Post-transplantation Cyclophosphamide: From HLA-Haploidentical to Matched-Related and Matched-Unrelated Donor Blood and Marrow Transplantation

Abstract

Following allogeneic blood and marrow transplantation (BMT), graft-versus-host disease (GvHD) continues to represent a significant cause of treatment failure, despite the routine use of conventional, mainly calcineurin inhibitor-based prophylaxis. Recently, post-transplant cyclophosphamide (PTCy) has emerged as a safe and efficacious alternative. First, omitting the need for ex vivo T-cell depletion in the setting of haploidentical transplantation, growing evidence supports PTCy role in GvHD prevention in matched-related and matched-unrelated transplants. Through improved understanding of GvHD pathophysiology and advancements in drug development, PTCy emerges as a unique opportunity to design calcineurin inhibitor-free strategies by integrating agents that target different stages of GvHD development.

Keywords: GvHD prevention; bortezomib; calcineurin inhibitor-free; matched unrelated donor; matched-related donor; post-transplant cyclophosphamide.

FIGURE 1

Mechanism of action of agents that may conceptually be added to PTCy to develop CN and mTORI-free combinations for GvHD prevention. DAMPS, damage-associated molecular patterns; PAMPS, pathogen-associated molecular patterns; BOR, bortezomib; ABA, abatacept; MHC II, major histocompatibility complex class II; UST, ustekinumab; TGF-β, transforming growth factor-β; HSC, hematopoietic stem cells; VEDO, vedolizumab; NATA, natalizumab.