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)

Basil Sharrack, Riccardo Saccardi, Tobias Alexander, Manuela Badoglio, Joachim Burman, Dominique Farge, Raffaella Greco, Helen Jessop, Majid Kazmi, Kirill Kirgizov, Myriam Labopin, Gianluigi Mancardi, Roland Martin, John Moore, Paolo A Muraro, Montserrat Rovira, Maria Pia Sormani, John A Snowden, 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), John Snowden, Riccardo Saccardi, Eoin McGrath, Franco Bambi, Fermín Sanchez-Guijo, Nina Worel, John Snowden, Tobias Alexander, Manuela Badolglio, Mario Abinun, Renate Arnold, Charlotte Brierley, Joachim Burman, Cristina Castilla-Llorente, Nichola Cooper, Thomas Daikeler, Nicoletta Del Papa, Dominique Farge, Jurgen Finke, Raffaella Greco, Hans Hagglund, Joerg Henes, Falk Hiepe, Helen Jessop, David Kiely, Myriam Labopin, Majid Kazmi, Kirill Kirgizov, Gianluigi Mancardi, Zora Marjanovic, Roland Martin, Thierry Martin, David Ma, John Moore, Paul Miller, Paolo Muraro, Maria-Carolina Oliveira, Alexey Polushin, Francesco Onida, Belinda Simoes, Mathieu Puyade, Igor Resnick, Montserrat Rovira, Riccardo Saccardi, Muhammad Saif, Ioanna Sakellari, Basil Sharrack, Emilian Snarski, Hans Ulrich Scherer, Claudia Sossa, Jeska de Vries-Bouwstra, Nico Wulffraat, Eleanora Zaccara, Basil Sharrack, Riccardo Saccardi, Tobias Alexander, Manuela Badoglio, Joachim Burman, Dominique Farge, Raffaella Greco, Helen Jessop, Majid Kazmi, Kirill Kirgizov, Myriam Labopin, Gianluigi Mancardi, Roland Martin, John Moore, Paolo A Muraro, Montserrat Rovira, Maria Pia Sormani, John A Snowden, 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), John Snowden, Riccardo Saccardi, Eoin McGrath, Franco Bambi, Fermín Sanchez-Guijo, Nina Worel, John Snowden, Tobias Alexander, Manuela Badolglio, Mario Abinun, Renate Arnold, Charlotte Brierley, Joachim Burman, Cristina Castilla-Llorente, Nichola Cooper, Thomas Daikeler, Nicoletta Del Papa, Dominique Farge, Jurgen Finke, Raffaella Greco, Hans Hagglund, Joerg Henes, Falk Hiepe, Helen Jessop, David Kiely, Myriam Labopin, Majid Kazmi, Kirill Kirgizov, Gianluigi Mancardi, Zora Marjanovic, Roland Martin, Thierry Martin, David Ma, John Moore, Paul Miller, Paolo Muraro, Maria-Carolina Oliveira, Alexey Polushin, Francesco Onida, Belinda Simoes, Mathieu Puyade, Igor Resnick, Montserrat Rovira, Riccardo Saccardi, Muhammad Saif, Ioanna Sakellari, Basil Sharrack, Emilian Snarski, Hans Ulrich Scherer, Claudia Sossa, Jeska de Vries-Bouwstra, Nico Wulffraat, Eleanora Zaccara

Abstract

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials.

Conflict of interest statement

JAS declares speaker fees at educational events supported by Sanofi, Janssen, Jazz, Mallinckrodt and Gilead, is a member of a trial IDMC for Kiadis Pharma and Chairs NHS England Clinical Reference Group (CRG) for Blood and Marrow Transplantation. RM has received personal remuneration for advisory functions and presentations by Merck, Teva, Sanofi, Novartis, Roche, Biogen, Cell Protect and Neuway Pharma. He is a co-founder and co-owner of Cellerys. PAM reports personal fees and non-financial support from Bayer, Biogen, Merck and Novartis, unrelated to the manuscript. PAM, BS and JS are grateful for support from the UK NIHR EME and Biomedical Research Centre funding schemes. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
EBMT ADWP activity—autologous HSCT for MS, other immune-mediated neurological diseases and other autoimmune diseases by year, 1994–2018 (N = 2766)
Fig. 2
Fig. 2
EBMT registry: overall national activity in autologous HSCT indicated for MS, other immune-mediated neurological diseases and other autoimmune diseases by country, 1994–2018 (N = 2766)
Fig. 3
Fig. 3
EBMT registry: relative activity according to reported multiple sclerosis type: RR-MS versus progressive MS (SPMS/PPMS) versus aggressive/malignant MS
Fig. 4
Fig. 4
Trends in transplant conditioning used for autologous HSCT in Multiple Sclerosis: BEAM-ATG versus Cy-ATG (EBMT Registry 1995–2018)

References

    1. Compston A, Coles A. Multiple sclerosis. Lancet. 2002;359:1221–31. doi: 10.1016/S0140-6736(02)08220-X.
    1. Mackenzie I, Morant S, Bloomfield G, MacDonald T, O’Riordan J. Incidence and prevalence of multiple sclerosis in the UK 1990-2010: a descriptive study in the General Practice Research Database. J Neurol Neurosurg Psychiatry. 2013;85:76–84. doi: 10.1136/jnnp-2013-305450.
    1. Moccia M, Palladino R, Lanzillo R, Carotenuto A, Russo C, Triassi M, et al. Healthcare costs for treating relapsing multiple sclerosis and the risk of progression: a retrospective Italian cohort study from 2001 to 2015. PLoS One. 2017;12:e0169489. doi: 10.1371/journal.pone.0169489.
    1. Lublin F, Reingold S, Cohen J, Cutter G, Sorensen P, Thompson A, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83:278–86. doi: 10.1212/WNL.0000000000000560.
    1. Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, et al. Evidence for a two-stage disability progression in multiple sclerosis. Brain. 2010;133:1900–13. doi: 10.1093/brain/awq076.
    1. Menon S, Shirani A, Zhao Y, Oger J, Traboulsee A, Freedman M, et al. Characterising aggressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013;84:1192–8. doi: 10.1136/jnnp-2013-304951.
    1. Kurtzke J. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) Neurology. 1983;33:1444–52. doi: 10.1212/WNL.33.11.1444.
    1. Giovannoni G, Turner B, Gnanapavan S, Offiah C, Schmierer K, Marta M. Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord. 2015;4:329–33. doi: 10.1016/j.msard.2015.04.006.
    1. Scolding N, Barnes D, Cader S, Chataway J, Chaudhuri A, Coles A, et al. Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol. 2015;15:273–9. doi: 10.1136/practneurol-2015-001139.
    1. Rotstein D, Healy B, Malik M, Chitnis T, Weiner H. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol. 2015;72:152–8. doi: 10.1001/jamaneurol.2014.3537.
    1. Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, EXPAND clinical investigators Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391:1263–73. doi: 10.1016/S0140-6736(18)30475-6.
    1. Montalban X, Hauser S, Kappos L, Arnold D, Bar-Or A, Comi G, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. New Engl J Med. 2017;376:209–20. doi: 10.1056/NEJMoa1606468.
    1. Kelsey P, Oliveira M, Badoglio M, Sharrack B, Farge D, Snowden JA. Haematopoietic stem cell transplantation in autoimmune diseases: From basic science to clinical practice. Curr Res Transl Med. 2016;64:71–82. doi: 10.1016/j.retram.2016.03.003.
    1. Bell S, Sharrack B, Snowden JA. Hematopoietic cell transplantation in multiple sclerosis. Curr Opin Biol Therapies. 2016;14:1–10.
    1. Muraro P, Pasquini M, Atkins H, Bowen J, Farge D, Fassas A, et al. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurol. 2017;74:459–69. doi: 10.1001/jamaneurol.2016.5867.
    1. Muraro P, Martin R, Mancardi G, Nicholas R, Sormani M, Saccardi R. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nature Rev Neurol. 2017;13:391–405. doi: 10.1038/nrneurol.2017.81.
    1. Burman J, Tolf A, Hägglund H, Askmark H. Autologous haematopoietic stem cell transplantation for neurological diseases. J Neurol Neurosurg Psychiatry. 2017;89:147–55. doi: 10.1136/jnnp-2017-316271.
    1. Alexander T, Farge D, Badoglio M, Lindsay J, Muraro P, Snowden JA. Hematopoietic stem cell therapy for autoimmune diseases—clinical experience and mechanisms. J Autoimmun. 2018;92:35–46. doi: 10.1016/j.jaut.2018.06.002.
    1. Snowden JA, Sharrack B, Akil M, Kiely D, Lobo A, Kazmi M, et al. Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases—a guide for the generalist. Clin Med. 2018;18:329–34. doi: 10.7861/clinmedicine.18-4-329.
    1. 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;14:127–35. doi: 10.1007/s11899-019-00505-z.
    1. Snowden JA, Badoglio M, Labopin M, Giebel S, McGrath E, Marjanovic Z, European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP); EBMT Paediatric Working Party (PWP); Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT); EBMT (JACIE) et al. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv. 2017;1:2742–55. doi: 10.1182/bloodadvances.2017010041.
    1. Passweg J, Baldomero H, Bader P, Basak G, Bonini C, Duarte R, 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;53:1139–48. doi: 10.1038/s41409-018-0153-1.
    1. Passweg J, Baldomero H, Basak G, Chabannon C, Corbacioglu S, Duarte R, 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. 10.1038/s41409-019-0465-9.
    1. Greco R, Labopin M, Badoglio M, Veys P, Furtado Silva J, Abinun M, et al. Allogeneic HSCT for autoimmune diseases: a retrospective study from the EBMT ADWP, IEWP, and PDWP Working Parties. Front Immunol. 2019;10:1570. doi: 10.3389/fimmu.2019.01570.
    1. Tyndall A, Gratwohl A. Blood and marrow stem cell transsplants in auto-immune disease: a consensus report written on behalf of the European League against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT) Bone Marrow Transplant. 1997;19:643–5. doi: 10.1038/sj.bmt.1700727.
    1. Snowden JA, Saccardi R, Allez M, Ardizzone S, Arnold R, Cervera R, et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012;47:770–90. doi: 10.1038/bmt.2011.185.
    1. Duarte R, Labopin M, Bader P, Basak G, Bonini C, Chabannon C, et al. Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant. 2019. (In press).
    1. Jessop H, Farge D, Saccardi R, Alexander T, Rovira M, Sharrack B, et al. General information for patients and carers considering haematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (ADs): a position statement from the EBMT Autoimmune Diseases Working Party (ADWP), the EBMT Nurses Group, the EBMT Patient, Family and Donor Committee and the Joint Accreditation Committee of ISCT and EBMT (JACIE) Bone Marrow Transplant. 2019;54:933–42. doi: 10.1038/s41409-019-0430-7.
    1. Fassas A, Anagnostopoulos A, Kazis A, Kapinas K, Sakellari I, Kimiskidis V, et al. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant. 1997;20:631–8. doi: 10.1038/sj.bmt.1700944.
    1. Burt RK, Traynor AE, Cohen B, Karlin KH, Davis FA, Stefoski D, et al. T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients. Bone Marrow Transplant. 1998;21:537–41. doi: 10.1038/sj.bmt.1701129.
    1. Mancardi G, Sormani M, Gualandi F, Saiz A, Carreras E, Merelli E, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology. 2015;84:981–8. doi: 10.1212/WNL.0000000000001329.
    1. Burt R, Loh Y, Cohen B, Stefosky D, Balabanov R, Katsamakis G, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009;8:244–53. doi: 10.1016/S1474-4422(09)70017-1.
    1. Burt R, Balabanov R, Han X, Sharrack B, Morgan A, Quigley K, et al. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2015;313:275–84. doi: 10.1001/jama.2014.17986.
    1. Atkins H, Bowman M, Allan D, Anstee G, Arnold D, Bar-Or A, et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016;388:576–85. doi: 10.1016/S0140-6736(16)30169-6.
    1. Nash R, Hutton G, Racke M, Popat U, Devine S, Steinmiller K, et al. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology. 2017;88:842–52. doi: 10.1212/WNL.0000000000003660.
    1. Mancardi G, Sormani M, Di Gioia M, Vuolo L, Gualandi F, Amato M, et al. Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience. Mult Scler J. 2012;18:835–42. doi: 10.1177/1352458511429320.
    1. Burman J, Iacobaeus E, Svenningsson A, Lycke J, Gunnarsson M, Nilsson P, et al. Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience. J Neurol Neurosurg Psychiatry. 2014;85:1116–21. doi: 10.1136/jnnp-2013-307207.
    1. Shevchenko J, Kuznetsov A, Ionova T, Melnichenko V, Fedorenko D, Kurbatova K, 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;94:1149–57. doi: 10.1007/s00277-015-2337-8.
    1. Sormani M, Muraro P, Saccardi R, Mancardi G. NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs. Mult Scler J. 2017;12:201–4. doi: 10.1177/1352458516645670.
    1. Sormani M, Muraro P, Schiavetti I, Signori A, Laroni A, Saccardi R, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis. Neurology. 2017;88:2115–22. doi: 10.1212/WNL.0000000000003987.
    1. Burt R, Balabanov R, Burman J, Sharrack B, Snowden J, Oliveira M, et al. Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis. JAMA. 2019;321:165–74. doi: 10.1001/jama.2018.18743.
    1. Burt RK, et al. Non-myeloablative haematopoietic stem cell transplantation (HSCT) versus disease modifying therapies (DMT) in patients with highly active Relapsing Remitting Multiple Sclerosis (RRMS) (abstract). Bone Marrow Transplant. 2019;53:13–4.
    1. Gelfand JM, Cree BAC, Hauser SL. Ocrelizumab and other CD20+ b-cell-depleting therapies in multiple sclerosis. Neurotherapeutics. 2017;4:835–41. doi: 10.1007/s13311-017-0557-4.
    1. Coles AJ, Cohen JA, Fox EJ, Giovannoni G, Hartung HP, Havrdova E, et al. CARE-MS II and CAMMS03409 Investigators. Alemtuzumab CARE-MS II 5-year follow-up: efficacy and safety findings. Neurology. 2017;89:1117–26. doi: 10.1212/WNL.0000000000004354.
    1. Havrdová E, Arnold D, Bar-Or A, Comi G, Hartung H, Kappos L, et al. No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a. Mult Scler J Exp Transl Clin. 2018;4:205521731876064.
    1. Burt R, Balabanov R, Voltarelli J, Barreira A, Burman J. Autologous hematopoietic stem cell transplantation for multiple sclerosis—if confused or hesitant, remember: ‘Treat with standard immune suppressive drugs and if no inflammation, no response’. Mult Scler J. 2012;18:772–5. doi: 10.1177/1352458512442993.
    1. Mancardi G, Sormani M, Muraro P, Boffa G, Saccardi R. Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis. Mult Scl J. 2018;24:245–55. doi: 10.1177/1352458517742532.
    1. Cohen J, Baldassari L, Atkins H, Bowen J, Bredeson C, Carpenter P, 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;25:845–54. doi: 10.1016/j.bbmt.2019.02.014.
    1. Kaunzner U, Kumar G, Askin G, Gauthier S, Nealon N, Vartanian T, et al. A study of patients with aggressive multiple sclerosis at disease onset. Neuropsychiatr Dis Treat. 2016;12:1907–12. doi: 10.2147/NDT.S111885.
    1. Alix J, Blackburn D, Sokhi D, Craven I, Sharrack B, Snowden J. Autologous hematopoietic stem cell transplantation following pulsed cyclophosphamide in a severely disabled patient with malignant multiple sclerosis. J Neurol. 2013;260:914–6. doi: 10.1007/s00415-012-6796-8.
    1. Mancardi G, Murialdo A, Rossi P, Gualandi F, Martino G, Marmont A, et al. Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Mult Scler J. 2005;11:367–71. doi: 10.1191/1352458505ms1181cr.
    1. Das J, Snowden J, Burman J, Freedman M, Atkins H, Bowman M. The use of autologous haematopoietic stem cell transplantation as a first line disease modifying therapy in patients with ‘aggressive’ multiple sclerosis. Mult Scler. 2018;24:87–88.
    1. Casanova B, Jarque I, Gascón F, Hernández-Boluda J, Pérez-Miralles F, de la Rubia J, et al. Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis. Neurological Sci. 2017;38:1213–21. doi: 10.1007/s10072-017-2933-6.
    1. Hawker K, O’Connor P, Freedman M, Calabresi P, Antel J, Simon J, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009;66:460–71. doi: 10.1002/ana.21867.
    1. Tur C, Montalban X, Tintore M, Nos C, Rio J, Aymerich F, et al. Interferon beta-1b for the treatment of primary progressive multiple sclerosis: five-year clinical trial follow-up. Arch Neurol. 2011;68:1421–7. doi: 10.1001/archneurol.2011.241.
    1. Otallah S, Banwell B pediatric multiple sclerosis: an update. Current Neurol Neurosci Reports. 2018;18. 10.1007/s11910-018-0886-7.
    1. Chitnis T, Arnold D, Banwell B, Brück W, Ghezzi A, Giovannoni G, et al. Trial of Fingolimod versus interferon Beta-1a in pediatric multiple sclerosis. New Engl J Med. 2018;379:1017–27. doi: 10.1056/NEJMoa1800149.
    1. Vermeulen M, Van Oers M. Successful autologous stem cell transplantation in a patient with chronic inflammatory demyelinating polyneuropathy. J Neurol Neurosurg Psychiatry. 2002;72:127–8. doi: 10.1136/jnnp.72.1.127.
    1. Oyama Y, Sufit R, Loh Y, Statkute L, Yaung K, Quigley K, et al. Nonmyeloablative autologous hematopoietic stem cell transplantation for refractory CIDP. Neurology. 2007;69:1802–3. doi: 10.1212/01.wnl.0000277266.53449.8b.
    1. Mahdi-Rogers M, Kazmi M, Fernei R, Hughes RA, Renaud S, Steck A, et al. Autologous periperhal blood stem cell transplantation for chronic acquired demyelinating neuropathy. J Peripheral Nerv Syst. 2009;14:118–24. doi: 10.1111/j.1529-8027.2009.00221.x.
    1. Bregante S, Gualandi F, van Lint M, Schenone A, Bacigalupo A, Marmont A. Sjögren’s syndrome associated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) treated with autologous and subsequently allogeneic haematopoietic SCT (HSCT) Bone Marrow Transplant. 2013;48:1139–40. doi: 10.1038/bmt.2013.18.
    1. Press R, Askmark H, Svenningsson A, Andersen O, Axelson H, Stromberg U, et al. Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP. J Neurol Neurosurg Psychiatry. 2013;85:618–24. doi: 10.1136/jnnp-2013-306014.
    1. Gozdziak P, Vinas R, Innocenti C, Burt R. Outcome of autologous non-myeloablative hematopoietic stem cell transplantation in patients with refractory chronic inflammatory demyelinating polyneuropathy (CIDP) Bone Marrow Transplant. 2017;52(Suppl 1):S40–S40.
    1. Bryant A, Atkins H, Pringle C, Allan D, Anstee G, Bence-Bruckler I, et al. Myasthenia gravis treated with autologous hematopoietic stem cell transplantation. JAMA Neurol. 2016;73:652–8. doi: 10.1001/jamaneurol.2016.0113.
    1. Håkansson I, Sandstedt A, Lundin F, Askmark H, Pirskanen R, Carlson K, et al. Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis—a case report. Neuromuscul Disord. 2017;27:90–93. doi: 10.1016/j.nmd.2016.09.020.
    1. Strober J, Cowan M, Horn B. Allogeneic hematopoietic cell transplantation for refractory myasthenia gravis. Arch Neurol. 2009;66:659–61. doi: 10.1001/archneurol.2009.28.
    1. Sossa Melo C, Peña A, Salazar L, Jiménez S, Gómez E, Chalela C, et al. Autologous hematopoietic stem cell transplantation in a patient with refractory seropositive myasthenia gravis: a case report. Neuromuscul Disord. 2019;29:142–5. doi: 10.1016/j.nmd.2018.11.008.
    1. Sanders S, Bredeson C, Pringle C, Martin L, Allan D, Bence-Bruckler I, et al. Autologous stem cell transplantation for stiff person syndrome. JAMA Neurol. 2014;71:1296–9. doi: 10.1001/jamaneurol.2014.1297.
    1. Thorpe A, Kass-Iliyyas L, Jessop H, Chantry A, Saraniagos P, Hadjivassiliou M, et al. Autologous haematopoietic stem cell transplantation in Stiff Person syndrome: the UK experience. Neurology. 2019;92.
    1. Greco R, Bondanza A, Oliveira M, Badoglio M, Burman J, Piehl F, et al. Autologous hematopoietic stem cell transplantation in neuromyelitis optica: a registry study of the EBMT autoimmune diseases working party. Mult Scler J. 2015;21:189–97. doi: 10.1177/1352458514541978.
    1. Peng F, Qiu W, Li J, Hu X, Huang R, Lin D, et al. A preliminary result of treatment of neuromyelitis optica with autologous peripheral hematopoietic stem cell transplantation. Neurologist. 2010;16:375–8. doi: 10.1097/NRL.0b013e3181b126e3.
    1. Xu J, Ji B, Su L, Dong H, Sun W, Wan S, et al. Clinical outcome of autologous peripheral blood stem cell transplantation in opticospinal and conventional of secondary progressive multiple sclerosis in a Chinese population. Ann Hematol. 2011;90:343–8. doi: 10.1007/s00277-010-1071-5.
    1. Matiello M, Pittock S, Porrata L, Weinshenker B. Failure of autologous hematopoietic stem cell transplantation to prevent relapse of neuromyelitis optica. Arch Neurol. 2011;68:933–5. doi: 10.1001/archneurol.2011.38.
    1. Aouad P, Li J, Arthur C, Burt R, Fernando S, Parratt J. Resolution of aquaporin-4 antibodies in a woman with neuromyelitis optica treated with human autologous stem cell transplant. J Clin Neurosci. 2015;22:1215–7. doi: 10.1016/j.jocn.2015.02.007.
    1. Burt RK, Balabanov R, Han X, Morgan A, Quigley K, Gastala J, et al. Autologous non-myeloablative hematopoietic stem cell transplantationin patients with Neuromyelitis Optica Spectrum Disorder (NMOSD): an open-label pilot study. Neurology. 2019. (In press)
    1. Burt R, Han X, Gozdziak P, Yaung K, Morgan A, Clendenan A, et al. Five year follow-up after autologous peripheral blood hematopoietic stem cell transplantation for refractory, chronic, corticosteroid-dependent systemic lupus erythematosus: effect of conditioning regimen on outcome. Bone Marrow Transplant. 2018;53:692–700. doi: 10.1038/s41409-018-0173-x.
    1. Alchi B, Jayne D, Labopin M, Kotova O, Sergeevicheva V, Alexander T, et al. Autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: data from the European Group for Blood and Marrow Transplantation registry. Lupus. 2013;22:245–53. doi: 10.1177/0961203312470729.
    1. Daikeler T, Kotter I, Bocelli Tyndall C, Apperley J, Attarbaschi A, Guardiola P, et al. Haematopoietic stem cell transplantation for vasculitis including Behcet’s disease and polychondritis: a retrospective analysis of patients recorded in the European Bone Marrow Transplantation and European League Against Rheumatism databases and a review of the literature. Ann Rheum Dis. 2007;66:202–7. doi: 10.1136/ard.2006.056630.
    1. Marmont A, Gualandi F, Piaggio G, Podestà M, Teresa van Lint M, Bacigalupo A, et al. Allogeneic bone marrow transplantation (BMT) for refractory Behçet’s disease with severe CNS involvement. Bone Marrow Transplant. 2006;37:1061–3. doi: 10.1038/sj.bmt.1705372.
    1. Alexander T. Autologous hematopoietic stem cell transplantation (HSCT) for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)—a EBMT retrospetive survey. Bone Marrow Transplant. 2019. (Submitted).
    1. Bingham S, Griffiths B, McGonagle D, Snowden JA, Morgan G, Emery P. Autologous stem cell transplantation for rapidly progressive Jo-1-positive polymyositis with long-term follow-up. Br J Haematol. 2001;113:840–1. doi: 10.1046/j.1365-2141.2001.02804-2.x.
    1. Holzer U, van Royen-Kerkhof A, van der Torre P, Kuemmerle-Deschner J, Well C, Handgretinger R, et al. Successful autologous stem cell transplantation in two patients with juvenile dermatomyositis. Scand J Rheumatol. 2010;39:88–92. doi: 10.3109/03009740903096622.
    1. Leone A, Radin M, Almarzooqi A, Al-Saleh J, Roccatello D, Sciascia S, et al. Autologous hematopoietic stem cell transplantation in systemic lupus erythematosus and antiphospholipid syndrome: A systematic review. Autoimmun Rev. 2017;16:469–77. doi: 10.1016/j.autrev.2017.03.008.
    1. Zhu J, Su G, Lai J, Dong B, Kang M, Li S, et al. Long-term follow-up of autologous hematopoietic stem cell transplantation for refractory juvenile dermatomyositis: a case-series study. Pediatr Rheumatol. 2018;16:7. doi: 10.1186/s12969-018-0284-3.
    1. Tack G, Wondergem M, Al-Toma A, Verbeek W, Schmittel A, Machado M, et al. Auto-SCT in refractory celiac disease type II patients unresponsive to cladribine therapy. Bone Marrow Transplant. 2011;46:840–6. doi: 10.1038/bmt.2010.199.
    1. Snowden JA, McGrath E, Duarte RF, Saccardi R, Orchard K, Worel N, et al. JACIE accreditation for blood and marrow transplantation: past, present and future directions of an international model for healthcare quality improvement. Bone Marrow Transplant. 2017;52:1367–71.
    1. Snarski E, Snowden J, Oliveira M, Simoes B, Badoglio M, Carlson K, et al. Onset and outcome of pregnancy after autologous haematopoietic SCT (AHSCT) for autoimmune diseases: a retrospective study of the EBMT autoimmune diseases working party (ADWP) Bone Marrow Transplant. 2015;50:216–20. doi: 10.1038/bmt.2014.248.
    1. Maciejewska M, Snarski E, Wiktor-Jedrzejczak W. A preliminary online study on menstruation recovery in women after autologous hematopoietic stem cell transplant for autoimmune disease. Exp Clin Transplant. 2016;14:665–9.
    1. Mariottini A, Innocenti C, Forci B, Magnani E, Mechi C, Barilaro A, et al. Safety and efficacy of autologous hematopoietic stem‐cell transplantation following natalizumab discontinuation in aggressive multiple sclerosis. Eur J Neurol. 2019;26:624–30. doi: 10.1111/ene.13866.
    1. Burt R, Fassas A, Snowden J, van Laar JM, Kozak T, Wulffraat N, et al. Special report. Collection of hematopoietic stem cells from patients with autoimmune diseases. Bone Marrow Transplant. 2001;28:1–12. doi: 10.1038/sj.bmt.1703081.
    1. Jantunen E, Fruehauf S. Importance of blood graft characteristics in auto-SCT: implications for optimizing mobilization regimens. Bone Marrow Transplant. 2011;46:627–35. doi: 10.1038/bmt.2010.320.
    1. Giralt S, Costa L, Schriber J, DiPersio J, Maziarz R, McCarty J, et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biol Blood Marrow Transplant. 2014;20:295–308. doi: 10.1016/j.bbmt.2013.10.013.
    1. Morris E, Sharrack B, Dalley C, Snowden J. The Uhthoff phenomenon: a potential post transplant complication in advanced progressive multiple sclerosis. Bone Marrow Transplant. 2007;40:1003–4. doi: 10.1038/sj.bmt.1705854.
    1. Burt R, Cohen B, Russell E, Spero K, Joshi A, Oyama Y, et al. Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores. Blood. 2003;102:2373–8. doi: 10.1182/blood-2003-03-0877.
    1. Curro’ D, Vuolo L, Gualandi F, Bacigalupo A, Roccatagliata L, Capello E, 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 J. 2015;21:1423–30. doi: 10.1177/1352458514564484.
    1. Gale R, Gómez‐Cruz G, Olivares‐Gazca J, León‐Peña A, Gómez‐Almaguer D, Gómez‐De‐León A, et al. Determine safety of outpatient chemotherapy and autotransplants using refrigerated, non‐frozen grafts in persons with multiple sclerosis. Clinical Transplant. 2019;33:e13567.
    1. Ruiz-Argüelles G, León-Peña A, León-González M, Nuñez-Cortes A, Olivares-Gazca J, Murrieta-Alvarez I, et al. A feasibility study of the full outpatient conduction of hematopoietic transplants in persons with multiple sclerosis employing autologous non-cryopreserved peripheral blood stem cells. Acta Haematologica. 2017;137:214–9. doi: 10.1159/000469655.
    1. Peffault de Latour R, Risitano A, Dufour C. Severe aplastic anemia and PNH. In: Carreras E, Dufour C, Mohty M, Kröger N, editorss. The EBMT Handbook: hematopoietic stem cell transplantation and cellular therapies. Springer; 2019. p. 579–585. Chapter 77. .
    1. Hamerschlak N, Rodrigues M, Moraes D, Oliveira M, Stracieri A, Pieroni F, et al. Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG. Bone Marrow Transplant. 2010;45:239–48. doi: 10.1038/bmt.2009.127.
    1. Moore J, Massey J, Ford C, Khoo M, Zaunders J, Hendrawan K, et al. Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis. J Neurol Neurosurg Psychiatry. 2019;90:514–21. doi: 10.1136/jnnp-2018-319446.
    1. Elmahdi S, Muramatsu H, Narita A, Torii Y, Ismael O, Kawashima N, et al. Correlation of rabbit antithymocyte globulin serum levels and clinical outcomes in children who received hematopoietic stem cell transplantation from an alternative donor. Pediatr Transplant. 2016;20:105–13. doi: 10.1111/petr.12620.
    1. Admiraal R, Nierkens S, de Witte M, Petersen E, Fleurke G, Verrest L, et al. Association between anti-thymocyte globulin exposure and survival outcomes in adult unrelated haemopoietic cell transplantation: a retrospective, pharmacodynamic cohort analysis. Lancet Haematol. 2017;4:e183–e191. doi: 10.1016/S2352-3026(17)30029-7.
    1. Scordo M, Bhatt V, Hilden P, Smith M, Thoren K, Cho C, et al. Standard Antithymocyte globulin dosing results in poorer outcomes in overexposed patients after Ex Vivo CD34+ selected allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2019. .
    1. Scheinberg P, Fischer S, Li L, Nunez O, Wu C, Sloand E, et al. Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. Blood. 2007;109:3219–24. doi: 10.1182/blood-2006-09-045625.
    1. Saccardi R, Kozak T, Bocelli-Tyndall C, Fassas A, Kazis A, Havrdova E, 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 J. 2006;12:814–23. doi: 10.1177/1352458506071301.
    1. Ros-Soto J, Anthias C, Madrigal A, Snowden J. Vitamin D: is it important in haematopoietic stem cell transplantation? A review. Bone Marrow Transplant. 2018;54:810–20. doi: 10.1038/s41409-018-0377-0.
    1. Majhail N, Rizzo J, Lee S, Aljurf M, Atsuta Y, Bonfim C, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Bone Marrow Transplant. 2012;47:337–41. doi: 10.1038/bmt.2012.5.
    1. Burman J, Fox R. Autologous hematopoietic stem cell transplantation for MS: Safer than previously thought. Neurology. 2017;88:2072–3. doi: 10.1212/WNL.0000000000003995.
    1. Mehra V, Rhone E, Widya S, Zuckerman M, Potter V, Raj K, et al. Epstein-Barr virus and monoclonal gammopathy of clinical significance in autologous stem cell transplantation for multiple sclerosis. Clin Infec Dis. 2019. e-pub ahead of print; 1093/cid/ciz047.
    1. Alexander T, Bondanza A, Muraro P, Greco R, Saccardi R, Daikeler T, et al. SCT for severe autoimmune diseases: consensus guidelines of the European Society for Blood and Marrow Transplantation for immune monitoring and biobanking. Bone Marrow Transplant. 2015;50:173–80. doi: 10.1038/bmt.2014.251.
    1. DeFilipp Z, Duarte R, Snowden J, Majhail N, Greenfield D, Miranda J, et al. Metabolic syndrome and cardiovascular disease after hematopoietic cell transplantation: screening and preventive practice recommendations from the CIBMTR and EBMT. Biol Blood Marrow Transplant. 2016;22:1493–503. doi: 10.1016/j.bbmt.2016.05.007.
    1. Coles A, Twyman C, Arnold D, Cohen J, Confavreux C, Fox E, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380:1829–39. doi: 10.1016/S0140-6736(12)61768-1.
    1. Daikeler T, Labopin M, Di Gioia M, Abinun M, Alexander T, Miniati I, et al. Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party. Blood. 2011;118:1693–8. doi: 10.1182/blood-2011-02-336156.
    1. Loh Y, Oyama Y, Statkute L, Quigley K, Yaung K, Gonda E, et al. Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used. Blood. 2007;109:2643–2548. doi: 10.1182/blood-2006-07-035766.
    1. Burt R, Marmont A, Oyama Y, Slavin S, Arnold R, Hiepe F, et al. Randomized controlled trials of autologous hematopoietic stem cell transplantation for autoimmune diseases: the evolution from myeloablative to lymphoablative transplant regimens. Arthritis Rheumatism. 2006;54:3750–60. doi: 10.1002/art.22256.
    1. Brinkman D, Jol-van der Zijde C, ten Dam M, te Boekhorst P, ten Cate R, Wulffraat N, et al. Resetting the adaptive immune system after autologous stem cell transplantation: lessons from responses to vaccines. J Clin Immunol. 2007;27:647–58. doi: 10.1007/s10875-007-9120-0.
    1. Cordonnier C, Einarsdottir S, Cesaro S, Di Blasi R, Mikulska M, Rieger C, et al. European Conference on Infections in Leukaemia group. Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7) Lancet Infect Dis. 2019;19:e200–e212. doi: 10.1016/S1473-3099(18)30600-5.
    1. Miller P, de Silva T, Skinner R, Gilleece M, Peniket A, Hamblin A, et al. Erratum: routine vaccination practice after adult and paediatric allogeneic haematopoietic stem cell transplant: a survey of UK NHS programmes. Bone Marrow Transplant. 2017;52:1082. doi: 10.1038/bmt.2017.87.
    1. Rubin L, Levin M, Ljungman P, Davies E, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2013;58:309–18. doi: 10.1093/cid/cit816.
    1. Burman J, Fransson M, Tötterman T, Fagius J, Mangsbo S, Loskog A. T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis. Immunology. 2013;140:211–9. doi: 10.1111/imm.12129.
    1. Abrahamsson S, Angelini D, Dubinsky A, Morel E, Oh U, Jones J, 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;136:2888–903. doi: 10.1093/brain/awt182.
    1. de Paula A, Sousa A, Malmegrim K, Panepucci R, Brum D, Barreira A, et al. Autologous haematopoietic stem cell transplantation reduces abnormalities in the expression of immune genes in multiple sclerosis. Clin Sci. 2015;128:111–20. doi: 10.1042/CS20140095.
    1. Massey J, Sutton I, Ma D, Moore J. Regenerating immunotolerance in multiple sclerosis with autologous hematopoietic stem cell transplant. Front Immunol. 2018;9:410. doi: 10.3389/fimmu.2018.00410.
    1. Muraro P, Douek D, Packer A, Chung K, Guenaga F, Cassiani-Ingoni R, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med. 2005;201:805–16. doi: 10.1084/jem.20041679.
    1. Muraro P, Robins H, Malhotra S, Howell M, Phippard D, Desmarais C, et al. T cell repertoire following autologous stem cell transplantation for multiple sclerosis. J Clin Invest. 2014;124:1168–72. doi: 10.1172/JCI71691.
    1. Darlington P, Touil T, Doucet J, Gaucher D, Zeidan J, Gauchat D, et al. Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation. Ann Neurol. 2013;73:341–54. doi: 10.1002/ana.23784.
    1. Darlington P, Stopnicki B, Touil T, Doucet J, Fawaz L, Roberts M, et al. Natural killer cells regulate Th17 cells after autologous hematopoietic stem cell transplantation for relapsing remitting multiple sclerosis. Front Immunol. 2018;9:834. doi: 10.3389/fimmu.2018.00834.
    1. Daikeler T, Hügle T, Farge D, Andolina M, Gualandi F, Baldomero H, et al. Allogeneic hematopoietic SCT for patients with autoimmune diseases. Bone Marrow Transplant. 2009;44:27–33. doi: 10.1038/bmt.2008.424.
    1. Greco R, Bondanza A, Vago L, Moiola L, Rossi P, Furlan R, et al. Allogeneic hematopoietic stem cell transplantation for neuromyelitis optica. Ann Neurol. 2014;75:447–53. doi: 10.1002/ana.24079.
    1. Luznik L, O’Donnell P, Symons H, Chen A, Leffell M, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–50. doi: 10.1016/j.bbmt.2008.03.005.
    1. Mussetti A, Greco R, Peccatori J, Corradini P. Post-transplant cyclophosphamide, a promising anti-graft versus host disease prophylaxis: where do we stand? Expert Rev Hematol. 2017;10:479–92. doi: 10.1080/17474086.2017.1318054.
    1. Laroni A, Rosbo N, Uccelli A. Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection. Immunol Lett. 2015;168:183–90. doi: 10.1016/j.imlet.2015.08.007.
    1. Scolding N, Pasquini M, Reingold S, Cohen J. Cell-based therapies for multiple sclerosis. Brain. 2017;140:2776–96. doi: 10.1093/brain/awx154.
    1. Rice C, Marks D, Ben-Shlomo Y, Evangelou N, Morgan P, Metcalfe C, et al. Assessment of bone marrow-derived cellular therapy in progressive multiple sclerosis (ACTiMuS): study protocol for a randomised controlled trial. Trials. 2015;16:463. doi: 10.1186/s13063-015-0953-1.
    1. Rice C, Marks D, Walsh P, Kane N, Guttridge M, Redondo J, et al. Repeat infusion of autologous bone marrow cells in multiple sclerosis: protocol for a phase I extension study (SIAMMS-II) BMJ Open. 2015;5:e009090. doi: 10.1136/bmjopen-2015-009090.
    1. Uccelli A, Laroni A, Brundin L, Clanet M, Fernandez O, Nabavi SM, MESEMS study group. et al. MEsenchymal StEm cells for multiple sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis. Trials. 2019;20:263. doi: 10.1186/s13063-019-3346-z.
    1. Chan J, Ban E, Chun K, Wang S, Bäckström B, Bernard C, et al. Transplantation of bone marrow transduced to express self-antigen establishes deletional tolerance and permanently remits autoimmune disease. J Immunol. 2008;181:7571–80. doi: 10.4049/jimmunol.181.11.7571.
    1. Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380:1829–39. doi: 10.1016/S0140-6736(12)61768-1.
    1. Atkins H. Stem cell transplantation to treat multiple sclerosis. JAMA. 2019;321:153–5. doi: 10.1001/jama.2018.20777.
    1. Tappenden P, Saccardi R, Confavreux C, Sharrack B, Muraro P, Mancardi G, et al. Autologous haematopoietic stem cell transplantation for secondary progressive multiple sclerosis: an exploratory cost-effectiveness analysis. Bone Marrow Transplant. 2010;45:1014–21. doi: 10.1038/bmt.2009.305.
    1. Tappenden P, Sharrack B, Burman J, Kazmi M, Saccardi R, Bermejo I, et al. Evaluating the clinical effectiveness of autologous haematopoietic stem cell transplantation versus disease-modifying therapy in multiple sclerosis using a matching-adjusted indirect comparison: an exploratory study from the Autoimmune Diseases Working Party (ADWP) of the European Society of Bone and Marrow Transplantation (EBMT), (abstract) Bone Marrow Transplant. 2017;52:S41–S41. doi: 10.1038/bmt.2016.212.
    1. Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380:1819–28. doi: 10.1016/S0140-6736(12)61769-3.
    1. Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, et al. Ocrelizumab versus interferon beta-1a in relaps- ing multiple sclerosis. N Engl J Med. 2017;376:221–34. doi: 10.1056/NEJMoa1601277.
    1. Giovannoni G, Cook S, Rammohan K, Rieckmann P, Sørensen PS, Vermersch P, et al. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis. Lancet Neurol. 2011;10:329–37. doi: 10.1016/S1474-4422(11)70023-0.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera