Post-transplant cyclophosphamide (PTCy) represents a major advance in immune tolerance and the prevention of graft versus host disease (GvHD) following allogeneic hematopoietic stem cell transplantation. Although it was initially introduced in the setting of haploidentical transplantation, its use has rapidly expanded to the setting of matched sibling and matched and mismatched unrelated donor transplants with encouraging results.
Thus far, PTCy has been mainly used in combination with calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF). However, our enhanced understanding of the pathophysiology of GvHD and the mechanisms of immune tolerance as well as the mode of action of PTCy allow moving beyond this standard combination of PTCy, CNI, and MMF aiming to augment efficacy, improve tolerability, and avoid many of the pitfalls of CNI. In addition, the recent data on the efficacy of co-stimulation blockade mitigating the risk of acute GvHD offers a unique opportunity to further advance the field. Costimulation blockade with abatacept has been shown to decrease the incidence of acute GvHD following matched and mismatched unrelated hematopoietic stem cell transplantation. This has led to the approval of abatacept for the prevention of GVHD in the US and Canada.
Preliminary data suggest that along with optimizing the dose of PTCy, innovative combinations with other agents such as proteasome inhibitors, co-stimulation blockade, and the novel approach of two-step transplants are all promising. Other approaches including DPP-4 and alpha4 beta7 integrin inhibition also warrant examination with PTCy.
Taken together, we believe that we are at the cusp of a new era of immune tolerance in hematopoietic stem cell transplantation that should be highlighted and shared with a wide audience.
How to move beyond the standard PTCy and its combinations with a CNI and MMF to improve GvHD prevention following allogeneic hematopoietic stem cell transplantation.
Improving the results of GvHD prevention following haploidentical or mismatched unrelated donor transplantation may also address a healthcare disparity issue due to the under-representation of matched unrelated donors from minority groups in the different registries.
In this Research Topic, we welcome review articles on the following topics:
-Better understanding of the mechanisms of action of PTCy
-Optimizing the schedule and dosing of PTCy
-Innovative combinations with PTCy including shortening the course of CNI, combinations with proteasome inhibitors, co-stimulation blockade, rATG, PPD-4 and integrin inhibitors
-Two-step transplantation approach
Dr. Samer Al-Homsi is on the Advisory Board at BMS (Bristol Myers Squibb)
Post-transplant cyclophosphamide (PTCy) represents a major advance in immune tolerance and the prevention of graft versus host disease (GvHD) following allogeneic hematopoietic stem cell transplantation. Although it was initially introduced in the setting of haploidentical transplantation, its use has rapidly expanded to the setting of matched sibling and matched and mismatched unrelated donor transplants with encouraging results.
Thus far, PTCy has been mainly used in combination with calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF). However, our enhanced understanding of the pathophysiology of GvHD and the mechanisms of immune tolerance as well as the mode of action of PTCy allow moving beyond this standard combination of PTCy, CNI, and MMF aiming to augment efficacy, improve tolerability, and avoid many of the pitfalls of CNI. In addition, the recent data on the efficacy of co-stimulation blockade mitigating the risk of acute GvHD offers a unique opportunity to further advance the field. Costimulation blockade with abatacept has been shown to decrease the incidence of acute GvHD following matched and mismatched unrelated hematopoietic stem cell transplantation. This has led to the approval of abatacept for the prevention of GVHD in the US and Canada.
Preliminary data suggest that along with optimizing the dose of PTCy, innovative combinations with other agents such as proteasome inhibitors, co-stimulation blockade, and the novel approach of two-step transplants are all promising. Other approaches including DPP-4 and alpha4 beta7 integrin inhibition also warrant examination with PTCy.
Taken together, we believe that we are at the cusp of a new era of immune tolerance in hematopoietic stem cell transplantation that should be highlighted and shared with a wide audience.
How to move beyond the standard PTCy and its combinations with a CNI and MMF to improve GvHD prevention following allogeneic hematopoietic stem cell transplantation.
Improving the results of GvHD prevention following haploidentical or mismatched unrelated donor transplantation may also address a healthcare disparity issue due to the under-representation of matched unrelated donors from minority groups in the different registries.
In this Research Topic, we welcome review articles on the following topics:
-Better understanding of the mechanisms of action of PTCy
-Optimizing the schedule and dosing of PTCy
-Innovative combinations with PTCy including shortening the course of CNI, combinations with proteasome inhibitors, co-stimulation blockade, rATG, PPD-4 and integrin inhibitors
-Two-step transplantation approach
Dr. Samer Al-Homsi is on the Advisory Board at BMS (Bristol Myers Squibb)