Graft-Versus-Host Disease - Episode 4

Case 1: Personal Approach to Treatment for Acute GVHD

Corey Cutler, MD, MPH, FRCPC: The patient was treated, as you noted, with 2 mg/kg of prednisone. Why don’t you tell us about the approach you would take. What other things could you consider?

Usama Gergis, MD, MBA: Well, this is the approach that I will take with this man. I pause a little because if this is the only problem that we are dealing with at this time, then I will indeed start with 2 mg/kg of prednisone. As I alluded earlier, I came from a T-cell–depleted institution, where viral infections were very high, and oftentimes we would have a similar case with a CMV [cytomegalovirus] viral load of something in the 50,000 copies/mL. Giving that much steroids can get the CMV or other viruses out of control, so for a case like that, we can start at a lower dose, typically either 1 mg/kg or 0.5 mg/kg and see what happens. The caveat to this is if he responds, great. If he does not respond, you will have to up the dose and start over before judging whether he is steroid refractory or not. I like to believe that there is still some art in the medicine that we do.

Corey Cutler, MD, MPH, FRCPC: What would you say is the likelihood that someone like this with very straightforward grade 2 GVHD [graft-vs-host disease] will be steroid responsive? What is the likelihood that they will be steroid refractory?

Usama Gergis, MD, MBA: It is a fifty-fifty chance. About 50% of the time, he will be steroid responsive. You taper the steroids over a long time, and graft-vs-host disease will not come back. That’s a 50% chance. The problem is the other 50%, where he either does not respond and falls into a steroid-refractory acute graft-vs-host disease. After 3 to 5 days his GVHD progresses or stays the same after a week or does not resolve in 4 weeks. That is basically the definition of steroid-refractory acute graft-vs-host disease. Or you start to taper the steroids. Once you start to do that, the diarrhea increases or he has more rash. That becomes steroid dependent. Fifty percent of the time, he will fall in to 1 of these 2 categories, either steroid nonresponsive, refractory, or dependent.

Corey Cutler, MD, MPH, FRCPC: Do either of you use biomarkers to either guide initial therapy or guide response to therapy, or is that something that is just for clinical trials?

Usama Gergis, MD, MBA: I have used it a couple of times, I must confess, in a very inconsistent way for reasons that are probably outside this discussion: insurance and other logistical issues. The 2 main biomarkers, ST2 and REG-3-alpha, have shown a benefit over and over. Again, I come from New York. I worked across Central Park from Mount Sinai, where the biomarkers were very popular.

Daniel Couriel, MD, MS: I don’t use them. I think they are experimental, and I don’t think their receiver operating characteristic curves are impressive. I do not think they have been validated prospectively, either, so for all those reasons, I do not. I respect other positions, and they are all that we have to give us some guidance. By saying this, I am not being critical of those who use it. It is just that I feel they need a little more work before I start considering them standard of care.

Corey Cutler, MD, MPH, FRCPC: That’s largely the approach we have here in Boston. We utilize them when they are part of a clinical trial, but we don’t use them outside the clinical trial for routine care at this time. That has been our approach.

Transcript edited for clarity.