High Serum Level of Antithymocyte Globulin Immediately before Graft Infusion Is Associated with a Low Likelihood of Chronic, But Not Acute, Graft-versus-Host Disease

Abstract

Rabbit antithymocyte globulin (ATG) is administered during transplant conditioning to decrease the risk of both acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD). Here we evaluated the relationship between the serum concentration of ATG (capable of binding to lymphocytes) immediately before graft infusion (day 0) or on day +7 or +28 post-transplantation and the development of aGVHD or cGVHD. We studied 180 patients whose conditioning included 4.5 mg/kg antithymocyte globulin (ATG; Thymoglobulin). For aGVHD, we found no association with ATG levels on day 0. Nevertheless, high day +7 and +28 ATG levels were associated with a low likelihood of aGVHD. For cGVHD, high ATG levels at all 3 time points (days 0, +7, and +28) were associated with a low likelihood of cGVHD. In conclusion, high-dose ATG administration at the time of graft infusion appears to inhibit the development of cGVHD, but not aGVHD; however, higher ATG levels on days +7 and +28 are associated with lower rates of both aGVHD and cGVHD.

Immune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation Following Flu-TBI versus TLI-ATG Conditioning

“…Importantly, ATG is unlikely to be the sole factor responsible for the lower incidence of chronic GVHD observed in TLI patients given that functional ATG levels in day 0 sera of our TLI patients were well below the threshold associated with a lower incidence of chronic GVHD in a recent paper by Chawla and colleagues (30). In murine models of allo-HCT, protection from GVHD following TLI/ATS conditioning depends on residual host iNKT cells (located mainly in the bone marrow) that secrete IL4, which in turn polarizes donor T cells toward a Th2 pattern.…”

“…1A, median functional ATG levels were 4.0 (range, 3.2-5.6) mg/L on day 0, 2.2 (range, 0.6-3.9) on day 3, and 0.95 (range, 0.34-1.49) on day 10 after transplantation. These day 0 levels are below the threshold of ATG levels associated with a lower incidence of chronic GVHD in a recent paper by Chawla and colleagues (8.12 mg/L) in patients given PBSC after conditioning with fludarabine, busulfan, and ATG (thymoglobulin, 4.5 mg/kg given from day À2 to day 0 before PBSC infusion) with or without TBI (30).…”

Impact of Serotherapy on Immune Reconstitution and Survival Outcomes After Stem Cell Transplantations in Children: Thymoglobulin Versus Alemtuzumab

“…This result is concordant with data from Bosch et al [6], in which higher levels of active ATG 1 week and 1 month after transplantation were associated with decreased CD4 and CD8 T cell counts in adults. In a recent publication on the impact of ATG serum levels on acute and chronic GVHD, Chawla et al [31] also reported a significant correlation between the decrease in active ATG level and the T cell count 1 month after HSCT. Whereas longer ATG exposure correlated with a slower T cell recovery, NK cell recovery was faster in patients with long active ATG exposure in our study.…”

Anti-thymocyte globulin as graft- versus -host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…The authors demonstrated that high levels of serum ATG-T on days 7 and 28 each correlated with a low incidence of acute and chronic GvHD, but also with a high incidence of post-transplant lymphoproliferative disorder . 41,42 In contrast, high ATG levels on day 0 were associated only with a low incidence of chronic GvHD. 42 Importantly, no associations were observed between ATG levels and relapse or non-relapse mortality.…”

“…41,42 In contrast, high ATG levels on day 0 were associated only with a low incidence of chronic GvHD. 42 Importantly, no associations were observed between ATG levels and relapse or non-relapse mortality. Subsequently, the same group demonstrated that high levels of ATG-T specificities capable of binding to Treg and invariant natural killer T cells on day 7 were associated with a low incidence of relapse.…”