title: Low intensity lympho-ablative regimen followed by autologous hematopoietic stem cell transplantation in severe forms of multiple sclerosis: A MRI-based clinical study.
abstract: BACKGROUND
  Autologous hematopoietic stem cell transplantation (AHSCT) has been successfully used to treat aggressive forms of multiple sclerosis (MS) that are unresponsive to approved therapies. In the last years, in view of the risk of mortality related to the procedure, the utilization of low-intensity conditioning regimens has been considered.
  
  
  OBJECTIVE
  To report magnetic resonance imaging (MRI) and clinical data in a small cohort of patients treated with a low-intensity lympho-ablative regimen, followed by AHSCT.
  
  
  METHODS
  Seven patients affected by relapsing-remitting MS (RRMS) underwent AHSCT, with cyclophosphamide 120 mg/kg in 2 days as the conditioning regimen; and were then followed with serial MRI evaluations until 36 months, with clinical evaluations until 60 months.
  
  
  RESULTS
  The mean number of gadolinium (Gd)-enhancing lesions significantly decreased after treatment, but a complete suppression of inflammatory activity was not obtained. No deaths occurred, but every patient developed adverse events, although not severe. After 5 years of follow-up, two patients remained stable, one patient markedly improved and four patients had a mild progression of the disease. Only one patient experienced a relapse after treatment.
  
  
  CONCLUSIONS
  A low-intensity conditioning regimen with AHSCT has a profound effect on MRI inflammation and relapses, but is not able to completely abrogate MRI activity and disease progression of aggressive RRMS.
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health; University of Genova; Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Curro'
authors.affiliation: Careggi University Hospital, University of Firenze, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Vuolo
authors.affiliation: Bone Marrow Transplantation Unit, San Martino Hospital, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.affiliation: Bone Marrow Transplantation Unit, San Martino Hospital, Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.affiliation: Department of Health Sciences and MRI Center for neurological diseases, University of Genova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Roccatagliata
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health; University of Genova; Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Capello
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health; University of Genova; Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Uccelli
authors.affiliation: Careggi University Hospital, University of Firenze, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.affiliation: Department of Health Sciences, University of Genova, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health; University of Genova; Italy/Department of Health Sciences, University of Genova, Italy glmancardi@neurologia.unige.it.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mancardi
mesh_terms: D000328:Adult; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy*; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: Aggressive multiple sclerosis; autologous hematopoietic stem cell transplantation; conditioning regimen; lympho-ablation; multiple sclerosis; relapsing–remitting multiple sclerosis; transplantation; treatment methods