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Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis

M C Vonk¹, Z Marjanovic², F H J van den Hoogen¹, S Zohar³, A V M B Schattenberg⁴, W E Fibbe⁵, J Larghero⁶, E Gluckman⁷, F W M B Preijers⁴, A P J van Dijk¹⁰, J J Bax¹¹, P Roblot¹², P L C M van Riel¹, J M van Laar⁸, D Farge⁹

¹ Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
² Assistance Publique Hôpitaux de Paris, Hôpital Hôtel-Dieu, Département d’Hématologie, Paris, France
³ Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Département d’Informatique Médicale et Biostatistiques, Paris, France
⁴ Department of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
⁵ Department of Hematology, Leiden University Medical Centre, Leiden, The Netherlands
⁶ Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Cell therapy Unit, Paris, France
⁷ Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Service de Greffe de Moelle, Paris, France
⁸ Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
⁹ Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Department of Internal Medicine and INSERM U 697 Paris, University Paris 7 Denis Diderot, France
¹⁰ Heart-Lung Centre, Department of Cardiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
¹¹ Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands
¹² Département de Médecine Interne, Hopital Universitaire La Miletrie, Poitiers, France

Madelon C Vonk, Department of Rheumatology, Radboud University Nijmegen Medical Centre, P.O.Box 9101, 6500 HB Nijmegen, The Netherlands; M.Vonk{at}reuma.umcn.nl; Dominique Farge, Service de Médecine Interne et Unité INSERM U667, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75 010 Paris France; dominique.farge-bancel{at}sls.ap-hop-paris.fr

Objective: Systemic sclerosis (SSc) is a generalised autoimmune disease, causing morbidity and a reduced life expectancy, especially in patients with rapidly progressive diffuse cutaneous SSc. As no proven treatment exists, autologous haematopoietic stem cell transplantation (HSCT) is employed as a new therapeutic strategy in patients with a poor prognosis. This study reports the effects on survival, skin and major organ function of HSCT in patients with severe diffuse cutaneous SSc.

Patients and methods: A total of 26 patients were evaluated. Peripheral blood stem cells were collected using cyclophosphamide (4 g/m²) and rHu G-CSF (5 to 10 µg/kg/day) and were reinfused after positive CD34+ selection. For conditioning, cyclophosphamide 200 mg/kg was used.

Results: After a median follow-up of 5.3 (1–7.5) years, 81% (n = 21/26) of the patients demonstrated a clinically beneficial response. The Kaplan–Meier estimated survival at 5 years was 96.2% (95% CI 89–100%) and at 7 years 84.8% (95% CI 70.2–100%) and event-free survival, defined as survival without mortality, relapse or progression of SSc, resulting in major organ dysfunction was 64.3% (95% CI 47.9–86%) at 5 years and 57.1% (95% CI 39.3–83%) at 7 years.

Conclusion: This study confirms that autologous HSCT in selected patients with severe diffuse cutaneous SSc results in sustained improvement of skin thickening and stabilisation of organ function up to 7 years after transplantation.

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