Autor:innen:
Dr. med. Ilijas Jelcic | Department of Neurology, University Hospital and University of Zurich | Switzerland
PD Dr. med. Antonia Müller | Department of Medical Oncology and Hematology, University Hospital and University of Zurich | Switzerland
Dr. med. Marc Hilty | Department of Neurology, University Hospital and University of Zurich | Switzerland
Dr. med. Ina Reichen | Department of Neurology, University Hospital and University of Zurich | Switzerland
Dr. med. Katja-Daniela Jordan | Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital and University of Zurich | Switzerland
Dr. med. Nathan Wolfensberger | Department of Medical Oncology and Hematology, University Hospital and University of Zurich | Switzerland
Panos Stathopoulos | Department of Neurology, University Hospital and University of Zurich | Switzerland
Josefine Ruder | Department of Neurology, University Hospital and University of Zurich | Switzerland
Prof. Dr. med. Susanne Wegener | Department of Neurology, University Hospital and University of Zurich | Switzerland
Katharina Ritter | Department of Medical Oncology and Hematology, University Hospital and University of Zurich | Switzerland
Dr. Magdalena Foege | Department of Neurology, University Hospital and University of Zurich | Switzerland
Dr. med. Andreas Lutterotti | Department of Neurology, University Hospital and University of Zurich | Switzerland
PD Dr. med. Urs Schanz | Department of Medical Oncology and Hematology, University Hospital and University of Zurich | Switzerland
Prof. Dr. med. Roland Martin | Department of Neurology, University Hospital and University of Zurich | Switzerland
Background and aim: Autologous hematopoietic stem cell transplantation (aHSCT) is used for the treatment of highly active relapsing-remitting or progressive multiple sclerosis (MS) since 1995. Based on strong data regarding efficacy and improved safety of aHSCT in MS, the Swiss Federal Office of Public Health (FOPH) granted approval in June 2018 with the requirement that patients participate in a prospective registry at our center (“aHSCT-in-MS”). We here present the first safety and efficacy data for aHSCT-in-MS in Switzerland.
Methods: Prospective cohort study on 35 MS patients treated with aHSCT at our center according to the BEAM-ATG protocol, because they experienced inflammatory breakthrough activity and/or progression of MS despite highly effective disease-modifying therapy (DMT). For safety analysis, adverse events (AE) of all 35 patients were examined. For efficacy analysis, outcome in 26 patients, who had >12 months of follow-up, was analyzed. Primary outcome was no evidence of disease activity (NEDA), i.e. no relapses, new or contrast-enhancing MRI lesions and clinical progression, defined as progressive worsening of expanded disability status scale (EDSS).
Results: At baseline, median age was 40 years (range 25-54), median disease duration 9.1 years (range 1.6-19.7) and median EDSS 4.8 (2.5-6.5). 15 (42.9%) patients had relapsing-remitting MS, 20 (57.1%) progressive MS. Failure of approved DMT before aHSCT included ocrelizumab (11), rituximab (11), fingolimod (11) and natalizumab (4). Mean post-aHSCT follow-up was 17.5 ± 12.5 months. Most patients developed infectious AE, most frequently mucositis and/or enteritis (29/35) and usually in the first 20 days post-aHSCT. Serious AE occurred in 22/35 patients with consecutive good recovery. 2 patients with secondary progressive MS committed assisted suicide 19 and 23 months post-aHSCT because of subjective perception of progression, although NEDA was confirmed in both cases. NEDA status was achieved in 19/26 (73.1%) patients at last follow-up. After 12 months, we observed sustained EDSS improvement in 14/26 (53.8%) patients, stable EDSS in 6/26 (23.1%) and EDSS-relevant progression in 6/26 (23.1%) patients.
Conclusion: Overall, safety of aHSCT-in-MS is acceptable, and efficacy outcomes are similar to other aHSCT studies and better than approved DMT. However, aHSCT-in-MS requires thorough psychiatric evaluation, vigilant monitoring (especially regarding infectious AE) and antimicrobial prophylaxis.