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, has been examined in pediatric hematopoietic cell transplant (HCT) and adult non-myeloablative 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 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, non-relapse 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 maxize cGRFS) in this HCT-setting, ATG dosing will need to take into consideration recipient weight, BMI and blood lymphocyte count as well as graft lymphocyte count. Further studies are required to 1) develop a modern ATG dosing schema, and, 2) demonstrate that adjusting ATG dose to target a particular AUC is feasible and leads to improved outcomes.