Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis: current status and optimization strategies

Abstract

Since its first application in HLA-haploidentical settings, post-transplant cyclophosphamide (PTCy) has become a standard for graft-versus-host disease (GVHD) prophylaxis, with its use expanding to matched and mismatched hematopoietic cell transplantation. Its major clinical advantages include versatility and cost-effectiveness, providing robust GVHD prevention independent of donor type, graft source, or conditioning intensity. The mechanism involves selective depletion of rapidly proliferating alloreactive T-cells, while sparing populations such as regulatory T cells. Current research focuses on optimizing the regimen, including conditioning, timing of calcineurin inhibitor initiation, and PTCy dosage. While the standard dose is 50 mg/kg/day on days +3 and +4, dose reduction is being investigated to mitigate toxicities, such as cardiotoxicity. While data suggest lower doses can hasten engraftment and reduce viral infections without compromising GVHD control, the ultimate impact on the graft-versus-leukemia effect remains to be elucidated.