A 61-Year-Old Man With Acute Graft-Versus-Host Disease - Episode 2
Usama Gergis, MD: Acute graft-versus-host disease [GVHD] is probably the most common adverse event following allogeneic transplantation. It affects 40% to 80% of all-comers, and the range is so wide because there are many factors: the intensity of the conditioning regimen, myeloablation versus reduced-intensity conditioning, T-cell depletion or T-cell repletion, the use of ATG [antithymocyte globulin], the use of Campath, or similar T-cell depletion agents. Acute graft-versus-host disease classically occurs in the first 100 days after transplantation. We say “classically” because they’re a huge overlap. I have many patients who develop acute graft-versus-host disease 6 months after transplantation. When we talk about chronic graft-versus-host disease, it classically occurs after 100 days in many patients. In the community of patients who have undergone transplantation, many will develop chronic graft-versus-host disease before day 100. Acute graft-versus-host disease is more of an acute inflammatory T-cell–mediated and cytokine-induced phenomenon. It typically affects the skin, the upper GI [gastrointestinal] tract, the lower GI tract, and the liver.
What is the definition of steroid-dependent acute-graft-versus-host disease? At the maximum dose of steroids 2 mg/kg prednisone equivalent per day, there is some improvement, but as soon as you taper down the steroids, graft-versus-host disease flares back up. So that is the definition of steroid-dependent graft-versus-host disease. We have steroid-dependent and steroid-refractory graft-versus-host disease. The approach to both is the same. You go to a second-line treatment. The prognosis for both is exactly the same: 50% treatment-related mortality at 6 months, 60% treatment-related mortality at 1 year, and response to second-line treatment, the only second-line treatment, ruxolitinib, is approximately 50% to 55%.
Now that we have gone into the definitions and the prognosis of patients with both steroid-refractory and steroid-dependent acute graft-versus-host disease, what is the best approach for steroid dose tapering after the initial response? The most common phrase that we say on the floor as surgeons who perform transplants is, “We hate steroids.” Steroids cause a multitude of adverse effects. Patients get deconditioned, they can’t sleep at night, they have immune suppression, diabetes, and a multitude of other problems. So, we like to taper down steroids as soon as possible. There are no real guidelines and we have to take as we go. I have a patient upstairs who’s in his 70s, so I am eager to decrease steroid use faster, just because of his deconditioning, diabetes, and other problems. So, in short, we taper steroids as soon as we get a response. The dilemma is that sometimes it’s very hard to do that, and when we taper steroids, the graft-versus-host disease comes back.
Transcript edited for clarity.