Reduced-intensity Immunoablation and Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Multiple Sclerosis

Summary

This is a patient-sponsored study that evaluates the safety and efficacy of reduced-intensity immunoablation followed by a single dose autologous hematopoetic stem cell transplantation in patients diagnosed with multiple sclerosis. Patients are followed-up after 1 month, 3 months, 6 months and 12 months post-transplantation.

Timeline

Start

2015-05-29

Primary completion

2020-05-29

Completion

2022-05-29

Publications

• Background Akkok CA, Liseth K, Hervig T, Ryningen A, Bruserud O, Ersvaer E. Use of different DMSO concentrations for cryopreservation of autologous peripheral blood stem cell grafts does not have any major impact on levels of leukocyte- and platelet-derived soluble mediators. Cytotherapy. 2009;11(6):749-60. doi: 10.3109/14653240902980443.
• Background Appelbaum FR, Bacigalupo A, Soiffer R. Anti-T cell antibodies as part of the preparative regimen in hematopoietic cell transplantation--a debate. Biol Blood Marrow Transplant. 2012 Jan;18(1 Suppl):S111-5. doi: 10.1016/j.bbmt.2011.11.002. No abstract available.
• Background 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 Jan 20;313(3):275-84. doi: 10.1001/jama.2014.17986.
• Background Burt RK, Loh Y, Cohen B, Stefoski D, Balabanov R, Katsamakis G, Oyama Y, Russell EJ, Stern J, Muraro P, Rose J, Testori A, Bucha J, Jovanovic B, Milanetti F, Storek J, Voltarelli JC, Burns WH. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009 Mar;8(3):244-53. doi: 10.1016/S1474-4422(09)70017-1. Epub 2009 Jan 29.
• Background Bruck W. The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage. J Neurol. 2005 Nov;252 Suppl 5:v3-9. doi: 10.1007/s00415-005-5002-7.
• Background von Budingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L, Glanville J, Cree BA, Gourraud PA, Schwartzburg A, Huerta G, Telman D, Sundar PD, Casey T, Cox DR, Hauser SL. B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest. 2012 Dec;122(12):4533-43. doi: 10.1172/JCI63842. Epub 2012 Nov 19.
• Background Cabezudo E, Dalmases C, Ruz M, Sanchez JA, Torrico C, Sola C, Querol S, Garcia J. Leukapheresis components may be cryopreserved at high cell concentrations without additional loss of HPC function. Transfusion. 2000 Oct;40(10):1223-7. doi: 10.1046/j.1537-2995.2000.40101223.x.
• Background Costantino CM, Baecher-Allan C, Hafler DA. Multiple sclerosis and regulatory T cells. J Clin Immunol. 2008 Nov;28(6):697-706. doi: 10.1007/s10875-008-9236-x. Epub 2008 Sep 2.
• Background De Boer F, Drager AM, Van der Wall E, Pinedo HM, Schuurhuis GJ. Changes in L-selectin expression on CD34-positive cells upon cryopreservation of peripheral blood stem cell transplants. Bone Marrow Transplant. 1998 Dec;22(11):1103-10. doi: 10.1038/sj.bmt.1701495.
• Background Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J, Ouyang J, Kozak T, Moore J, Kotter I, Chesnel V, Marmont A, Gratwohl A, Saccardi R. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica. 2010 Feb;95(2):284-92. doi: 10.3324/haematol.2009.013458. Epub 2009 Sep 22.
• Background Fassas A, Anagnostopoulos A, Kazis A, Kapinas K, Sakellari I, Kimiskidis V, Tsompanakou A. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant. 1997 Oct;20(8):631-8. doi: 10.1038/sj.bmt.1700944.
• Background Fassas A, Kimiskidis VK. Autologous hemopoietic stem cell transplantation in the treatment of multiple sclerosis: rationale and clinical experience. J Neurol Sci. 2004 Aug 15;223(1):53-8. doi: 10.1016/j.jns.2004.04.020.
• Background Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Lassmann H. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009 May;132(Pt 5):1175-89. doi: 10.1093/brain/awp070. Epub 2009 Mar 31.
• Background Iannalfi A, Bambi F, Tintori V, Lacitignola L, Bernini G, Mariani MP, Sanvito MC, Pagliai F, Brandigi F, Muscarella E, Tapinassi F, Faulkner L. Peripheral blood progenitor uncontrolled-rate freezing: a single pediatric center experience. Transfusion. 2007 Dec;47(12):2202-6. doi: 10.1111/j.1537-2995.2007.01447.x. Epub 2007 Aug 21.
• Background Mancardi GL, Sormani MP, Gualandi F, Saiz A, Carreras E, Merelli E, Donelli A, Lugaresi A, Di Bartolomeo P, Rottoli MR, Rambaldi A, Amato MP, Massacesi L, Di Gioia M, Vuolo L, Curro D, Roccatagliata L, Filippi M, Aguglia U, Iacopino P, Farge D, Saccardi R; ASTIMS Haemato-Neurological Collaborative Group, On behalf of the Autoimmune Disease Working Party (ADWP) of the European Group for Blood and Marrow Transplantation (EBMT); ASTIMS Haemato-Neurological Collaborative Group On behalf of the Autoimmune Disease Working Party ADWP of the European Group for Blood and Marrow Transplantation EBMT. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology. 2015 Mar 10;84(10):981-8. doi: 10.1212/WNL.0000000000001329. Epub 2015 Feb 11.
• Background Passweg JR, Baldomero H, Bregni M, Cesaro S, Dreger P, Duarte RF, Falkenburg JH, Kroger N, Farge-Bancel D, Gaspar HB, Marsh J, Mohty M, Peters C, Sureda A, Velardi A, Ruiz de Elvira C, Madrigal A; European Group for Blood and Marrow Transplantation. Hematopoietic SCT in Europe: data and trends in 2011. Bone Marrow Transplant. 2013 Sep;48(9):1161-7. doi: 10.1038/bmt.2013.51. Epub 2013 Apr 15.
• Background Reich-Slotky R, Colovai AI, Semidei-Pomales M, Patel N, Cairo M, Jhang J, Schwartz J. Determining post-thaw CD34+ cell dose of cryopreserved haematopoietic progenitor cells demonstrates high recovery and confirms their integrity. Vox Sang. 2008 May;94(4):351-7. doi: 10.1111/j.1423-0410.2007.001028.x. Epub 2008 Jan 2.
• Background Shevchenko JL, Kuznetsov AN, Ionova TI, Melnichenko VY, Fedorenko DA, Kartashov AV, Kurbatova KA, Gorodokin GI, Novik AA. Autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis. Exp Hematol. 2012 Nov;40(11):892-8. doi: 10.1016/j.exphem.2012.07.003. Epub 2012 Jul 4.
• Background Snowden JA, Saccardi R, Allez M, Ardizzone S, Arnold R, Cervera R, Denton C, Hawkey C, Labopin M, Mancardi G, Martin R, Moore JJ, Passweg J, Peters C, Rabusin M, Rovira M, van Laar JM, Farge D; EBMT Autoimmune Disease Working Party (ADWP); Paediatric Diseases Working Party (PDWP). Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012 Jun;47(6):770-90. doi: 10.1038/bmt.2011.185. Epub 2011 Oct 17.
• Background Steinman L. A molecular trio in relapse and remission in multiple sclerosis. Nat Rev Immunol. 2009 Jun;9(6):440-7. doi: 10.1038/nri2548.
• Background Zozulya AL, Wiendl H. The role of regulatory T cells in multiple sclerosis. Nat Clin Pract Neurol. 2008 Jul;4(7):384-98. doi: 10.1038/ncpneuro0832. Epub 2008 Jun 24.

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