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Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study

Annals of Hematology volume 89, pages 851–859 (2010)Cite this article

Abstract

The best antithymocyte globulin preparation for first-line immune suppression in patients with severe aplastic anemia is still not clear. The aim of this study was to compare hematological response and overall survival in patients submitted to horse or rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia. We retrospectively compared 71 consecutive patients with severe aplastic anemia, classified according to the antithymocyte globulin preparation. Analyses included variables related to patients and to immune suppression. Forty two patients (59.1%) received horse and 29 (40.9%) rabbit antithymocyte globulin. Response rates were higher at 6 months in patients submitted to horse in comparison to rabbit antithymocyte globulin (59.5% versus 34.5% respectively, p = 0.05). Median time to response was similar between the two groups (99 versus 88.5 days, respectively, for horse and rabbit antithymocyte globulin; p = 0.98). Overall survival at 2 years was significantly higher in patients submitted to horse in comparison to rabbit antithymocyte globulin (78.4% versus 55.4%, p = 0.03). Post-treatment response was strongly associated with survival at 2 years (97% in responders versus 41.2% in non-responders, p < 0.001). Use of rabbit antithymocyte globulin was an independent predictor of death (odds ratio 2.5; 95% confidence interval 1.03–6.04; p = 0.04). Rabbit antithymocyte globulin was associated with a significant and prolonged lymphopenia in comparison with horse antithymocyte globulin. Our data suggest the superiority of horse over rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia, both regarding hematological response and survival.

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References

  1. Bacigalupo A, Passweg J (2009) Diagnosis and treatment of acquired aplastic anemia. Hematol Oncol Clin North Am 23:159–170

    Article  PubMed  Google Scholar 

  2. Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC et al (2009) Guidelines for the diagnosis and management of acquired aplastic anaemia. Br J Haematol 147:43–70

    Article  CAS  PubMed  Google Scholar 

  3. Champlin R, Ho W, Gale RP (1983) Antithymocyte globulin treatment in patients with aplastic anemia. N Engl J Med 308:113–118

    Article  CAS  PubMed  Google Scholar 

  4. Frickhofen N, Heimpel H, Kaltwasser GP, Schrezenmeier H (2003) Antithymocyte globulin with or without cyclosporine A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood 101:1236–1242

    Article  CAS  PubMed  Google Scholar 

  5. Bacigalupo A, Bruno B, Saracco P, Di Bona E, Locasciulli A, Locatelli F et al (2000) Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. Blood 95:1931–1934

    CAS  PubMed  Google Scholar 

  6. Rosenfeld S, Follmann D, Nunez O, Young NS (2003) Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA 289:1130–1135

    Article  CAS  PubMed  Google Scholar 

  7. Mohty M (2007) Mechanisms of action of antithymocyte globulin: T cell depletion and beyond. Leukemia 21:1387–1394

    Article  CAS  PubMed  Google Scholar 

  8. Di Bona E, Rodeghiero F, Bruno B, Gabbas A, Foa P, Locasciulli A et al (1999) Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy. Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Br J Haematol 107:330–334

    Article  PubMed  Google Scholar 

  9. Scheinberg P, Nunez O, Young NS (2006) Retreatment with rabbit anti-thymocyte globulin and ciclosporin for patients with relapsed or refractory severe aplastic anaemia. Br J Haematol 133:622–627

    Article  CAS  PubMed  Google Scholar 

  10. Bacigalupo A, Hows JM, Gluckman E, Nissen C, Marsh J, Van Lint MT et al (1988) Bone marrow transplantation (BMT) versus immunosuppression for the treatment of severe aplastic anaemia (SAA): a report of the EBMT SAA Working Party. Br J Haematol 70:177–182

    Article  CAS  PubMed  Google Scholar 

  11. Scheinberg Ph WuCO, Nunez O, Pr S, Boss C, Sloand EM et al (2009) Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporin, with or without sirolimus: a prospective randomized study. Haematologica 94:348–354

    Article  CAS  Google Scholar 

  12. Valdez JM, Scheinberg P, Young NS, Walsh TJ (2009) Infections in patients with aplastic anemia. Semin Hematol 46:269–276

    Article  PubMed  Google Scholar 

  13. Maschan MA, Novichkova G, Baidildina DD, Suntzova EV, Kravchenko EG, Goronkova OV et al (2004) Horse ATG (ATGAM) versus rabbit ATG (Fresenius) for treatment of aplastic anemia in children: results of prospective double-blind randomized single-centre trial. Bone Marrow Transplant 33(Suppl 1):S27

    Google Scholar 

  14. Zheng Y, Liu Y, Chu Y (2006) Immunosuppressive therapy for acquired severe aplastic anemia (SAA): a prospective comparison of four different regimens. Exp Hematol 34:826–831

    Article  CAS  PubMed  Google Scholar 

  15. Vallejo C, Montesinos P, Rosell A, Brunet S, Pérez E, Petit J et al (2009) Comparison between lymphoglobuline and thymoglobuline-based immunosuppressive therapy as first-line treatment for patients with aplastic anemia. Haematologica 94(Suppl 2):451

    Google Scholar 

  16. Locasciulli A, Oneto R, Bacigalupo A, Socié G, Korthof E, Bekassy A et al (2007) Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT). Haematologica 92:11–18

    Article  CAS  PubMed  Google Scholar 

  17. Führer M, Rampf U, Baumann I, Faldum A, Niemeyer C, Janka-Schaub G et al (2005) Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival. Blood 106:2102–2104

    Article  PubMed  CAS  Google Scholar 

  18. Marsh JC, Hows JM, Bryett KA, Al-Hashimi S, Fairhead SM, Gordon-Smith EC (1987) Survival after antilymphocyte globulin therapy for aplastic anemia depends on disease severity. Blood 70:1046–1052

    CAS  PubMed  Google Scholar 

  19. Scheinberg P, Fischer SH, Li L, Nunez O, Wu CO, Sloand EM et al (2007) Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. Blood 109:3219–3224

    Article  CAS  PubMed  Google Scholar 

  20. Thomas FT, Griesedieck C, Thomas J, Carver M, Whitley T, Warren R et al (1984) Differential effects of horse ATG and rabbit ATG on T cell and T cell subset levels measured by monoclonal antibodies. Transplant Proc 16:1561–1563

    CAS  PubMed  Google Scholar 

  21. Scheinberg P, Wu CO, Nunez O, Young NS (2009) Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol 144:206–216

    Article  CAS  PubMed  Google Scholar 

  22. Solomou EE, Rezvani K, Mielke S, Malide D, Keyvanfar K, Visconte V et al (2007) Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia. Blood 110:1603–1606

    Article  CAS  PubMed  Google Scholar 

  23. Chen J, Ellison FM, Eckhaus MA, Smith AL, Keyvanfar K, Calado RT et al (2007) Minor antigen h60-mediated aplastic anemia is ameliorated by immunosuppression and the infusion of regulatory T cells. J Immunol 178:4159–4168

    CAS  PubMed  Google Scholar 

  24. Sewgobind VD, Kho MM, van der Laan LJ, Hendrikx TK, van Dam T, Tilanus HW et al (2009) The effect of rabbit anti-thymocyte globulin induction therapy on regulatory T cells in kidney transplant patients. Nephrol Dial Transplant 24:1635–1644

    Article  CAS  PubMed  Google Scholar 

  25. Lopez M, Clarkson MR, Albin M, Sayegh MH, Najafian N (2006) A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. J Am Soc Nephrol 17:2844–2853

    Article  CAS  PubMed  Google Scholar 

  26. Ruzek MC, Waire JS, Hopkins D, Lacorcia G, Sullivan J, Roberts BL et al (2008) Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo. Blood 111:1726–1734

    Article  CAS  PubMed  Google Scholar 

  27. Feng X, Kajigaya S, Solomou EE, Keyvanfar K, Xu X, Raghavachari N et al (2008) Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro. Blood 111:3675–3683

    Article  CAS  PubMed  Google Scholar 

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The authors reported no potential conflicts of interest.

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Authors and Affiliations

  1. Hematopoietic Stem Cell Program, Hemorio, Rua Frei Caneca, 8, Rio de Janeiro, RJ, 20.211-030, Brazil

    Elias Hallack Atta, Danielle Saldanha Peixoto Dias & Vera Lúcia Neves Marra

  2. Instituto Nacional de Câncer, CEMO, Praça Cruz Vermelha, 23, Rio de Janeiro, RJ, 20.230-130, Brazil

    Elias Hallack Atta & Alexandre Mello de Azevedo

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  1. Elias Hallack Atta
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  2. Danielle Saldanha Peixoto Dias
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  3. Vera Lúcia Neves Marra
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Correspondence to Elias Hallack Atta.

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Author contributions

EHA: conception and design of the study, analysis and interpretation of data, drafting the manuscript; DSDP: conception and design of the study, analysis and interpretation of data; VLNM: analysis and interpretation of data, drafting the manuscript; AMA: analysis and interpretation of data, drafting the manuscript. All authors approved the final version submitted for publication.

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Atta, E.H., Dias, D.S.P., Marra, V.L.N. et al. Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study. Ann Hematol 89, 851–859 (2010). https://doi.org/10.1007/s00277-010-0944-y

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  • DOI: https://doi.org/10.1007/s00277-010-0944-y

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