Addressing Unmet Needs in Acute and Chronic GvHD - Episode 1

Historical Management, Incidence, and Risk Factors of GvHD

Yi-Bin A. Chen, MD:Graft-vs-host disease [GVHD] remains if not the major, then a major complication of allogeneic transplantation, despite attempts to improve on its treatment over the last several decades. What we have seen is there is definitely a change in graft-vs-host disease. We do know over the last couple of decades that we see much less severe acute graft-vs-host disease, and that has contributed to an overall improvement in the outcomes of our patients. There are a lot of things responsible for that. That includes better HLA typing of recipients and donors. That includes a better understanding for us, as practitioners, of whom to transplant in terms of patient selection. And that includes a gradual decrease in the conditioning regimen that we’ve used. Overall, there’s been a decrease in the severity and, thankfully, the percentage of patients who die from acute graft-vs-host disease early on after transplant.

Unfortunately, treatment paradigms have not evolved entirely. While we have used a series of additional agents to try to improve on the treatment of graft-vs-host disease and the prevention of such, it was perhaps not until recently that we started to make some improvements.

The historical treatment of graft-vs-host disease was rooted in systemic immunosuppression. We all felt that the underpinnings of graft-vs-host disease were donor cells attacking normal host tissue. Intuitively, the treatment aimed to suppress the donor immune system. The drawback to that type of therapy was that as additional immunosuppression was added, these patients were prone to more infections; and there was likely a decrease in the ability to battle these infections as well as battle the underlying malignancy. Traditional immunosuppression has fallen by the wayside in recent developments for the treatment of graft-vs-host disease as we’re all looking toward other avenues to treat this disease.

The overall incidence of acute and chronic graft-vs-host disease at our center hasn’t really changed over the last couple of decades. What we have seen is a decrease in the severity and a change in the timelines. Historically, graft-vs-host disease was defined in patients who were much more homogenous. They were all receiving myeloablative bone marrow transplants and were younger. These days, the patients we treat are much more heterogeneous. Many are older. Many are receiving reduced-intensity transplants. The majority of patients receive peripheral blood stem cell grafts instead of just bone marrow. And the regimens we’re using to prevent graft-vs-host disease are varied. All these things affect what we call the immune reconstitution after transplant, and that ultimately affects the timeline of graft-vs-host disease.

We used to define acute and chronic graft-vs-host disease based on a 100-day timeline. Patients who developed GVHD before 100 days were classified as acute. Patients who developed GVHD after 100 days were classified as chronic. With all our heterogeneous practices in transplant, these timelines are now no longer accurate, and graft-vs-host disease is wholly defined by clinical manifestations. Nevertheless, if we accurately define graft-vs-host disease, the incidence hasn’t really changed. At our center, I’ll classify acute graft-vs-host disease as I sit and talk to patients. In patients for whom I actually have to do something in terms of treatment, this probably occurs in about 25% to 30% of our patients after transplant. Chronic graft-vs-host disease—in the same way, where I actually have to do active management in about 40% of patients.

The traditional risk factors for graft-vs-host disease have been defined in large studies. Those clinical factors include less HLA matching between donor and recipient. The intensity of the conditioning regimens certainly appears to put patients at risk for more graft-vs-host disease. Use of total-body irradiation certainly puts patients at risk for graft-vs-host disease. There’s evidence that older patients and older donors lead to an increased risk for graft-vs-host disease. There is also definitely some evidence that a female donor into a male recipient leads to more chronic-vs-versus host disease that is possibly more acute. In many studies, the leading factor for chronic graft-vs-host disease is the development of acute graft-vs-host disease. These are the main risk factors that we see. There are others as well that have been defined in small studies here or there, but those are the main ones.

Transcript edited for clarity.