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JAMA. 2015 Jan 20;313(3):275-84. doi: 10.1001/jama.2014.17986.

Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis.

Author information

1
Division of Immunotherapy, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
2
Department of Neurology, Rush University Medical Center, Chicago, Illinois.
3
Academic Department of Neuroscience, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, England.
4
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
5
Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
6
Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
7
Department of Neuro-Radiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
8
Division of Clinical Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
9
Department of Neuroscience and Neurology, Uppsala University, Uppsala, Sweden.

Abstract

IMPORTANCE:

No current therapy for relapsing-remitting multiple sclerosis (MS) results in significant reversal of disability.

OBJECTIVE:

To determine the association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability and other clinical outcomes in patients with MS.

DESIGN, SETTING, AND PARTICIPANTS:

Case series of patients with relapsing-remitting MS (n = 123) or secondary-progressive MS (n = 28) (mean age, 36 years; range, 18-60 years; 85 women) treated at a single US institution between 2003 and 2014 and followed up for 5 years. Final follow-up was completed in June 2014.

INTERVENTIONS:

Treatment with cyclophosphamide and alemtuzumab (22 patients) or cyclophosphamide and thymoglobulin (129 patients) followed by infusion of unmanipulated peripheral blood stem cells.

MAIN OUTCOMES AND MEASURES:

Primary end point was reversal or progression of disability measured by change in the Expanded Disability Status Scale (EDSS) score of 1.0 or greater (score range, 0-10). Secondary outcomes included changes in the Neurologic Rating Scale (NRS) score of 10 or greater (score range, 0-100), Multiple Sclerosis Functional Composite (MSFC) score, quality-of-life Short Form 36 questionnaire scores, and T2 lesion volume on brain magnetic resonance imaging scan.

RESULTS:

Outcome analysis was available for 145 patients with a median follow-up of 2 years and a mean of 2.5 years. Scores from the EDSS improved significantly from a pretransplant median of 4.0 to 3.0 (interquartile range [IQR], 1.5 to 4.0; n = 82) at 2 years and to 2.5 (IQR, 1.9 to 4.5; n = 36) at 4 years (P < .001 at each assessment). There was significant improvement in disability (decrease in EDSS score of ≥1.0) in 41 patients (50%; 95% CI, 39% to 61%) at 2 years and in 23 patients (64%; 95% CI, 46% to 79%) at 4 years. Four-year relapse-free survival was 80% and progression-free survival was 87%. The NRS scores improved significantly from a pretransplant median of 74 to 88.0 (IQR, 77.3 to 93.0; n = 78) at 2 years and to 87.5 (IQR, 75.0 to 93.8; n = 34) at 4 years (P < .001 at each assessment). The median MSFC scores were 0.38 (IQR, -0.01 to 0.64) at 2 years (P < .001) and 0.45 (0.04 to 0.60) at 4 years (P = .02). Total quality-of-life scores improved from a mean of 46 (95% CI, 43 to 49) pretransplant to 64 (95% CI, 61 to 68) at a median follow-up of 2 years posttransplant (n = 132) (P < .001). There was a decrease in T2 lesion volume from a pretransplant median of 8.57 cm3 (IQR, 2.78 to 22.08 cm3) to 5.74 cm3 (IQR, 1.88 to 14.45 cm3) (P < .001) at the last posttransplant assessment (mean follow-up, 27 months; n = 128).

CONCLUSIONS AND RELEVANCE:

Among patients with relapsing-remitting MS, nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes. These preliminary findings from this uncontrolled study require confirmation in randomized trials.

PMID:
25602998
DOI:
10.1001/jama.2014.17986
[Indexed for MEDLINE]

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