Rabbit Antithymocyte Globulin Serum Levels: Factors Impacting the Levels and Clinical Outcomes Impacted by the Levels.

ABSTRACT

Antithymocyte globulin (ATG) levels and clearance vary significantly among patients receiving the same weight-based dose of ATG. To date, ATG area under the curve (AUC), its determinants, and its impact on clinical outcomes have been examined in pediatric hematopoietic cell transplant (HCT) and adult nonmyeloablative HCT. Here we set out to examine ATG AUC in 219 uniformly treated adults undergoing myeloablative allogeneic HCT at our institution. Sera were collected for the determination of pre- or post-HCT ATG AUC. The lowest quintiles of pre- and post-HCT AUC were associated with inferior chronic graft-versus-host disease (GVHD) and relapse-free survival (cGRFS) and a higher risk of acute GVHD, respectively. The highest pre- or post-HCT ATG AUC quintiles were not associated with risk of death, nonrelapse mortality, or relapse. Factors most strongly associated with AUC were day -2 recipient absolute lymphocyte count, body mass index (BMI), and graft lymphocyte content. To achieve ideal pre-HCT AUC (avoiding low AUC to maximize cGRFS) in this HCT setting, ATG dosing will need to take into consideration recipient weight, BMI, and blood and graft lymphocyte counts. Further studies are required to develop a modern ATG dosing schema and to demonstrate that adjusting ATG dose to target a particular AUC is feasible and leads to improved outcomes.