Faculty Collaboration Database

Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA Neurol 2017 Apr 01;74(4):459-469

Date

02/28/2017

Pubmed ID

28241268

Pubmed Central ID

PMC5744858

DOI

10.1001/jamaneurol.2016.5867

Scopus ID

2-s2.0-85015108062 (requires institutional sign-in at Scopus site)   193 Citations

Abstract

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.

Author List

Muraro PA, Pasquini M, Atkins HL, Bowen JD, Farge D, Fassas A, Freedman MS, Georges GE, Gualandi F, Hamerschlak N, Havrdova E, Kimiskidis VK, Kozak T, Mancardi GL, Massacesi L, Moraes DA, Nash RA, Pavletic S, Ouyang J, Rovira M, Saiz A, Simoes B, Trnený M, Zhu L, Badoglio M, Zhong X, Sormani MP, Saccardi R, Multiple Sclerosis–Autologous Hematopoietic Stem Cell Transplantation (MS-AHSCT) Long-term Outcomes Study Group

Author

Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Child
Cohort Studies
Disability Evaluation
Disease-Free Survival
Female
Hematopoietic Stem Cell Transplantation
Humans
International Cooperation
Kaplan-Meier Estimate
Male
Middle Aged
Multiple Sclerosis
Transplantation, Autologous
Treatment Outcome
Young Adult