Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia

Abstract

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, P<0.001) and chronic (20% versus 9%, P<0.001) graft-versus-host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3-year overall survival, 87% and 92%, P=0.76, respectively. Among recipients of unrelated donor transplants, acute graft-versus-host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, P<0.001) but not chronic graft-versus-host disease (38% versus 32%, P=0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, P=0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia.

Figure 1.

Acute and chronic graft-versus-host disease (GvHD). The adjusted cumulative incidence of grade II – IV acute GvHD (A) and chronic GvHD (B) after HLA-matched sibling transplant, and grade II – IV acute GvHD (C) and chronic GvHD (D) after unrelated donor transplant. h-ATG: horse derived ATG; r-ATG: rabbit derived ATG.

Figure 2.

Overall survival. The probability of overall survival after HLA-matched sibling transplant adjusted for age and time from diagnosis to transplant (A) and unrelated donor transplant adjusted for comorbidity index and donor-recipient HLA match (B). h-ATG: horse derived ATG; r-ATG: rabbit derived ATG.