Immunoablative therapy followed by autologous hematopoietic stem cell transplantation as the first-line disease-modifying therapy in patients with multiple sclerosis
Language English Country Czech Republic Media print-electronic
Document type Journal Article
PubMed
37337857
DOI
10.5507/bp.2023.023
Knihovny.cz E-resources
- Keywords
- autologous hematopoietic stem cell transplantation, immunoablative therapy, multiple sclerosis,
- MeSH
- Humans MeSH
- Transplantation Conditioning methods MeSH
- Recurrence MeSH
- Multiple Sclerosis * therapy etiology MeSH
- Hematopoietic Stem Cell Transplantation * adverse effects methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Immunoablative therapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is one of the possible disease-modifying therapies (DMTs) for patients with multiple sclerosis (MS). In this case series, we would like to present six patients with MS, who underwent AHSCT as the first-line DMT. CASE REPORTS: Six MS patients with a rapid progression of disability with or without relapses underwent AHSCT as the first-line DMT at the University Hospital Ostrava between 2018 and 2021. The conditioning regimens for AHSCT used were a medium-intensity regime BEAM (Carmustine, Etoposid, Cytarabin, Melphalan) and low-intensity regime based on Cyclophosphamide. Four out of six patients showed some disability progression after AHSCT, so the rapid progression of MS was just slowed down by AHSCT. One patient developed activity on magnetic resonance imaging three months after AHSCT, and two experienced mild relapses during the follow-up period. None of our patients developed grade 4 non-hematological toxicity; all infections were mild. In one patient, an allergic reaction probably to dimethyl sulfoxide was observed. CONCLUSION: Our case series of 6 patients shows that AHSCT is a promising therapeutic approach to slow down the rapid progression of clinical disability in MS patients with a good safety profile.
Department of Clinical Neurosciences Faculty of Medicine University of Ostrava Czech Republic
Department of Hematooncology Faculty of Medicine University of Ostrava Czech Republic
Department of Hematooncology University Hospital Ostrava Czech Republic
Department of Neurology University Hospital Ostrava Czech Republic
See more in PubMed
Montalban X, Gold R, Thompson AJ, Otero-Romero S, Amato MP, Chandraratna D, Clanet M, Comi G, Derfuss T, Fazekas F, Hartung HP, Havrdova E, Hemmer B, Kappos L, Liblau R, Lubetzki C, Marcus E, Miller DH, Olsson T, Pilling S, Selmaj K, Siva A, Sorensen PS, Sormani MP, Thalheim C, Wiendl H, Zipp F. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler 2018;24(2):96-120. DOI
Piehl F. Current and emerging disease-modulatory therapies and treatment targets for multiple sclerosis. Intern Med 2021;289(6):771-91. DOI
Havrdova E, Pitha J, Nytrova P, Liba Z. Česká neurologická společnost ČLS JEP. KKNEU0031 - Klinický doporučený postup pro diagnostiku a léčbu roztroušené sklerózy a neuromyelitis optica a onemocnění jejího širšího spektra, verze 2.0. 2020 Mar. Available from: https://www.czech-neuro.cz/content/uploads/2020/04/rs_odborna-2.0_final_pub_web-2.pdf. (In Czech)
Arrambide G, Iacobaeus E, Amato MP, Derfuss T, Vukusic S, Hemmer B, Brundin L, Tintore M; 2018 ECTRIMS Focused Workshop Group. Aggressive multiple sclerosis (2): Treatment. Mult Scler 2020;26(9):1045-63. DOI
Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med 2017;376(3):221-34. DOI
Gärtner J, Hauser SL, Bar-Or A, Montalban X, Cohen JA, Cross AH, Deiva K, Ganjgahi H, Häring DA, Li B, Pingili R, Ramanathan K, Su W, Willi R, Kieseier B, Kappos L. Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II. Mult Scler 2022;28(10):1562-75. DOI
Das J, Snowden JA, Burman J, Freedman MS, Atkins H, Bowman M, Burt RK, Saccardi R, Innocenti C, Mistry S, Laud PJ, Jessop H, Sharrack B. Autologous haematopoietic stem cell transplantation as a first-line disease-modifying therapy in patients with 'aggressive' multiple sclerosis. Mult Scler 2021;27(8):1198-204. DOI
Sormani MP, Muraro PA, Schiavetti I, Signori A, Laroni A, Saccardi R, Mancardi GL. Autologous hematopoietic stem cell transplantation in multiple sclerosis: A meta-analysis. Neurology 2017; 88(22):2115-22. DOI
Burt RK, Balabanov R, Han X, Sharrack B, Morgan A, Quigley K, Yaung K, Helenowski IB, Jovanovic B, Spahovic D, Arnautovic I, Lee DC, Benefield BC, Futterer S, Oliveira MC, Burman J. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA 2015;313(3):275-84. DOI
Carreras E, Dufour C, Mohty M, Kröger N, editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th ed. Cham (CH): Springer; 2019. DOI
Häußler V, Ufer F, Pöttgen J, Wolschke C, Friese MA, Kröger N, Heesen C, Stellmann JP. aHSCT is superior to alemtuzumab in maintaining NEDA and improving cognition in multiple sclerosis. Ann Clin Transl Neurol 2021;8(6):1269-78. DOI
Zhukovsky C, Sandgren S, Silfverberg T, Einarsdottir S, Tolf A, Landtblom AM, Novakova L, Axelsson M, Malmestrom C, Cherif H, Carlson K, Lycke J, Burman J. Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing-remitting multiple sclerosis: an observational study. J Neurol Neurosurg Psychiatry 2021;92(2):189-94. DOI
Boffa G, Lapucci C, Sbragia E, Varaldo R, Raiola AM, Currò D, Roccatagliata L, Capello E, Laroni A, Mikulska M, Gualandi F, Uccelli A, Angelucci E, Mancardi GL, Inglese M. Aggressive multiple sclerosis: a single-centre, real-world treatment experience with autologous haematopoietic stem cell transplantation and alemtuzumab. Eur J Neurol 2020;27(10):2047-55. DOI
Windrum P, Morris TC, Drake MB, Niederwieser D, Ruutu T; EBMT Chronic Leukaemia Working Party Complications Subcommittee. Variation in dimethyl sulfoxide use in stem cell transplantation: A survey of EBMT centres. Bone Marrow Transplant 2005;36(7):601-3. DOI