Experimental data and early phase I/II studies suggest that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) can arrest progression of severe autoimmune diseases. We have evaluated the toxicity and disease response in 473 patients with severe autoimmune disease treated with autologous HSCT between 1995 and 2003, from 110 centers participating in the European Group for Blood and Marrow Transplantation (EBMT) autoimmune disease working party database. Survival, transplant-related mortality, treatment response and disease progression were assessed. In all, 420 patients (89%; 86±4% at 3 years, median follow-up 20 months) were alive, 53 (11%) had died from transplant-related mortality (N=31; 7±3% at 3 years) or disease progression (N=22; 9±4% at 3 years). Of 370 patients, 299 evaluable for response (81%) showed a treatment response, which was sustained in 213 (71% of responders). Response was associated with disease (P<0.001), was better in patients who received cyclophosphamide during mobilization (relative risk (RR)3.28 (1.57–6.83)) and was worse with increasing age (>40 years, RR0.29 (0.11–0.82)). Disease progression was associated with disease (P<0.001) and conditioning intensity (high intensity, RR1; intermediate intensity, RR1.81 (0.96–3.42)); low intensity, RR2.34 (1.074–5.11)). These data from the collective EBMT experience support the hypothesis that autologous HSCT can alter disease progression in severe autoimmune disease.
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We would like to acknowledge the participating centres, the support of the project by the EBMT corporate members (Amgen Europe, Hoffmann-La Roche Ltd, Gilead Sciences, Baxter Oncology, Pharmacia Corporation, Chugai-Aventis, Fresenius HemoCare, SangStat, Schering AG, Gambro BCT, Elan Pharmaceuticals, Miltenyl Biotec GmbH, Therakos, Wyeth-Lederlé, Astra, Cobe International, Nextar, Liposome Co., Imtix, the Horton Foundation, the Swiss National Research Foundation, the Regional Cancer League Basel and the Délégation Régionale à la Recherche Clinique (DRRC), Assistance Publique-Hôpitaux de Paris (AP-HP), the French Ministry of Health (Programme Hospitalier de Recherche Clinique: PHRC 1997 AOM 97-030) and Professor E Gluckman, Hôpital St Louis, Paris).
List of participating centers:
Austria: Vienna, Vienna University Hospital; Australia: Brisbane, Mater Hospital; Hobart, Royal Hobart Hospital; Melbourne, Royal Melbourne Hospital; Perth, Sir Charles Gairdner Hospital; Royal Perth Hospital; Sydney, St Vincent's Hospital; Belgium: Brussels, Children University Hospital, Erasmus Hospital, Institut Jules Bordet; Liège, Centre Hospitalier Universitaire; Leuven, University Hospital Gasthuisberg; China: Nanjing, Gu Lou Hospital; Peking, Peking University Medical Center Hospital; Zhengzhou, The Third People Hospital of Zhengzhou; Czech Republic: Pilsen, Charles University Hospital; Prague, University Hospital Kralovske Vinohrady, University Hospital Motol; Finland: Kuopio, Kuopio University Hospital; Turku, Turku University Central Hospital; France: Besançon, Hôpital Jean Minijoz; Brest, Hôpital Morvan; Clermont Ferrant, Centre Hospitalier Universitaire; Lille, Hôpital Claude Huriez; Limoges, Centre Hospitalier Regional Universitaire Limoges; Marseilles, Institut Paoli Calmettes; Paris, Centre Hospitalier Universitaire Cochin, Hôpital Necker, Hôpital St Antoine, Hôpital St Louis, Pitie-Salpetriere; Strassbourg, Hôpital Universitaire de Hautepierre; Toulouse, Hôpital de Purpan; Germany: Berlin, Universitätsklinikum Charité, Charité-Virchow Klinikum; Bochum, University Hospital Knappschfts-Krankenhaus; Dresden, Universitätsklinikum; Düsseldorf, Henrich Heine Universität; Erlangen, University Hospital; Frankfurt, Universitätsklinikum; Freiburg, Klinikum der Albert-Ludwigs Universität Freiburg; Halle, Martin-Luther-Universität; Hannover, Medizinische Hochschule; Heidelberg, University of Heidelberg; Jena, University of Jena; Münster, Universitätsklinik; Tübingen, Medizinische Universitätsklinik; Wiesbaden, Deutsche Zentrum für Krankeitsdiagnostik; Hungary: Miskolc, Postgraduate Medical School; Greece: Thessaloniki, George Papanicolaou Hospital; Israel: Haifa, Rambam Medical Center; Jerusalem, Hadassah University Hospital; Italy: Cagliari, University of Cagliari; Ferrara, Ospedale St Anna; Firenze, Ospedale di Careggi, Ospedale Pediatrico ‘A.Meyer’; Genova, Ospedale San Martino; Milano, Ospedale San Raffaele; Modena, University of Modena; Monza, Ospedale San Gerardo; Torino, Ospedale San Luigi Orbassano; Padova, University Hospital; Palermo, Ospedale Oncologico ‘La Maddalena’; Pavia, Policlinico San Matteo; Pescara, Ospedale Civile; Pisa, University of Pisa; Reggio Emilia, Arcispedale Santa Maria Nuova; Reggio Calabria, Azienda Ospedaliera Bianchi-Melacrino-Morelli; Roma, Ospedale San Camillo, Università ‘La Sapienza’, Università Tor Vergata; Trieste, Istituto per l’Infanzia Burlo Garofolo; Udine, University Hospital; Japan: Osaka, Osaka Medical Center; The Netherlands: Leiden, Leiden University Medical Center; Nijmegen, University Medical Center St Radboud; Rotterdam, Erasmus University Medical Center; Utrecht, University Medical Center; Poland: Poznan, K. Marcinkowski University; Russia: Novosibirsk, Institute of Clinical Immunology; St Petersburg, St Petersburg State I. Pavlov Medical University; Slovakia: Bratislava, University Hospital; Spain: Barcelona, Hospital Clinic, Hospital Santa Creu i Sant Pau, Hospital Vall d'Hebron; Cádiz , Hospital del SAS; Lugo, Hospital Xeral-Calde; Madrid, Clinica Puerta de Hierro, Hospital Infantil La Paz, Hospital G.U. Gregorio Maranon, Hospital de la Princesa; Malaga, Hospital Carlos Haya; Palma de Mallorca, Hospital San Dureta; Santander, Hospital Universitario ‘Marquéz de Valdecilla’; Sevilla, Hospital Universitario Virgen del Rocio; Valencia, Hospital Clinico Universitario; Sweden: Göteborg, Sahlgrenska University Hospital; Lund, University Hospital; Uppsala, University Hospital; Switzerland: Basel, Kantonsspital; Zürich, University Children Hospital; UK: Birmingham, University of Birmingham; Leeds, University of Leeds; Liverpool, Royal Liverpool University Hospital; London, Great Ormond Street Hospital, Hammersmith Hospital, Royal Free Hospital, St George's Hospital, University College Hospital; Newcastle, Royal Victoria Infirmary; Nottingham, Nottingham City Hospital.
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Gratwohl, A., Passweg, J., Bocelli-Tyndall, C. et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases. Bone Marrow Transplant 35, 869–879 (2005). https://doi.org/10.1038/sj.bmt.1704892
- autoimmune disease
- autologous hematopoietic stem cell transplantation
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