Maria Pia Sormani1, Paolo A Muraro2, Irene Schiavetti2, Alessio Signori2, Alice Laroni2, Riccardo Saccardi2, Gian Luigi Mancardi2. 1. From the Departments of Health Sciences (M.P.S., I.S., A.S.) and Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health (A.L., G.L.M.), University of Genoa, Italy; Division of Brain Sciences (P.A.M.), Imperial College, London, UK; IRCCS Azienda Ospedaliera Universitaria San Martino-IST (A.L., G.L.M.), Genoa; and Cell Therapy and Transfusion Medicine Unit (R.S.), Careggi University Hospital, Firenze, Italy. mariapia.sormani@unige.it. 2. From the Departments of Health Sciences (M.P.S., I.S., A.S.) and Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health (A.L., G.L.M.), University of Genoa, Italy; Division of Brain Sciences (P.A.M.), Imperial College, London, UK; IRCCS Azienda Ospedaliera Universitaria San Martino-IST (A.L., G.L.M.), Genoa; and Cell Therapy and Transfusion Medicine Unit (R.S.), Careggi University Hospital, Firenze, Italy.
Abstract
OBJECTIVE: To summarize the evidence on immunoablative therapy followed by autologous hematopoietic stem cell transplantation (aHSCT) to manage severe and treatment-refractory multiple sclerosis (MS). METHODS: We collected all the published studies of aHSCT in any form of MS from 1995 to 2016, carefully excluding reports that were updated in subsequent studies. Endpoints were transplant-related mortality (TRM), rate of disease progression, and no evidence of disease activity (NEDA) status. A weighted metaregression based on a Poisson model was run, assessing whether there were study-specific characteristics with an effect on TRM and progression. RESULTS: Fifteen studies including 764 transplanted patients were pooled in the meta-analysis. The pooled estimate of TRM was 2.1% (95% confidence interval [CI] 1.3%-3.4%). TRM was higher in older studies (p = 0.014) and in studies with a lower proportion of patients with relapsing-remitting MS (RRMS) (p = 0.028). A higher baseline Expanded Disability Status Scale (p = 0.013) was also significantly associated with a higher TRM. Pooled rate of progression was 17.1% at 2 years (95% CI 9.7%-24.5%) and 23.3% (95% CI 16.3%-31.8%) at 5 years. Lower 2-year progression rate was significantly associated with higher proportions of patients with RRMS (p = 0.004). The pooled proportion of NEDA patients at 2 years was 83% (range 70%-92%) and at 5 years was 67% (range 59%-70%). CONCLUSIONS: The emerging evidence on this therapeutic approach in MS indicates that the largest benefit/risk profile form this therapeutic approach can be obtained in patients with aggressive MS with a relapsing-remitting course and who have not yet accumulated a high level of disability.
OBJECTIVE: To summarize the evidence on immunoablative therapy followed by autologous hematopoietic stem cell transplantation (aHSCT) to manage severe and treatment-refractory multiple sclerosis (MS). METHODS: We collected all the published studies of aHSCT in any form of MS from 1995 to 2016, carefully excluding reports that were updated in subsequent studies. Endpoints were transplant-related mortality (TRM), rate of disease progression, and no evidence of disease activity (NEDA) status. A weighted metaregression based on a Poisson model was run, assessing whether there were study-specific characteristics with an effect on TRM and progression. RESULTS: Fifteen studies including 764 transplanted patients were pooled in the meta-analysis. The pooled estimate of TRM was 2.1% (95% confidence interval [CI] 1.3%-3.4%). TRM was higher in older studies (p = 0.014) and in studies with a lower proportion of patients with relapsing-remitting MS (RRMS) (p = 0.028). A higher baseline Expanded Disability Status Scale (p = 0.013) was also significantly associated with a higher TRM. Pooled rate of progression was 17.1% at 2 years (95% CI 9.7%-24.5%) and 23.3% (95% CI 16.3%-31.8%) at 5 years. Lower 2-year progression rate was significantly associated with higher proportions of patients with RRMS (p = 0.004). The pooled proportion of NEDA patients at 2 years was 83% (range 70%-92%) and at 5 years was 67% (range 59%-70%). CONCLUSIONS: The emerging evidence on this therapeutic approach in MS indicates that the largest benefit/risk profile form this therapeutic approach can be obtained in patients with aggressive MS with a relapsing-remitting course and who have not yet accumulated a high level of disability.
Authors: Anastasie M Dunn-Pirio; Benjamin M Heyman; Dan S Kaufman; Revere P Kinkel Journal: Curr Treat Options Neurol Date: 2019-10-17 Impact factor: 3.598
Authors: Caila B Vaughn; Dejan Jakimovski; Katelyn S Kavak; Murali Ramanathan; Ralph H B Benedict; Robert Zivadinov; Bianca Weinstock-Guttman Journal: Nat Rev Neurol Date: 2019-06 Impact factor: 42.937
Authors: J Das; J A Snowden; J Burman; M S Freedman; H Atkins; M Bowman; R K Burt; R Saccardi; C Innocenti; S Mistry; P J Laud; H Jessop; B Sharrack Journal: Mult Scler Date: 2021-02-10 Impact factor: 6.312
Authors: Maria T Cencioni; Miriam Mattoscio; Roberta Magliozzi; Amit Bar-Or; Paolo A Muraro Journal: Nat Rev Neurol Date: 2021-06-01 Impact factor: 42.937