Dominique Farge

MD, PhD, Head of Unit of Internal Medicine
Autoimmune and Vascular Diseases, Saint-Fouis- Lariboisiere Hospital, Paris, France
Dominique Farge
Assistance Publique-Hopitaux de Paris, (AP-HP) France St Louis Hospital
Internal Medicine, Autoimmune Diseases and Vascular Pathology Unit, UF 04 INSERM UMRS 1160, University Denis Diderot, Paris 7 France
35 years of medical experience and hospital-university practice in France 25 years of international academic research
Majors: Internal medicine and vascular diseases (CNU 53-01); competency: oncology Knight of the National Order of the Fegion of Honor (2010),
Knight of the National Order of Merit (2001)

Tel: + 33 (0) /64 (sec)
Mobile: + 33 (0)

1995: Professor of the University, Hospital Practitioner, (Exceptional Class 2011), St-Fouis APHP, University Paris 7
1995: Oncology competency, appointment to the National Ordinal Council 1992: PhD. UPMC. Paris 6
1991: Full time Hospital Practitioner in Internal Medicine (Major)
1990: Specialist in Internal Medicine, appointment to the National Ordinal Council
1984: Master of Sciences, immunology-nephrology (High Honors), Mac Gill University, Montreal, Canada
1983: Educational Commission for Foreign Medical Graduates Certification
1983: Doctoral thesis, University Paris 7, «Rifampicine and response to rejection in renal transplantation»
1981: Competitive exam for Medical Residency in Paris AP-PH Hospitals 1975: French Baccalaureate in Science
2017- 2020: Adjunct Professor, Departement de Medecine Interne, University Mac Gill, Montreal, Canada. Chef de Departement: Pr. James Martin
Since 2017: Coordinator of the Centre of Reference for Rare Autoimmune Diseases in lie de France (ST Louis UF 04, constitutive center) and of MATHEC (French network for stem cell therapy for auto-immune diseases,
Since 2010: Head of Unit, Internal Medicine, autoimmune and vascular diseases, Saint-Louis- I ariboisiere Hospital, Paris
Since 2018: Coordinator of Paris St-Louis Hospital, Center of Reference for Rare Auto-immune in Ile-de-France (UF04, FAI2R, PNMR 3)
2008-2017: Constitutive Member of the Centre of Paris Reference for Scleroderma and Vasculitis in Rare Diseases, and responsible for cell therapy for auto-immune diseases (UH 04 St-Louis Hospital, FAI2R, PNMR 2)
1995-2010: Deputy Head of Unit, Internal Medicine and vascular diseases, Saint-Louis Hospital, Paris
1992-1995: University Hospital Practitioner, Internal Medicine and vascular diseases, Pr. Rouffy, Saint-Louis Hospital, Paris
1991-1992: Senior Resident, Internal Medicine and vascular diseases, Pr. Rouffy, Saint-Louis Hospital, Paris
1988-1991: Senior Resident, cardiac surgery and heart lung transplantation, Pr. Carpentier, Broussais Hospital, Paris
1986-1988: Senior Resident, nephrology and kidney transplantation, Pr. Bariety, Broussais Hospital, Paris
1984-1986: Medical Residency, Internal Medicine, in Paris AP-HP Hospitals 1983-1984: Clinical Research Fellow, Royal Victoria Hospital, Montreal Canada 1981-1983: Medical Residency, Internal Medicine, in Paris AP-HP Hospitals
Since 2019-present: Coordinator Team 3 "MATHEC-EUROCORD" Stem cell therapy for autoimmune and non malignant disease within the Paris 7 university Research team EA-3518 (Head Pr H Dombret)
Since 2017-present: Coordinator of St-Louis, MATHEC Centre de Reference des Maladies auto- immunes systemiques Rares d'He-de-France (site constitutif) for stem cell therapy in autoimmune diseases (3rd French Orphan Rare Diseases Plan)
Since 2015: President and founder of the French Research Group on stem cell therapy in Autoimmune Diseases under the auspices of French Society of Bone marrow Transplantation and Cellular Therapy Center of Reference In lie de France for Rare Autoimmune Diseases (, PNMR3).
Since 2010: Responsible for national clinical practice guidelines MATHEC (Indication of Transplants in auto-immune and auto-inflammatory diseases) under the supervision of Scientific Council of SFGM-TC
Since 2004: Member of Unit INSERM U 697 (A Mauviel 2004 -2008), then U 976 (A Bensussan), 2013-2018 UMRS 11 60 Auto-immunity and allo-immunity Transplantation (A.Toubert) and since 2018 EA 3518 (Eurocord-MATHEC)
Since 2004: Co-responsible for Professional Degree in Cued Speach, University Paris 6 Since 2003: Member of College of Professors of Vascular Medicine (CEMV)
Since 1994: Coordinating Professor for angiology and vascular diseases, University Paris 7
Since 1990: Member of the French Society of Internal Medicine and President of the National Congress ofSNFMI (2011)
Since 2014: Member of the Board of Eurocord (www.eurocord.orgl
Since 2007: Co-founder and Chair (2007-2012), Secretary (2012-2018), President elect (since 2018) of French-speaking Group Thrombosis & Cancer (GFTC, www.thrombose-cancer.coml Since 2000: Member of the scientific board of French-speaking Research Group on Scleroderma President (2010-2014) and Board Member (2014-2018) elect of the GFRS and member since 2018: International academic cooperation
Since 2013: Co-Founder and Chair of the International Initiative on Thrombosis and Cancer; http// (International section of the GFCT)
Since 2009: Co-Responsible for the French-Chinese Cooperation and agreement framework to develop innovative stem cell therapies in auto-immunes diseases between of the department of Internal Medicine, St-Louis Hospital- Paris 7 University and the department of Hematology of the Affiliated Hospital of Nanjing University Medical School, China.
Since 1998: member of the Autoimmune Diseases Working Party (ADWP-EBMT) European Bone Marrow Transplant Association ( member (1998-2004), secretary (2004-10), elected Chair (2010-2013-2016), member (since 2016)
Autologous Stem Cell Transplantation in Systemic Sclerosis
the EBMT
Experience after 20 Years
What is the Next Step?

Sharing the Experience at International Conference in Moscow, Russia, November 2019
Systemic Sclerosis (SSc) is an immune mediated rare AD disease (prevalence 50-300 per million persons), characterized by progressive fibrosis in the skin and internal organs (1) and no standard treatment has yet demonstrated any efficacy in this diseases. According to the extent of heart, lung and kidney involvement in rapidly progressive diffuse cutaneous SSc, the respective 5 year (2) and 10 year (3 mortality rates are up to 30% and 50%. In this context, since the first EBMT consensus in 1997, the use of autologous hematopoietic stem cell transplantation has progressively increased with more than 4000 patients treated by AHSCT worldwide for an AD alone. Among the 3000 patients treated by AHSCT recorded until July 2019 in the EBMT registry, more than 600 patients have been treated for SSc (4). Results analysis from the early phase I-II trials showed that AHSCT in SSc induced major regression of clinical and histological dermal fibrosis (5) with and regression on lung fibrosis son CT scan (6, 7) which had never been previously observed with any other treatment in SSc. Prolonged follow-up of patients up to 7 years confirmed sustained improved functional status, fall in

skin score and stabilisation of lung function, whereas death from disease progression was lower compared to the 5-year mortality rate estimated at 30% in such severe SSc patients (8). The number of indications have increased (4) since three randomized clinical trials (ASSIST, in 2011 (7), ASTIS in 2014 (9 ) and SCOT in 2018 (10) successively demonstrated that AHSCT allows better overall survival and event free survival as compared to cyclophosphamide iv for early rapidly progressive SSc with significant gains, both at 1 and 2 years until 7 years after aHSCT. The mechanisms of action are related to intense initial immunosuppression, that allows eradication of the patient s autoimmune activated cells, and during the immune reconstitution process after aplasia, the capacity to reset the immune response as evidenced by subsequent thymic reprocessing or increased regulatory T-cell activity after AHSCT in SSc patients (11, 12). While gaining experience in the field with increased activity over the years, patient selection and center activity were shown to be important determinant of the observed responses (8). Patient selection directly affects transplant outcomes (13). In SSc patients, specific attention should be given for careful pretransplant evaluation of SSc-cardiac involvement, which requires not only echocardiography, but cardiac magnetic resonance, right heart catheterization with fluid overload, and 24-hour cardiac rhythm registration (Holter) (14). In conclusion, the use of aHSCT in severe and rapidly progressive SSc patients has shown impressive clinical results, with significant improvement in patients quality of life (15) and survival (7, 8, 9).

Worldwide collaboration using shared protocols and common data reporting and analysis will allow to improve patient care and to build the next international trials, so that the AHSCT procedure can be safer (16), while treating SSc patients at an earlier stage of their disease, after careful pretransplant evaluation in accredited expert center, where both disease experts and hematologists have agreed to work in tandem.
2013 classification criteria for systemic sclerosis: an American College of Rheumatology/ European League against Rheumatism collaborative initiative Arthritis Rheum. 2013 November; 65(11): 2737- 274

Fransen Jl, Popa-Diaconu D, Hesselstrand R Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres. Ann Rheum Dis. 2011 Oct;70(10): 1788-92.

Elhai M, Meune C, Boubaya M, Avouac J et al; EUSTAR group. Mapping and predicting mortality from systemic sclerosis. Ann Rheum Dis. 2017 Nov;76(ll):1897-1905. doi: 10.1136/annrheumdis2017-211448

Snowden JA, Badoglio M, Labopin et al Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv. 2017 Dec 20;l(27):2742-2755.

Verrecchia F, Laboureau J, Verola O, et al. Skin involvement in scleroderma—where histological and clinical scores meet. Rheumatology (Oxford). 2007;46(5):833-841.

Launay D, Marjanovic Z, de Bazelaire C, et al. Autologous hematopoietic stem cell transplant in systemic sclerosis: quantitative high resolution computed tomography of the chest scoring. J. Rheumatol. 2009;36(7): 1460-1463.

Burt RK, Shah SJ, Dill K, et al. Autologous non-myeloablative haematopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomized phase 2 study. Lancet. 2011 Aug 6;378(9790):498-506

Farge D, Labopin M, Tyndall A, 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):284-292.

van Laar JM and Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, et al, Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial JAMA. 2014;311:2490-8.

Sullivan KM, Goldmuntz EA, Keyes-Elstein L, et al; SCOT Study Investigators. Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma. N Engl J Med. 2018 Jan 4;378(l):35-47.

Farge D, Henegar C, Carmagnat M, et al. Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis. Arthritis Rheum. 2005;52(5):1555-1563.

Farge D, Arruda LC, Brigant F, Clave E, et al Long-term immune reconstitution and T cell repertoire analysis after autologous hematopoietic stem cell transplantation in systemic sclerosis patients. J Hematol Oncol. 2017 Jan 19; 10(1 ):21.

Snowden JA, Saccardi R, Allez M, Ardizzone S, Arnold R, Cervera R, et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012 Jun;47(6):770—90.

Farge D, Burt RK, Oliveira MC, et al. Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners. Bone Marrow Transplant. 2017 Nov;52(ll):1495-1503.

Puyade N, Maltez N, Lansiaux P, Pugnet G, Roblot P, Colmegna I, Hudson M, Farge D Healthrelated quality of life in systemic sclerosis before and after autologous hematopoietic stem cell transplant - a systematic review Rheumatology (Oxford). 2019 Aug 27. P

Burt RK, Farge D.Systemic sclerosis: Autologous HSCT is efficacious, but can we make it safer? Nat Rev Rheumatol. 2018 Apr;14(4):189-191.