https://jamanetwork.com/journals/jama/article-abstract/2720728

 

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

Richard K. Burt, MD1Roumen Balabanov, MD2Joachim Burman, MD3; et alBasil Sharrack, MD4John A. Snowden, MD5Maria Carolina Oliveira, MD6Jan Fagius, MD3John Rose, MD7Flavia Nelson, MD8Amilton Antunes Barreira, MD9Kristina Carlson, MD10Xiaoqiang Han, MD1Daniela Moraes, MD6Amy Morgan, APRN1Kathleen Quigley, RN1Kimberly Yaung, RN1Regan Buckley, RN1Carri Alldredge, RN1Allison Clendenan, APRN1Michelle A. Calvario, APRN1Jacquelyn Henry, APRN1Borko Jovanovic, PhD11Irene B. Helenowski, PhD11

JAMA. 2019;321(2):165-174. doi:10.1001/jama.2018.18743

 

Question  Is nonmyeloablative autologous hematopoietic stem cell transplantation (HSCT) more effective than disease-modifying therapy for patients with highly active relapsing-remitting multiple sclerosis (MS)?

Findings  In this randomized clinical trial that included 110 patients with relapsing-remitting MS, treatment with nonmyeloablative HSCT compared with disease-modifying therapy resulted in a significantly prolonged time to disease progression (hazard ratio, 0.07).

Meaning  In this preliminary study, nonmyeloablative HSCT was more effective than disease-modifying therapy for patients with relapsing-remitting MS.

Abstract

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 (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).

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.

Trial Registration  ClinicalTrials.gov Identifier: NCT00273364

Editorial

Stem Cell Transplantation to Treat Multiple Sclerosis

 

 

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