title: Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores.
abstract: There were 21 patients with rapidly progressive multiple sclerosis (MS) treated on a phase 1/2 study of intense immune suppressive therapy and autologous hematopoietic stem cell (HSC) support with no 1-year mortality. Following transplantation, one patient had a confirmed acute attack of MS. Neurologic progression defined by the expanded disability status scale (EDSS) did not increase in disability by 1.0 or more steps in any of 9 patients with a pretransplantation EDSS of 6.0 or less. In 8 of 12 patients with high pretransplantation disability scores (EDSS > 6.0), progressive neurologic disability as defined by at least a 1-point increase in the EDSS has occurred and was manifested as gradual neurologic deterioration. There were 2 patients with a pretransplantation EDSS of 7.0 and 8.0 who died from complications of progressive disease at 13 and 18 months following treatment. Our experience suggests that intense immune suppression using a total body irradiation (TBI)-based regimen and hematopoietic stem cell transplantation (HSCT) are not effective for patients with progressive disease and high pretransplantation disability scores. Further studies are necessary to determine the role of intense immune suppressive therapy and HSC support in ambulatory patients with less accumulated disability and more inflammatory disease activity. Specifically, more patients and longer follow-up would be required in patients with an EDSS of 6.0 or less before drawing conclusions on this subgroup.
authors.affiliation: Department of Neurology, Northwestern University Medical School, Chicago, IL, USA. rburt@northwestern.edu
authors.forename: Richard K
authors.initials: RK
authors.lastname: Burt
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Cohen
authors.forename: Eric
authors.initials: E
authors.lastname: Russell
authors.forename: Kenneth
authors.initials: K
authors.lastname: Spero
authors.forename: Akash
authors.initials: A
authors.lastname: Joshi
authors.forename: Yu
authors.initials: Y
authors.lastname: Oyama
authors.forename: William J
authors.initials: WJ
authors.lastname: Karpus
authors.forename: Kehuan
authors.initials: K
authors.lastname: Luo
authors.forename: Borko
authors.initials: B
authors.lastname: Jovanovic
authors.forename: Ann
authors.initials: A
authors.lastname: Traynor
authors.forename: Karyn
authors.initials: K
authors.lastname: Karlin
authors.forename: Dusan
authors.initials: D
authors.lastname: Stefoski
authors.forename: William H
authors.initials: WH
authors.lastname: Burns
mesh_terms: D000328:Adult; D003131:Combined Modality Therapy; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology / Q000628:therapy*; D017211:Treatment Failure; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents