Dr David Snyder Discusses Treating GVHD, the Differences Between Chronic and Acute GVHD

Ruxolitinib was recently approved to treat acute graft-versus-host disease (GVHD), and trials are ongoing to understand the best way to use the treatment with transplantation, said David Snyder, MD, associate chair of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

Transcript

When does graft-versus-host disease occur, and what is the difference between acute and chronic graft-versus-host disease?

So, GVHD, or graft-versus-host disease is an immune reaction where the donor’s T lymphocytes recognize minor antigen differences on the surface of the cells of the patient and try to react against them. In a sense, the graft tries to reject the patient instead of the patient rejecting the graft.

We talk about acute and chronic GVHD. By definition, acute GVHD is any reaction that occurs within the first 100 days after transplant, and chronic GVHD is reactions that occur after 100 days. But that’s somewhat an oversimplification. There are some differences in the mechanism of those reactions and there can be overlap. So, some patients may have what looks like chronic GVHD earlier than day 100, and conversely some might have acute GVHD that comes on after day 100. But that remains one of the biggest challenges to success from transplantation, and fortunately there are some improvements being made.

Ironically, ruxolitinib, which is the drug we use as our JAK 2 inhibitor treating myelofibrosis, was just recently approved as treatment for refractory acute GVHD, so it does inhibit the JAK 2/STAT pathway, which is important in these inflammatory immune reactions, as well. We, and others, are trying to study what’s the best way to use JAK 2 inhibitors in the context of transplantation—in terms of pretransplant, peri-transplant, and posttransplant.

And we have a trial at City of Hope, where we’re giving our patients ruxolitinib from day minus 3 to day plus 30 of the transplant procedure to see what impact that might have on some of the morbidities that could occur, including the incidence of graft-versus-host disease.