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JAMA Neurol. 2015 Feb;72(2):159-69. doi: 10.1001/jamaneurol.2014.3780.

High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3-year interim report.

Author information

1
Colorado Blood Cancer Institute, Denver.
2
Department of Neurology, Baylor College of Medicine, Houston, Texas.
3
Department of Neurology and Neuroscience, The Ohio State University, Columbus.
4
Division of Cancer Medicine, Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston.
5
Blood and Marrow Transplant Program, Division of Hematology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus.
6
Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
7
Department of Medicine, Division of Brain Sciences, Imperial College London, London, England.
8
Department of Neurology, City of Hope National Medical Center, Duarte, California.
9
Hematology and Blood and Marrow Transplant, University of California, San Francisco, Medical Center, San Francisco10Clinical Trials Group, Immune Tolerance Network, San Francisco, California.
10
Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas12Neurology Section, Veterans Affairs North Texas Health Care System, Dallas13associate editor, JAMA Neurology.
11
Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada15NeuroRx, Montreal, Quebec, Canada.
12
Rho Inc, Chapel Hill, North Carolina.
13
Biomarker and Discovery Research, Immune Tolerance Network, San Francisco, California.
14
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington19Medical Oncology Division, University of Washington Medical Center, Seattle.
15
Department of Neurology, University of Washington Medical Center, Seattle.
16
Department of Rehabilitation Medicine, University of Washington, Seattle.
17
Swedish Neuroscience Institute, Seattle, Washington.

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.

PMID:
25546364
PMCID:
PMC5261862
DOI:
10.1001/jamaneurol.2014.3780
[Indexed for MEDLINE]
Free PMC Article

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