title: Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life.
abstract: Hematopoietic stem cell transplantation (HSCT) has been proposed for the treatment of severe multiple sclerosis (MS). In a phase 2 multicenter study we selected 19 non-primary progressive MS patients showing high disease activity on the basis of both brain magnetic resonance imaging (MRI) and sustained clinical deterioration despite conventional treatments. After stem cell mobilization with cyclophosphamide (CY) and filgrastim, patients were conditioned with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), cytosine arabinoside, etoposide, and melphalan (BEAM) followed by antithymocyte globulin (ATG). Unmanipulated peripheral blood stem cells (PBSCs) were then infused. No maintenance treatment was administered with a median follow-up of 36 months (range, 12 to 72 months). All patients showed clinical stabilization or improvement; 3 subsequently deteriorated, 1 beyond the baseline. No MRI active lesions were detected after the HSCT except in 1 patient who showed a new lesion at 4.5 years. Infections were limited and restricted to 3 months after HSCT. Health-related quality of life was assessed through the 54-item MS quality of life (MSQOL-54) questionnaire, showing a statistically significant improvement in both composite scores and in most of the individual domains. HSCT is able to induce a prolonged clinical stabilization in severe progressive MS patients, resulting in both sustained treatment-free periods and quality of life improvement.
authors.affiliation: Bone Marrow Transplantation Unit, Careggi Hospital, University of Florence, Italy. r.saccardi@dac.unifi.it
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Mancardi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Solari
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Bartolomeo
authors.forename: Amedea
authors.initials: A
authors.lastname: Donelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.forename: Angelo
authors.initials: A
authors.lastname: Guerrasio
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Nasa
authors.forename: Alessandra
authors.initials: A
authors.lastname: Murialdo
authors.forename: Francesca
authors.initials: F
authors.lastname: Pagliai
authors.forename: Federico
authors.initials: F
authors.lastname: Papineschi
authors.forename: Barbara
authors.initials: B
authors.lastname: Scappini
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Marmont
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000000981:diagnostic imaging / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D011034:Podophyllotoxin / Q000008:administration & dosage; D011788:Quality of Life; D011859:Radiography; D012189:Retrospective Studies; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D003561:Cytarabine; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine