https://orcid.org/0000-0003-2956-0848
Key Points
PTCy-based GvHD prophylaxis was associated with improvement in GRFS, NRM, and OS after MSD PBSC transplant without increasing relapse risk.
The addition of anti-thymocyte globulin to PTCy was associated with an increase in CMV and EBV reactivation without further improving GRFS.
Post-transplant cyclophosphamide (PTCy) is a promising graft-versus-host disease (GvHD) prophylaxis in haploidentical and matched unrelated donor hematopoietic stem cell transplantation (HSCT), but its role in matched sibling donor (MSD) transplants remains unclear.We conducted a retrospective study of 413 MSD-HSCT patients receiving peripheral blood stem cell (PBSC) grafts from January 2010 to January 2023. Patients were categorized into four groups: Group I (CNI + MTX or MMF), Group II (CNI + MTX or MMF + ATG), Group III (PTCy + ATG + CNI), and Group IV (PTCy + CNI + MMF). PTCy was associated with a significant reduction in grade II-IV [HR 0.6, p=0.01] and grade III-IV acute GvHD [HR 0.2, p=0.001] as well as all grade chronic GvHD [HR 0.5, p=0.007] and moderate-severe chronic GvHD [HR 0.4, p=0.001] compared to CNI+MTX (or MMF) containing regimens. PTCy did not increase relapse risk; PTCy reduced NRM [HR 0.3, p<0.002], leading to improved GvHD-free/relapse-free survival (GRFS) [HR 0.4, p<0.001]. PTCy was also associated with improved overall survival [HR 0.56, p=0.01]. Bloodstream infections are increased with PTCy [HR: 1.5, p=0.001]. The addition of ATG to PTCy did not further improve the GRFS and was associated with a higher incidence of clinically significant Cytomegalovirus (CMV) [HR 2.16, p=0.002] and Epstein-Barr virus reactivation (EBV) [HR 9.5, p<0.001] and a numerical increase in NRM [HR 1.7, p=0.2]. PTCy significantly appeared to improve GRFS in the MSD setting using PBSC grafts. The addition of ATG to PTCy increases csCMV and csEBV reactivation without further improving GRFS. Prospective trials and PTCy dose optimization are warranted.
