Inside the Clinic: Acute Graft-versus-Host Disease - Episode 11
Corey S. Cutler, MD, MPH, FRCPC: Welcome to this edition of OncLive Insights, “Inside the Clinic: Acute Graft-Versus-Host Disease.” I’m Dr Corey Cutler. I’m the medical director of the Stem Cell Transplantation Program at the Dana-Farber Cancer Institute in Boston. I’m joined today by my colleague, Dr Joseph Antin.
Joseph Antin, MD: I am a professor of medicine at Harvard Medical School and the emeritus chief of stem cell transplantation at Dana-Farber Cancer Institute. Dr Cutler and I have worked together for many years. One of our principal research interests and clinical interests is…the diagnosis and treatment of acute and chronic graft-versus-host disease (GVHD).
Corey S. Cutler, MD, MPH, FRCPC: So today we’ll be talking mostly about acute GVHD. Perhaps I’ll have you start, Dr Antin, by giving us a little bit of background on things like the overall incidence and the organs that are involved in acute GVHD.
Joseph Antin, MD: Well let me start off by describing what’s really going on with GVHD. When transplantations are performed, there is a difference in histocompatibility antigens between the donor and the recipient. While we say patients are fully HLA matched, that’s really an exaggeration. The only people who are truly perfectly matched are identical twins. And consequently, there are what we call minor histocompatibility differences that can be recognized by the immune system and generate an immunological response that we call GVHD.
These vary from 1 or 2 antigens to possibly…a dozen or more antigens, and thus it’s sometimes difficult to predict the potential severity of GVHD. But in essence what’s going on is that the T cells that are transferred from the donor to the recipient recognize minor histocompatibility antigens in the context of a conditioning regimen and the underlying inflammatory processes and generate an immune response that’s essentially identical to what would be generated if there were an infection.
The target organs are principally skin, gut, and liver, and these are organs that function as barriers to the environment. They’re the ones that have the highest percentage of dendritic cells—antigen presenting cells—whose normal function is to generate an immune response.
The other factor that is important in terms of peripheral blood versus bone marrow transplantation is the number of T cells that are introduced—which we will get to later—and HLA disparity, which is relevant as well because we’re increasingly doing transplants across HLA barriers. So, Corey, why don’t you comment on the incidence of and severity of GVHD in that context.
Corey S. Cutler, MD, MPH, FRCPC: Acute GVHD occurs in approximately 30% to 35% of individuals who receive a transplant from a matched related donor, probably closer to 50% of individuals who receive a transplant from a matched unrelated donor, and probably…a slightly higher percentage of individuals who receive a transplant from a mismatched or half-matched or haploidentical donor.
Cord blood transplants tend to have slightly lower rates of GVHD. And as you already mentioned, acute GVHD really affects 3 organs only: the skin, the intestinal tract, and the liver. We always grade and stage these organs. So each individual is given an organ stage based on the percentage of body surface involvement for the skin, based on the volume of diarrhea and the number of bowel movements per day for the intestinal tract, and based on the level of rise of bilirubin for the liver. We take the individual organ stages and come up with an overall grade of acute GVHD, and that’s how, as transplanters, we can talk among ourselves and discuss severity. In addition to the clinical presentation of GVHD we now have the opportunity to use some biomarkers and some diagnostic pathology. What are your thoughts on the role of these modalities today?
Joseph Antin, MD: Well, the group at Mount Sinai Hospital led by James Ferrara, MD, and John Levine, MD, has pioneered the use of biomarkers to…predict outcomes for GVHD. Biomarkers don’t actually predict the onset or the incidence of GVHD, but they can predict its severity and transplant-related mortality. They are still investigational, although you can obtain a commercial measurement of biomarkers.
In my view, biomarkers are principally useful…to inform decisions regarding clinical trials. For instance, if you had a biomarker that is elevated and suggests that a patient is likely to have a high mortality related to GVHD, they might be eligible for an investigational study of more intensive immunosuppression. In contrast, if the patient had a low biomarker risk profile, then you probably would not want to start them on an investigational regimen, because they’re much more likely to respond effectively to corticosteroids.
Transcript Edited for Clarity