The impact of rabbit anti-thymocyte globulin (thymoglobulin) timing and dosing on pediatric stem cell transplantation outcomes: Time to move forward.

Anti-thymocyte globulin (ATG) remains integral to graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT), yet its optimal dosing is unresolved. Excessive immunosuppression can impair immune reconstitution and increase infection-related morbidity. This review summarizes evidence on the timing, dosing, and pharmacologic modeling of rabbit ATG (Thymoglobulin) in pediatric HSCT. Early investigations demonstrated that reduced ATG exposure, achieved through lower or earlier dosing, enhanced CD4 recovery and lowered viral reactivation rates, whereas higher exposure delayed immune recovery and increased severe infections. Pharmacokinetic and pharmacodynamic analyses identified absolute lymphocyte count and body weight and graft source as key determinants of ATG disposition, supporting the development of model-based dosing (MBD) strategies that individualize exposure according to patient and graft characteristics. Across multiple clinical studies, MBD achieved superior CD4 reconstitution, significantly reduced viral reactivation, and decreased chronic GvHD and graft failure without significantly increasing acute GvHD. Survival outcomes improved in patients reaching early CD4 recovery under individualized dosing. Optimal results were associated with high ATG exposure before transplantation and low exposure afterward. Collectively, current data indicate that MBD provides a rational, safe, and effective framework to balance GvHD prevention with immune recovery in pediatric HSCT. Further studies in peripheral blood and haploidentical transplantation settings are warranted to validate and expand this approach.