Antithymocyte globulin and posttransplant cyclophosphamide in graft vs. host disease prophylaxis: comparison or combination.

PURPOSE OF REVIEW: Antithymocyte globulin (ATG) and posttransplant cyclophosphamide (PTCy) play essential roles in graft-vs.-host disease (GvHD) prophylaxis. ATG is considered the standard of care for matched related and unrelated donor (MRD/MUD) transplantation, while PTCy is the preferred approach for T cell-replete haploidentical transplantation. In recent years, PTCy has gained popularity in the MRD/MUD setting, prompting the publication of several large retrospective studies comparing the efficacy of ATG and PTCy, either as standalone regimens or in combination. This review aims to critically analyze the findings of these studies and provide context for the ongoing debate regarding the optimal prophylactic approach.

RECENT FINDINGS: Large retrospective studies have compared ATG and PTCy in adult MRD/MUD recipients, yielding mixed results. These studies share several limitations, including their retrospective design, variability in ATG dosing and scheduling, and the inclusion of patients who underwent transplantation during different time periods. Additionally, the combination of PTCy and ATG in haploidentical transplantation has demonstrated potential in reducing GvHD incidence.

SUMMARY: The optimal regimen for GvHD prophylaxis remains undefined. PTCy has been widely adopted for MRD/MUD transplantation, and its combination with ATG is being actively explored in the haploidentical setting. However, the current body of evidence is largely based on retrospective studies, underscoring the need for well designed prospective trials to clarify the comparative benefits of these strategies.