Current role of ATG in GVHD prevention: optimizing post-transplantation outcomes through combination with PTCY

Graft versus host disease (GVHD) is one of the major complications of allogeneic hematopoietic cell transplantation (allo-HCT), contributing significantly to post-transplant morbidity and mortality. Anti-thymocyte globulin (ATG) is a widely used GVHD prophylaxis in combination with a calcineurin inhibitor and an antimetabolite. Post-transplant cyclophosphamide (PTCy) has been a milestone in haploidentical transplantation, and its use has expanded to allo-HCT performed from matched related and unrelated donors with notable success. In this review, we discuss how post-transplantation outcomes can be optimized through a combination of ATG with PTCY. We summarize the biological rationale, current clinical evidence, and remaining uncertainties regarding this dual in vivo T-cell depletion strategy, highlighting its potential to enhance GVHD control, reduce immunosuppressive burden, and improve survival across different donor settings.