Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis

2017 ◽  
Vol 24 (3) ◽  
pp. 245-255 ◽  
Author(s):  
Gianluigi Mancardi ◽  
Maria Pia Sormani ◽  
Paolo A Muraro ◽  
Giacomo Boffa ◽  
Riccardo Saccardi

In the majority of relapsing multiple sclerosis patients, the disease can be quite easily controlled by already available, approved therapies. There are, however, some aggressive cases who continue to have clinical and magnetic resonance imaging (MRI) activity in spite of the treatment. These are the cases who may now receive benefit from intense immunosuppression followed by autologous haematopoietic stem cell transplantation (aHSCT). In this review, we describe the method and the rationale of aHSCT, the more recently published studies that demonstrate its efficacy in selected multiple sclerosis cases, the problems related to safety and the transplant-related mortality risk of the procedure. A description of the ideal patient who can take advantage of aHSCT is outlined and, finally, the ongoing studies which are near to completion or are close to starting are briefly reported.

2010 ◽  
Vol 16 (6) ◽  
pp. 685-693 ◽  
Author(s):  
Eva Krasulová ◽  
Marek Trněný ◽  
Tomáš Kozák ◽  
Blanka Vacková ◽  
David Pohlreich ◽  
...  

There are multiple sclerosis patients who suffer from an aggressive course of the disease with severe relapses and rapid accumulation of disability despite adequate treatment. In such cases high-dose immunoablation with autologous haematopoietic stem cell transplantation (ASCT) may be considered. Our objective was to report our experience with 26 multiple sclerosis patients treated with ASCT within the years 1998—2008. Twenty-six patients (Expanded Disability Status Scale 2.5—7.5 (median 6.0), multiple sclerosis duration 2—19 years (median 7)) with aggressive multiple sclerosis underwent autologous haematopoietic stem cell transplantation. Stem cells were mobilized by high-dose cyclophosphamide and granulocyte colony-stimulating factor, BEAM (carmustine, etoposide, cytarabine, melphalan) was used for immunoablation. Patients were evaluated at baseline and every six months post ASCT for adverse events and clinical outcome. Follow-up period was 11—132 months (median 66). Progression-free survival was calculated using the Kaplan— Meier method. At 3 and 6 years of follow-up 70.8% and 29.2% of patients respectively were free of progression. Patients with relapsing multiple sclerosis course, disease duration <5 years and age <35 years had a more favourable outcome. There was no death within 100 days after ASCT. We conclude that ASCT represents a viable and effective treatment option for aggressive multiple sclerosis.


2004 ◽  
Vol 10 (3) ◽  
pp. 284-289 ◽  
Author(s):  
Kathleen M Healey ◽  
Steven Z Pavletic ◽  
Jinan Al-Omaishi ◽  
M Patricia Leuschen ◽  
Samuel J Pirruccello ◽  
...  

This article describes outcomes in four patients with advanced multiple sclerosis up to two years after autologous haematopoietic stem cell transplantation using a total-body irradiation-based preparative regimen. MRI and C SF analyses demonstrated clear suppression of the inflammatory processes. The results demonstrate however, a dissociation of inflammation parameters and functional disability findings raising questions about optimal future stem cell transplantatio n strategies for this disease.


Brain ◽  
2007 ◽  
Vol 130 (5) ◽  
pp. 1254-1262 ◽  
Author(s):  
I. Metz ◽  
C. F. Lucchinetti ◽  
H. Openshaw ◽  
A. Garcia-Merino ◽  
H. Lassmann ◽  
...  

2017 ◽  
Vol 13 (7) ◽  
pp. 391-405 ◽  
Author(s):  
Paolo A. Muraro ◽  
Roland Martin ◽  
Giovanni Luigi Mancardi ◽  
Richard Nicholas ◽  
Maria Pia Sormani ◽  
...  

2012 ◽  
Vol 18 (6) ◽  
pp. 825-834 ◽  
Author(s):  
R Saccardi ◽  
MS Freedman ◽  
MP Sormani ◽  
H Atkins ◽  
D Farge ◽  
...  

Background: Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of them having been recruited in small, single-centre, phase 1–2 uncontrolled trials. Clinical and magnetic resonance imaging outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted during the relapsing–remitting phase than in those in the secondary progressive stage. Objectives: An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of discussing a controlled clinical trial, to be designed within the new scenarios of evolving MS treatments. Conclusions: Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.


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