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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

Abstract

Some patients with systemic lupus erythematosus (SLE) are refractory to traditional therapies, dependent on chronic corticosteroids, have organ damage, and are at high risk of mortality. In this group of patients, we report outcome at a median of five years after autologous hematopoietic stem cell transplant (HSCT) using two different non-myeloablative regimens. Four patients received a conditioning regimen of cyclophosphamide (200 mg/kg) and alemtuzumab (60 mg), while 26 patients underwent conditioning with cyclophosphamide (200 mg/kg), rATG (Thymoglobulin) (5.5 mg/kg), and rituximab 1000 mg. Unselected peripheral blood stem cells were infused on day 0. There were no treatment related deaths. Of the four patients treated with cyclophosphamide and alemtuzumab, none entered remission. For the 26 patients treated with cyclophosphamide, rATG, and rituximab, disease remission defined as no immune suppressive drugs except hydroxychloroquine and/or 10 mg or less of prednisone a day was 92% at 6 months, 92% at one year, 81% at 2 years, 71% at 3 years, and 62% at 4 and 5 years post-HSCT. Autologous HSCT outcome is dependent on the conditioning regimen but prior organ damage may cause lingering symptoms.

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References

  1. La Paglia GMC, Leone MC, Lepri G, Vagelli R, Valentini E, Alunno A, et al. One year in review 2017: systemic lupus erythematosus. Clin Exp Rheumatol. 2017;35:551–61.

    PubMed  Google Scholar 

  2. Wallace J, Lyon I. Pierre Cazenave and the first detailed modern description of lupus erythematosus. Seminars. Arthritis Rheum. 1999;28:305–13.

    CAS  Article  Google Scholar 

  3. Jacobson DL, Gange SJ, Rose NR, Graham NM. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 1997;84:223–43.

    CAS  Article  Google Scholar 

  4. Hochberg MC, Perlmutter DL, Medsger TA, Steen V, Weisman MH, White B, et al. Prevalence of self-reported physician-diagnosed systemic lupus erythematosus in the USA. Lupus. 1995;4:454–6.

    CAS  Article  Google Scholar 

  5. Cervera R, Abarca-Costalago M, Abramovicz D, Allegri F, Annunziata P, Aydintug AO, et al. Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the “Euro-Lupus Project”. Autoimmun Rev. 2006;5:180–6.

    Article  Google Scholar 

  6. Voss A, Laustrup H, Hjelmborg J, Junker P. Survival in systemic lupus erythematosus, 1995–2010. A prospective study in a Danish community. Lupus. 2013;22:1185–91.

    CAS  Article  Google Scholar 

  7. Tarr T, Papp G, Nagy N, Cserép E, Zeher M. Chronic high-dose glucocorticoid therapy triggers the development of chronic organ damage and worsens disease outcome in systemic lupus erythematosus. Clin Rheumatol. 2017;36:327–33.

    Article  Google Scholar 

  8. 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;295:527–35.

    CAS  Article  Google Scholar 

  9. Burt RK, Loh Y, Pearce W, Beohar N, Barr WG, Craig R, et al. J. Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA. 2008;299:925–36.

    CAS  Article  Google Scholar 

  10. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.

    CAS  Article  Google Scholar 

  11. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992;35:630–40.

    CAS  Article  Google Scholar 

  12. Wilson WA, Gharavi AE, Piette JC. International classification criteria for antiphospholipid syndrome: synopsis of a post-conference workshop held at the Ninth International (Tours) aPL Symposium. Lupus. 2001;10:457–60.

    CAS  Article  Google Scholar 

  13. Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996;39:363–9.

    CAS  Article  Google Scholar 

  14. Petri M, Jones RJ, Brodsky RA. High-dose cyclophosphamide without stem cell transplantation in systemic lupus erythematosus. Arthritis Rheum. 2003;48:166–73.

    CAS  Article  Google Scholar 

  15. Novitzky N, Thomas V, du Toit C. Prevention of graft vs. host disease with alemtuzumab ‘in the bag’ decreases early toxicity of stem cell transplantation and in multiple myeloma is associated with improved long-term outcome. Cytotherapy. 2008;10:45–53.

    CAS  Article  Google Scholar 

  16. Leone A, Radin M, Almarzooqi AM, Al-Saleh J, Roccatello D, Sciascia S, et al. Autologous hematopoietic stem cell transplantation in Systemic Lupus Erythematosus and antiphospholipid syndrome: A systematic review. Autoimmun Rev. 2017;16:469–77.

    Article  Google Scholar 

  17. Illei GG, Cervera R, Burt RK, Doria A, Hiepe F, Jayne D, et al. Current state and future directions of autologous hematopoietic stem cell transplantation in systemic lupus erythematosus. Ann Rheum Dis. 2011;70:2071–4.

    Article  Google Scholar 

  18. Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S, et al. 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. 2009;113:214–23.

    CAS  Article  Google Scholar 

  19. Zhang L, Bertucci AM, Ramsey-Goldman R, Burt RK, Datta SK. Regulatory T cell (Treg) subsets return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+Treg cells are associated with immunological remission of lupus. J Immunol. 2009;183:6346–58.

    CAS  Article  Google Scholar 

  20. van Vollenhoven RF, Voskuyl A, Morand E, Aranow C. Remission in SLE: closing in on the target. Ann Rheum Dis. 2015;74:2103–6.

    Article  Google Scholar 

  21. Wilhelm TR, Magder LS, Petri M. Remission in systemic lupus erythematosus: durable remission is rare. Ann Rheum Dis. 2017;76:547–53.

    Article  Google Scholar 

  22. Chambers SA, Allen E, Rahman A, Isenberg D. Damage and mortality in a group of British patients with systemic lupus erythematosus followed up for over 10 years. Rheumatology. 2009;48:673–5.

    Article  Google Scholar 

  23. Conti F, Ceccarelli F, Perricone C, Leccese I, Massaro L, Pacucci VA, et al. The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort. Lupus. 2016;25:719–26.

    CAS  Article  Google Scholar 

  24. Rahman P, Gladman DD, Urowitz MB, Hallett D, Tam LS. Accrual of organ damage over time in patients with systemic lupus erythematosus. Lupus. 2001;10:93–6.

    CAS  Article  Google Scholar 

  25. Gladman DD, Urowitz MB, Rahman P, Ibañez D, Tam LS. Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol. 2003;30:1955–9.

    PubMed  Google Scholar 

  26. Banchereau R, Hong S, Cantarel B, Baldwin N, Baisch J, Edens M, et al. Personalized immunomonitoring uncovers molecular networks that stratify lupus patients. Cell . 2016;165:1548–50.

    CAS  Article  Google Scholar 

  27. Banchereau R, Cepika AM, Banchereau J, Pascual V. Understanding human autoimmunity and autoinflammation through transcriptomics. Annu Rev Immunol. 2017;35:337–70.

    CAS  Article  Google Scholar 

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Correspondence to Richard K. Burt.

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Burt, R.K., Han, X., Gozdziak, P. et al. 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 (2018). https://doi.org/10.1038/s41409-018-0173-x

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