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The efficacy of rabbit antithymocyte globulin with cyclosporine in comparison to horse antithymocyte globulin as a first-line treatment in adult patients with severe aplastic anemia: a single-center retrospective study

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Abstract

Antithymocyte globulin (ATG) is the drug of choice for immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA) ineligible for allogeneic stem cell transplantation. Recently, rabbit ATG with cyclosporine A has been used as a first-line IST regimen in patients with SAA because of unavailability of horse ATG. We retrospectively analyzed adult SAA patients who were treated with horse ATG (n = 46) or rabbit ATG (n = 53) between Feb 2001 and May 2010 to compare hematologic response and survival. Overall response rates at 3, 6, 12, and 18 months were similar in both the horse and rabbit ATG groups: 28.3 versus 35.8 % (P = 0.421), 39.1 versus 45.3 % (P = 0.537), 45.7 versus 49.1 % (P = 0.735), and 47.8 versus 50.9 % (P = 0.757), respectively. The complete response (CR) rate at 6 months in the horse ATG was significantly superior in comparison with the rabbit ATG (13.0 versus 1.9 %, P = 0.031). But CR rates became similar in both groups after 6 months: 17.4 versus 11.3 % (P = 0.387) at 12 months and 21.7 versus 22.6 % (P = 0.914) at 18 months. Lymphocyte depletion after ATG was more profound and protracted in the rabbit ATG group compared to the horse ATG group. Overall survival (P = 0.460) and failure-free survival (P = 0.911) were not significantly different between the two groups. Our retrospective study demonstrated that the efficacy of first-line IST with rabbit ATG is similar to that with horse ATG. However, the time from treatment to CR was longer with rabbit ATG than with horse ATG, partly due to more profound and protracted lymphocyte depletion.

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References

  1. Young NS (2002) Acquired aplastic anemia. Ann Intern Med 136(7):534–546

    Article  PubMed  Google Scholar 

  2. Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108(8):2509–2519. doi:10.1182/blood-2006-03-010777

    Article  PubMed  CAS  Google Scholar 

  3. Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H (2003) Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood 101(4):1236–1242. doi:10.1182/blood-2002-04-1134

    Article  PubMed  CAS  Google Scholar 

  4. 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(7):826–831. doi:10.1016/j.exphem.2006.03.017

    Article  PubMed  CAS  Google Scholar 

  5. 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(9):1130–1135

    Article  PubMed  CAS  Google Scholar 

  6. Speck B, Gratwohl A, Nissen C, Leibundgut U, Ruggero D, Osterwalder B, Burri HP, Cornu P, Jeannet M (1981) Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation. Br Med J (Clin Res Ed) 282(6267):860–863

    Article  CAS  Google Scholar 

  7. Locasciulli A, Oneto R, Bacigalupo A, Socie G, Korthof E, Bekassy A, Schrezenmeier H, Passweg J, Fuhrer M (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(1):11–18

    Article  PubMed  CAS  Google Scholar 

  8. 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(6):622–627. doi:10.1111/j.1365-2141.2006.06098.x

    Article  PubMed  CAS  Google Scholar 

  9. Feng X, Kajigaya S, Solomou EE, Keyvanfar K, Xu X, Raghavachari N, Munson PJ, Herndon TM, Chen J, Young NS (2008) Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro. Blood 111(7):3675–3683. doi:10.1182/blood-2008-01-130146

    Article  PubMed  CAS  Google Scholar 

  10. Mohty M (2007) Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia 21(7):1387–1394. doi:10.1038/sj.leu.2404683

    Article  PubMed  CAS  Google Scholar 

  11. Afable MG 2nd, Shaik M, Sugimoto Y, Elson P, Clemente M, Makishima H, Sekeres MA, Lichtin A, Advani A, Kalaycio M, Tiu RV, O’Keefe CL, Maciejewski JP (2011) Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia. Haematologica 96(9):1269–1275. doi:10.3324/haematol.2011.042622

    Article  PubMed  CAS  Google Scholar 

  12. Atta EH, Dias DS, Marra VL, de Azevedo AM (2010) 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(9):851–859. doi:10.1007/s00277-010-0944-y

    Article  PubMed  CAS  Google Scholar 

  13. Scheinberg P, Nunez O, Weinstein B, Biancotto A, Wu CO, Young NS (2011) Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med 365(5):430–438. doi:10.1056/NEJMoa1103975

    Article  PubMed  CAS  Google Scholar 

  14. Marsh JC, Bacigalupo A, Schrezenmeier H, Tichelli A, Risitano AM, Passweg JR, Killick SB, Warren AJ, Foukaneli T, Aljurf M, Al-Zahrani HA, Schafhausen P, Roth A, Franzke A, Brummendorf TH, Dufour C, Oneto R, Sedgwick P, Barrois A, Kordasti S, Elebute MO, Mufti GJ, Socie G (2012) Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party. Blood 119(23):5391–5396. doi:10.1182/blood-2012-02-407684

    Article  PubMed  CAS  Google Scholar 

  15. Battiwalla M, Hepgur M, Pan D, McCarthy PL, Ahluwalia MS, Camacho SH, Starostik P, Wallace PK (2010) Multiparameter flow cytometry for the diagnosis and monitoring of small GPI-deficient cellular populations. Cytometry B Clin Cytom 78(5):348–356. doi:10.1002/cyto.b.20519

    PubMed  Google Scholar 

  16. Oelschlaegel U, Besson I, Arnoulet C, Sainty D, Nowak R, Naumann R, Bux Y, Ehninger G (2001) A standardized flow cytometric method for screening paroxysmal nocturnal haemoglobinuria (PNH) measuring CD55 and CD59 expression on erythrocytes and granulocytes. Clin Lab Haematol 23(2):81–90

    Article  PubMed  CAS  Google Scholar 

  17. Bacigalupo A, Passweg J (2009) Diagnosis and treatment of acquired aplastic anemia. Hematol Oncol Clin North Am 23(2):159–170. doi:10.1016/j.hoc.2009.01.005

    Article  PubMed  Google Scholar 

  18. Scheinberg P, Wu CO, Nunez O, Boss C, Sloand EM, Young NS (2009) Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study. Haematologica 94(3):348–354. doi:10.3324/haematol.13829

    Article  PubMed  CAS  Google Scholar 

  19. Marsh J, Schrezenmeier H, Marin P, Ilhan O, Ljungman P, McCann S, Socie G, Tichelli A, Passweg J, Hows J, Raghavachar A, Locasciulli A, Bacigalupo A (1999) Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: a report from the European Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia Working Party. Blood 93(7):2191–2195

    PubMed  CAS  Google Scholar 

  20. Bacigalupo A, Bruno B, Saracco P, Di Bona E, Locasciulli A, Locatelli F, Gabbas A, Dufour C, Arcese W, Testi G, Broccia G, Carotenuto M, Coser P, Barbui T, Leoni P, Ferster A (2000) Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio Osseo (GITMO). Blood 95(6):1931–1934

    PubMed  CAS  Google Scholar 

  21. Kojima S, Hibi S, Kosaka Y, Yamamoto M, Tsuchida M, Mugishima H, Sugita K, Yabe H, Ohara A, Tsukimoto I (2000) Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood 96(6):2049–2054

    PubMed  CAS  Google Scholar 

  22. Scheinberg P, Nunez O, Wu C, Young NS (2006) Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil. Br J Haematol 133(6):606–611. doi:10.1111/j.1365-2141.2006.06085.x

    Article  PubMed  CAS  Google Scholar 

  23. Scheinberg P, Fischer SH, Li L, Nunez O, Wu CO, Sloand EM, Cohen JI, Young NS, John Barrett A (2007) Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. Blood 109(8):3219–3224. doi:10.1182/blood-2006-09-045625

    Article  PubMed  CAS  Google Scholar 

  24. Feng X, Scheinberg P, Biancotto A, Rios O, Donaldson S, Wu CO, Zheng H, Sato K, McCoy J, Young NS (2011) Different in vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia. ASH Annual Meeting Abstracts 118(21):2399

    Google Scholar 

  25. Solomou EE, Rezvani K, Mielke S, Malide D, Keyvanfar K, Visconte V, Kajigaya S, Barrett AJ, Young NS (2007) Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia. Blood 110(5):1603–1606. doi:10.1182/blood-2007-01-066258

    Article  PubMed  CAS  Google Scholar 

  26. Chen J, Ellison FM, Eckhaus MA, Smith AL, Keyvanfar K, Calado RT, Young NS (2007) Minor antigen h60-mediated aplastic anemia is ameliorated by immunosuppression and the infusion of regulatory T cells. J Immunol 178(7):4159–4168

    PubMed  CAS  Google Scholar 

  27. Jeong DC, Chung NG, Lee JW, Jang PS, Cho B, Kim HK (2011) Long-term outcome of immunosuppressive therapy with rabbit antithymocyte globulin (rATG) for childhood severe aplastic anemia for 15 years. ASH Annual Meeting Abstracts 118(21):1346

    Google Scholar 

  28. Yamazaki H, Saito C, Sugimori N, Hosokawa K, Kiyu Y, Mochizuki K, Takamatsu H, Nakao S (2011) Thymoglobuline is as effective as lymphoglobuline in japanese patients with aplastic anemia possessing increased glycosylphosphatidylinositol-anchored protein (GPI-AP) deficient cells. ASH Annual Meeting Abstracts 118(21):1339

    Google Scholar 

  29. Maluf EM, Pasquini R, Eluf JN, Kelly J, Kaufman DW (2002) Aplastic anemia in Brazil: incidence and risk factors. Am J Hematol 71(4):268–274. doi:10.1002/ajh.10232

    Article  PubMed  Google Scholar 

  30. Young NS, Kaufman DW (2008) The epidemiology of acquired aplastic anemia. Haematologica 93(4):489–492. doi:10.3324/haematol.12855

    Article  PubMed  Google Scholar 

  31. Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Leaverton PE, Shapiro S, Young NS (2006) The epidemiology of aplastic anemia in Thailand. Blood 107(4):1299–1307. doi:10.1182/blood-2005-01-0161

    Article  PubMed  CAS  Google Scholar 

  32. Yang C, Zhang X (1991) Incidence survey of aplastic anemia in China. Chin Med Sci J 6(4):203–207

    PubMed  CAS  Google Scholar 

  33. Saracco P, Quarello P, Iori AP, Zecca M, Longoni D, Svahn J, Varotto S, Del Vecchio GC, Dufour C, Ramenghi U, Bacigalupo A, Locasciulli A (2008) Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long-term observation follow-up. Br J Haematol 140(2):197–205. doi:10.1111/j.1365-2141.2007.06903.x

    Article  PubMed  CAS  Google Scholar 

  34. Scheinberg P, Wu CO, Nunez O, Young NS (2009) Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol 144(2):206–216. doi:10.1111/j.1365-2141.2008.07450.x

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jong Wook Lee.

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Shin, SH., Yoon, JH., Yahng, SA. et al. The efficacy of rabbit antithymocyte globulin with cyclosporine in comparison to horse antithymocyte globulin as a first-line treatment in adult patients with severe aplastic anemia: a single-center retrospective study. Ann Hematol 92, 817–824 (2013). https://doi.org/10.1007/s00277-013-1674-8

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