Evaluating Strategies and Approaches to Prevent Graft-Versus-Host Disease

Benjamin Watkins, MD, Tulane University School of Medicine, New Orleans, Louisiana, shares insights into evolving options and approaches for the prevention of the development of graft-versus-host disease (GVHD) following allogeneic stem cell transplant (ASCT).

Transcript:

Hello, my name is Ben Watkins. I'm at the Tulane University School of Medicine and I'm going to be talking today a little bit about one of the papers recently published, called, “The Controversies and Expectations for the Prevention of Graft-Versus-Host Disease.” 

Acute and chronic graft-versus-host disease remain major contributors to the morbidity and mortality associated with allogeneic stem cell transplant. While many of the mechanisms responsible for the development of the disease have been discovered, there also remains a lot we don't know. Importantly though, significant advances have been made recently in the prevention of the disease. 

While new drugs and techniques have emerged on the scene, one of the most important factors in the prevention of GVHD is the selection of the donor. Matched sibling transplant remains the gold standard. However, alternative donor sources like unrelated donor, including those that are mismatched and haploidentical transplant, have become safer. Choosing the right donor has become increasingly more complex, with multiple factors to take into consideration as prioritization of HLA [human leukocyte antigen matching] has become much more sophisticated. 

Once a donor is chosen, there are also a number of decisions to be made in the prevention of GVHD. It is actually quite wonderful that we are now at this point in which we have a number of good options for the prevention of GVHD.

These options include things like abatacept, ATG [antithymocyte globulin], post-transplant cyclophosphamide, graft manipulation techniques like CD45RA depletion, and alpha-beta T-cell depletion, as well as a number of other new agents and approaches that are currently being evaluated in clinical trials. 

The question is, how do you choose which one to use? This isn't an easy answer and should be individualized for the patient in front of you. Each approach carries its own risks and benefits.

There are some patients with infectious risks that would benefit from quicker immune reconstitution. While others may be at very high risk for relapse and would benefit from increased graft-versus-leukemia effects or might be at high risk for graft failure. While others may come into transplant with poor organ function or a history of noncompliance or increased risk of GVHD. 

All of these factors need to be taken into consideration with each patient. It'd be easy if there was just 1 answer for all patients, but that's just not the case. We must take a personalized approach to the prevention of graft-versus-host disease. 

Source:

Watkins B, Williams K. Controversies and expectations for the prevention of GVHD: A biological and clinical perspective. Front. Immunol. 23 November 2022. Sec. Alloimmunity and Transplantation. doi:10.3389/fimmu.2022.1057694