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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.
- Source :
-
JAMA [JAMA] 2019 Jan 15; Vol. 321 (2), pp. 165-174. - Publication Year :
- 2019
-
Abstract
- Importance: Hematopoietic stem cell transplantation (HSCT) represents a potentially useful approach to slow or prevent progressive disability in relapsing-remitting multiple sclerosis (MS).<br />Objective: To compare the effect of nonmyeloablative HSCT vs disease-modifying therapy (DMT) on disease progression.<br />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.<br />Interventions: Patients were randomized to receive HSCT along with cyclophosphamide (200 mg/kg) and antithymocyte globulin (6 mg/kg) (n = 55) or DMT of higher efficacy or a different class than DMT taken during the previous year (n = 55).<br />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.<br />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).<br />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.<br />Trial Registration: ClinicalTrials.gov Identifier: NCT00273364.
- Subjects :
- Adolescent
Adult
Antilymphocyte Serum therapeutic use
Combined Modality Therapy
Cyclophosphamide therapeutic use
Disease Progression
Female
Humans
Immunologic Factors therapeutic use
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting drug therapy
Young Adult
Hematopoietic Stem Cell Transplantation adverse effects
Immunosuppressive Agents therapeutic use
Multiple Sclerosis, Relapsing-Remitting therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1538-3598
- Volume :
- 321
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- JAMA
- Publication Type :
- Academic Journal
- Accession number :
- 30644983
- Full Text :
- https://doi.org/10.1001/jama.2018.18743