IMPORTANCE: Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies. OBJECTIVE: To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS: Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015. EXPOSURES: Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen. MAIN OUTCOMES AND MEASURES: The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models. RESULTS: Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95). CONCLUSIONS AND RELEVANCE: In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS.

Biostatistics Unit University of Genoa Genova Italy

Bone Marrow Transplant Unit Hospital Israelita Albert Einstein São Paulo Brazil

Bone Marrow Transplantation Unit San Martino Hospital Genova Italy

Center for International Blood and Marrow Transplant Research Division of Hematology and Oncology Department of Medicine Medical College of Wisconsin Milwaukee

Clinical Hematology University of Ottawa and The Ottawa Hospital Research Institute Ottawa Ontario Canada

Colorado Blood Cancer Institute Denver

Department of Clinical Medicine Ribeirão Preto School of Medicine University of São Paulo São Paulo Brazil

Department of Hematology Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing China

Department of Hematology Aristotle University of Thessaloniki Thessaloniki Greece

Department of Internal Medicine and Haematology 3rd Faculty of Medicine Charles University and Faculty Hospital Kralovske Vinohrady Prague Czech Republic

Department of Medicine Charles University General Hospital Prague Czech Republic

Department of Neurology 1st Medical Faculty Charles University Prague Czech Republic

Department of Neuroscience Rehabilitation Ophthalmology Genetics and Maternal and Child Health University of Genoa Genova Italy

Department of Neurosciences Careggi University Hospital University of Florence Firenze Italy

Division of Brain Sciences Imperial College London London England

Division of Neurology Department of Medicine University of Ottawa and The Ottawa Hospital Research Institute Ottawa Ontario Canada

Drum Tower Hospital of Nanjing Medical University Nanjing China

European Blood and Marrow Transplant Paris Office Hôpital Saint Antoine Paris France

Experimental Transplantation and Immunology Branch National Cancer Institute National Institutes of Health Bethesda Maryland

Fred Hutchinson Cancer Research Center and University of Washington Seattle

Haematology Department Careggi University Hospital Firenze Italy

Hematology Service Hospital Clinic and Neurology Service Universitat de Barcelona Barcelona Spain

Hospital Clinic and Institut d'Investigació August Pi i Sunyer Universitat de Barcelona Barcelona Spain

Internal Medicine Autoimmune and Vascular Diseases Unit Unité Fonctionnelle 04 Assistance Publique Hôpitaux de Paris Saint Louis Hospital Institut National de la Santé et de la Récherche Médicale Unité Mixte de Recherche 1160 Paris France

Laboratory of Clinical Neurophysiology Aristotle University of Thessaloniki Thessaloniki Greece

Multiple Sclerosis Center Swedish Neuroscience Institute Seattle Washington

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Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis

The current standing of autologous haematopoietic stem cell transplantation for the treatment of multiple sclerosis

Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases