title: Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Division of Brain Sciences, Imperial College London, London, England.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Muraro
authors.affiliation: Center for International Blood and Marrow Transplant Research, Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Pasquini
authors.affiliation: Clinical Hematology, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Harold L
authors.initials: HL
authors.lastname: Atkins
authors.affiliation: Multiple Sclerosis Center, Swedish Neuroscience Institute, Seattle, Washington.
authors.forename: James D
authors.initials: JD
authors.lastname: Bowen
authors.affiliation: 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.
authors.forename: Dominique
authors.initials: D
authors.lastname: Farge
authors.affiliation: Department of Hematology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Fassas
authors.affiliation: Division of Neurology, Department of Medicine, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Freedman
authors.affiliation: Fred Hutchinson Cancer Research Center and University of Washington, Seattle.
authors.forename: George E
authors.initials: GE
authors.lastname: Georges
authors.affiliation: Bone Marrow Transplantation Unit, San Martino Hospital, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.affiliation: Bone Marrow Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Nelson
authors.initials: N
authors.lastname: Hamerschlak
authors.affiliation: Department of Neurology, First Medical Faculty, Charles University, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Laboratory of Clinical Neurophysiology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Vassilios K
authors.initials: VK
authors.lastname: Kimiskidis
authors.affiliation: Department of Internal Medicine and Haematology, Third Faculty of Medicine, Charles University and Faculty Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kozak
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genova, Italy.
authors.forename: Giovanni L
authors.initials: GL
authors.lastname: Mancardi
authors.affiliation: Department of Neurosciences, Careggi University Hospital, University of Florence, Firenze, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Massacesi
authors.affiliation: Department of Clinical Medicine, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Moraes
authors.affiliation: Colorado Blood Cancer Institute, Denver.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Steven
authors.initials: S
authors.lastname: Pavletic
authors.affiliation: Department of Hematology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ouyang
authors.affiliation: Hematology Service, Hospital Clinic and Neurology Service, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rovira
authors.affiliation: Hospital Clinic and Institut d'Investigació August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.affiliation: Department of Clinical Medicine, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Belinda
authors.initials: B
authors.lastname: Simoes
authors.affiliation: Department of Medicine, Charles University General Hospital, Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Trnený
authors.affiliation: Drum Tower Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: European Blood and Marrow Transplant Paris Office, Hôpital Saint Antoine, Paris, France.
authors.forename: Manuela
authors.initials: M
authors.lastname: Badoglio
authors.affiliation: Center for International Blood and Marrow Transplant Research, Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Biostatistics Unit, University of Genoa, Genova, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.affiliation: Haematology Department, Careggi University Hospital, Firenze, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D004185:Disability Evaluation; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007391:International Cooperation; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000601:surgery*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult