Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline

Antonios Bayas; Achim Berthele; Norbert Blank; Peter Dreger; Simon Faissner; Manuel A Friese; Lisa-Ann Gerdes; Oliver Martin Grauer; Vivien Häussler; Christoph Heesen; Dietlinde Janson; Mirjam Korporal-Kuhnke; Markus Kowarik; Nikolaus Kröger; Jan D Lünemann; Roland Martin; Uwe Meier; Sven Meuth; Paolo Muraro; Michael Platten; Lucas Schirmer; Klarissa Hanja Stürner; Jan Patrick Stellmann; Christof Scheid; Florian Then Bergh; Clemens Warnke; Brigitte Wildemann; Tjalf Ziemssen

doi:10.1177/17562864231180730

Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline

Ther Adv Neurol Disord. 2023 Sep 28:16:17562864231180730. doi: 10.1177/17562864231180730. eCollection 2023.

Authors

Antonios Bayas¹, Achim Berthele², Norbert Blank³, Peter Dreger⁴, Simon Faissner⁵, Manuel A Friese⁶, Lisa-Ann Gerdes⁷, Oliver Martin Grauer⁸, Vivien Häussler⁹, Christoph Heesen^{10

11}, Dietlinde Janson¹², Mirjam Korporal-Kuhnke¹³, Markus Kowarik¹⁴, Nikolaus Kröger¹², Jan D Lünemann¹⁵, Roland Martin¹⁶, Uwe Meier¹⁷, Sven Meuth¹⁸, Paolo Muraro¹⁹, Michael Platten²⁰, Lucas Schirmer²⁰, Klarissa Hanja Stürner²¹, Jan Patrick Stellmann²², Christof Scheid²³, Florian Then Bergh²⁴, Clemens Warnke²⁵, Brigitte Wildemann¹³, Tjalf Ziemssen²⁶

Affiliations

¹ Department of Neurology and Clinical Neurophysiology, Faculty of Medicine, University of Augsburg, Augsburg.
² Department of Neurology, School of Medicine, Technical University of Munich, Munich.
³ Rheumatology Section, Interdisciplinary Centre for Chronic Inflammatory Diseases, Heidelberg University Hospital, Heidelberg.
⁴ Spokesman German Working Group for Haematopoietic Stem Cell Transplantation and Cellular Therapy e.V., Heidelberg University Hospital, Heidelberg.
⁵ Department of Neurology, University Hospital of Ruhr-University Bochum, St. Josef-Hospital, Bochum.
⁶ Institute of Neuroimmunology and Multiple Sclerosis (INIMS) and Department of Neurology, University Medical Center Hamburg-Eppendorf.
⁷ Institut für Klinische Neuroimmunologie am Klinikum der Ludwig-Maximilians-Universität München, München.
⁸ Department of Neurology with Institute for Translational Neurology, University Hospital Münster, Münster.
⁹ Institute of Neuroimmunology and Multiple Sclerosis (INIMS) and Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg.
¹⁰ Institute of Neuroimmunology and Multiple Sclerosis (INIMS) and Department of Neurology University Medical Center Hamburg-Eppendorf.
¹¹ Clinical and Rehabilitative MS Research, Institute for Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Hamburg-Eppendorf (UKE), Martinistrasse 52, D-20246 Hamburg, Germany.
¹² Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg.
¹³ AG Neuroimmunology, Neurological Clinic, Heidelberg University Hospital, Heidelberg.
¹⁴ Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls University of Tübingen, Tübingen, Kröger.
¹⁵ Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster.
¹⁶ Institute of Experimental Neurology, University Hospital Zurich, Zurich, Switzerland.
¹⁷ Chairman of the Professional Association of German Neurologists, Neurocentrum Grevenbroich, Grevenbroich.
¹⁸ Medical Faculty, Department of Neurology, University Hospital Düsseldorf, Düsseldorf.
¹⁹ Department of Brain Sciences, Imperial College London, London, UK.
²⁰ Department of Neurology, Mannheim Center for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Heidelberg.
²¹ Department of Neurology, Christian-Albrechts-Universität Kiel, Kiel.
²² Centre de Résonance Magnétique Biologique et Médicale, Aix-Marseille Université, Marseille.
²³ Clinic I for Internal Medicine, University Hospital Cologne, Cologne.
²⁴ Clinic and Polyclinic for Neurology, University of Leipzig, Leipzig.
²⁵ University of Cologne, Faculty of Medicine and University Hospital Cologne, Clinic and Polyclinic of Neurology, Cologne.
²⁶ Center of Clinical Neuroscience, Department of Neurology, University Clinic Carl Gustav Carus Dresden, Technische Universität Dresden.

Abstract

Background: While substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS), a high percentage of treated patients still show progression and persistent inflammatory activity. Autologous haematopoietic stem cell transplantation (AHSCT) aims at eliminating a pathogenic immune repertoire through intense short-term immunosuppression that enables subsequent regeneration of a new and healthy immune system to re-establish immune tolerance for a long period of time. A number of mostly open-label, uncontrolled studies conducted over the past 20 years collected about 4000 cases. They uniformly reported high efficacy of AHSCT in controlling MS inflammatory disease activity, more markedly beneficial in relapsing-remitting MS. Immunological studies provided evidence for qualitative immune resetting following AHSCT. These data and improved safety profiles of transplantation procedures spurred interest in using AHSCT as a treatment option for MS.

Objective: To develop expert consensus recommendations on AHSCT in Germany and outline a registry study project.

Methods: An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of virtual meetings.

Results: We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS based on the Swiss criteria. Current data indicate that patients who are most likely to benefit from AHSCT have relapsing-remitting MS and are young, ambulatory and have high disease activity. Treatment data with AHSCT will be collected within the German REgistry Cohort of autologous haematopoietic stem CeLl trAnsplantation In MS (RECLAIM).

Conclusion: Further clinical trials, including registry-based analyses, are urgently needed to better define the patient characteristics, efficacy and safety profile of AHSCT compared with other high-efficacy therapies and to optimally position it as a treatment option in different MS disease stages.

Keywords: Autologous haematopoietic stem cell transplantation (AHSCT); multiple sclerosis; registry study; treatment recommendation.

Plain language summary

Autologous haematopoietic stem cell transplantation for multiple sclerosis Substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS) during the last 20 years. However, in a relevant percentage of patients, the disease cannot completely be contained. Autologous haematopoietic stem cell transplantation (AHSCT) enables rebuilding of a new and healthy immune system and to potentially stop the autoimmune disease process for a long time. A number of studies documenting 4000 cases cumulatively over the past 20 years reported high efficacy of AHSCT in controlling MS inflammatory disease activity. These data and improved safety profiles of the treatment procedures spurred interest in using AHSCT as a treatment option for MS. An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of video calls to develop recommendations and outline a registry study project. We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS. Current data indicate that patients are most likely to benefit from AHSCT if they are young, ambulatory, with high disease activity, that is, relapses or new magnetic resonance imaging (MRI) lesions. Treatment data with AHSCT will be collected within the German REgistry Cohort of autoLogous haematopoietic stem cell transplantation MS (RECLAIM). Further clinical trials including registry-based analyses and systematic follow-up are urgently needed to better define the optimal patient characteristics as well as the efficacy and safety profile of AHSCT compared with other high-efficacy therapies. These will help to position AHSCT as a treatment option in different MS disease stages.