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01-06-2016 | Review Article

Autologous hematopoietic stem cell transplantation in multiple sclerosis: 20 years of experience

Authors: Daniela Currò, Gianluigi Mancardi

Published in: Neurological Sciences | Issue 6/2016

Abstract

Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) has been widely used in the last 20 years for the treatment of aggressive forms of autoimmune disorders, especially multiple sclerosis (MS). All clinical studies, although small and uncontrolled, demonstrate a great efficacy of this procedure in halting inflammation and disease activity, even in those patients affected by “malignant forms” of MS. The long-term follow-up has also revealed the possible maintenance of positive results in the course of time, and this evidence is supported by immunological data that suggest the possibility of a resetting of the immune system after AHSCT. The safety of AHSCT has improved in the last years, but the transplant related mortality is still nowadays of about 1-2 %, pointing out that a careful selection of patients to submit to AHSCT is mandatory. The long clinical experience allowed to identify the ideal candidate: a young patient, with a short disease duration, with recurring and disabling relapses and the presence of inflammatory activity on brain magnetic resonance scans, unresponsive to approved therapies. A large, randomized clinical study comparing AHSCT with the best approved therapies is still necessary to confirm the role of transplantation in MS treatment.

Van Gelder M, van Bekkum DW (1995) Treatment of relapsing experimental autoimmune encephalomyelitis in rats with allogeneic bone marrow transplantation from a resistant strain. Bone Marrow Transplant 16:343–351PubMed

Van Gelder M, Kinwel-Bohré EP, van Bekkum DW (1993) Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT. Bone Marrow Transplant 11:233–241PubMed

Van Gelder M, van Bekkum DW (1996) Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation. Bone Marrow Transplant 18:1029–1034PubMed

Fassas A, Anagnostopoulos A, Kazis A et al (1997) Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first result of a pilot study. Bone Marrow Transplant 20:631–638CrossRefPubMed

Statkute L, Verda L, Oyama Y et al (2007) Mobilization, harvesting and selection of peripheral blood stem cells in patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 39:317–329CrossRefPubMed

Dubinsky AN, Burt RK, Martin R, Muraro PA (2010) T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft. Bone Marrow Transplant 45:325–331CrossRefPubMed

Nash RA, Bowen JD, McSweeney PA et al (2003) High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Blood 102:2364–2372CrossRefPubMedPubMedCentral

Statkute L, Verda L, Oyama Y et al (2000) Mobilization, harvesting and selection of peripheral blood stem cells in patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 39:317–329CrossRef

Carreras E, Saiz A, Marin P et al (2003) CD34+ selected autologous peripheral blood stem cell transplantation for multiple sclerosis: report of the toxicity and treatment results at one year follow-up in 15 patients. Hematologica 88:306–314

10.

Burt RK, Cohen BA, Russel E et al (2003) Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of intense immune suppression to prevent disease progression in patients with high disability scores. Blood 102:2373–2378CrossRefPubMed

11.

Moore J, Brooks P, Milliken S et al (2002) A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis. Arthritis Rheum 46:2301–2309CrossRefPubMed

12.

Samijn JP, te Boekhorst PA, Mondria T et al (2006) Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis. J Neurol Neurosurg Psychiatry 77:46–50CrossRefPubMedPubMedCentral

13.

Openshaw H, Lund BT, Kashyap A et al (2000) Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: report of toxicity and immunological monitoring. Biol Blood Marrow Transplant 6:563–575CrossRefPubMed

14.

Freedman MS, Atkins DL, Arnold A et al (2007) Immune ablation and autologous stem cell transplantation for aggressive multiple sclerosis: interim 5 year report (abstract). Mult Scler 13(suppl 2):S22

15.

Fassas A, Kimiskidis VK, Sakellari I et al (2011) Long-term results of stem cell transplantation for MS: a single-center experience. Neurology 76:1066–1070CrossRefPubMed

16.

Gratwohl A, Passweg J, Bocelli-Tyndall C et al (2005) Autologous hematopoietic stem cell transplantation for autoimmune diseases. Bone Marrow Transplant 35:869–879CrossRefPubMed

17.

Saccardi R, Kozak T, Bocelli-Tyndall C et al (2006) 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 12:814–823CrossRefPubMed

18.

Chen B, Zhou M, Ouyang J et al (2012) Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China. Neurol Sci 33:881–886CrossRefPubMed

19.

Hamerschlak N, Rodrigues M, Moraes DA et al (2010) Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG. Bone Marrow Transplant 45:239–248CrossRefPubMed

20.

Burman J, Iacobaeus E, Svenningsson A et al (2014) Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience. J Neurol Neurosurg Psychiatry 85:1116–1121CrossRefPubMed

21.

Krasulová E, Trneny M, Kozák T et al (2010) High-dose immunoablation with autologous haematopoietic stem cell transplantation in aggressive multiple sclerosis: a single centre 10-year experience. Mult Scler 16:685–693CrossRefPubMed

22.

Shevchenko YL, Novik AA, Kuznetsov AN et al (2008) High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Exp Hematol 36:922–928CrossRefPubMed

23.

Xu J, Ji BX, Dong HQ, Sun XJ, Liu CY (2006) Clinical outcomes after autologous haematopoietic stem cell transplantation in patients with progressive multiple sclerosis. Chin Med J (Engl) 119:1851–1855

24.

Mancardi GL, Sormani MP, Di Gioia M et al (2012) Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience. Mult Scler 18:835–842CrossRefPubMed

25.

Nash RA, Hutton GJ, Racke MK et al (2015) High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing–remitting multiple sclerosis (HALT-MS). A 3-year interim report. JAMA Neurol 72(2):159–169CrossRefPubMed

26.

Saiz A, Blanco Y, Berenguer J et al (2008) Clinical outcome 6 years after autologous hematopoietic stem cell transplantation in multiple sclerosis. Neurologia 23:405–407PubMed

27.

Shevchenko YL, Novik AA, Kuznetsov AN et al (2012) High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Exp Hematol 40:892–898CrossRefPubMed

28.

Burt RK, Loh Y, Cohen B et al (2009) Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol 8:244–253CrossRefPubMed

29.

Curro’ D, Vuolo L, Gualandi F et al. (2015) 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 11:1423–1430CrossRef

30.

Fassas A, Passweg JR, Anagnostopoulos A et al (2002) Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol 249:1088–1097CrossRefPubMed

31.

Farge D, Labopin M, Tyndall A et al (2010) 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 95:284–292CrossRefPubMed

32.

Shevchenko JL, Kuznetsov AN, Ionova TI et al (2015) Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician’s and patient’s perspectives. Ann Hematol 94:1149–1157CrossRefPubMed

33.

Burt RK, Balabanov R, Han X et al (2015) Association of non myeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing–remitting multiple sclerosis. JAMA 313:275–284CrossRefPubMed

34.

Hauser SL (2015) Hematopoietic stem cell transplantation for MS: extraordinary evidence still needed. JAMA 313:251–252CrossRefPubMed

35.

Gholipour T, Haely B, Baruch NF et al (2011) Demographic and clinical characteristics of malignant multiple sclerosis. Neurology 76:1996–2001CrossRefPubMed

36.

Mancardi GL, Murialdo A, Rossi P et al (2005) Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Mult Scler 11:367–371CrossRefPubMed

37.

Alix JJ, Blackburn DJ, Sokhi D et al (2013) Autologous hematopoietic stem cell transplantation following pulsed cyclophosphamide in a severely disabled patient with malignant multiple sclerosis. J Neurol 260:914–916CrossRefPubMed

38.

Fagius J, Lundgren J, Oberg G (2009) Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler 15:229–237CrossRefPubMed

39.

Saccardi R, Mancardi G, Solari A et al (2005) Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life. Blood 105:2601–2607CrossRefPubMed

40.

Guimarães FAB, De Oliveira-Cardoso EA, Mastropietro AP et al (2010) Impact of autologous hematopoietic stem cell transplantation on the quality of life of patients with multiple sclerosis. Arq Neuropsiquiatr 68:522–527CrossRefPubMed

41.

Mancardi GL, Saccardi R, Filippi M et al (2001) Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. Neurology 57:62–68CrossRefPubMed

42.

Chen JT, Collins DL, Atkins HL et al (2006) Brain atrophy after immunoablation and stem cell transplantation in multiple sclerosis. Neurology 66:1935–1937CrossRefPubMed

43.

Inglese M, Mancardi GL, Pagani E et al (2004) Brain tissue loss occurs after suppression of enhancement in patients with multiple sclerosis treated with autologous haematopoietic stem cell transplantation. J Neurol Neurosurg Psychiatry 75:643–644PubMedPubMedCentral

44.

Roccatagliata L, Rocca MA, Valsasina P et al (2007) The long-term effect of AHSCT on MRI measures of MS evolution: a five-year follow-up study. Mult Scler 13:1068–1070CrossRefPubMed

45.

Rocca MA, Mondria T, Valsasina P et al (2007) A three-year study of brain atrophy after autologous hematopoietic stem cell transplantation in rapidly evolving secondary progressive multiple sclerosis. Am J Neuroradiol 28:1659–1661CrossRefPubMed

46.

Daikeler T, Labopin M, Di Gioia M et al (2011) Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party. Blood 118:1693–1698CrossRefPubMed

47.

Snarski E, Snowden JA, Oliveira MC et al (2015) 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 50:216–220CrossRefPubMed

48.

Calvet L, Cabrespine A, Boiret-Dupré N et al (2013) Hematologic, immunologic reconstitution, and outcome of 342 autologous peripheral blood stem cell transplantations after cryopreservation in a −80 °C mechanical freezer and preserved less than 6 months. Transfusion 53:570–578CrossRefPubMed

49.

Muraro PA, Douek DC, Packer A et al (2005) Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med 201(805):816

50.

Muraro PA, Robins H, Malhotra S et al (2014) T cell repertoire following autologous stem cell transplantation for multiple sclerosis. J Clin Invest 124:1168–1172CrossRefPubMedPubMedCentral

51.

Darlington PJ, Touil T, Doucet JS et al (2013) Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation. Ann Neurol 73:341–354CrossRefPubMed

52.

Abrahamsson SV, Angelini DF, Dubinsky AN et al (2013) Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis. Brain 136:2888–2903CrossRefPubMedPubMedCentral

53.

Mancardi GL, Sormani MP, Gualandi F et al (2015) Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology 84:981–988CrossRefPubMed

54.

Kozak T, Havrdova E, Pit’ha J et al (2008) Immunoablative therapy with autologous PBPC transplantation in the treatment of poor risk multiple sclerosis. Bone Marrow Transplant 41(suppl 1):S18

55.

Ni XS, Ouyang J, Zhu WH et al (2006) Autologous hematopoietic stem cell transplantation for progressive multiple sclerosis: report of efficacy and safety at three years of follow-up in 21 patients. Clin Transplant 20:485–489CrossRefPubMed

56.

Bowen JD, Kraft GH, Wundes A et al (2012) Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results. Bone Marrow Transplant 47:946–951CrossRefPubMed

57.

Saccardi R, Freedman MS, Sormani MP et al (2012) A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper. Mult Scler 18:825CrossRefPubMedPubMedCentral

Title: Autologous hematopoietic stem cell transplantation in multiple sclerosis: 20 years of experience
Authors: Daniela Currò
Gianluigi Mancardi
Publication date: 01-06-2016
Publisher: Springer Milan
Published in: Neurological Sciences / Issue 6/2016
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-016-2564-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Autologous hematopoietic stem cell transplantation in multiple sclerosis: 20 years of experience

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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