Journal ArticleDOI
Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study.
A Fassas,Jakob Passweg,Achilles Anagnostopoulos,Aristidis Kazis,Tomas Kozak,Eva Havrdova,Enric Carreras,Francesc Graus,Ashwin Kashyap,Harry Openshaw,M. Schipperus,Eric Deconinck,G. L. Mancardi,Alberto M. Marmont,J. Hansz,Marco Rabusin,F. J. Zuazu Nagore,J. Besalduch,T. Dentamaro,L. Fouillard,Bernd Hertenstein,G. La Nasa,Marco Musso,Federico Papineschi,J. M. Rowe,Riccardo Saccardi,Andreas J. Steck,Ludwig Kappos,Alois Gratwohl,Alan Tyndall,Marrow Transplantation +30 more
TLDR
Autologous HSCT suggest positive early results in the management of progressive MS and is feasible and is being utilised in the planning of future trials to reduce transplant related mortality.Abstract:
Rationale Phase I/II studies of autologous hematopoietic stem cell transplantation (HSCT) for multiple sclerosis (MS) were initiated, based on results of experimental transplantation in animal models of multiple sclerosis and clinical observations in patients treated concomitantly for malignant disease. Patients Eighty-five patients with progressive MS were treated with autologous HSCT in 20 centers and reported to the autoimmune disease working party of the European Group for Blood and Marrow Transplantation (EBMT). 52 (61 %) were female, median age was 39 [20-58] years. The median interval from diagnosis to transplant was 7 [1-26] years. Patients suffered from severe disease with a median EDSS score of 6.5 [4.5-8.5]. Active disease prior to transplant was documented in 79 of 82 evaluable cases. Results The stem cell source was bone marrow in 6 and peripheral blood in 79, and stem cells were mobilized into peripheral blood using either cyclophosphamide combined with growth factors or growth factors alone. Three patients experienced transient neurological complications during the mobilization phase. The high dose regimen included combination chemotherapy, with or without anti-lymphocyte antibodies or, with or without, total body irradiation. The stem cell transplants were purged of lymphocytes in 52 patients. Median follow-up was 16 [3-59] months. There were 7 deaths, 5 due to toxicity and infectious complications, 2 with neurological deterioration. The risk of death of any cause at 3 years was 10 (±7)% (95 % confidence interval). Neurological deterioration during transplant was observed in 22 patients; this was transient in most but was associated with MS progression in 6 patients. Neurological improvement by ≥ 1 point in the EDSS score was seen in 18 (21 %) patients. Confirmed progression-free survival was 74 (±12)% at 3 years being 66 (±23)% in patients with primary progressive MS but higher in patients with secondary progressive or relapsing-remitting MS, 78 (±13)%; p = 0.59. The probability of confirmed disease progression was 20 (±11)%. MRI data were available in 78 patients before transplant showing disease activity (gadolinium enhancing, new or enlarging lesions) in 33 %. Posttransplant MRI showed activity at any time in 5/61 (8 %) evaluable cases. Conclusion Autologous HSCT suggest positive early results in the management of progressive MS and is feasible. These multicentre data suggest an association with significant mortality risks especially in some patient groups and are being utilised in the planning of future trials to reduce transplant related mortality.read more
Citations
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Cyclophosphamide and cancer: golden anniversary.
TL;DR: The chemistry, pharmacology, clinical toxic effects and current clinical applications of cyclophosphamide in cancer and autoimmune disorders, and the development of high-dose cycloph phosphamide for BMT and the treatment of autoimmune diseases are discussed.
Journal ArticleDOI
Primary-progressive multiple sclerosis
TL;DR: MRI of the brain and spinal cord, and examination of the CSF, are important investigations for diagnosis; conventional immunomodulatory therapies, such as interferon beta and glatiramer acetate, are ineffective.
Journal ArticleDOI
Recommended Standard of Cerebrospinal Fluid Analysis in the Diagnosis of Multiple Sclerosis: A Consensus Statement
Mark S. Freedman,Edward J. Thompson,Florian Deisenhammer,Gavin Giovannoni,Guy Grimsley,Geoffrey Keir,Sten Öhman,Michael K. Racke,Mohammad K. Sharief,Christian Sindic,Finn Sellebjerg,Wallace W. Tourtellotte +11 more
TL;DR: In this article, the authors proposed new criteria for the diagnosis of multiple sclerosis (MS) using both clinical and paraclinical criteria, the latter involving information obtained from magnetic resonance imaging, evoked potentials, and cerebrospinal fluid (CSF) analysis.
Journal ArticleDOI
Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients
Setareh Shams'ili,Joost Grefkens,Bertie de Leeuw,Martin J. van den Bent,Herbert Hooijkaas,Bronno van der Holt,Charles J. Vecht,Peter A. E. Sillevis Smitt +7 more
TL;DR: The relative frequency of the antineuronal antibodies associated with PCD is examined, the neurological symptoms and signs, associated tumours, disability and survival between groups of PCD with different antibodies are compared and patient-, tumour- and treatment-related characteristics are attempted.
Recommended Standard of Cerebrospinal Fluid Analysis in the Diagnosis of Multiple Sclerosis
Mark S. Freedman,Edward J. Thompson,Florian Deisenhammer,Gavin Giovannoni,Guy Grimsley,Geoffrey Keir,Sten Öhman,Michael K. Racke,Mohammad K. Sharief,Christian Sindic,Finn Sellebjerg,Wallace W. Tourtellotte +11 more
TL;DR: Recommendations for establishing a standard for the evaluation of CSF in patients suspected of having MS should greatly complement the new criteria in ensuring that a correct diagnosis of MS is being made.
References
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Journal ArticleDOI
The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability.
Brian G. Weinshenker,B. Bass,George P.A. Rice,John H. Noseworthy,W. Carriere,J. Baskerville,George C. Ebers +6 more
TL;DR: The outcome of multiple sclerosis, assessed according to the Kurtzke Disability Status Scale, was reviewed in 1,099 consecutive patients followed in London, Canada, between 1972 and 1984 and the rate at which disability develops after the onset of a progressive phase of MS is presented.
Journal ArticleDOI
The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis.
D. A. Cottrell,M. Kremenchutzky,George P.A. Rice,W. J. Koopman,Walter Hader,J. Baskerville,George C. Ebers +6 more
TL;DR: From clinical onset, rate of progression was faster in the PP- multiple sclerosis group than in the secondary progressive (SP)-multiple sclerosis group, and when the rates of progression from onset of the progressive phase to DSS 6, 8 and 10 were compared, SP-multiple sclerosis had a more rapid progressive phase.
Journal ArticleDOI
Irradiation induces neural precursor-cell dysfunction
TL;DR: It is shown that the deficit in neurogenesis reflects alterations in the microenvironment that regulates progenitor-cell fate, as well as a defect in the proliferative capacity of the neural progenitors in the irradiated hippocampus.
Journal ArticleDOI
Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis
TL;DR: Treatment with interferon β-1b is the first treatment to show a therapeutic effect in patients with SP-MS, and delayed progression for 9–12 months in a study period of 2–3 years.
Journal ArticleDOI
Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading
Stephen D. Miller,Carol L. Vanderlugt,Wendy Smith Begolka,Winnie Pao,Robert L. Yauch,Katherine L. Neville,Yael Katz-Levy,AM Carrizosa,Byung S. Kim +8 more
TL;DR: It is shown that beginning 3–4 weeks after disease onset, T-cell responses to multiple myelin autoepitopes arise in an ordered progression and may play a pathologic role in chronic disease.
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