Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Marmont AM (1995) Who really discovered aplastic anemia? Haematologica 80:294

    CAS  PubMed  Google Scholar 

  2. Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108:2509–2519

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 480–489

  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 29:2230–2239

    Article  PubMed Central  PubMed  Google Scholar 

  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 92:11–18

    Article  CAS  PubMed  Google Scholar 

  6. Bacigalupo A (2007) Aplastic anemia: pathogenesis and treatment. Hematol Am Soc Hematol Educ Program 23-8

  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 109:3219–3224

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 107:330–334

    Article  PubMed  Google Scholar 

  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 23:1297–1302

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 89:851–859

    Article  CAS  PubMed  Google Scholar 

  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 84:154–159

    Article  CAS  PubMed  Google Scholar 

  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 365:430–438

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 96:1269–1275

    Article  PubMed Central  CAS  PubMed  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, 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 19:5391–5396

    Article  Google Scholar 

  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 157:312–320

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 138:1105–1111

    Article  CAS  PubMed  Google Scholar 

  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 92:817–824

    Article  CAS  PubMed  Google Scholar 

  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 98:319–322

    Article  CAS  PubMed  Google Scholar 

  19. Martínez-Camblor P, Corral N (2012) A general bootstrap algorithm for hypothesis testing. J Stat Plan Inference 142:589–600

    Article  Google Scholar 

  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 16.58-17.08

  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 147:43–70

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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.

Funding

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

Author information

Authors and Affiliations

  1. Hospital Universitario Donostia, Doctor Begiristain Kalea117, 20080, Donostia/San Sebastián, Gipuzkoa, Spain

    Carlos Vallejo & Consolación Rayón

  2. Hospital Universitario La Fe, Valencia, Spain

    Pau Montesinos

  3. Hospital Clínico de Madrid, Madrid, Spain

    Marta Polo

  4. Hospital Universitario de Burgos, Burgos, Spain

    Beatriz Cuevas

  5. Hospital Universitario La Paz, Madrid, Spain

    Marta Morado

  6. Hospital Universitario V. Victoria, Málaga, Spain

    Ana Rosell

  7. Hospital Universitari Germans Trias i Pujol, Barcelona, Spain

    Blanca Xicoy

  8. Hospital Universitario Gregorio Marañón, Madrid, Spain

    José L. Díez

  9. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

    José L. Díez

  10. Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Olga Salamero

  11. Grupo Español de Trasplante Hematopoyético, Oviedo, Spain

    Ángel Cedillo

  12. Oficina de Investigación Biosanitaria (OIB) de Asturias, Oviedo, Spain

    Pablo Martínez

  13. Universidad Autonoma de Chile, Santiago, Chile

    Pablo Martínez

Authors
  1. Carlos Vallejo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pau Montesinos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marta Polo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beatriz Cuevas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marta Morado
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana Rosell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Blanca Xicoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. José L. Díez
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Olga Salamero
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ángel Cedillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Pablo Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Consolación Rayón
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

The Bone Marrow Failure Spanish Study Group (Pethema-GETH)

Corresponding author

Correspondence to Carlos Vallejo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vallejo, C., Montesinos, P., Polo, M. et al. Rabbit antithymocyte globulin versus horse antithymocyte globulin for treatment of acquired aplastic anemia: a retrospective analysis. Ann Hematol 94, 947–954 (2015). https://doi.org/10.1007/s00277-015-2305-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-015-2305-3

Keywords

Search

Navigation