HIGH-DOSE IMMUNOSUPRESSIVE THERAPY AND STEV HAEMOPOETIC CELL TRANPLANTATION IN REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS WITH KIDNEY INVOLVEMENT: LONG-TERM RESULTS


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Abstract

Aim. Analysis of efficacy of high dose immunosuppressive therapy combined with transplantation of autologous stem cells in systemic lupus erythematosus and lupus nephritis, refractory to standard treatment regimens.
Methods. 10 patients with systemic lupus erythematosus and lupus nephritis, refractory to standard treatment regimens, were included into the study. All patients were women in age 18 - 36 years. 5 patients had lupus nephritis class IV, 5 - lupus nephritis class III. High dose immunosuppressive therapy was performed in 10 of this patients, in 9 of them - in combination with autologous stem cells transplantation. Bone marrow was used as a source of stem cells in 1 patient, in 9 they were mobilized by cyclophosphamide and colony-stimulatinmg factor. Treament efficacy was assessed during 1 and 12 months, 5-year survival was also determined.
Results. Early (day 11 and 22) mortality from infectious complications was detected in 2 patients. In 1 month systemic lupus erythematosus activity decreased from III to I in degree in 6 patients, in 1 patient - from III to II, in 1 patient remission developed without stem cell transplantation. SLEDAI index, as well as serum level of anti-DNA antibodies, erythrocyte sedimentation rate, proteinuria also decreased. In 12 months disease was stable. In final analysis (median 39,6 ± 6,9 months after stem cell transplantation) incomplete remissiom was detected in 6 patients, lupus nephritis progression - in 1. 5-year survival was 78%. Renal mortality was not detected. In early period after stem cell transplantation systemic infectious complications, that lead to death, were detected in 2 patients, neutropenia - in 9, thrombocytopenia - in 5, enteropathy - in 1, mucositis - in 1, curable bacterial infection - in 1. In long term follow-up in 1 mild cytopenia was seen, in 1 - recurrent herpes infection, in 3 - hyperuricemia, in 2 - interstitial nephrititis. In 1 patient renal cell carcinoma was diagnosed and successful kidney resection was performed.
Conclusion. High dose immunosuppressive therapy combined with transplantation of autologous stem cells can be effective in more than 50% of patients with systemic autologous stem cells lupus erythematosus and lupus nephritis, refractory to standard treatment regimens.

References

  1. Клюквина Н.Г., Насонова В.А., Насонов Е.Л. Перспективы применения микофенолата мофетила при прогностически неблагоприятных вариантах системной красной волчанки. РМЖ 2006; 14: 593-599.
  2. Davidson A., Aranow C. Pathogenesis and treatment of systemic lupus erythematosus nephritis Curr Opion Rheumatol. 2006; 18: 468-475.
  3. Goldblatt F., Isenberg D.A. New therapies for systemic lupus erythematosus. Clin Exp Immunol 2005; 140: 205-212.
  4. Сизикова С.А., Лисуков И.Ф., Кулагин А.Д. и соавт. Высокодозная иммуносупрессивная терапия с аутологичной трасплантацией стволовых кроветворных клеток при аутоиммунных заболеваниях. Тер. арх. 2002; 7: 22-26.
  5. Lisukov I.A., Sizikova S.A., Kulagin A.D. et al. High-dose immunosuppression with autologous stem cell transplantation in severe refractory systemic lupus erythematosus. Lupus 2004; 13: 89-94.
  6. Jayne D., Passweg J., Marmont A. et al. Autologous stem cell transplantation for systemic lupus erythematosus. Lupus 2004; 13: 168-176.
  7. Tyndall A. Cellular therapy of systemic lupus erythematosus. Lupus 2009; 18: 387-393.
  8. Burt R.K., Slavin S., Burns W.H., Marmont A.M. Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure? Blood 2002; 99: 768-784.
  9. Marmont A.M. New horizons in the treatment of autoimmune disease: immunoablation and stem cell transplantation. Annu Rev Med 2000; 51: 115-134.
  10. van Bekkum D.W. Autologous stem cell transplantation for treatment autoimmune diseases. Stem Cells 1999; 17: 172-178.
  11. Alexander T., Thiel A., Rosen O. 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 juvenile and tolerant immune system. Blood 2009; 113: 214-223.
  12. Nevessignsky M.T., Ferster A. Hematopoietic stem cell transplantation for severe autoimmune diseases: new perspectives. Nephrol Dial Transplant 2006; 21: 1154-1157.
  13. Ramos R.E., Jimener M.N.E., Salina R.A. Hematopoietic stem cell transplantation in the management of systemic lupus erythematosus resistant to treatment. Rev Alerg Mex 2004; 51: 61-65.
  14. Tyndall A., Gratwohl A. Consensus statement. Blood and marrow stem cell transplants in autoimmune disease. A consensus report written on behalf of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Trasplantation (EBMT). Br J Rheumat 1997; 36: 390-392.
  15. Hugle T., van Laar J.M. Stem cell transplantation for rheumatic autoimmune diseases. Arthritis Research Therapy 2008; 10: 217-226.
  16. Hochberg M.C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.
  17. Bombardier C., Gladman D. Derivation of the SLEDAI. A disease activity index for lupus patients.The committee on prognosis studies in SLE. Arthritis Rheum 1992; 35: 630-640.
  18. Weening JJ <http://www.ncbi.nlm.nih.gov/pubmed?term=%22Weening%20JJ%22%5BAuthor%5D>, D'Agati VD <http://www.ncbi.nlm.nih.gov/pubmed?term=%22D%27Agati%20VD%22%5BAuthor%5D>, Schwartz MM <http://www.ncbi.nlm.nih.gov/pubmed?term=%22Schwartz%20MM%22%5BAuthor%5D>, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. <javascript:AL_get(this,%20'jour',%20'J%20Am%20Soc%20Nephrol.');> 2004 Feb; 15(2):241-50.
  19. Bobba RS, Johnson SR, Davis AM. A review of the Sapporo and revised Sapporo criteria for the classification of antiphospholipid syndrome. Where do the revised Sapporo criteria add value? <http://www.ncbi.nlm.nih.gov/pubmed/17552042> J Rheumatol. 2007 Jul;34(7):1522-7.
  20. Насонова В.А. Системная красная волчанка. М.: Медицина. 1972.
  21. Cutler S.J., Ederer F. Maximum utilization of the life table method in analyzing suevival. J Chron Dis 1958; 8: 699-712.
  22. Talaulikar D., Tymms K.E., Prosser I., Smith R. Autologous blood stem cell transplantation with in vivo T-cell depletion for life threatening refractory systemic lupus erythematosus. Lupus 2004; 14: 159-163.
  23. Sullivan (Chair) K.M., Parkman R., Walters M.C. Bone marrow transplantation for nonmalignant diseases. Hematology 2000; 319-338.
  24. Насонов ЕЛ. Внедрение высоких медицинских технологий в ревматологии: проблемы и решения. Научно-практич. ревматол. 2008; 2: 4-5.
  25. van Bekkum D.W. Immune ablation and stem-cell therapy in autoimmune disease. Arthritis Res 2000; 2: 281-284.
  26. Barron K.S., Wallase C., Woolerey A. et al. Autologous stem cell transplantation for pediatric rheumatic diseases. J Rheumatol 2001; 28: 2337-2358.
  27. Marmont A.M. Immunoablation followered or not by stem cells as an intense therapy for severe autoimmune diseases. New perspectives, new problems. Haematologica 2001; 86: 337-345.
  28. Tyndall A., Gratwohl A. Consensus statement. Blood and marrow stem cell transplants in autoimmune disease. A consensus report written on behalf of the European League Against Rheumatism (EULAR) and the European Group for Blood and Vfrrow Transplantation (EBMT). Br J Rheumat 1997; 36: 390-392.
  29. Brodsky R.A., Petri M., Smith D. et al. Immunoablative high-dose cyclophoshamide without stem-cell rescue for refractory, severe autoimmune diseases. Ann Intern Med 1998; 129: 1031-1035.
  30. Petri M., Jones R.J., Brodsky R.A. High-dose cyclophoshamide without stem cell transplantation in systemic lupus erythematosus. Arthritis Rheum 2003; 48: 166-173.
  31. Petri M., Brodsky R.A. High-dose cyclophoshamide and stem cell transplantation for refractory systemic lupus erythematosus. JAMA 2006; 295: 559-604/
  32. Burt R.K., Traynor A.E., Stakute L. et al. Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus. JAMA 2006; 295: 527-535.
  33. Соловьев С.К., Котовская М.А., Насонов Е.Л. Ритуксимаб в лечении системной красной волчанки. РМЖ. 2005; 13: 1731-1735.
  34. Arzoo K., Sadeghi S., Liebman H. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Ann Rheum Dis 2000; 61: 922-924.
  35. Chambers S.A., Isenberg D. Anti-B cell therapy (rituximab) in the treatment of autoimmune diseases. Lupus 2005; 14: 20-214.
  36. Leandro M.J., Ehrenstein M.R., Edwards J.C. Ttratment of refractory lupus nephritis with B lymphocyte depletion. Arthritis Rheum 2003; 48: 378.
  37. Looney R.J. Treating human autoimmune disease by depleting B cells. Ann Rheum Dis 2002; 61: 863-866.
  38. Tyndall A., Saccardi R. Hematopoietic stem cell transplantation in the treatment of autoimmune disease: results from phase I/II studies, prospective randomized trials and future directions. Clin Exper Immunol 2005; 141: 1-9.
  39. Burt R.K., Marmont A.M., Oyama Y. et al. Randomized controlled trials of hematopoietic stem cell transplantation for autoimmune diseases: the evolution from myeloablative to lymphoablative trasolant regimens. Arthritis Rheum. 2006; 54: 3750-3760.
  40. Kamrava K., Abshey A., Holman P. et al. T-cell depletion improves outcome after autologous stem cell transplantation in patients with systemic lupus erythematosus (SLE). Bone Marrow Transplant. 2005; 35: 205-206.
  41. Bohgaki T., Atsurni T., Koike T. Multiple autoimmune diseases after autologous stem cell transplantation. N Engl J Med 2007; 357: 2734-2736.
  42. Burt R.K., Loh Y., Pearce W. et al. Clinical applications of blood-derived and marrow-derived stem cell for nonmalignant diseases. JAMA 2008; 299: 925-936.
  43. Loh Y., Oyama Y., Statkute L. et al. Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role conditioning regimen used. Blood 2007; 109: 2643-2648.
  44. Parikh C.R., Coca S.G. Acute renal failure in hematopoietic cell transplantation. Kidney Int 2006; 69: 430-435.
  45. Burt R.K., Traynor A.E., Pope R. et al. Treatment of autoimmune diseases by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation. Blood 1998; 92: 3505-3514.
  46. Traynor A.E., Barr W.G., Rosa R.M et al. Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients. Arthritis Rheumat 2002; 46: 2917-2923.
  47. Brunner M., Greinix H.T., Redlich P. et al. Autologous blood stem cell transplantation in refractory systemic lupus erythematosus with severe pulmonary impairment. A case report. Arthritis Rheum 2002; 67: 1580-1584.
  48. Statkute L., Traynor A.E., Oyama Yu et al. Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation. Blood, 2005; 106: 2700-2709.
  49. Voltarelli J.C., Ouyang J. Haematopoietic stem cell transplantation for autoimmune diseases in developing countries: current status and future prospectives. Bone Marrow Trasplant 2003; 32: 69-71.
  50. Farge D., Labopin M., Tyndall A. et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observation study on 12 years of experience from the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Autoimmune Diseases. Haematologica 2010; 95: 284-292

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