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Title: Rabbit antithymocyte globulin dose does not affect response or survival as first-line therapy for acquired aplastic anemia: a multicenter retrospective study
Authors: CLE, Diego V.ATTA, Elias H.DIAS, Danielle S. P.LIMA, Carlos B. L.BONDUEL, MarianaSCIUCCATI, GabrielaMEDEIROS, Larissa A.OLIVEIRA, Michel M. deFONSECA, Patricia B. BlumSAAD, Sara T. O.HAMERSCHLAK, NelsonSALVINO, Marco A.GARANITO, Marlene P.PAZIN-FILHO, AntonioSCHEINBERG, PhillipCALADO, Rodrigo T.
Citation: ANNALS OF HEMATOLOGY, v.97, n.11, p.2039-2046, 2018
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 3months was 17% (95%CI, 11-23%) for r-ATG and 44% (95%CI, 33-55%) for h-ATG (p<0.001). At 6months, 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 5years 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 5mg/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.
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