title: CD34+ selected autologous peripheral blood stem cell transplantation for multiple sclerosis: report of toxicity and treatment results at one year of follow-up in 15 patients.
abstract: OBJECTIVE
  Autologous stem cell transplantation (ASCT) is currently being evaluated as a therapy for patients with multiple sclerosis (MS). We report the results of a phase II trial to evaluate feasibility and toxicity of CD34+ selected ASCT (CD34+/ASCT) and treatment results at one year of follow-up.
  
  
  METHODS
  Patients with advanced secondary progressive (SP) or relapsing-remitting (RR) MS and confirmed worsening of the extended disability status scale (EDSS) in the previous year despite interferon or other immunotherapies were included. Peripheral blood stem cells were obtained by leukaphereses after mobilization with cyclophosphamide (Cy) and granulocyte colony-stimulating factor (G-CSF). CD34+ selection was performed by means of an Isolex 300 or CliniMACS device. BCNU, Cy and antithymocyte globulin (ATG) were administered as conditioning regimen.
  
  
  RESULTS
  Fifteen patients (9 SPMS and 6 RRMS) with a median EDSS of 6.0 (4.5-6.5) and a median of 3 (1-7) relapses in the previous year were included. Mobilization was unsuccessful in one patient. During mobilization, one patient had a transient neurologic deterioration. The main complication during ASCT were engraftment syndrome, which developed in three patients, CMV reactivation in one, and neurologic deterioration in two patients coinciding with high-fever related to ATG. Hematologic recovery was fast and complete in all cases. At 12 months, the EDSS had improved in three patients, worsened in two and remained stable in nine. Despite withdrawal of all immunosuppressive therapy only two patients had relapses. Magnetic resonance imaging showed disappearance of enhanced T1 lesions but oligoclonal bands persisted in the cerebrospinal fluid of all evaluated cases.
  
  
  CONCLUSIONS
  CD34+/ASCT using BCNU, Cy and ATG as conditioning regimen has an acceptable toxicity and clearly reduces the progression of MS. Further follow-up is necessary to establish the real impact of this procedure on the long-term evolution of the disease.
authors.affiliation: BMT Unit, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. carreras@clinic.ub.es
authors.forename: Enric
authors.initials: E
authors.lastname: Carreras
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.forename: Pedro
authors.initials: P
authors.lastname: Marín
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rovira
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Marta
authors.initials: M
authors.lastname: Aymerich
authors.forename: Miquel
authors.initials: M
authors.lastname: Lozano
authors.forename: Francesc
authors.initials: F
authors.lastname: Fernández-Avilés
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Izpizua
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.forename: Francesc
authors.initials: F
authors.lastname: Graus
mesh_terms: D000328:Adult; D018952:Antigens, CD34; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007107:Immune System / Q000166:cytology; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D012008:Recurrence; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34