The Changing Landscape of Chronic Graft vs. Host Disease - Episode 4

Frontline Management of GVHD

,

Michael Bishop, MD, leads the discussion on approaching the first-line management of acute GVHD and the importance of early intervention for patients at risk for the disease.

John DiPersio, MD, PhD: Let’s talk about how we’d manage patients who get transplanted. The first issue we’re presented with after a transplant, when they develop symptoms and signs of acute GVHD [graft-vs-host disease]. I’m wondering, Mike, how you initially manage your patients with acute GVHD.

Michael Bishop, MD: With acute or a chronic?

John DiPersio, MD, PhD: Acute.

Michael Bishop, MD: It’s the same thing I learned when I was a fellow. The first 3 treatments for graft-vs-host disease are steroids, steroids, and steroids. I still think corticosteroids form the foundation. For acute graft-vs-host disease, most of the time they’re going to be on a calcineurin inhibitor. We’ll add corticosteroids, and we’ll do 1 to 2 mg/kg. I might make that even 0.5 mg/kg, and it will have to do with the organ involvement and the severity.

If I have somebody with grade 2 cutaneous graft-vs-host disease, I may use 0.5 mg/kg. If I have somebody with rip-roaring GI [gastrointestinal] and hepatic graft-vs-host disease, I’ll definitely use over 1 mg/kg, and I’ll usually use 2 mg/kg to try to begin the process. I’ll be thinking very quickly. One thing that’s underappreciated and comes back is early intervention. I’ll be looking for the steroid-refractory patients. At that point, I’ll be looking to add an additional agent. Most commonly it will be ruxolitinib. Ruxolitinib has changed our management of acute graft-vs-host disease. We have to make sure we identify those steroid-refractory patients as soon as possible.

John DiPersio, MD, PhD: I agree. As I was referring to initially, early intervention—there’s a prophylactic treatment, there are preventive therapies, and there are treatment-related approaches. To intervene too late is a problem because once you get a lot of tissue damage, then you get the circular circuits of inflammation that are hard to stop after awhile.

Michael Bishop, MD: In that context, John, do you use biomarkers? For early intervention do you do biomarker studies on your patients for early identification of patients at risk for acute graft-vs-host disease?

John DiPersio, MD, PhD: We haven’t generally. Obviously in select clinical trials, we do. We’ve come a long way with biomarkers, but they’re still not mainstream. What is the best day to get these biomarkers, which is the most predictive? James Ferrara and John Levine would provide some better insights than either you or I could. But there’s still debate about whether it’s at 7 days or at 21 days. The timing for these biomarkers as the most predictive for severe GVHD is a little debatable at this point.

Transcript Edited for Clarity