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Stem Cell Therapy as a Treatment for Autoimmune Disease—Updates in Lupus, Scleroderma, and Multiple Sclerosis

  • Autoimmunity (TK Tarrant, Section Editor)
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Abstract

Purpose of Review

Evidence for hematopoietic stem cell transplantation (HCT) in autoimmune disease has been building since the 1990s; however, many clinicians may not yet be aware of its applications to autoimmune disease. We review the basic tenets of HCT and evidence for autologous HCT in multiple sclerosis (MS), systemic sclerosis (SSc), and lupus with an emphasis on recent advanced phase trials.

Recent Findings

In MS, the phase 3 randomized MIST trial and the phase 2 randomized ASTIMS trial demonstrated the efficacy of autologous HCT in refractory MS over disease-modifying therapies and mitoxantrone, respectively. In SSc, the phase 3 randomized ASTIS trial and the phase 2 randomized SCOT trial demonstrated the efficacy of autologous HCT in advanced SSc compared to cyclophosphamide.

Summary

The evidence for HCT in autoimmune diseases continues to grow, particularly in MS and SSc. In lupus, large, comparative trials are still needed. Across autoimmune diseases, questions that still remain to be answered include optimizing patient selection to limit TRM, the appropriate use of MAC, and the necessity for graft manipulation. Furthermore, collaboration between disease-specific and transplant physicians is imperative to expand the appropriate use of HCT in routine clinical practice.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 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(2):152–8.

    Article  PubMed  Google Scholar 

  2. Sepriano A, Kerschbaumer A, Smolen JS, van der Heijde D, Dougados M, van Vollenhoven R, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2020;79(6):760–70.

    Article  CAS  PubMed  Google Scholar 

  3. Claflin SB, Broadley S, Taylor BV. The effect of disease modifying therapies on disability progression in multiple sclerosis: a systematic overview of meta-analyses. Front Neurol. 2018;9:1150.

    Article  PubMed  Google Scholar 

  4. Rawla P, Sunkara T, Raj JP. Role of biologics and biosimilars in inflammatory bowel disease: current trends and future perspectives. J Inflamm Res. 2018;11:215–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nelson JL, Torrez R, Louie FM, Choe OS, Storb R, Sullivan KM. Pre-existing autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation. J Rheumatol Suppl. 1997;48:23–9.

    CAS  PubMed  Google Scholar 

  6. Tyndall A, Gratwohl A. 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. 1997;19(7):643–5.

    Article  CAS  PubMed  Google Scholar 

  7. Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, van Laar J, et al. 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;95(2):284–92.

    Article  PubMed  Google Scholar 

  8. Snowden JA, et al. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv. 2017;1(27):2742–55. Review of stem cell transplants across all autoimmune diseases.

  9. Atkins HL, Freedman MS. Five questions answered: a review of autologous hematopoietic stem cell transplantation for the treatment of multiple sclerosis. Neurotherapeutics. 2017;14(4):888–93.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ghimire S, et al. Pathophysiology of GvHD and other HSCT-related major complications. Front Immunol. 2017;8:79.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jagasia M, Arora M, Flowers MED, Chao NJ, McCarthy PL, Cutler CS, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012;119(1):296–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Daikeler T, et al. Allogeneic hematopoietic SCT for patients with autoimmune diseases. Bone Marrow Transplant. 2009;44(1):27–33.

    Article  CAS  PubMed  Google Scholar 

  13. Tyndall A. Successes and failures of stem cell transplantation in autoimmune diseases. Hematol Am Soc Hematol Educ Program. 2011;2011:280–4.

    Article  Google Scholar 

  14. Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM. Genetic and environmental risk factors for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):3–18.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Clarke A, Vyse TJ. Genetics of rheumatic disease. Arthritis Res Ther. 2009;11(5):248.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Oliveira MC, et al. Does ex vivo CD34+ positive selection influence outcome after autologous hematopoietic stem cell transplantation in systemic sclerosis patients? Bone Marrow Transplant. 2016;51(4):501–5. Review of utility of CD34 selection for autologous transplant.

  17. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15(12):1628–33.

    Article  PubMed  PubMed Central  Google Scholar 

  18. D'Souza A, Lee S, Zhu X, Pasquini M. Current use and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant. 2017;23(9):1417–21.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Korbling M, Freireich EJ. Twenty-five years of peripheral blood stem cell transplantation. Blood. 2011;117(24):6411–6.

    Article  CAS  PubMed  Google Scholar 

  20. van Laar JM, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014;311(24):2490–8.

    Article  PubMed  Google Scholar 

  21. Sullivan KM, et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med. 2018;378(1):35–47. Pivotal trial of SCT for Systemic sclerosis.

  22. Auletta JJ, Lazarus HM. Immune restoration following hematopoietic stem cell transplantation: an evolving target. Bone Marrow Transplant. 2005;35(9):835–57.

    Article  CAS  PubMed  Google Scholar 

  23. Majhail NS, Rizzo JD, Lee SJ, Aljurf M, Atsuta Y, Bonfim C, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18(3):348–71.

    Article  PubMed  Google Scholar 

  24. Akizuki M, Reeves JP, Steinberg AD. Expression of autoimmunity by NZB/NZW marrow. Clin Immunol Immunopathol. 1978;10(3):247–50.

    Article  CAS  PubMed  Google Scholar 

  25. Kawamura M, Hisha H, Li Y, Fukuhara S, Ikehara S. Distinct qualitative differences between normal and abnormal hemopoietic stem cells in vivo and in vitro. Stem Cells. 1997;15(1):56–62.

    Article  CAS  PubMed  Google Scholar 

  26. Levite M, Zinger H, Mozes E, Reisner Y. Systemic lupus erythematosus-related autoantibody production in mice is determined by bone marrow-derived cells. Bone Marrow Transplant. 1993;12(3):179–83.

    CAS  PubMed  Google Scholar 

  27. Marmont AM. Stem cell transplantation for severe autoimmune diseases: progress and problems. Haematologica. 1998;83(8):733–43.

    CAS  PubMed  Google Scholar 

  28. Gratwohl A, et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases. Bone Marrow Transplant. 2005;35(9):869–79.

    Article  CAS  PubMed  Google Scholar 

  29. Tyndall A, Black C, Finke J, Winkler J, Mertlesmann R, Peter HH, et al. Treatment of systemic sclerosis with autologous haemopoietic stem cell transplantation. Lancet. 1997;349(9047):254.

    Article  CAS  PubMed  Google Scholar 

  30. 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(2):165–74.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Burt RK, Traynor A, Statkute L, Barr WG, Rosa R, Schroeder J, et al. Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus. JAMA. 2006;295(5):527–35.

    Article  CAS  PubMed  Google Scholar 

  32. Boumpas DT, Austin HA III, Balow JE, Vaughan EM, Yarboro CH, Klippel JH, et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet. 1992;340(8822):741–5.

    Article  CAS  PubMed  Google Scholar 

  33. Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med. 1996;125(7):549–57.

    Article  CAS  PubMed  Google Scholar 

  34. Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354(25):2655–66.

    Article  CAS  PubMed  Google Scholar 

  35. Tehlirian CV, Hummers LK, White B, Brodsky RA, Wigley FM. High-dose cyclophosphamide without stem cell rescue in scleroderma. Ann Rheum Dis. 2008;67(6):775–81.

    Article  CAS  PubMed  Google Scholar 

  36. 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 Exp Med. 2005;201(5):805–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hugle T, Daikeler T. Stem cell transplantation for autoimmune diseases. Haematologica. 2010;95(2):185–8.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lutter L, Spierings J, van Rhijn-Brouwer FCC, van Laar JM, van Wijk F. Resetting the T cell compartment in autoimmune diseases with autologous hematopoietic stem cell transplantation: an update. Front Immunol. 2018;9:767. Review of mechanisms by which transplant may lead to benefit.

  39. Cull G, Hall D, Fabis-Pedrini MJ, Carroll WM, Forster L, Robins F, et al. Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS. Mult Scler J Exp Transl Clin. 2017;3(1):2055217317700167.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Soiffer RJ, et al. Prospective, randomized, double-blind, phase III clinical trial of anti-T-lymphocyte globulin to assess impact on chronic graft-versus-host disease-free survival in patients undergoing HLA-matched unrelated myeloablative hematopoietic cell transplantation. J Clin Oncol. 2017;35(36):4003–11. Pivotal trial of SCT for multiple sclerosis.

  41. Avecilla ST, Goss C, Bleau S, Tonon JA, Meagher RC. How do I perform hematopoietic progenitor cell selection? Transfusion. 2016;56(5):1008–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. 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(2):159–69.

    Article  PubMed  PubMed Central  Google Scholar 

  43. 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(4):459–69.

    Article  PubMed  PubMed Central  Google Scholar 

  44. 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(6):835–42.

    Article  CAS  PubMed  Google Scholar 

  45. 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(10):1116–21.

    Article  PubMed  Google Scholar 

  46. Burt RK, 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(3):275–84.

    Article  PubMed  Google Scholar 

  47. Rae-Grant A, et al. Comprehensive systematic review summary: disease-modifying therapies for adults with multiple sclerosis: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology. 2018;90(17):789–800.

    Article  PubMed  Google Scholar 

  48. 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(2):201–4. Review of effect of transplant on patients with MS.

  49. 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(10):981–8.

    Article  CAS  PubMed  Google Scholar 

  50. Shevchenko JL, Kuznetsov AN, Ionova TI, Melnichenko VY, Fedorenko DA, Kartashov AV, et al. Autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis. Exp Hematol. 2012;40(11):892–8.

    Article  PubMed  Google Scholar 

  51. Shevchenko YL, Novik AA, Kuznetsov AN, Afanasiev BV, Lisukov IA, Kozlov VA, et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Exp Hematol. 2008;36(8):922–8.

    Article  CAS  PubMed  Google Scholar 

  52. Burt RK, 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(3):244–53.

    Article  CAS  PubMed  Google Scholar 

  53. Bowen JD, Kraft GH, Wundes A, Guan Q, Maravilla KR, Gooley TA, et al. Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results. Bone Marrow Transplant. 2012;47(7):946–51.

    Article  CAS  PubMed  Google Scholar 

  54. Del Papa N, et al. Autologous hematopoietic stem cell transplantation for treatment of systemic sclerosis. Front Immunol. 2018;9:2390.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016;4(9):708–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Burt RK, Shah SJ, Dill K, Grant T, Gheorghiade M, Schroeder J, et al. 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. 2011;378(9790):498–506.

    Article  CAS  PubMed  Google Scholar 

  57. Furst DE, Clements PJ, Steen VD, Medsger TA Jr, Masi AT, D'Angelo WA, et al. The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis. J Rheumatol. 1998;25(1):84–8.

    CAS  PubMed  Google Scholar 

  58. DeMarco PJ, Weisman MH, Seibold JR, Furst DE, Wong WK, Hurwitz EL, et al. Predictors and outcomes of scleroderma renal crisis: the high-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial. Arthritis Rheum. 2002;46(11):2983–9.

    Article  CAS  PubMed  Google Scholar 

  59. Caron M, et al. Pulmonary function tests as outcomes for systemic sclerosis interstitial lung disease. Eur Respir Rev. 2018;27(148):170102.

    Article  PubMed  Google Scholar 

  60. Ayano M, Tsukamoto H, Mitoma H, Kimoto Y, Akahoshi M, Arinobu Y, et al. CD34-selected versus unmanipulated autologous haematopoietic stem cell transplantation in the treatment of severe systemic sclerosis: a post hoc analysis of a phase I/II clinical trial conducted in Japan. Arthritis Res Ther. 2019;21(1):30.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721–31.

    Article  CAS  PubMed  Google Scholar 

  62. Borba HH, et al. Efficacy and safety of biologic therapies for systemic lupus erythematosus treatment: systematic review and meta-analysis. BioDrugs. 2014;28(2):211–28.

    Article  CAS  PubMed  Google Scholar 

  63. Duxbury B, Combescure C, Chizzolini C. Rituximab in systemic lupus erythematosus: an updated systematic review and meta-analysis. Lupus. 2013;22(14):1489–503.

    Article  CAS  PubMed  Google Scholar 

  64. Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012;64(4):1215–26.

    Article  CAS  PubMed  Google Scholar 

  65. Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 2010;62(1):222–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Cao C, Wang M, Sun J, Peng X, Liu Q, Huang L, et al. Autologous peripheral blood haematopoietic stem cell transplantation for systemic lupus erythematosus: the observation of long-term outcomes in a Chinese centre. Clin Exp Rheumatol. 2017;35(3):500–7.

    PubMed  Google Scholar 

  67. Leng XM, et al. Good outcome of severe lupus patients with high-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation: a 10-year follow-up study. Clin Exp Rheumatol. 2017;35(3):494–9. Recent demonstrating effiacy of SCT in SLE.

  68. Song XN, Lv HY, Sun LX, Meng JB, Wang JK, Zhang JQ, et al. Autologous stem cell transplantation for systemic lupus erythematosus: report of efficacy and safety at 7 years of follow-up in 17 patients. Transplant Proc. 2011;43(5):1924–7.

    Article  PubMed  Google Scholar 

  69. Loh Y, Oyama Y, Statkute L, Traynor A, Satkus J, Quigley K, et al. Autologous hematopoietic stem cell transplantation in systemic lupus erythematosus patients with cardiac dysfunction: feasibility and reversibility of ventricular and valvular dysfunction with transplant-induced remission. Bone Marrow Transplant. 2007;40(1):47–53.

    Article  CAS  PubMed  Google Scholar 

  70. Jayne D, Tyndall A. Autologous stem cell transplantation for systemic lupus erythematosus. Lupus. 2004;13(5):359–65.

    Article  CAS  PubMed  Google Scholar 

  71. Jayne D, Passweg J, Marmont A, Farge D, Zhao X, Arnold R, et al. Autologous stem cell transplantation for systemic lupus erythematosus. Lupus. 2004;13(3):168–76.

    Article  PubMed  Google Scholar 

  72. Burt RK, Traynor AE, Pope R, Schroeder J, Cohen B, Karlin KH, et al. Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation. Blood. 1998;92(10):3505–14.

    Article  CAS  PubMed  Google Scholar 

  73. Rosen O, Thiel A, Massenkeil G, Hiepe F, Häupl T, Radtke H, et al. Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells. Arthritis Res. 2000;2(4):327–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Tsukamoto H, Nagafuji K, Horiuchi T, Miyamoto T, Aoki K, Takase K, et al. A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease. Ann Rheum Dis. 2006;65(4):508–14.

    Article  CAS  PubMed  Google Scholar 

  75. Petri M, Brodsky RA, Jones RJ, Gladstone D, Fillius M, Magder LS. High-dose cyclophosphamide versus monthly intravenous cyclophosphamide for systemic lupus erythematosus: a prospective randomized trial. Arthritis Rheum. 2010;62(5):1487–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC, USA

    Sendhilnathan Ramalingam

  2. Division of Rheumatology and Immunology, Duke University School of Medicine, Box 3874, Durham, NC, 27710, USA

    Ankoor Shah

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  1. Sendhilnathan Ramalingam
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Highlights

Multiple Sclerosis

(1)ASTIMS (autologous hematopoietic stem cell transplantation in multiple sclerosis)—phase 2 randomized trial of HCT with myeloablative conditioning vs mitoxantrone for refractory RRMS or SPMS. Twenty-one patients were enrolled in this study that showed a 79% reduction in new T2-weighted MRI lesions with HCT; there was no TRM associated with HCT.

(2)MIST (multiple sclerosis international stem cell transplant)—phase 3 randomized trial of 110 patients to HCT with non-myeloablative conditioning vs choice of disease-modifying therapy for refractory RRMS. Disease progression at 5 years occurred in 10% in the HCT group vs 75% in the DMT group; there was no TRM associated with HCT.

Systemic Sclerosis

(1)ASTIS (autologous stem cell transplantation international scleroderma)—phase 3 trial of 156 patients randomized to HCT with non-myeloablative conditioning or cyclophosphamide for severe SSc. Grafts were manipulated to enrich for CD34+ cells. While TRM was 10% in the HCT group, long-term mortality was significantly lower with HCT 16.5% vs 26% with cyclophosphamide. Furthermore, HCT was associated with improved skin disease, pulmonary function, and quality of life over cyclophosphamide.

(2)SCOT (scleroderma: cyclophosphamide or transplantation)—phase 2 trial of 75 patients randomized to HCT with myeloablative conditioning including total body irradiation, or cyclophosphamide for severe SSc. Grafts were manipulated to enrich for CD34+ cells. The global rank composite score, a unique endpoint incorporating several factors including mortality, measures of significant disease, and quality of life, favored HCT at 54 months; HCT was also associated with improved OS at 6 years (86% vs 51%) and significantly lower need for later disease-modifying therapy (9% HCT vs 44%). TRM in the HCT arm was 3% (1 patient) at 54 months and 6% (2 patients) at 72 months with no deaths in the first year.

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Ramalingam, S., Shah, A. Stem Cell Therapy as a Treatment for Autoimmune Disease—Updates in Lupus, Scleroderma, and Multiple Sclerosis. Curr Allergy Asthma Rep 21, 22 (2021). https://doi.org/10.1007/s11882-021-00996-y

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