1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Medicine
  4. Volume 72, 2021
  5. Article

Annual Review of Medicine

Volume 72, 2021

Hematopoietic Stem Cell Transplantation for Autoimmune Disease

Abstract

The introduction of targeted biologic therapies has changed the treatment landscape for autoimmune diseases (ADs) substantially, but although these therapies provide more specificity, they require continuous administration, rarely restore organ function or reverse disability, and are not curative. Over the last 25 years, hematopoietic stem cell transplantation (HSCT) has been increasingly used to treat patients in whom the risk:benefit ratio of HSCT is acceptable. In contrast to chronic suppression of immune function, this intensive one-off procedure aims to provide treatment-free remissions by the reinduction of self-tolerance. The European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) has been central to development of this approach, with over 3,300 HSCT registrations for ADs. Recent data have improved the evidence base to support autologous HSCT in multiple sclerosis, systemic sclerosis, and Crohn's disease, along with a wide range of rarer disease indications, and autologous HSCT has become an integral part of treatment algorithms in various ADs.

Keyword(s): autoimmune diseases, autoimmunity, cell therapy, Crohn's disease, hematopoietic stem cell transplantation, HSCT, multiple sclerosis, systemic sclerosis
Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-070119-115617
2021-01-27
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/med/72/1/annurev-med-070119-115617.html?itemId=/content/journals/10.1146/annurev-med-070119-115617&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Rose NR. 2016. Prediction and prevention of autoimmune disease in the 21st century: a review and preview. Am. J. Epidemiol. 183:403–6
     [Google Scholar]
  2. 2. 
    Tappenden P, Wang Y, Sharrack B et al. 2019. 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). Bone Marrow Transplant 55:1473–75
     [Google Scholar]
  3. 3. 
    Wang L, Wang FS, Gershwin ME 2015. Human autoimmune diseases: a comprehensive update. J. Intern. Med. 278:369–95
     [Google Scholar]
  4. 4. 
    Snowden JA, Badoglio M, Labopin M et al. 2017. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv 1:2742–55
     [Google Scholar]
  5. 5. 
    Passweg JR, Baldomero H, Bader P et al. 2018. 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 53:1139–48
     [Google Scholar]
  6. 6. 
    Duarte RF, Labopin M, Bader P et al. 2019. Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant 54:1525–52
     [Google Scholar]
  7. 7. 
    Alexander T, Arnold R, Hiepe F, Radbruch A 2016. Resetting the immune system with immunoablation and autologous haematopoietic stem cell transplantation in autoimmune diseases. Clin. Exp. Rheumatol. 34:53–57
     [Google Scholar]
  8. 8. 
    Swart JF, Delemarre EM, van Wijk F et al. 2017. Haematopoietic stem cell transplantation for autoimmune diseases. Nat. Rev. Rheumatol. 13:244–56
     [Google Scholar]
  9. 9. 
    Abrahamsson S, Muraro PA. 2008. Immune re-education following autologous hematopoietic stem cell transplantation. Autoimmunity 41:577–84
     [Google Scholar]
  10. 10. 
    Arruda LCM, Malmegrim KCR, Lima-Junior JR et al. 2018. Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients. Blood Adv 2:126–41
     [Google Scholar]
  11. 11. 
    Alexander T, Thiel A, Rosen O et al. 2009. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood 113:214–23
     [Google Scholar]
  12. 12. 
    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. 201:805–16
     [Google Scholar]
  13. 13. 
    Delemarre EM, van den Broek T, Mijnheer G et al. 2016. Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells. Blood 127:91–101
     [Google Scholar]
  14. 14. 
    Alexander T, Samuelson C, Daikeler T et al. 2019. Autologous haematopoietic stem cell transplantation (HSCT) for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: a retrospective survey of patients reported to European Society for Blood and Marrow Transplantation (EBMT) registry. Bone Marrow Transplant 55:1512–15
     [Google Scholar]
  15. 15. 
    Snowden JA, Passweg J, Moore JJ et al. 2004. Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR. J. Rheumatol. 31:482–88
     [Google Scholar]
  16. 16. 
    Lindsay JO, Allez M, Clark M, Labopin M, Ricart E et al. 2017. Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an analysis of pooled data from the ASTIC trial. Lancet Gastroenterol. Hepatol. 2:399–406
     [Google Scholar]
  17. 17. 
    Snowden JA, Panes J, Alexander T et al. 2018. Autologous haematopoietic stem cell transplantation (AHSCT) in severe Crohn's disease: a review on behalf of ECCO and EBMT. J. Crohn's Colitis 12:476–88
     [Google Scholar]
  18. 18. 
    Jessop H, Farge D, Saccardi R et al. 2019. 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 54:933–42
     [Google Scholar]
  19. 19. 
    Sharrack B, Saccardi R, Alexander T et al. 2020. 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 55:283–306
     [Google Scholar]
  20. 20. 
    Farge D, Burt RK, Oliveira MC et al. 2017. Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners. Bone Marrow Transplant 52:1495–503
     [Google Scholar]
  21. 21. 
    Fassas A, Anagnostopoulos A, Kazis A et al. 1997. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant 20:631–38
     [Google Scholar]
  22. 22. 
    Tyndall A, Gratwohl A. 1997. Blood and marrow stem cell transplants 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 19:643–45
     [Google Scholar]
  23. 23. 
    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 8:244–53
     [Google Scholar]
  24. 24. 
    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 102:2364–72
     [Google Scholar]
  25. 25. 
    Saiz A, Blanco Y, Carreras E et al. 2004. Clinical and MRI outcome after autologous hematopoietic stem cell transplantation in MS. Neurology 62:282–84
     [Google Scholar]
  26. 26. 
    Krasulova E, Trneny M, Kozak 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. 16:685–93
     [Google Scholar]
  27. 27. 
    Fassas A, Kimiskidis VK, Sakellari I et al. 2011. Long-term results of stem cell transplantation for MS: a single-center experience. Neurology 76:1066–70
     [Google Scholar]
  28. 28. 
    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. 18:835–42
     [Google Scholar]
  29. 29. 
    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 85:1116–21
     [Google Scholar]
  30. 30. 
    Shevchenko JL, Kuznetsov AN, Ionova TI et al. 2012. Autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis. Exp. Hematol. 40:892–98
     [Google Scholar]
  31. 31. 
    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 72:159–69
     [Google Scholar]
  32. 32. 
    Burt RK, Balabanov R, Han X et al. 2015. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA 313:275–84
     [Google Scholar]
  33. 33. 
    Radaelli M, Merlini A, Greco R et al. 2014. Autologous bone marrow transplantation for the treatment of multiple sclerosis. Curr. Neurol. Neurosci. Rep. 14:478
     [Google Scholar]
  34. 34. 
    Burt RK, Balabanov R, Voltarelli J et al. 2012. 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. 18:772–75
     [Google Scholar]
  35. 35. 
    Bell SM, Sharrack B, Snowden JA 2017. Autologous hematopoietic cell transplantation in multiple sclerosis. Expert Opin. Biol. Ther. 17:77–86
     [Google Scholar]
  36. 36. 
    Fagius J, Lundgren J, Oberg G 2009. Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult. Scler. 15:229–37
     [Google Scholar]
  37. 37. 
    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. 18:825–34
     [Google Scholar]
  38. 38. 
    Snowden JA, Badoglio M, Labopin M et al. 2017. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv 1:2742–55
     [Google Scholar]
  39. 39. 
    Muraro PA, Pasquini M, Atkins HL et al. 2017. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurol 74:459–69
     [Google Scholar]
  40. 40. 
    Muraro PA, Martin R, Mancardi GL et al. 2017. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat. Rev. Neurol. 13:391–405
     [Google Scholar]
  41. 41. 
    Mancardi GL, Sormani MP, Gualandi F et al. 2015. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology 84:981–88
     [Google Scholar]
  42. 42. 
    Nash RA, Hutton GJ, Racke MK et al. 2017. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology 88:842–52
     [Google Scholar]
  43. 43. 
    Atkins HL, Bowman M, Allan D et al. 2016. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet 388:576–85
     [Google Scholar]
  44. 44. 
    Mancardi GL, Murialdo A, Rossi P et al. 2005. Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Mult. Scler. 11:367–71
     [Google Scholar]
  45. 45. 
    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. 260:914–16
     [Google Scholar]
  46. 46. 
    Burt RK, Balabanov R, Burman J et al. 2019. Effect of nonmyeloablative hematopoietic stem cell transplantation versus continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis: a randomized clinical trial. JAMA 321:165–74
     [Google Scholar]
  47. 47. 
    Giovannoni G, Turner B, Gnanapavan S et al. 2015. Is it time to target no evident disease activity (NEDA) in multiple sclerosis. Mult. Scler. Relat. Disord. 4:329–33
     [Google Scholar]
  48. 48. 
    Ismail A, Sharrack B, Saccardi R et al. 2019. Autologous haematopoietic stem cell therapy for multiple sclerosis: a review for supportive care clinicians on behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation. Curr. Opin. Support. Palliat. Care 13:394–401
     [Google Scholar]
  49. 49. 
    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 46:2301–9
     [Google Scholar]
  50. 50. 
    Brinkman DM, de Kleer IM, ten Cate R et al. 2007. Autologous stem cell transplantation in children with severe progressive systemic or polyarticular juvenile idiopathic arthritis: long-term follow-up of a prospective clinical trial. Arthritis Rheum 56:2410–21
     [Google Scholar]
  51. 51. 
    Burt RK, Traynor A, Statkute L et al. 2006. Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus. JAMA 295:527–35
     [Google Scholar]
  52. 52. 
    Alchi B, Jayne D, Labopin M et al. 2013. Autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: data from the European Group for Blood and Marrow Transplantation registry. Lupus 22:245–53
     [Google Scholar]
  53. 53. 
    Burt RK, Han X, Gozdziak P et al. 2018. 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 53:692–700
     [Google Scholar]
  54. 54. 
    Snowden JA, Saccardi R, Allez M et al. 2012. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 47:770–90
     [Google Scholar]
  55. 55. 
    Burt RK, Shah SJ, Dill K et al. 2011. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet 378:498–506
     [Google Scholar]
  56. 56. 
    van Laar JM, Farge D, Sont JK et al. 2014. Autologous hematopoietic stem cell transplantation versus intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA 311:2490–98
     [Google Scholar]
  57. 57. 
    Sullivan KM, Goldmuntz EA, Furst DE 2018. Autologous stem-cell transplantation for severe scleroderma. N. Engl. J. Med. 378:1066–67
     [Google Scholar]
  58. 58. 
    Henes J, Oliveira MC, Labopin M et al. 2020. Autologous stem cell transplantation for progressive systemic sclerosis: a prospective non-interventional study from the European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party. Haematologica 105: In press. https://doi.org/10.3324/haematol.2019.230128
    [Crossref] [Google Scholar]
  59. 59. 
    Kowal-Bielecka O, Fransen J, Avouac J et al. 2017. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann. Rheum. Dis. 76:1327–39
     [Google Scholar]
  60. 60. 
    Oyama Y, Craig RM, Traynor AE et al. 2005. Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease. Gastroenterology 128:552–63
     [Google Scholar]
  61. 61. 
    Snowden JA, Ansari A, Sachchithanantham S et al. 2014. Autologous stem cell transplantation in severe treatment-resistant Crohn's disease: long-term follow-up of UK patients treated on compassionate basis. QJM 107:871–77
     [Google Scholar]
  62. 62. 
    Jauregui-Amezaga A, Rovira M, Marin P et al. 2016. Improving safety of autologous haematopoietic stem cell transplantation in patients with Crohn's disease. Gut 65:1456–62
     [Google Scholar]
  63. 63. 
    Lopez-Garcia A, Rovira M, Jauregui-Amezaga A et al. 2017. Autologous haematopoietic stem cell transplantation for refractory Crohn's disease: efficacy in a single-centre cohort. J. Crohn's Colitis 11:1161–68
     [Google Scholar]
  64. 64. 
    Ruiz MA, Kaiser RL Jr., de Quadros LG et al. 2017. Low toxicity and favorable clinical and quality of life impact after non-myeloablative autologous hematopoietic stem cell transplant in Crohn's disease. BMC Res. Notes 10:495
     [Google Scholar]
  65. 65. 
    Brierley CK, Castilla-Llorente C, Labopin M et al. 2018. Autologous haematopoietic stem cell transplantation for Crohn's disease: a retrospective survey of long-term outcomes from the European Society for Blood and Marrow Transplantation. J. Crohn's Colitis 12:1097–103
     [Google Scholar]
  66. 66. 
    Hawkey CJ, Allez M, Clark MM et al. 2015. Autologous hematopoetic stem cell transplantation for refractory Crohn disease: a randomized clinical trial. JAMA 314:2524–34
     [Google Scholar]
  67. 67. 
    Snowden JA, Hawkey C, Hind D et al. 2019. Autologous stem cell transplantation in refractory Crohn's disease—low intensity therapy evaluation (ASTIClite): study protocols for a multicentre, randomised controlled trial and observational follow up study. BMC Gastroenterol 19:82
     [Google Scholar]
  68. 68. 
    Pockley AG, Lindsay JO, Foulds GA et al. 2018. Immune reconstitution after autologous hematopoietic stem cell transplantation in Crohn's disease: current status and future directions. A review on behalf of the EBMT Autoimmune Diseases Working Party and the Autologous Stem Cell Transplantation In Refractory CD—Low Intensity Therapy Evaluation Study Investigators. Front. Immunol. 9:646
     [Google Scholar]
  69. 69. 
    Sureda A, Bader P, Cesaro S et al. 2015. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant 50:1037–56
     [Google Scholar]
  70. 70. 
    Bernardo ME, Piras E, Vacca A et al. 2012. Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan. Blood 120:473–76
     [Google Scholar]
  71. 71. 
    Greco R, Bondanza A, Vago L et al. 2014. Allogeneic hematopoietic stem cell transplantation for neuromyelitis optica. Ann. Neurol. 75:447–53
     [Google Scholar]
  72. 72. 
    Daikeler T, Hugle T, Farge D et al. 2009. Allogeneic hematopoietic SCT for patients with autoimmune diseases. Bone Marrow Transplant 44:27–33
     [Google Scholar]
  73. 73. 
    Rabusin M, Snowden JA, Veys P et al. 2013. Long-term outcomes of hematopoietic stem cell transplantation for severe treatment-resistant autoimmune cytopenia in children. Biol. Blood Marrow Transplant. 19:666–69
     [Google Scholar]
  74. 74. 
    Oyama Y, Traynor AE, Barr W, Burt RK 2003. Allogeneic stem cell transplantation for autoimmune diseases: nonmyeloablative conditioning regimens. Bone Marrow Transplant 32:Suppl. 1S81–83
     [Google Scholar]
  75. 75. 
    Passweg JR, Rabusin M, Musso M et al. 2004. Haematopoetic stem cell transplantation for refractory autoimmune cytopenia. Br. J. Haematol. 125:749–55
     [Google Scholar]
  76. 76. 
    Nash RA. 2003. Allogeneic HSCT for autoimmune diseases: conventional conditioning regimens. Bone Marrow Transplant 32:Suppl. 1S77–80
     [Google Scholar]
  77. 77. 
    Luznik L, Fuchs EJ. 2010. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation. Immunol. Res. 47:65–77
     [Google Scholar]
  78. 78. 
    Bonifazi F, Rubio MT, Bacigalupo A et al. 2020. Rabbit ATG/ATLG in preventing graft-versus-host disease after allogeneic stem cell transplantation: consensus-based recommendations by an international expert panel. Bone Marrow Transplant 55:1093–102
     [Google Scholar]
  79. 79. 
    Gooley TA, Chien JW, Pergam SA et al. 2010. Reduced mortality after allogeneic hematopoietic-cell transplantation. N. Engl. J. Med. 363:2091–101
     [Google Scholar]
  80. 80. 
    Greco R, Labopin M, Badoglio M et al. 2019. Allogeneic HSCT for autoimmune diseases: a retrospective study from the EBMT ADWP, IEWP, and PDWP Working Parties. Front. Immunol. 10:1570
     [Google Scholar]
  81. 81. 
    Passweg JR, Baldomero H, Basak GW et al. 2019. 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 54:1575–85
     [Google Scholar]
/content/journals/10.1146/annurev-med-070119-115617
Loading
Hematopoietic Stem Cell Transplantation for Autoimmune Disease
Annual Review of Medicine 72, 215 (2021); https://doi.org/10.1146/annurev-med-070119-115617
/content/journals/10.1146/annurev-med-070119-115617
/content/journals/10.1146/annurev-med-070119-115617
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error