Annals of Hematology

, Volume 94, Issue 6, pp 947–954 | Cite as

Rabbit antithymocyte globulin versus horse antithymocyte globulin for treatment of acquired aplastic anemia: a retrospective analysis

  • Carlos Vallejo
  • Pau Montesinos
  • Marta Polo
  • Beatriz Cuevas
  • Marta Morado
  • Ana Rosell
  • Blanca Xicoy
  • José L. Díez
  • Olga Salamero
  • Ángel Cedillo
  • Pablo Martínez
  • Consolación Rayón
  • The Bone Marrow Failure Spanish Study Group (Pethema-GETH)
Original Article


Studies comparing rabbit antithymocyte globulin (rATG) and horse ATG (hATG) in patients with aplastic anemia (AA) have shown conflicting results. These studies included fewer than 60 subjects in the rATG arm with relatively short follow-up. A total of 169 patients treated with rATG and 62 treated with hATG were included in this retrospective analysis, across 33 centers. Patients were treated with rATG or hATG plus cyclosporine A. Over half were classified, as having severe AA (SAA) or very severe AA (VSAA), and the mean follow-up was 45 months. There was no significant difference detected in cumulative response to treatment or survival between the rATG and hATG groups. The response to treatment was 63 % in the rATG group versus 66 % in the hATG group at 3 months. By 12 months, this pattern had reversed, and 84 % of rATG patients had responded to treatment versus 76 % in the hATG group (n.s.). Early mortality due to infection tended to be higher with rATG compared to hATG (n.s). rATG and hATG would seem to be therapeutically equivalent in SAA and VSAA. However, patients treated with rATG may take longer to respond than those treated with hATG and may also require more active prevention of early infections.


Aplastic anemia Antibody therapy Clinical aspects Immunotherapy Late effects of therapy 



The authors would like to thank the following centers that contributed cases for analysis: S. Brunet (H. U. Sant Pau, Barcelona), L. Yáñez (H. U. Valdecilla, Santander), Á. Bendaña (C. H. U. S. Compostela, Pontevedra), J. de la Serna (H. U. Doce de Octubre, Madrid), M. González (H. Niño Jesús, Madrid), E. Pérez (H. U. M. Meseguer, Murcia), A. Sampol (H. U. Son Dureta, P. Mallorca), C. García (H. G. Alicante), I. Espigado (H. U. V. Rocío, Sevilla), MJ. Requena (H. Severo Ochoa, Madrid), A. Cantalapiedra (H. U. Río Ortega, Valladolid), J. Petit (I. C. Oncología, Barcelona), R. Campo (H. Son Llatzer, P. Mallorca), M. Sanz (H. Río Carrión, Palencia), L. Vázquez (H. U. Salamanca), R. Arranz (H. U. La Princesa, Madrid), A. Bailén (H. U. Carlos Haya, Málaga), MC. Viguria (C. H. Navarra), J. Bergua (H. Cáceres), M. López (H. Alcalá de Henares, Madrid), P. García (H. U. La Paz Infantil, Madrid), Á. Dasi (H. U. La Fe Infantil, Valencia), C. Solano (H. Clínico de Valencia), J. Moraleda (H. U. V. Arrixaca, Murcia). The authors would also like to thank E. Mayor (H. U. Central de Asturias) for support with data management; E. Berlanas (RPS Research Iberica, Spain) for data monitoring and quality control. Denise Bumford, a freelance medical writer supported by funding from Sanofi Aventis Group, provided drafts and editorial assistance to the authors during preparation of this manuscript.

Author contributions

CV and the Bone Marrow Failure Spanish Study Group (Pethema-GETH) designed and performed the research and analyzed and interpreted the data. Denise Bumford a freelance medical writer supported by funding from Sanofi Aventis Group, developed a draft manuscript for author review. CV, PM(2), MP, BC, MM, AR, BX, JLD, OS, ÁC, PM(12,13) and CR critically reviewed the manuscript and approved the final version for journal submission.

Conflict of interest

CV and JLD have received speaker fees from Sanofi Aventis Group. PM(2), MP, BC, MM, AR, BX, OS, ÁC, PM(12,13), and CR report no conflicts of interest.


The services of the freelance medical writer were supported by a grant from Sanofi Aventis group.


  1. 1.
    Marmont AM (1995) Who really discovered aplastic anemia? Haematologica 80:294PubMedGoogle Scholar
  2. 2.
    Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108:2509–2519CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Passweg J, Bacigalupo A, Locasciulli A, for the EBMT Aplastic Anaemia Working Party (2008) HSCT for aplastic anaemia in adults. In: Apperley J, Carreras E, Gluckman E, Masszi T (eds) Haematopoietic stem cell transplantation. EBMT-ESH Handbook, pp 480–489Google Scholar
  4. 4.
    Wingard JR, Majhail NS, Brazauskas R, Wang Z, Sobocinski KA, Jacobsohn D, Sorror ML, Horowitz MM, Bolwell B, Rizzo JD, Socié G (2011) Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol 29:2230–2239CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Locasciulli A, Oneto R, Bacigalupo A, Socié G, Korthof E, Bekassy A, Schrezenmeier H, Passweg J, Führer M, Severe Aplastic Anemia Working Party of the European Blood and Marrow Transplant Group (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 92:11–18CrossRefPubMedGoogle Scholar
  6. 6.
    Bacigalupo A (2007) Aplastic anemia: pathogenesis and treatment. Hematol Am Soc Hematol Educ Program 23-8Google Scholar
  7. 7.
    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 109:3219–3224CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Di Bona E, Rodeghiero F, Bruno B, Gabbas A, Foa P, Locasciulli A, Rosanelli C, Camba L, Saracco P, Lippi A, Iori AP, Porta F, De Rossi G, Comotti B, Iacopino P, Dufour C, Bacigalupo A (1999) Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatmentfor aplastic anaemia patients unresponsive to a first courseof intensive immunosuppressive therapy; Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Br J Haematol 107:330–334CrossRefPubMedGoogle Scholar
  9. 9.
    Garg R, Faderl S, Garcia-Manero G, Cortes J, Koller C, Huang X, York S, Pierce S, Brandt M, Beran M, Borthakur G, Kantarjian H, Ravandi F (2009) Phase II study of rabbit anti-thymocyte globulin, cyclosporine and granulocyte colony-stimulating factor in patients with aplastic anemia and myelodysplastic syndrome. Leukemia 23:1297–1302CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Atta EH, Dias DSP, Marra VLN, 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 89:851–859CrossRefPubMedGoogle Scholar
  11. 11.
    Chang MH, Kim KH, Kim HS, Jun HJ, Kim DH, Jang JH, Kim K, Jung CW (2010) Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia. Eur J Haematol 84:154–159CrossRefPubMedGoogle Scholar
  12. 12.
    Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, Young NS (2011) Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med 365:430–438CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Afable MG 2nd, Shaik M, Sugimoto M, 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 96:1269–1275CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Marsh JC, Bacigalupo A, Schrezenmeier H, Tichelli A, Risitano AM, Passweg JR, Killick SB, Warren AJ, Foukaneli T, Aljurf M, Al-Zahrani HA, Höchsmann B, Schafhausen P, Roth A, Franzke A, Brummendorf TH, Dufour C, Oneto R, Sedgwick P, Barrois A, Kordasti S, Elebute MO, Mufti GJ, Socie G, European Blood and Marrow Transplant Group Severe Aplastic Anaemia Working Party (2012) Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party. Blood 19:5391–5396CrossRefGoogle Scholar
  15. 15.
    Kadia TM, Borthakur G, Garcia-Manero G, Faderl S, Jabbour E, Estrov Z, York S, Huang X, Pierce S, Brandt M, Koller C, Kantarjian HM, Ravandi F (2012) Final results of the phase II study of rabbit anti-thymocyte globulin, ciclosporin, methylprednisone, and granulocytecolony-stimulating factor in patients with aplastic anaemia and myelodysplastic syndrome. Br J Haematol 157:312–320CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Chen C, Xue HM, Xu HG, Li Y, Huang K, Zhou DH, Guo HX, Fang JP, Huang SL (2012) Rabbit-antithymocyte globulin combined with cyclosporine A as a first-line therapy: improved, effective, and safe for children with acquired severe aplastic anemia. J Cancer Res Clin Oncol 138:1105–1111CrossRefPubMedGoogle Scholar
  17. 17.
    Shin SH, Yoon JH, Yahng SA, Lee SE, Cho BS, Eom KS, Kim YJ, Lee S, Min CK, Kim HJ, Cho SG, Kim DW, Min WS, Park CW, Lee JW (2013) 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 92:817–824CrossRefPubMedGoogle Scholar
  18. 18.
    Sakamoto T, Obara N, Kurita N, Sakata-Yanagimoto M, Nishikii H, Yokoyama Y, Suzukawa K, Hasegawa Y, Chiba S (2013) Effectiveness and safety of rabbit anti-thymocyte globulin in Japanese patients with aplastic anemia. Int J Hematol 98:319–322CrossRefPubMedGoogle Scholar
  19. 19.
    Martínez-Camblor P, Corral N (2012) A general bootstrap algorithm for hypothesis testing. J Stat Plan Inference 142:589–600CrossRefGoogle Scholar
  20. 20.
    Vallejo C, on behalf of the BM failure Spanish Study Group (Pethema-GETH) (2013) The Spanish experience of rabbit and horse ATG. 39th Meeting of the European Group for Blood and Marrow Transplantation (EBMT), 7-10 April 2013, London, UK. Working party session aplastic anaemia, 8 April 16.58-17.08Google Scholar
  21. 21.
    Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC, Keidan J, Laurie A, Martin A, Mercieca J, Killick SB, Stewart R, Yin JA, British Committee for Standards in Haematology (2009) Guidelines for the management of aplastic anaemia. Br J Haematol 147:43–70CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Carlos Vallejo
    • 1
  • Pau Montesinos
    • 2
  • Marta Polo
    • 3
  • Beatriz Cuevas
    • 4
  • Marta Morado
    • 5
  • Ana Rosell
    • 6
  • Blanca Xicoy
    • 7
  • José L. Díez
    • 8
    • 9
  • Olga Salamero
    • 10
  • Ángel Cedillo
    • 11
  • Pablo Martínez
    • 12
    • 13
  • Consolación Rayón
    • 1
  • The Bone Marrow Failure Spanish Study Group (Pethema-GETH)
  1. 1.Hospital Universitario DonostiaDonostia/San SebastiánSpain
  2. 2.Hospital Universitario La FeValenciaSpain
  3. 3.Hospital Clínico de MadridMadridSpain
  4. 4.Hospital Universitario de BurgosBurgosSpain
  5. 5.Hospital Universitario La PazMadridSpain
  6. 6.Hospital Universitario V. VictoriaMálagaSpain
  7. 7.Hospital Universitari Germans Trias i PujolBarcelonaSpain
  8. 8.Hospital Universitario Gregorio MarañónMadridSpain
  9. 9.Instituto de Investigación Sanitaria Gregorio MarañónMadridSpain
  10. 10.Hospital Universitari Vall d’HebronBarcelonaSpain
  11. 11.Grupo Español de Trasplante HematopoyéticoOviedoSpain
  12. 12.Oficina de Investigación Biosanitaria (OIB) de AsturiasOviedoSpain
  13. 13.Universidad Autonoma de ChileSantiagoChile

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