation between the number of CD34+ cells infused and the time to engraftment (Spearman: r2= -0.31; p< .01), while the number of infused CD34+ cells or addition of G-CSF until aplasia recovery were not associated with a reduced number of infectious complications (p=0.32). At two years, PFS was 81.8%, OS was 90% and RESP was 88.7%. The 100 day NRM was 6.25% (n=5) with four deaths from cardiac events. Mean mRSS decreased from 23.9 at baseline to 14.2 at month 12 and 12.6 at month 24 (n=55, p< 0.001). Regarding lung function, mean FVC increased from 73.6% at baseline to 79.5% at month 12, and 80.6% at month 24 (n=37, p< 0.001); mean DLCO was 60.2% at baseline, 59.7% at month 12 and 60.4% at month 24 (n=35). By multivariate analysis, baseline mRSS >24 and older age at transplant were associated with lower PFS. CD34+-selection was associated with better RESP.

Conclusion: The NISCC1 study is the largest prospective cohort today demonstrating the efficacy and safety of aHSCT in eighty severe SSc patients in a real-life setting. NISCC1 showed superior response in patients with CD34+ graft selection with regard to response to treatment no increase in the rate of infectious complications.

Kaplan-Mayer curves showing data for overall survival -OS-, progression free survival -PFS-, progression and non-relapse -treatment- related mortality -NRM- over time

Disclosure: J. Henes, None; M. Oliveira, None; M. Labopin, None; M. Badoglio, None; H. Scherer, None; N. Del Papa, None; T. Daikeler, None; M. Schmalzing, AbbVie, Actelion, BMS, Celgene, Chugai/Roche, Genzyme, Hexal/Sandoz, Janssen-Cilag, MSD, Novartis, Pfizer, Sanofi Pasteur, Shire (Baxalta), UCB, 2, 5, 7, 8; R. Schroers, None; T. Martin, None; G. Pugnet, None; B. Simoes, None; D. Michonneau, None; E. Marijt, None; B. Lioure, None; J. Bay, None; J. Snowden, None; M. Rovira, None; A. Huynh, None; F. Onida, None; L. Kanz, None; Z. Marjanovic, None; D. Farge, None.

To cite this abstract in AMA style:

Henes J, Oliveira M, Labopin M, Badoglio M, Scherer H, Del Papa N, Daikeler T, Schmalzing M, Schroers R, Martin T, Pugnet G, Simoes B, Michonneau D, Marijt E, Lioure B, Bay J, Snowden J, Rovira M, Huynh A, Onida F, Kanz L, Marjanovic Z, Farge D. Baseline Skin Score, Older Age and CD34-selection Influence the Outcome of Autologous Stem Cell Transplantation for Systemic Sclerosis – Results of a Prospective Non-interventional Study from the European Society for Blood & Marrow Transplantation (EBMT) [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/baseline-skin-score-older-age-and-cd34-selection-influence-the-outcome-of-autologous-stem-cell-transplantation-for-systemic-sclerosis-results-of-a-prospective-non-interventional-study-from/. Accessed .

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