• Giovanni L Mancardi, Maria P Sormani, Francesca Gualandi, Albert Saiz, Eric Carreras, Elisa Merelli, Amedea Donelli, Alessandra Lugaresi, Paolo Di Bartolomeo, Maria R Rottoli, Alessandro Rambaldi, Maria P Amato, Luca Massacesi, Massimo Di Gioia, Luisa Vuolo, Daniela Currò, Luca Roccatagliata, Massimo Filippi, Umberto Aguglia, Pasquale Iacopino, Dominique Farge, Riccardo Saccardi, ASTIMS Haemato-Neurological Collaborative Group, On behalf of the Autoimmune Disease Working Party (ADWP) of the European Group for Blood and Marrow Transplantation (EBMT), and ASTIMS Haemato-Neurological Collaborative Group On behalf of the Autoimmune Disease Working Party ADWP of the European Group for Blood and Marrow Transplantation EBMT.
• From the MRI Center for Neurological Diseases (L.R.), Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health (G.L.M., D.C.), and the Biostatistic Unit, Department of Health Sciences (M.P.S., L.R.), University of Genova; the Bone Marrow Transplantation Unit (F.G.), S. Martino Hospital, Genova, Italy; the Service of Neurology (A.S.) and the Hematology Department (E.C.), Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic, University of Barcelona, Spain; the Department of Neurosciences (E.M.) and the Bone Marrow Transplantation Unit, Department of Hematology and Oncology (A.D.), University of Modena and Reggio Emilia; the MS Center, Department of Neuroscience, Imaging and Clinical Sciences (A.L.), University Gabriele D'Annunzio, Chieti-Pescara; the Bone Marrow Transplant Center, Department of Hematology (P.D.B.), Spirito Santo Hospital, Pescara; the Multiple Sclerosis Unit Ospedale Papa Giovanni XXIII (M.R.R.), Bergamo; the Hematology and Bone Marrow Transplant Unit Azienda Ospedaliera Papa Giovanni XXIII (A.R.), Bergamo; Division Neurology 1 (M.P.A.) and Division Neurology 2, Drug and Child Health (L.M., L.V.), Department of Neurosciences, and Bone Marrow Transplantation Unit (M.D.G., R.S.), Careggi University Hospital, University of Firenze; the Neuroimaging Research Unit (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; the Department of Medical and Surgical Sciences (U.A.), Magna Graecia University of Catanzaro; the Advanced Cellular Therapy Center IRCCS "Istituto Tumori Giovanni Paolo II" Bari (P.I.), Italy; and the Internal Medicine and Vascular Disease Unit (D.F.), Assistance Publique Hospitaux de Paris (AP-HP) INSERM U 796, Paris 7 University, Saint-Louis Hospital, Paris, France. glmancardi@neurologia.unige.it.
• Neurology. 2015 Mar 10; 84 (10): 981-8.

ObjectiveTo assess in multiple sclerosis (MS) the effect of intense immunosuppression followed by autologous hematopoietic stem cells transplantation (AHSCT) vs mitoxantrone (MTX) on disease activity measured by MRI.MethodsWe conducted a multicenter, phase II, randomized trial including patients with secondary progressive or relapsing-remitting MS, with a documented increase in the last year on the Expanded Disability Status Scale, in spite of conventional therapy, and presence of one or more gadolinium-enhancing (Gd+) areas. Patients were randomized to receive intense immunosuppression (mobilization with cyclophosphamide and filgrastim, conditioning with carmustine, cytosine-arabinoside, etoposide, melphalan, and anti-thymocyte globulin) followed by AHSCT or MTX 20 mg every month for 6 months. The primary endpoint was the cumulative number of new T2 lesions in the 4 years following randomization. Secondary endpoints were the cumulative number of Gd+ lesions, relapse rate, and disability progression. Safety and tolerability were also assessed. Twenty-one patients were randomized and 17 had postbaseline evaluable MRI scans.ResultsAHSCT reduced by 79% the number of new T2 lesions as compared to MTX (rate ratio 0.21, p = 0.00016). It also reduced Gd+ lesions as well as the annualized relapse rate. No difference was found in the progression of disability.ConclusionIntense immunosuppression followed by AHSCT is significantly superior to MTX in reducing MRI activity in severe cases of MS. These results strongly support further phase III studies with primary clinical endpoints. The study was registered as EUDRACT No. 2007-000064-24.© 2015 American Academy of Neurology.

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