Giacomo Boffa1, Luca Massacesi2, Matilde Inglese3, Alice Mariottini4, Marco Capobianco5, Moiola Lucia6, Maria Pia Amato7, Salvatore Cottone8, Francesca Gualandi9, Marco De Gobbi10, Raffaella Greco11, Rosanna Scimè12, Jessica Frau13, Giovanni Bosco Zimatore14, Antonio Bertolotto15, Giancarlo Comi16, Antonio Uccelli17, Alessio Signori18, Emanuele Angelucci19, Chiara Innocenti20, Fabio Ciceri21, Anna Maria Repice22, Maria Pia Sormani23, Riccardo Saccardi24, Gianluigi Mancardi25. 1. Giacomo Boffa, Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, San Martino Hospital, Genoa/Italy. 2. Luca Massacesi Department of Neurosciences Drugs and Child Health and Department of Neurology 2, Careggi University Hospital, Florence, Italy. 3. Matilde Inglese Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa and Ospedale Policlinico San Martino, IRCCS, Genoa, Italy m.inglese@unige.it. 4. Alice Mariottini Department of Neurosciences Drugs and Child Health and Department of Neurology 2, Careggi University Hospital, Florence, Italy. 5. Marco Capobianco Department of Neurology, San Luigi Gonzaga Hospital, Orbassano, Italy. 6. Lucia Moiola Department of Neurology, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan/Italy. 7. Maria Pia Amato Department NEUROFARBA, Section Neurological Sciences University of Florence IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy. 8. Salvatore Cottone Department of Neurology, Villa Sofia Hospital, Palermo/Italy. 9. Francesca Gualandi Department of Haematology and Bone Marrow Transplant Unit, Policlinico San Martino IRCCS, Genoa/Italy. 10. Marco De Gobbi Department of Clinical and Biological Sciences, Haematopoietic Stem Cell Transplant Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano/Italy. 11. Raffaella Greco Department of Haematology and Bone marrow transplant, VitaSalute San Raffaele University, San Raffaele Scientific Institute, Milan/Italy. 12. Rosanna Scimè Department of Haematology, Villa Sofia Hospital, Palermo/Italy. 13. Jessica Frau Multiple Sclerosis Center, Department of Medical Sciences and Public Health University of Cagliari,Binaghi Hospital Cagliari/Italy. 14. Giovanni Bosco Zimatore Department of Neurology, Ospedale Generale Regionale "F. Miulli", Acquaviva delle Fonti, BA, Italy. 15. Antonio Bertolotto Department of Neurology, San Luigi Gonzaga Hospital, Orbassano, Italy. 16. Giancarlo Comi Department of Neurology, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan/Italy. 17. Antonio Uccelli Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa and Ospedale Policlinico San Martino, IRCCS, Genoa, Italy. 18. Alessio Signori Biostatistics Unit, University of Genoa, Genoa/Italy. 19. Giacomo Boffa, Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, San Martino Hospital, Genoa/Italy m.inglese@unige.it. 20. Chiara Innocenti Cell Therapy and Transfusion Medicine Unit, Careggi University Hospital, Florence/Italy. 21. Fabio Ciceri Department of Haematology and Bone marrow transplant, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan/Italy. 22. Anna Maria Repice Department of Neurosciences Drugs and Child Health and Department of Neurology 2, Careggi University Hospital, Florence, Italy. 23. Maria Pia Sormani Biostatistics Unit, University of Genoa, Genoa/Italy. 24. Riccardo Saccardi Cell Therapy and Transfusion Medicine Unit, Careggi University Hospital, Florence/Italy. 25. Gianluigi Mancardi Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa and Ospedale Policlinico San Martino, IRCCS, Genoa, Italy and IRCCS Scientific Clinical Institutes Maugeri, Pavia-Genoa Nervi/Italy.
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 transplant in a large cohort of MS patients. METHODS: To be included, a minimum data set (consisting of age, MS phenotype, EDSS at baseline, information on transplant technology and at least 1 follow-up visit after transplant) was required. RESULTS: 210 patients were included [relapsing-remitting (RR)MS=122(58%)]. Median baseline EDSS was 6(1-9), mean follow-up was 6.2(±5.0) years. Among RRMS patients, disability worsening-free survival (95%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 RRMS patients, EDSS significantly reduced after aHSCT [p=0.001; mean EDSS change per year -0.09 (95%CI=-0.15 to -0.04%)]. In RRMS patients, the use of the BEAM+ATG conditioning protocol was independently associated with a reduced risk of NEDA-3 failure [HR=0.27(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.
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 transplant in a large cohort of MS patients. METHODS: To be included, a minimum data set (consisting of age, MS phenotype, EDSS at baseline, information on transplant technology and at least 1 follow-up visit after transplant) was required. RESULTS: 210 patients were included [relapsing-remitting (RR)MS=122(58%)]. Median baseline EDSS was 6(1-9), mean follow-up was 6.2(±5.0) years. Among RRMS patients, disability worsening-free survival (95%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 RRMS patients, EDSS significantly reduced after aHSCT [p=0.001; mean EDSS change per year -0.09 (95%CI=-0.15 to -0.04%)]. In RRMS patients, the use of the BEAM+ATG conditioning protocol was independently associated with a reduced risk of NEDA-3 failure [HR=0.27(0.14-0.50), p<0.001]. Three patientsdied 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.
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