Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis
Authors: Richard K. Burt, Roumen Balabanov, Joachim Burman, Basil Sharrack, John A. Snowden, Maria Carolina Oliveira, Jan Fagius, John Rose, Flavia Nelson, Amilton Antunes Barreira, Kristina Carlson, Xiaoqiang Han, Daniela Moraes, Amy Morgan, Kathleen Quigley, Kimberly Yaung, Regan Buckley, Carri Alldredge, Allison Clendenan, Michelle A. Calvario, Jacquelyn Henry, Borko Jovanovic, Irene B. Helenowski
Journal: JAMA (2019)

<h3>Importance</h3> Hematopoietic stem cell transplantation (HSCT) represents a potentially useful approach to slow or prevent progressive disability in relapsing-remitting multiple sclerosis (MS). <h3>Objective</h3> To compare the effect of nonmyeloablative HSCT vs disease-modifying therapy (DMT) on disease progression. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> 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). <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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;<i>P</i> &lt; .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;<i>P</i> &lt; .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). <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT00273364