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Original Investigation
April 2017

Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

Author Affiliations
  • 1Division of Brain Sciences, Imperial College London, London, England
  • 2Center for International Blood and Marrow Transplant Research, Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee
  • 3Clinical Hematology, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  • 4Multiple Sclerosis Center, Swedish Neuroscience Institute, Seattle, Washington
  • 5Internal 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
  • 6Department of Hematology, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 7Division of Neurology, Department of Medicine, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  • 8Fred Hutchinson Cancer Research Center and University of Washington, Seattle
  • 9Bone Marrow Transplantation Unit, San Martino Hospital, Genova, Italy
  • 10Bone Marrow Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
  • 11Department of Neurology, First Medical Faculty, Charles University, Prague, Czech Republic
  • 12Laboratory of Clinical Neurophysiology, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 13Department of Internal Medicine and Haematology, Third Faculty of Medicine, Charles University and Faculty Hospital Kralovske Vinohrady, Prague, Czech Republic
  • 14Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genova, Italy
  • 15Department of Neurosciences, Careggi University Hospital, University of Florence, Firenze, Italy
  • 16Department of Clinical Medicine, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil
  • 17Colorado Blood Cancer Institute, Denver
  • 18Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 19Department of Hematology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
  • 20Hematology Service, Hospital Clinic and Neurology Service, Universitat de Barcelona, Barcelona, Spain
  • 21Hospital Clinic and Institut d’Investigació August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
  • 22Department of Medicine, Charles University General Hospital, Prague, Czech Republic
  • 23Drum Tower Hospital of Nanjing Medical University, Nanjing, China
  • 24European Blood and Marrow Transplant Paris Office, Hôpital Saint Antoine, Paris, France
  • 25Biostatistics Unit, University of Genoa, Genova, Italy
  • 26Haematology Department, Careggi University Hospital, Firenze, Italy

Copyright 2017 American Medical Association. All Rights Reserved.

JAMA Neurol. 2017;74(4):459-469. doi:10.1001/jamaneurol.2016.5867
Key Points

Question  What are the long-term outcomes after autologous hematopoietic stem cell transplantation for the treatment of multiple sclerosis?

Findings  In this multicenter cohort study of 281 patients with predominantly progressive forms of multiple sclerosis who underwent autologous hematopoietic stem cell transplant between 1995 and 2006, transplant-related mortality was 2.8% within 100 days of transplant, and neurological progression-free survival was 46% at 5 years. Younger age, relapsing form of multiple sclerosis, fewer prior immunotherapies, and lower neurological disability score were significantly associated with better outcomes.

Meaning  The results support the rationale for further randomized clinical trials of autologous hematopoietic stem cell transplantation for the treatment of multiple sclerosis.


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.