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

Abstract

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.

• Authors: Diego V Clé, 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
• Journal: Annals of hematology (Ann Hematol) Vol. 97 Issue 11 Pg. 2039-2046 (Nov 2018) ISSN: 1432-0584 [Electronic] Germany
• PMID: 29978284 (Publication Type: Comparative Study, Journal Article, Multicenter Study)

Chemical References

• Antilymphocyte Serum
• Cyclosporine

Topics

• Adolescent
• Adult
• Aged
• Anemia, Aplastic (drug therapy, mortality)
• Antilymphocyte Serum (administration & dosage)
• Child
• Child, Preschool
• Cyclosporine (administration & dosage)
• Disease-Free Survival
• Female
• Humans
• Infant
• Male
• Middle Aged
• Retrospective Studies
• Survival Rate