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Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.ORCID iD: 0000-0002-7045-1806
Sheffield Teaching Hosp NHS Fdn Trust, Dept Neurosci, Sheffield, S Yorkshire, England;Sheffield Teaching Hosp NHS Fdn Trust, Sheffield NIHR Translat Neurosci BBC, Sheffield, S Yorkshire, England;Univ Sheffield, Sheffield, S Yorkshire, England.
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2019 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 321, no 2, p. 165-174Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE Hematopoietic stem cell transplantation (HSCT) represents a potentially useful approach to slow or prevent progressive disability in relapsing-remitting multiple sclerosis (MS).

OBJECTIVE To compare the effect of nonmyeloablative HSCT vs disease-modifying therapy (DMT) on disease progression.

DESIGN, SETTING, AND PARTICIPANTS Between September 20, 2005, and July 7, 2016, a total of 110 patients with relapsing-remitting MS, at least 2 relapses while receiving DMT in the prior year, and an Expanded Disability Status Scale (EDSS; score range, 0-10 [10 = worst neurologic disability]) score of 2.0 to 6.0 were randomized at 4 US, European, and South American centers. Final follow-up occurred in January 2018 and database lock in February 2018.

INTERVENTIONS Patients were randomized to receive HSCT along with cyclophosphamide (200mg/kg) and antithymocyte globulin (6mg/kg) (n = 55) or DMT of higher efficacy or a different class than DMT taken during the previous year (n = 55).

MAIN OUTCOMES AND MEASURES The primary end point was disease progression, defined as an EDSS score increase after at least 1 year of 1.0 point or more (minimal clinically important difference, 0.5) on 2 evaluations 6 months apart, with differences in time to progression estimated as hazard ratios. RESULTS Among 110 randomized patients (73 [66%] women; mean age, 36 [SD, 8.6] years), 103 remained in the trial, with 98 evaluated at 1 year and 23 evaluated yearly for 5 years (median follow-up, 2 years; mean, 2.8 years). Disease progression occurred in 3 patients in the HSCT group and 34 patients in the DMT group. Median time to progression could not be calculated in the HSCT group because of too few events; it was 24 months (interquartile range, 18-48 months) in the DMT group (hazard ratio, 0.07; 95% CI, 0.02-0.24; P < .001). During the first year, mean EDSS scores decreased (improved) from 3.38 to 2.36 in the HSCT group and increased (worsened) from 3.31 to 3.98 in the DMT group (between-group mean difference,-1.7; 95% CI,-2.03 to -1.29; P < .001). There were no deaths and no patients who received HSCT developed nonhematopoietic grade 4 toxicities (such as myocardial infarction, sepsis, or other disabling or potential life-threatening events).

CONCLUSIONS AND RELEVANCE In this preliminary study of patients with relapsing-remitting MS, nonmyeloablative HSCT, compared with DMT, resulted in prolonged time to disease progression. Further research is needed to replicate these findings and to assess long-term outcomes and safety.

Place, publisher, year, edition, pages
AMER MEDICAL ASSOC , 2019. Vol. 321, no 2, p. 165-174
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-375869DOI: 10.1001/jama.2018.18743ISI: 000455606300015PubMedID: 30644983OAI: oai:DiVA.org:uu-375869DiVA, id: diva2:1285255
Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved

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Burman, JoachimFagius, JanCarlson, Kristina

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