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Multiple Sclerosis => TREATMENTS => Topic started by: agate on April 11, 2017, 11:06:07 am

Title: (Abst.) Long-term outcomes after AHSCT for MS [5-year study of 281 PwMS]
Post by: agate on April 11, 2017, 11:06:07 am
From JAMA Neurology (April 2017):

Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

Paolo A. Muraro, MD1; Marcelo Pasquini, MD2; Harold L. Atkins, MD3; James D. Bowen, MD4; Dominique Farge, MD5; Athanasios Fassas, MD6; Mark S. Freedman, MD7; George E. Georges, MD8; Francesca Gualandi, MD9; Nelson Hamerschlak, MD10; Eva Havrdova, MD11; Vassilios K. Kimiskidis, MD12; Tomas Kozak, MD13; Giovanni L. Mancardi, MD14; Luca Massacesi, MD15; Daniela A. Moraes, MD16; Richard A. Nash, MD17; Steven Pavletic, MD18; Jian Ouyang, MD19; Montserrat Rovira, MD20; Albert Saiz, MD21; Belinda Simoes, MD16; Marek Trněný, MD22; Lin Zhu, MD23; Manuela Badoglio, MSc24; Xiaobo Zhong, MS2; Maria Pia Sormani, PhD25; Riccardo Saccardi, MD26; for the Multiple Sclerosis–Autologous Hematopoietic Stem Cell Transplantation (MS-AHSCT) Long-term Outcomes Study Group

Author Affiliations

1Division of Brain Sciences, Imperial College London, London, England
2Center for International Blood and Marrow Transplant Research, Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee
3Clinical Hematology, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
4Multiple Sclerosis Center, Swedish Neuroscience Institute, Seattle, Washington
5Internal Medicine, Autoimmune and Vascular Diseases Unit, Unité Fonctionnelle 04, Assistance Publique–Hôpitaux de Paris Saint-Louis Hospital, Institut National de la Santé et de la Récherche Médicale Unité Mixte de Recherche 1160, Paris, France
6Department of Hematology, Aristotle University of Thessaloniki, Thessaloniki, Greece
7Division of Neurology, Department of Medicine, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
8Fred Hutchinson Cancer Research Center and University of Washington, Seattle
9Bone Marrow Transplantation Unit, San Martino Hospital, Genova, Italy
10Bone Marrow Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
11Department of Neurology, First Medical Faculty, Charles University, Prague, Czech Republic
12Laboratory of Clinical Neurophysiology, Aristotle University of Thessaloniki, Thessaloniki, Greece
13Department of Internal Medicine and Haematology, Third Faculty of Medicine, Charles University and Faculty Hospital Kralovske Vinohrady, Prague, Czech Republic
14Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genova, Italy
15Department of Neurosciences, Careggi University Hospital, University of Florence, Firenze, Italy
16Department of Clinical Medicine, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil
17Colorado Blood Cancer Institute, Denver
18Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
19Department of Hematology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
20Hematology Service, Hospital Clinic and Neurology Service, Universitat de Barcelona, Barcelona, Spain
21Hospital Clinic and Institut d’Investigació August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
22Department of Medicine, Charles University General Hospital, Prague, Czech Republic
23Drum Tower Hospital of Nanjing Medical University, Nanjing, China
24European Blood and Marrow Transplant Paris Office, Hôpital Saint Antoine, Paris, France
25Biostatistics Unit, University of Genoa, Genova, Italy
26Haematology Department, Careggi University Hospital, Firenze, Italy


In this multicenter cohort study of 281 patients with predominantly progressive forms of multiple sclerosis who underwent autologous hematopoietic stem cell transplant between 1995 and 2006, transplant-related mortality was 2.8% within 100 days of transplant, and neurological progression-free survival was 46% at 5 years. Younger age, relapsing form of multiple sclerosis, fewer prior immunotherapies, and lower neurological disability score were significantly associated with better outcomes.


The results support the rationale for further randomized clinical trials of autologous hematopoietic stem cell transplantation for the treatment of multiple sclerosis.


Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies.


To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.

Design, Setting, and Participants 

Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015.


Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen.

Main Outcomes and Measures

The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models.


Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality.

The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years.

Factors associated with neurological progression after transplant were older age (hazard ratio
, 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95).

Conclusions and Relevance 

In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS. (
Title: Long-term outcomes after HSCT in MS (MS International Federation)
Post by: agate on May 08, 2017, 11:36:24 am
This study is discussed in this article, "Long-term outcomes after HSCT in MS" from the MS International Federation (May 8, 2017): (
Title: Re: (Abst.) Long-term outcomes after AHSCT for MS [5-year study of 281 PwMS]
Post by: agate on June 18, 2017, 04:06:52 pm
An article by some of the same authors, in Nature abstracted in PubMed, June 18, 2017:

Nat Rev Neurol. 2017 Jun 16.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

Muraro PA1, Martin R2, Mancardi GL3,4, Nicholas R1, Sormani MP5, Saccardi R6.

Author information
Division of Brain Sciences, Imperial College London, Burlington Danes Building, 190 Du Cane Road, London W12 0NN, UK.
Neuroimmunology and Multiple Sclerosis Research, Neurology Clinic, University Hospital Zurich, University Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Largo Paolo Daneo 3, 16145 Genova, Italy.
Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genoa, Italy.
Biostatistics Unit, Department of Health Sciences (DISSAL), University of Genoa, Via Pastore 1, 16132, Genova, Italy.
Cell Therapy and Transfusion Medicine Unit, Careggi University Hospital, Largo Brambilla, 3-50134 Firenze, Italy.

Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders.

Results from ∼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers.

Indeed, studies have demonstrated that AHSCT can entirely suppress MS disease activity for 4-5 years in 70-80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005.

Current evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity. Clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of AHSCT against highly active MS drugs.