February 23, 2021; 96 (8) Article
Long-term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis
View ORCID ProfileGiacomo Boffa, View ORCID ProfileLuca Massacesi, Matilde Inglese, View ORCID ProfileAlice Mariottini, Marco Capobianco, Lucia Moiola, Maria Pia Amato, Salvatore Cottone, Francesca Gualandi, Marco De Gobbi, Raffaella Greco, Rosanna Scimè, Jessica Frau, Giovanni Bosco Zimatore, View ORCID ProfileAntonio Bertolotto, Giancarlo Comi, Antonio Uccelli, Alessio Signori, Emanuele Angelucci, Chiara Innocenti, Fabio Ciceri, Anna Maria Repice, Maria Pia Sormani, Riccardo Saccardi, Gianluigi Mancardi, ; on behalf of the Italian BMT-MS Study Group
First published January 20, 2021, DOI: https://doi.org/10.1212/WNL.0000000000011461
Giacomo Boffa
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Luca Massacesi
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Matilde Inglese
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Alice Mariottini
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Marco Capobianco
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Lucia Moiola
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Maria Pia Amato
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Salvatore Cottone
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Francesca Gualandi
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Marco De Gobbi
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Raffaella Greco
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Rosanna Scimè
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Jessica Frau
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Giovanni Bosco Zimatore
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Antonio Bertolotto
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Giancarlo Comi
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Antonio Uccelli
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Alessio Signori
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Emanuele Angelucci
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Chiara Innocenti
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Fabio Ciceri
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Anna Maria Repice
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Maria Pia Sormani
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Riccardo Saccardi
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Gianluigi Mancardi
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
From the Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (G.B., M.I., A.U., G.M.) and Biostatistics Unit (A.S., M.P.S.), University of Genoa; San Martino Hospital (G.B.), Genoa; Department of Neurosciences Drugs (L. Massacesi, A.M., A.M.R.), Child Health and Department of Neurology 2 (L. Massacesi, A.M., A.M.R.), and Cell Therapy and Transfusion Medicine Unit (C.I., R. Saccardi), Careggi University Hospital, Florence; Ospedale Policlinico San Martino (M.I., A.U., G.M.), IRCCS, Genoa; Department of Neurology (M.C., A.B.), San Luigi Gonzaga Hospital, Orbassano; Department of Neurology (L. Moiola, G.C.) and Department of Haematology and Bone Marrow Transplant (R.G., F.C.), Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan; Department NEUROFARBA (M.P.A.), Section Neurological Sciences, University of Florence IRCCS Fondazione Don Carlo Gnocchi; Department of Neurology (S.C.) and Department of Haematology (R. Scimè), Villa Sofia Hospital, Palermo; Department of Haematology and Bone Marrow Transplant Unit (F.G., E.A.), Policlinico San Martino IRCCS, Genoa; Department of Clinical and Biological Sciences (M.D.G.), Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano; Multiple Sclerosis Center (J.F.), Department of Medical Sciences and Public Health University of Cagliari; Binaghi Hospital (J.F.), Cagliari; Department of Neurology (G.B.Z.), Ospedale Generale Regionale “F. Miulli,” Acquaviva delle Fonti, BA; and IRCCS Scientific Clinical Institutes Maugeri (G.M.), Pavia-Genoa Nervi, Italy.
Long-term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis
Giacomo Boffa, Luca Massacesi, Matilde Inglese, Alice Mariottini, Marco Capobianco, Lucia Moiola, Maria Pia Amato, Salvatore Cottone, Francesca Gualandi, Marco De Gobbi, Raffaella Greco, Rosanna Scimè, Jessica Frau, Giovanni Bosco Zimatore, Antonio Bertolotto, Giancarlo Comi, Antonio Uccelli, Alessio Signori, Emanuele Angelucci, Chiara Innocenti, Fabio Ciceri, Anna Maria Repice, Maria Pia Sormani, Riccardo Saccardi, Gianluigi Mancardi
Neurology Feb 2021, 96 (8) e1215-e1226; DOI: 10.1212/WNL.0000000000011461
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Abstract
Objective To determine whether autologous hematopoietic stem cell transplantation (aHSCT) is able to induce durable disease remission in people with multiple sclerosis (MS), we analyzed the long-term outcomes after transplantation in a large cohort of patients with MS.
Methods To be included, a minimum dataset (consisting of age, MS phenotype, Expanded Disability Status Scale [EDSS] score at baseline, information on transplantation technology, and at least 1 follow-up visit after transplantation) was required.
Results Two hundred ten patients were included (relapsing-remitting [RR] MS 122 [58%]). Median baseline EDSS score was 6 (1–9); mean follow-up was 6.2 (±5.0) years. Among patients with RRMS, disability worsening–free survival (95% confidence interval [CI]) was 85.5% (76.9%–94.1%) at 5 years and 71.3% (57.8%–84.8%) at 10 years. In patients with progressive MS, disability worsening–free survival was 71.0% (59.4%–82.6%) and 57.2% (41.8%–72.7%) at 5 and 10 years, respectively. In patients with RRMS, EDSS significantly reduced after aHSCT (p = 0.001; mean EDSS change per year −0.09 [95% CI −0.15% to −0.04%]). In patients with RRMS, the use of the BCNU+Etoposide+Ara-C+Melphalan (BEAM) + anti-thymocyte globulin (ATG) conditioning protocol was independently associated with a reduced risk of no evidence of disease activity 3 failure (hazard ratio 0.27 [95% CI 0.14–0.50], p < 0.001). Three patients died within 100 days from aHSCT (1.4%); no deaths occurred in patients transplanted after 2007.
Conclusions aHSCT prevents disability worsening in the majority of patients and induces durable improvement in disability in patients with RRMS. The BEAM + ATG conditioning protocol is associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity.
Classification of Evidence This study provides Class IV evidence that for people with MS, aHSCT induces durable disease remission in most patients.
Glossary
- aHSCT=
- autologous hematopoietic stem cell transplantation;
- ATG=
- anti-thymocyte globulin;
- CI=
- confidence interval;
- CY=
- cyclophosphamide;
- DMT=
- disease-modifying therapy;
- EDSS=
- Expanded Disability Status Scale;
- HR=
- hazard ratio;
- MS=
- multiple sclerosis;
- NEDA=
- no evidence of disease activity;
- RRMS=
- relapsing-remitting MS
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Coinvestigators are listed in appendix 2 at the end of the article.
Class of Evidence: NPub.org/coe
- Received May 11, 2020.
- Accepted in final form October 23, 2020.
- © 2021 American Academy of Neurology
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