Frontline Management of Acute Graft-Versus-Host Disease

Transcript:

Corey S. Cutler, MD, MPH, FRCPC: Perhaps we can…talk a little bit about the management of acute graft-versus-host disease (GVHD).… At our center we typically use corticosteroids as the first-line therapy for acute GVHD, and we generally start at a dose of 1 to 2 mg per kilogram of body weight for recipients. For individuals who have skin disease only, we sometimes use lower doses such as 1 mg/kg. But by and large the standard of care at our center is 2 mg/kg. There also is a role for topical therapy for the skin that involves topical steroids or topical immunosuppressants and even topical steroids for the intestinal tract in the form of nonabsorbable oral steroids. How long do you treat patients with acute GVHD for at those high doses of steroids?

Joseph Antin, MD: Well, that’s a critical issue and despite the fact that we’ve been doing transplantation for 40 years, the exact dose and exact schedule are really not well established. What has been accepted as a criterion for steroid resistance is when the patient’s condition deteriorates within 3 days or doesn’t respond within 7 days.

For those patients who are improving, we generally will continue them on the starting dose until things are under decent control: the rash is mostly resolved or the diarrhea is substantially better. Typically, I will continue them on high doses of steroids until they’re still restarting to form stool, or at least until it’s become thick enough that it’s no longer like dysentery or pure water. And then we taper 10% per week or something of that order.

We can talk about investigational approaches subsequently. I think there’s some limitations to the definition of steroid resistance in that, if you think about it, if you were to denude somebody’s intestinal tract by some mechanism that you could stop instantaneously, how long would it take for the diarrhea to go away? And I think it takes longer than a week for most people, certainly for people with severe GVHD. And what that translates into is that we often make the assessment that the patient’s disease has failed to respond to steroids prematurely. And this results in the piling on of additional immunosuppression, or the initiation of investigational agents, prior to the time that the patient really needs this additional treatment.

This is in fact one of the places where the biomarkers may be helpful, because that’s exactly the type of patient you want to identify: the type of patient who is likely to go on and develop severe GVHD that has an underlying mortality versus the type of patient who is likely to respond and get better, even if the initial manifestations of GVHD are severe.

Transcript Edited for Clarity