Transplante Autólogo de Células-Tronco Hematopoiéticas no Tratamento da Esclerose Múltipla: Começo de uma Nova Era?

Autores

DOI:

https://doi.org/10.46531/sinapse/AR/220018/2023

Palavras-chave:

Esclerose Múltipla/tratamento, Transplante Autólogo, Transplante de Células-Tronco Hematopoéticas

Resumo

O transplante autólogo de células-tronco hematopoéticas (AHSCT) tem vindo a ganhar destaque nos últimos 20 anos no âmbito das doenças autoimunes, em particular da esclerose múltipla. Este procedimento permite a erradicação do sistema imunológico autorreativo e a sua posterior reconstituição a partir de células-tronco hematopoiéticas, constituindo um processo de “reiniciação imunológica”, através da diversificação do repertório de células T e da restauração da sua rede regulatória, redução da resposta da interleucina-17 e normalização da expressão de microRNAs e perfis de expressão génica. Evidências crescentes sugerem que o AHSCT pode suprimir totalmente a atividade da doença em 70%-92% dos casos, aos 2 anos, uma taxa superior à das atuais terapêuticas aprovadas. A sua eficácia foi também demonstrada a nível da atrofia cerebral, biomarcadores séricos e do líquido cefalorraquidiano, cognição, fadiga e qualidade de vida. Com o aumento da experiência e desenvolvimento dos protocolos, os riscos do procedimento têm vindo a diminuir para níveis considerados aceitáveis. Os eventos adversos mais comuns são precoces e correspondem a toxicidades orgânicas, citopenias e infeções, porém, a longo prazo, está descrita a possibilidade de autoimunidade secundária e malignidade. Nos estudos mais recentes, a mortalidade relacionada com o tratamento é estimada em 0,2%. A eficácia máxima verifica-se em doentes mais jovens, com menor duração da doença, menos comorbilidades e evidência de doença muito ativa ou refratária ao tratamento. Assim, o AHSCT surge como uma nova alternativa de tratamento na EM, em centros especializados que assegurem adequada seleção do protocolo e correto acompanhamento do doente para otimizar a segurança do mesmo. A presente revisão, baseada em estudos publicados entre 2016 e 2021, que incluíram 20 ou mais doentes, pretende esclarecer e sistematizar a informação existente sobre o AHSCT tanto no que diz respeito aos mecanismos de ação subjacentes, procedimentos e protocolos existentes, bem como benefícios e riscos associados.

Downloads

Não há dados estatísticos.

Referências

Das J, Sharrack B, Snowden JA. Autologous hematopoietic stem-cell transplantation in neurological disorders: current approach and future directions. Expert Rev Neurother. 2020;20:1299-313. doi: 10.1080/14737175.2020.1820325.

Sormani MP, Muraro PA, Schiavetti I, Signori A, Laroni A, Saccardi R, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis A meta-analysis. Neurology. 2017;88:2115-22.

Rotstein DL, Healy BC, Malik MT, Chitnis T, Weiner HL. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol. 2015;72:152–8.

Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol. 2019;26:27-40. doi: 10.1111/ene.13819.

Sharrack B, Saccardi R, Alexander T, Badoglio M, Burman J, Farge D, 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;55:283-306. doi: 10.1038/s41409-019-0684-0.

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.

Atkins HL, Bowman M, Allan D, Anstee G, Arnold DL, BarOr 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.

Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, Oliveira MC, 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;321:165–74.

Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Steinmiller KC, et al. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology. 2017;88:842-852.

Mancardi GL, Sormani MP, di Gioia M, Vuolo L, Gualandi F, Amato MP, et al. Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: The Italian multi-centre experience. Mult Scler. 2012;18:835-42. doi: 10.1177/1352458511429320.

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.

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. 2015;21:1423–30.

Chen B, Zhou M, Ouyang J, Zhou R, Xu J, Zhang Q, et al. Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China. Neurol Sci. 2012;33:881–6.

Muraro PA, Pasquini M, Atkins HL, Bowen JD, Farge D, Fassas A, et al. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurol. 2017;74:459–69.

Shevchenko JL, Kuznetsov AN, Ionova TI, Melnichenko VY, Fedorenko DA, Kurbatova KA, 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 Hemat. 2015;94:1149–57.

Mancardi GL, Sormani MP, 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.

Moore JJ, Massey JC, Ford CD, Khoo ML, Zaunders JJ, 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.

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. doi: 10.1038/bmt.2017.54.

Saccardi R, Gualandi F. Hematopoietic stem cell transplantation procedures. Autoimmunity. 2008;41:570–6.

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.

Bose G, Freedman MS. Recent advances and remaining questions of autologous hematopoietic stem cell transplantation in multiple sclerosis. J Neurol Sci. 2021;421:117324. doi: 10.1016/j.jns.2021.117324.

Atkins HL, Freedman MS. Hematopoietic stem cell therapy for multiple sclerosis: top 10 lessons learned. Neurotherapeutics. 2013;10:68-76. doi: 10.1007/s13311-012-0162-5.

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;13:391-405. doi: 10.1038/nrneurol.2017.81.

Nash RA, Bowen JD, McSweeney PA, Pavletic SZ, Maravilla KR, Park MS, et al. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Blood. 2003;102:2364–72.

Samijn JPA, te Boekhorst PAW, Mondria T, van Doorn PA, Flach HZ, van der Meché FGA, et al. Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006;77:46-50. doi: 10.1136/jnnp.2005.063883.

Snowden JA, Badoglio M, Labopin M, Giebel S, McGrath E, Marjanovic Z, et al. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv. 2017;1:2742–55.

Alexander T, Bondanza A, Muraro PA, 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.

Massey JC, Sutton IJ, Ma DDF, Moore JJ. Regenerating immunotolerance in multiple sclerosis with autologous hematopoietic stem cell transplant. Front Immunol. 2018;9:410. doi: 10.3389/fimmu.2018.00410.

Muraro PA, 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.

Muraro PA, Douek DC, Packer A, Chung K, Guenaga FJ, Cassiani-Ingoni R, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Expl Med. 2005;201:805–16.

Abrahamsson S, Angelini DF, Dubinsky AN, Morel E, Oh U, Jones JL, 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.

Darlington PJ, Touil T, Doucet JS, 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.

Sun W, Popat U, Hutton G, Zang YCQ, Krance R, Carrum G, et al. Characteristics of T-cell receptor repertoire and myelin-reactive T cells reconstituted from autologous haematopoietic stem-cell grafts in multiple sclerosis. Brain. 2004;127:996-1008. doi: 10.1093/brain/awh117.

Burt RK, Padilla J, Begolka WS, Dal Canto MC, Miller SD. Effect of Disease Stage on Clinical Outcome After Syngeneic Bone Marrow Transplantation for Relapsing Experimental Autoimmune Encephalomyelitis. Blood. 1998;91:2609-16.

Burman J, Fransson M, Tötterman TH, Fagius J, Mangsbo SM, Loskog ASI. T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis. Immunology. 2013;140:211–9.

Arruda LC, de Azevedo JT, de Oliveira GL, Scortegagna GT, Rodrigues ES, Palma PVB, et al. Immunological correlates of favorable long-term clinical outcome in multiple sclerosis patients after autologous hematopoietic stem cell transplantation. Clin Immunol. 2016;169:47–57.

Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Vol. 15, Nature Reviews Immunology. Nat Rev Immunol. 2015;15:545-58. doi: 10.1038/nri3871.

Arruda LCM, Lorenzi JCC, Sousa APA, Zanette DL, Palma PVB, Panepucci RA, et al. Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients. Bone Marrow Transplant. 2015;50:380-9. doi: 10.1038/bmt.2014.277.

Autran B, Leblond V, Sadat-Sowti B, Lefranc E, Got P, Sutton L, et al. A Soluble Factor Released by CDSfCD57+ Lymphocytes From Bone Marrow Transplanted Patients Inhibits Cell-Mediated Cytolysis. Blood. 1991;77:2237-41.

Mollet L, Sadat-Sowti B, Rg Duntze J, Leblond V, Bergeron F, Calvez V, et al. CD8 hi CD57 T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity. Int Immunol. 1998;10:311-23. doi: 10.1093/ intimm/10.3.311.

Kebir H, Ifergan I, Alvarez JI, Bernard M, Poirier J, Arbour N, et al. Preferential recruitment of interferon-ć-expressing TH17 cells in multiple sclerosis. Ann Neurol. 2009;66:390–402

Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD. MicroRNAs: New regulators of immune cell development and function. Nat Immunol. 2008;9:839-45. doi: 10.1038/ni.f.209.

Paraboschi EM, Soldà G, Gemmati D, Orioli E, Zeri G, Benedetti MD, et al. Genetic association and altered gene expression of mir-155 in multiple sclerosis patients. Int J Mol Sci. 2011;12:8695-712. doi: 10.3390/ijms12128695.

Murugaiyan G, Beynon V, Mittal A, Joller N, Weiner HL. Silencing MicroRNA-155 Ameliorates Experimental Autoimmune Encephalomyelitis. J Immunol. 2011;187:2213–21.

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:e24604. doi: 10.1371/journal. pone.0024604.

Keller A, Leidinger P, Steinmeyer F, Stähler C, Franke A, Hemmrich-Stanisak G, et al. Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. Mult Scler. 2014;20:295-303. doi: 10.1177/1352458513496343.

Feng X, Petraglia AL, Chen M, Byskosh P v, Boos MD, Reder AT. Low expression of interferon-stimulated genes in active multiple sclerosis is linked to subnormal phosphorylation of STAT1. J Neuroimmunol. 2002;129:205-15.

Huang B, Zhao J, Lei Z, Shen S, Li D, Shen GX, et al. miR142-3p restricts cAMP production in CD4+CD25T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA. EMBO Rep. 2009;10:180–5.

Liu X, Robinson SN, Setoyama T, Tung SS, D’Abundo L, Shah MY, et al. FOXP3 is a direct target of miR15a/16 in umbilical cord blood regulatory T cells. Bone Marrow Transpl. 2014;49:793–9.

Abrahamsson S, Muraro PA. Immune re-education following autologous hematopoietic stem cell transplantation. Autoimmunity. 2008;41:577–84.

Karnell FG, Lin D, Motley S, Duhen T, Lim N, Campbell DJ, et al. Reconstitution of immune cell populations in multiple sclerosis patients after autologous stem cell transplantation. Clin Exp Immunol. 2017;189:268-78. doi: 10.1111/ cei.12985.

Darlington PJ, Stopnicki B, Touil T, Doucet JS, Fawaz L, Roberts ME, 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.

Sousa A de PA, Malmegrim KCR, Panepucci RA, Brum DS, Barreira AA, dos Santos AC, et al. Autologous haematopoietic stem cell transplantation reduces abnormalities in the expression of immune genes in multiple sclerosis. Clin Sci. 2015;128:111–20.

Zhukovsky C, Sandgren S, Silfverberg T, Einarsdottir S, Tolf A, Landtblom AM, et al. Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing-remitting multiple sclerosis: An observational study. J Neurol Neurosurg Psychiatry. 2021;92:189-94. doi: 10.1136/jnnp-2020-323992.

Boffa G, Lapucci C, Sbragia E, Varaldo R, Raiola AM, Currò D, et al. Aggressive multiple sclerosis: a single-centre, realworld treatment experience with autologous haematopoietic stem cell transplantation and alemtuzumab. Eur J Neurol. 2020;27:2047–55. doi: 10.1111/ene.14324.

Mariottini A, Filippini S, Innocenti C, Forci B, Mechi C, Barilaro A, et al. Impact of autologous haematopoietic stem cell transplantation on disability and brain atrophy in secondary progressive multiple sclerosis. Mult Scler. 2021;27:61-70. doi: 10.1177/1352458520902392.

Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Griffith LM, 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;72:159–69. doi: 10.1001/jamaneurol.2014.3780.

Casanova B, Jarque I, Gascón F, Hernández-Boluda JC, 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. Neurol Sci. 2017;38:1213-21. doi: 10.1007/ s10072-017-2933-6.

Sormani MP, Muraro PA, 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. 2017;23:201-4. doi: 10.1177/1352458516645670.

Dwyer MG, Hagemeier J, Bergsland N, Horakova D, Korn JR, Khan N, et al. Establishing pathological cut-offs for lateral ventricular volume expansion rates. Neuroimage Clin. 2018;18:494-501. doi: 10.1016/j.nicl.2018.02.009.

Lee H, Narayanan S, Brown RA, Chen JT, Atkins HL, Freedman MS, et al. Brain atrophy after bone marrow transplantation for treatment of multiple sclerosis. Mult Scler. 2017;23:420-31. doi: 10.1177/1352458516650992.

Larsson D, Åkerfeldt T, Carlson K, Burman J. Intrathecal immunoglobulins and neurofilament light after autologous haematopoietic stem cell transplantation for multiple sclerosis. Mult Scler. 2020;26:1351-9. doi: 10.1177/1352458519863983.

Chitnis T, Gonzalez C, Healy BC, Saxena S, Rosso M, Barro C, et al. Neurofilament light chain serum levels correlate with 10-year MRI outcomes in multiple sclerosis. Ann Clin Transl Neurol. 2018;5:1478–91. doi: 10.1002/acn3.638.

Novakova L, Zetterberg H, Sundström P, Axelsson M, Khademi M, Gunnarsson M, et al. Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. Neurology. 2017;89:2230–7.

Cantó E, Barro C, Zhao C, Caillier SJ, Michalak Z, Bove R, et al. Association between Serum Neurofilament Light Chain Levels and Long-term Disease Course among Patients with Multiple Sclerosis Followed up for 12 Years. JAMA Neurol. 2019;76:1359–66.

Thebault S, Abdoli M, Fereshtehnejad SM, Tessier D, Tabard-Cossa V, Freedman MS. Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis. Sci Rep. 2020;10:10381. doi: 10.1038/s41598-02067504-6.

Thebault S, Tessier DR, Lee H, Bowman M, Bar-Or A, Arnold DL, et al. High serum neurofilament light chain normalizes after hematopoietic stem cell transplantation for MS. Neurol Neuroimmunol Neuroinflamm. 2019;6:e598. doi: 10.1212/NXI.0000000000000598.

Bose G, Atkins HL, Bowman M, Freedman MS. Autologous hematopoietic stem cell transplantation improves fatigue in multiple sclerosis. Mult Scler. 2019;25:1764-72. doi: 10.1177/1352458518802544.

Giedraitiene N, Kizlaitiene R, Peceliunas V, Griskevicius L, Kaubrys G. Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis. Sci Rep. 2020;10:21286. doi: 10.1038/s41598-020-78160-1.

Cancer Institute N. Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 [Internet]. 2017. [cited 2022 Jan 16]. Available from: https://www.meddra.org/

Guida M, Castaldi MA, Rosamilio R, Giudice V, Orio F, Selleri C. Reproductive issues in patients undergoing Hematopoietic Stem Cell Transplantation: an update. J Ovarian Res. 2016;9:72. doi: 10.1186/s13048-016-0279-y.

Snarski E, Snowden JA, Oliveira MC, 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.

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. 2006 ;12:814–23.

Ge F, Lin H, Li Z, Chang T. Efficacy and safety of autologous hematopoietic stem-cell transplantation in multiple sclerosis: a systematic review and meta-analysis. Neurol Sci. 2019;40:479–87.

Alix JJP, Blackburn DJ, Sokhi D, Craven I, Sharrack B, Snowden JA. 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.

Das J, Snowden JA, Burman J, Freedman MS, Atkins H, Bowman M, et al. Autologous haematopoietic stem cell transplantation as a first-line disease-modifying therapy in patients with ‘aggressive’ multiple sclerosis. Mult Scler. 2021;27:1198-204. doi: 10.1177/1352458520985238.

Mancardi GL, 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. 2005;11:367–71.

Kappos L, Bar-Or A, Cree BAC, Fox RJ, Giovannoni G, Gold R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391:1263–73.

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.

Ocrelizumab or Alemtuzumab Compared With Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis - a Phase-2 Randomised Controlled Trial - Full Text View - ClinicalTrials.gov [Internet]. [cited 2022 Jan 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT0497100 5?id=NCT04047628+OR+NCT04971005+OR+NCT05029 206+OR+NCT03113162+OR+NCT03477500+OR+NCT00716066&draw=2&rank=2&load=cart

RCT Comparing Autologous Hematopoietic Stem Cell Transplantation Versus Alemtuzumab in MS. ClinicalTrials. gov [Internet]. [cited 2022 Jan 16]. Available from: https:// clinicaltrials.gov/ct2/show/NCT03477500?id=NCT0404762 8+OR+NCT04674280+OR+NCT04971005+OR+NCT0502 9206+OR+NCT03113162+OR+NCT03477500+OR+NCT0 0716066&draw=2&rank=5&load=cart

Best Available Therapy Versus Autologous Hematopoetic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS). ClinicalTrials.gov [Internet]. [cited 2022 Jan 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT04047628?id=NCT0 4047628+OR+NCT04674280+OR+NCT04971005+OR+N CT05029206+OR+NCT03113162+OR+NCT03477500+OR +NCT00716066&draw=2&rank=4&load=cart

Clinical Trials Register [Internet]. [cited 2022 Jan 16]. Available from: https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-001549-42/GB

Downloads

Publicado

2024-03-26

Como Citar

1.
Gonçalves MF, Nunes C, Santana I, Correia I. Transplante Autólogo de Células-Tronco Hematopoiéticas no Tratamento da Esclerose Múltipla: Começo de uma Nova Era?. Sinapse [Internet]. 26 de Março de 2024 [citado 11 de Outubro de 2024];23(1):29-41. Disponível em: https://sinapse.pt/index.php/journal/article/view/31

Edição

Secção

Artigo de Revisão

Artigos mais lidos do(s) mesmo(s) autor(es)