Autologous Hematopoietic Stem Cell Transplantation (AHSCT): An Evolving Treatment Avenue in Multiple Sclerosis

References

• Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician. 2004;70(10):1935–1944.
   PubMed Web of Science ®Google Scholar
• Doshi A, Chataway J. Multiple sclerosis, a treatable disease. Clin Med. 2016;16(Suppl 6):s53–s59. doi:10.7861/clinmedicine.16-6-s53
   PubMedGoogle Scholar
• Wallin MT, Culpepper WJ, Nichols E; GBD 2016 Multiple Sclerosis Collaborators. Global, regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(3):269–285. doi:10.1016/S1474-4422(18)30443-5
   PubMed Web of Science ®Google Scholar
• Ahlgren C, Odén A, Lycke J. High nationwide prevalence of multiple sclerosis in Sweden. Mult Scler. 2011;17(8):901–908. doi:10.1177/1352458511403794
   PubMed Web of Science ®Google Scholar
• Bergamaschi R. Prognostic factors in multiple sclerosis. Int Rev Neurobiol. 2007;79:423–447.
   PubMed Web of Science ®Google Scholar
• McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol. 2007;8(9):913–919. doi:10.1038/ni1507
   PubMed Web of Science ®Google Scholar
• Pandit L, Murthy JM. Treatment of multiple sclerosis. Ann Indian Acad Neurol. 2015;50(Suppl 3):S65–S69. doi:10.4103/0972-2327.83094
   Web of Science ®Google Scholar
• Hartung DM, Bourdette DN, Ahmed SM, Whitham RH. The cost of multiple sclerosis drugs in the US and the pharmaceutical industry: too big to fail? Neurology. 2015;84(21):2185–2192. doi:10.1212/WNL.0000000000001608
   PubMed Web of Science ®Google Scholar
• Arneth BM. Impact of B cells to the pathophysiology of multiple sclerosis. J Neuroinflammation. 2019;16(1):128. doi:10.1186/s12974-019-1517-1
   PubMed Web of Science ®Google Scholar
• Kalincik T, Brown JWL, Robertson N, et al. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study. Lancet Neurol. 2017;16(4):271–281. doi:10.1016/S1474-4422(17)30007-8
   PubMed Web of Science ®Google Scholar
• Mancardi G, Sormani MP, Muraro PA, Boffa G, Saccardi R. Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis. Mult Scler. 2018;24(3):245–255. doi:10.1177/1352458517742532
   Web of Science ®Google Scholar
• Atkins HL, Bowman M, Allan D, et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group Phase 2 trial. Lancet. 2016;388(10044):576–585. doi:10.1016/S0140-6736(16)30169-6
   PubMed Web of Science ®Google Scholar
• Curro’ D, Vuolo L, Gualandi F, et al. Low intensity lympho-ablative regimen followed by autologous hematopoietic stem cell transplantation in severe forms of multiple sclerosis: a MRI-based clinical study. Mult Scler. 2015;21(11):1423–1430. doi:10.1177/1352458514564484
   Web of Science ®Google Scholar
• Nash RA, Hutton GJ, Racke MK, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3-year interim report. JAMA Neurol. 2015;72(2):159–169. doi:10.1001/jamaneurol.2014.3780
   PubMed Web of Science ®Google Scholar
• Sharrack B, Saccardi R, Alexander T, et al. Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE). Bone Marrow Transplant. 2020;55(2):283–306. doi:10.1038/s41409-019-0684-0
   PubMed Web of Science ®Google Scholar
• Cohen JA, Baldassari LE, Atkins HL, et al. Autologous hematopoietic cell transplantation for treatment-refractory relapsing multiple sclerosis: position statement from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2019;25(5):845–854. doi:10.1016/j.bbmt.2019.02.014
   PubMed Web of Science ®Google Scholar
• Bertolotto A, Martire S, Mirabile L, Capobianco M, De Gobbi M, Cilloni D. Autologous Hematopoietic Stem Cell Transplantation (AHSCT): standard of care for relapsing-remitting multiple sclerosis patients. Neurol Ther. 2020;9(2):197–203. doi:10.1007/s40120-020-00200-9
   Web of Science ®Google Scholar
• Sormani MP, Snowden JA; European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT) and EBMT (JACIE). Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE). Bone Marrow Transplant. 2020;55(2):283–306.
   Web of Science ®Google Scholar
• Miller AE, Chitnis T, Cohen BA, et al. Autologous hematopoietic stem cell transplant in multiple sclerosis: recommendations of the National Multiple Sclerosis Society. JAMA Neurol. 2021;78(2):241–246. doi:10.1001/jamaneurol.2020.4025
   Web of Science ®Google Scholar
• Passweg J, Baldomero H, Bader P, et al. Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant. 2018;53:1139–1148. doi:10.1038/s41409-018-0153-1
   PubMed Web of Science ®Google Scholar
• Passweg JR, Baldomero H, Basak GW, et al. The EBMT activity survey report 2017: a focus on allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies. Bone Marrow Transplant. 2019;54(10):1575–1585. doi:10.1038/s41409-019-0465-9
   PubMed Web of Science ®Google Scholar
• Snowden JA, Badoglio M, Labopin M, et al. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv. 2017;1:2742–2755. doi:10.1182/bloodadvances.2017010041
   PubMed Web of Science ®Google Scholar
• Fassas A, Anagnostopoulos A, Kazis A, et al. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant. 1997;20:631–638. doi:10.1038/sj.bmt.1700944
   PubMed Web of Science ®Google Scholar
• Burt RK, Traynor AE, Cohen B, et al. T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients. Bone Marrow Transplant. 1998;21:537–541. doi:10.1038/sj.bmt.1701129
   PubMed Web of Science ®Google Scholar
• Zhukovsky C, Sandgren S, Silfverberg T, et al. Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing-remitting multiple sclerosis: an observational study. J Neurol Neurosurg Psychiatry. 2020;jnnp-2020-323992.
   Web of Science ®Google Scholar
• Boffa G, Lapucci C, Sbragia E, et al. Aggressive multiple sclerosis: a single-centre, real-world treatment experience with autologous haematopoietic stem cell transplantation and alemtuzumab. Eur J Neurol. 2020;27(10):2047–2055. doi:10.1111/ene.14324
   Web of Science ®Google Scholar
• Chen B, Zhou M, Ouyang J, et al. Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China. Neurol Sci. 2012;33(4):881–886. doi:10.1007/s10072-011-0859-y
   PubMed Web of Science ®Google Scholar
• Mancardi GL, Sormani MP, Di Gioia M, et al. Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience. Mult Scler. 2012;18(6):835–842. doi:10.1177/1352458511429320
   PubMed Web of Science ®Google Scholar
• Muraro PA, Pasquini M, Atkins HL, et al. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurol. 2017;74(4):459–469. doi:10.1001/jamaneurol.2016.5867
   PubMed Web of Science ®Google Scholar
• Burt RK, Balabanov R, Burman J, et al. Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis: a randomized clinical trial. JAMA. 2019;321(2):165–174. doi:10.1001/jama.2018.18743
   PubMed Web of Science ®Google Scholar
• Patti F. Optimizing the benefit of multiple sclerosis therapy: the importance of treatment adherence. Patient Prefer Adherence. 2010;4:1–9. doi:10.2147/PPA.S8230
   PubMed Web of Science ®Google Scholar
• Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899–910. doi:10.1056/NEJMoa044397
   PubMed Web of Science ®Google Scholar
• Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):911–923. doi:10.1056/NEJMoa044396
   PubMed Web of Science ®Google Scholar
• Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870–1880. doi:10.1056/NEJMoa1107829
   PubMed Web of Science ®Google Scholar
• Kappos L, Radue EW, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387–401.
   PubMed Web of Science ®Google Scholar
• Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–415. doi:10.1056/NEJMoa0907839
   PubMed Web of Science ®Google Scholar
• Sormani MP, Muraro PA, Schiavetti I, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a meta-analysis. Neurology. 2017;88(22):2115–2122. doi:10.1212/WNL.0000000000003987
   PubMed Web of Science ®Google Scholar
• Tolf A, Fagius J, Carlson K, et al. Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation. Acta Neurol Scand. 2019;140(5):320–327. doi:10.1111/ane.13147
   Web of Science ®Google Scholar
• Burman J, Iacobaeus E, Svenningsson A, et al. Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience. J Neurol Neurosurg Psychiatry. 2014;85(10):1116–1121. doi:10.1136/jnnp-2013-307207
   PubMed Web of Science ®Google Scholar
• Mancardi GL, Sormani MP, Gualandi F, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a Phase II trial. Neurology. 2015;84(10):981–988. doi:10.1212/WNL.0000000000001329
   PubMed Web of Science ®Google Scholar
• Burt RK, Balabanov R, Han X, et al. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2015;313(3):275–284. doi:10.1001/jama.2014.17986
   PubMed Web of Science ®Google Scholar
• Moore JJ, Massey JC, Ford CD, et al. Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(5):514–521. doi:10.1136/jnnp-2018-319446
   PubMed Web of Science ®Google Scholar
• Casanova B, Jarque I, Gascón F, et al. Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis. Neurol Sci. 2017;38(7):1213–1221. doi:10.1007/s10072-017-2933-6
   Web of Science ®Google Scholar
• Muraro PA, Martin R, Mancardi GL, Nicholas R, Sormani MP, Saccardi R. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat Rev Neurol. 2017;13(7):391–405. doi:10.1038/nrneurol.2017.81
   PubMed Web of Science ®Google Scholar
• Nash RA, Hutton GJ, Racke MK, et al. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology. 2017;88(9):842–852. doi:10.1212/WNL.0000000000003660
   PubMed Web of Science ®Google Scholar
• Fassas A, Kimiskidis VK, Sakellari I, et al. Long-term results of stem cell transplantation for MS: a single-center experience. Neurology. 2011;76(12):1066–1070. doi:10.1212/WNL.0b013e318211c537
   PubMed Web of Science ®Google Scholar
• Coles AJ, Cohen JA, Fox EJ, et al. Alemtuzumab CARE-MS II 5-year follow-up: efficacy and safety findings. Neurology. 2017;89(11):1117–1126. doi:10.1212/WNL.0000000000004354
   PubMed Web of Science ®Google Scholar
• Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221–234. doi:10.1056/NEJMoa1601277
   PubMed Web of Science ®Google Scholar
• Das J, Sharrack B, Snowden JA. Autologous haematopoietic stem cell transplantation in multiple sclerosis: a review of current literature and future directions for transplant haematologists and oncologists. Curr Hematol Malig Rep. 2019;14(2):127–135. doi:10.1007/s11899-019-00505-z
   PubMed Web of Science ®Google Scholar
• Burt RK, Loh Y, Cohen B, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009;8(3):244–253. doi:10.1016/S1474-4422(09)70017-1
   PubMed Web of Science ®Google Scholar
• Saccardi R, Kozak T, Bocelli-Tyndall C, et al. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12(6):814–823. doi:10.1177/1352458506071301
   PubMed Web of Science ®Google Scholar
• Sharrack B, Saccardi R, Alexander T, et al. Autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis. Exp Hematol. 2012;40(11):892–898. doi:10.1016/j.exphem.2012.07.003
   Web of Science ®Google Scholar
• Shevchenko JL, Kuznetsov AN, Ionova TI, et al. Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician’s and patient’s perspectives. Ann Hematol. 2015;94(7):1149–1157. doi:10.1007/s00277-015-2337-8
   PubMed Web of Science ®Google Scholar
• Dunn-Pirio AM, Heyman BM, Kaufman DS, Kinkel RP. Outcomes and cost-effectiveness of autologous hematopoietic cell transplant for multiple sclerosis. Curr Treat Options Neurol. 2019;21(10):53. doi:10.1007/s11940-019-0588-8
   Web of Science ®Google Scholar
• Hamerschlak N, Rodrigues M, Moraes DA, et al. Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG. Bone Marrow Transplant. 2010;45(2):239–248. doi:10.1038/bmt.2009.127
   Web of Science ®Google Scholar
• Snowden JA, Saccardi R, Allez M, et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012;47(6):770–790. doi:10.1038/bmt.2011.185
   PubMed Web of Science ®Google Scholar
• Ni XS, Ouyang J, Zhu WH, Wang C, Chen B. Autologous hematopoietic stem cell transplantation for progressive multiple sclerosis: report of efficacy and safety at three yr of follow up in 21 patients. Clin Transplant. 2006;20(4):485–489. doi:10.1111/j.1399-0012.2006.00510.x
   PubMed Web of Science ®Google Scholar
• Bowen JD, Kraft GH, Wundes A, et al. Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results. Bone Marrow Transplant. 2012;47(7):946–951. doi:10.1038/bmt.2011.208
   PubMed Web of Science ®Google Scholar
• Burman J, Fransson M, Tötterman TH, Fagius J, Mangsbo SM, Loskog AS. T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis. Immunology. 2013;140(2):211–219. doi:10.1111/imm.12129
   PubMed Web of Science ®Google Scholar
• Darlington PJ, Touil T, Doucet JS, et al. Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation. Ann Neurol. 2013;73(3):341–354. doi:10.1002/ana.23784
   PubMed Web of Science ®Google Scholar
• Karnell FG, Lin D, Motley S, et al. Reconstitution of immune cell populations in multiple sclerosis patients after autologous stem cell transplantation. Clin Exp Immunol. 2017;189(3):268–278. doi:10.1111/cei.12985
   Web of Science ®Google Scholar
• Delemarre EM, van den Broek T, Mijnheer G, et al. Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells. Blood. 2016;127(1):91–101. doi:10.1182/blood-2015-06-649145
   PubMed Web of Science ®Google Scholar
• de Paula A, Sousa A, Malmegrim KC, et al. Autologous haematopoietic stem cell transplantation reduces abnormalities in the expression of immune genes in multiple sclerosis. Clin Sci (Lond). 2015;128(2):111–120. doi:10.1042/CS20140095
   Web of Science ®Google Scholar
• Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704. doi:10.1146/annurev.immunol.26.021607.090331
   PubMed Web of Science ®Google Scholar
• Arruda LC, Lorenzi JC, Sousa AP, et al. Autologous hematopoietic SCT normalizes miR-16, −155 and −142-3p expression in multiple sclerosis patients. Bone Marrow Transplant. 2015;50(3):380–389. doi:10.1038/bmt.2014.277
   PubMed Web of Science ®Google Scholar
• Waschbisch A, Atiya M, Linker RA, Potapov S, Schwab S, Derfuss T. Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis. PLoS One. 2011;6(9):e24604.
   PubMed Web of Science ®Google Scholar
• Keller A, Leidinger P, Steinmeyer F, et al. Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. Mult Scler. 2014;20(3):295–303. doi:10.1177/1352458513496343
   PubMed Web of Science ®Google Scholar
• Bomprezzi R, Ringnér M, Kim S, et al. Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease. Hum Mol Genet. 2003;12(17):2191–2199. doi:10.1093/hmg/ddg221
   PubMed Web of Science ®Google Scholar
• Sharief MK, Douglas M, Noori M, Semra YK. The expression of pro- and anti-apoptosis Bcl-2 family proteins in lymphocytes from patients with multiple sclerosis. J Neuroimmunol. 2002;125(1–2):155–162.
   Web of Science ®Google Scholar
• De Oliveira GL, Ferreira AF, Gasparotto EP, et al. Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation. Clin Exp Immunol. 2017;187(3):383–398. doi:10.1111/cei.12895
   Web of Science ®Google Scholar
• Gosselin D, Rivest S. Immune mechanisms underlying the beneficial effects of autologous hematopoietic stem cell transplantation in multiple sclerosis. Neurotherapeutics. 2011;8(4):643–649. doi:10.1007/s13311-011-0062-0
   Web of Science ®Google Scholar
• Harris KM, Lim N, Lindau P, et al. Extensive intrathecal T cell renewal following hematopoietic transplantation for multiple sclerosis. JCI Insight. 2020;5(2):e127655. doi:10.1172/jci.insight.127655
   Web of Science ®Google Scholar
• Abrahamsson SV, Angelini DF, Dubinsky AN, et al. Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis. Brain. 2013;136(Pt 9):2888–2903. doi:10.1093/brain/awt182
   PubMed Web of Science ®Google Scholar