High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3-year interim report.
Richard A. Nash,George J. Hutton,Michael K. Racke,Uday R. Popat,Steven M. Devine,Linda M. Griffith,Paolo A. Muraro,Harry Openshaw,Peter H. Sayre,Olaf Stüve,Olaf Stüve,Douglas L. Arnold,Meagan E. Spychala,Kaitlyn C. McConville,Kristina M. Harris,Deborah Phippard,George E. Georges,George E. Georges,Annette Wundes,George H. Kraft,James D. Bowen +20 more
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TLDR
HALT-MS was an ongoing, multicenter, single-arm, phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling, and was effective for inducing sustained remission of active RRMS at 3 years.Abstract:
Importance Most patients with relapsing-remitting (RR) multiple sclerosis (MS) who receive approved disease-modifying therapies experience breakthrough disease and accumulate neurologic disability. High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic cell transplant (HCT) may, in contrast, induce sustained remissions in early MS. Objective To evaluate the safety, efficacy, and durability of MS disease stabilization through 3 years after HDIT/HCT. Design, setting, and participants Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) is an ongoing, multicenter, single-arm, phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling. Participants are evaluated through 5 years after HCT. This report is a prespecified, 3-year interim analysis of the trial. Thirty-six patients with RRMS from referral centers were screened; 25 were enrolled. Interventions Autologous peripheral blood stem cell grafts were CD34+ selected; the participants then received high-dose treatment with carmustine, etoposide, cytarabine, and melphalan as well as rabbit antithymocyte globulin before autologous HCT. Main outcomes and measures The primary end point of HALT-MS is event-free survival defined as survival without death or disease activity from any one of the following outcomes: (1) confirmed loss of neurologic function, (2) clinical relapse, or (3) new lesions observed on magnetic resonance imaging. Toxic effects are reported using National Cancer Institute Common Terminology Criteria for Adverse Events. Results Grafts were collected from 25 patients, and 24 of these individuals received HDIT/HCT. The median follow-up period was 186 weeks (interquartile range, 176-250) weeks). Overall event-free survival was 78.4% (90% CI, 60.1%-89.0%) at 3 years. Progression-free survival and clinical relapse-free survival were 90.9% (90% CI, 73.7%-97.1%) and 86.3% (90% CI, 68.1%-94.5%), respectively, at 3 years. Adverse events were consistent with expected toxic effects associated with HDIT/HCT, and no acute treatment-related neurologic adverse events were observed. Improvements were noted in neurologic disability, quality-of-life, and functional scores. Conclusions and relevance At 3 years, HDIT/HCT without maintenance therapy was effective for inducing sustained remission of active RRMS and was associated with improvements in neurologic function. Treatment was associated with few serious early complications or unexpected adverse events.read more
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Diagnosis and Treatment of Multiple Sclerosis: A Review.
TL;DR: A review of the evidence regarding diagnosis and treatment of MS can be found in this paper, where nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS.
Journal ArticleDOI
Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial
Harold L. Atkins,Harold L. Atkins,Harold L. Atkins,Marjorie Bowman,Marjorie Bowman,David S. Allan,David S. Allan,David S. Allan,Grizel Anstee,Douglas L. Arnold,Amit Bar-Or,Isabelle Bence-Bruckler,Isabelle Bence-Bruckler,Paul Birch,Christopher Bredeson,Christopher Bredeson,Christopher Bredeson,Jacqueline T. Chen,Jacqueline T. Chen,Dean Fergusson,Dean Fergusson,Mike Halpenny,Linda Hamelin,Lothar Huebsch,Lothar Huebsch,Brian Hutton,Pierre Laneuville,Yves Lapierre,Hyun-Woo Lee,Lisa Martin,Sheryl McDiarmid,Paul O'Connor,Tim Ramsay,Tim Ramsay,Mitchell Sabloff,Mitchell Sabloff,Lisa Walker,Lisa Walker,Mark S. Freedman,Mark S. Freedman,Mark S. Freedman +40 more
TL;DR: The first treatment to fully halt all detectable CNS inflammatory activity in patients with multiple sclerosis for a prolonged period in the absence of any ongoing disease-modifying drugs is described.
Journal ArticleDOI
Can We Design a Nogo Receptor-Dependent Cellular Therapy to Target MS?
TL;DR: The current review outlines novel means to achieve neurorepair with biologicals that may be directed to sites of active demyelination and the Nogo-A receptor-dependent signaling mechanism, which has raised considerable interest in neurological disease paradigms.
Journal ArticleDOI
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,Roumen Balabanov,Joachim Burman,Basil Sharrack,John A. Snowden,Maria Carolina Oliveira,Jan Fagius,John W. Rose,Flavia Nelson,Amilton Antunes Barreira,Kristina Carlson,Xiaoqiang Han,Daniela A. Moraes,Amy Morgan,Kathleen Quigley,Kimberly Yaung,Regan Buckley,Carri Alldredge,Allison M. Clendenan,Michelle A. Calvario,Jacquelyn Henry,Borko Jovanovic,Irene Helenowski +22 more
TL;DR: In this preliminary study of patients with relapsing-remitting MS, nonmyeloablative HSCT, compared with DMT, resulted in prolonged time to disease progression, with significant differences in time to progression estimated as hazard ratios.
Journal ArticleDOI
Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis
Paolo A. Muraro,Roland Martin,Giovanni Luigi Mancardi,Richard Nicholas,Maria Pia Sormani,Riccardo Saccardi +5 more
TL;DR: Evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity, and clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of A HSCT against highly active MS drugs.
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