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Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia

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Abstract

Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 109/L (OR 7.64, P < 0.001) were independent risk factors for early mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 109/L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.

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Author information

Authors and Affiliations

  1. BONE - Brazilian Marrow Failure Network, São Paulo, Brazil

    Elias H. Atta, Carlos B. L. Lima, Diego V. Clé, Larissa A. Medeiros, Michel M. Oliveira, Marco A. Salvino, Marlene P. Garanito, Patricia B. Blum Fonseca, Sara Teresinha O. Saad, Rodrigo T. Calado & Phillip Scheinberg

  2. CEMO, National Cancer Institute, Praça da Cruz Vermelha, 23, Rio de Janeiro, RJ, 20230-130, Brazil

    Elias H. Atta

  3. Hemorio, Rio de Janeiro, Brazil

    Carlos B. L. Lima & Danielle S. P. Dias

  4. University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, Brazil

    Diego V. Clé & Rodrigo T. Calado

  5. Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina

    Mariana M. Bonduel & Gabriela B. Sciuccati

  6. Federal University of Paraná, Curitiba, Brazil

    Larissa A. Medeiros & Michel M. Oliveira

  7. Federal University of Bahia, Salvador, Brazil

    Marco A. Salvino

  8. University of São Paulo, São Paulo, Brazil

    Marlene P. Garanito

  9. Hospital Pediátrico Darcy Vargas, São Paulo, Brazil

    Patricia B. Blum Fonseca

  10. University of Campinas, Campinas, Brazil

    Sara Teresinha O. Saad

  11. Centro Oncológico Antonio Ermirio de Moraes, Hospital São José e Beneficência Portuguesa, São Paulo, Brazil

    Phillip Scheinberg

Authors
  1. Elias H. Atta
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  2. Carlos B. L. Lima
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  3. Danielle S. P. Dias
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  4. Diego V. Clé
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  5. Mariana M. Bonduel
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  6. Gabriela B. Sciuccati
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  7. Larissa A. Medeiros
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  8. Michel M. Oliveira
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  9. Marco A. Salvino
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  10. Marlene P. Garanito
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  11. Patricia B. Blum Fonseca
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  12. Sara Teresinha O. Saad
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  13. Rodrigo T. Calado
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  14. Phillip Scheinberg
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Contributions

DSPD, MMB, GBS: data collection and drafting the manuscript; all the other authors: design of the study, data collection, data analysis, drafting the manuscript. All authors approved the final version submitted for publication.

Corresponding author

Correspondence to Elias H. Atta.

Ethics declarations

This study was approved by the respective local institutional review boards and was in accordance with the Declaration of Helsinki. All patients gave written informed consent allowing the use of their medical records for clinical research.

Conflict of interest

The authors declare that they have no conflict of interest.

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Atta, E.H., Lima, C.B.L., Dias, D.S.P. et al. Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia. Ann Hematol 96, 1907–1914 (2017). https://doi.org/10.1007/s00277-017-3086-7

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  • DOI: https://doi.org/10.1007/s00277-017-3086-7

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