Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

Autor: Giovanni Luigi Mancardi, Lin Zhu, Montserrat Rovira, Harold L. Atkins, George E. Georges, Athanasios Fassas, Nelson Hamerschlak, Marek Trněný, Luca Massacesi, Xiaobo Zhong, James Bowen, Jian Ouyang, Dominique Farge, Francesca Gualandi, Manuela Badoglio, Richard A. Nash, Maria Pia Sormani, Albert Saiz, Eva Havrdova, V K Kimiskidis, Paolo A. Muraro, Daniela A. Moraes, Mark S. Freedman, Marcelo C. Pasquini, Tomas Kozak, Belinda Pinto Simões, Riccardo Saccardi, Steven Z. Pavletic
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
BLOOD
International Cooperation
Kaplan-Meier Estimate
Cohort Studies
Disability Evaluation
0302 clinical medicine
Child
Hazard ratio
Hematopoietic Stem Cell Transplantation
Middle Aged
Treatment Outcome
Cohort
WORKING PARTY
Female
DOSE IMMUNOSUPPRESSIVE THERAPY
Life Sciences & Biomedicine
Cohort study
Adult
medicine.medical_specialty
Multiple Sclerosis
Adolescent
PHASE
Clinical Neurology
IMMUNOABLATION
AUTOIMMUNE-DISEASES
Transplantation
Autologous
Disease-Free Survival
03 medical and health sciences
REPERTOIRE
Young Adult
Internal medicine
medicine
Humans
Progression-free survival
Survival analysis
SOBREVIVÊNCIA LIVRE DE DOENÇA
EUROPEAN GROUP
Expanded Disability Status Scale
Science & Technology
business.industry
Retrospective cohort study
MS
Surgery
Transplantation
030104 developmental biology
Neurology (clinical)
Neurosciences & Neurology
business
030217 neurology & neurosurgery
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 2168-6157
Popis: Importance Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies. Objective To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort. Design, Setting, and Participants Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015. Exposures Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen. Main Outcomes and Measures The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models. Results Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95). Conclusions and Relevance In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS.
Databáze: OpenAIRE
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