Graft-Versus-Host Disease - Episode 12

Case 1: Treating Acute Graft-Versus-Host Disease

Bart L. Scott, MD: What is our institution’s preference for grading and staging acute GvHD [graft-versus-host disease]? We use the IBMTR [International Bone Marrow Transplant Registry] grading system, with a combination with the Glucksberg scale. We consider the quantity of diarrhea and the organs that are involved, and that would primarily be the skin, the gut, and the liver.

In this regard the patients received GvHD prophylaxis with tacrolimus and methotrexate. On day +22, the presumption is that the patient is still on full-dose therapeutic tacrolimus. There are 2 options, in my opinion, for treating this acute GvHD presentation. One would be high-dose steroid therapy, which is what this patient received. The alternative treatment would be sirolimus.

There was a trial comparing sirolimus to high-dose steroids for initial presentations of acute GvHD, which potentially showed equivalent outcomes. Another option besides steroids would be starting the patient on rapamycin and sirolimus.

What are the outcomes with initial systemic corticosteroid therapy for patients with grade 2 to 4 acute GvHD? When I think about this question, I try to assess level of data and what’s the best data to answer this question. There was a randomized trial comparing 2 mg/kg to 5 mg/kg high-dose steroid therapy for patients who develop steroid-refractory GvHD.

In the patient population that was considered for enrollment, the risk of developing steroid-refractory acute GvHD in that setting was approximately 30%—meaning that 70% of patients did respond to the high-dose steroid therapy. Among the patients with grade 2 to 4 GvHD who do require steroid therapy, the overall response rate to steroids is about 70%. There are some nuances to that. The type of organ involvement and the severity of the grading system all affect the potential response to steroids.

I generally wait about a week, sometimes 10 days, and then start a rapid taper. There was a clinical trial looking at the addition of beclomethasone for the prevention of GvHD recurrence. In this trial the patients were treated for a total duration of 10 days, and then the steroids were rapidly tapered. The addition of the beclomethasone allowed patients to be more successfully tapered. We generally also start patients on budesonide if they have lower GI [gastrointestinal] tract symptoms, as this patient does, because this patient has some diarrhea. We’d be talking about giving the patient about 10 days of therapy with concurrent beclomethasone-budesonide, followed by a rapid taper as they remain on the beclomethasone and budesonide.

Transcript edited for clarity.