Annals of Hematology

, Volume 97, Issue 11, pp 2039–2046 | Cite as

Rabbit antithymocyte globulin dose does not affect response or survival as first-line therapy for acquired aplastic anemia: a multicenter retrospective study

  • Diego V. CléEmail author
  • Elias H. Atta
  • Danielle S. P. Dias
  • Carlos B. L. Lima
  • Mariana Bonduel
  • Gabriela Sciuccati
  • Larissa A. Medeiros
  • Michel M. de Oliveira
  • Patricia B. Blum Fonseca
  • Sara T. O. Saad
  • Nelson Hamerschlak
  • Marco A. Salvino
  • Marlene P. Garanito
  • Antonio Pazin-Filho
  • Phillip Scheinberg
  • Rodrigo T. Calado
Original Article


In a prospective randomized study, treatment for aplastic anemia (AA) with rabbit antithymocyte globulin (r-ATG) and cyclosporine showed inferior hematological response and survival in comparison to horse antithymocyte globulin (h-ATG) and cyclosporine. However, h-ATG was discontinued in most Asian, South American, and European countries, where r-ATG became the only ATG formulation available. We retrospectively evaluated consecutive patients with acquired AA who received either rabbit (n = 170) or horse (n = 85) ATG and cyclosporine for first-line treatment from 1992 to 2014 in seven referral centers in Brazil and Argentina. Overall response at 3 months was 17% (95%CI, 11–23%) for r-ATG and 44% (95%CI, 33–55%) for h-ATG (p < 0.001). At 6 months, it was 31% (95%CI, 34–39%) for r-ATG and 59% (95%CI, 48–69%) for h-ATG (p < 0.001). Overall survival at 5 years was 57% (95%CI, 47–65%) for r-ATG and 80% (95%CI, 69–87%) for h-ATG (log-rank = 0.001). Relapse was significantly higher in patients receiving h-ATG (28%; 95%CI, 17–43%) as compared to r-ATG (9.4%; 95%CI, 4–21%; log-rank, p = 0.01). The type of ATG was the only factor associated with both response and survival. The r-ATG dose varied from 1 to 5 mg/kg/day, but it did not correlate with outcomes. In summary, this is the largest multicenter study comparing the two ATG formulations in AA. Our results indicate that the dose of r-ATG does not influence hematologic response or survival in first-line therapy for acquired AA. Considering the toxicity and costs of r-ATG, our findings challenge its aggregate benefit to cyclosporine therapy and further strengthen that h-ATG should remain standard therapy in AA.


Aplastic anemia Antithymocyte globulin ATG dose Response Survival 


Authors’ contributions

DVC, EHA, DSPD, CBLL, MB, GS, LAM, MMO, PBBF, STOS, NH, MAS, and MPG collected patient data and participated in interim discussions. DVC, RTC, and APF performed the statistical analysis. DVC, RTC, and PS participated in study conceptualization, data analysis as well as interim discussions; oversaw the analysis; and wrote the paper. All authors approved the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

The study was approved in 12/29/2014 by the ethics committee at the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP, Ribeirão Preto, SP, Brazil, under the reference number 958.097.

Informed consent

Informed consent was obtained from all participants and was waived from those who lost follow-up and were not found.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Diego V. Clé
    • 1
    Email author
  • Elias H. Atta
    • 2
    • 3
  • Danielle S. P. Dias
    • 2
  • Carlos B. L. Lima
    • 2
  • Mariana Bonduel
    • 4
  • Gabriela Sciuccati
    • 4
  • Larissa A. Medeiros
    • 5
  • Michel M. de Oliveira
    • 5
  • Patricia B. Blum Fonseca
    • 6
  • Sara T. O. Saad
    • 7
  • Nelson Hamerschlak
    • 8
  • Marco A. Salvino
    • 9
  • Marlene P. Garanito
    • 10
  • Antonio Pazin-Filho
    • 1
  • Phillip Scheinberg
    • 1
    • 11
  • Rodrigo T. Calado
    • 1
  1. 1.Department of Internal Medicine, Ribeirão Preto School of MedicineUniversity of São PauloRibeirão PretoBrazil
  2. 2.CEMO, Brazilian National Cancer InstituteRio de JaneiroBrazil
  3. 3.Haematopoietic Stem Cell ProgramRio de JaneiroBrazil
  4. 4.Servicio de Hematología-OncologíaHospital de Pediatría “Prof. Dr. Juan P. Garrahan”Buenos AiresArgentina
  5. 5.Bone Marrow Transplantation UnitFederal University of ParanáCuritibaBrazil
  6. 6.Darcy Vargas Children’s HospitalSão PauloBrazil
  7. 7.Hematology and Transfusion Medicine CenterHemocentro, University of CampinasCampinasBrazil
  8. 8.Hospital Israelita Albert EinsteinSão PauloBrazil
  9. 9.Bone Marrow Transplantation unitFederal University of BahiaSalvadorBrazil
  10. 10.Children’s InstituteUniversity of São Paulo School of MedicineSão PauloBrazil
  11. 11.Centro Oncológico do Hospital A Beneficência PortuguesaSão PauloBrazil

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