Open this publication in new window or tab >>Univ Sheffield, Sheffield, S Yorkshire, England;Sheffield Teaching Hosp NHS Fdn Trust, Dept Haematol & Oncol, Sheffield, S Yorkshire, England;Sheffield Teaching Hosp NHS Fdn Trust, Dept Metab, Sheffield, S Yorkshire, England.
Univ Sao Paulo, Ctr Cell Based Therapy, Dept Internal Med, Ribeirao Preto Med Sch, Ribeirao Preto, Brazil.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Univ Utah, Dept Neurol, Salt Lake City, UT USA.
Univ Minnesota, Dept Neurol, Div Multiple Sclerosis, Minneapolis, MN 55455 USA.
Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav Sci, Ribeirao Preto, Brazil.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Univ Sao Paulo, Ctr Cell Based Therapy, Dept Internal Med, Ribeirao Preto Med Sch, Ribeirao Preto, Brazil.
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Northwestern Univ, Dept Med, Div Immunotherapy, Feinberg Sch Med, Chicago, IL 60611 USA.
Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
Show others...
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
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-375869 (URN)10.1001/jama.2018.18743 (DOI)000455606300015 ()30644983 (PubMedID)
2019-02-042019-02-042019-02-04Bibliographically approved