Advances in Steroid-Refractory Acute GVHD - Episode 1

Initial Approach to Treating GVHD

Claudio Anasetti, MD:Transplantation of hematopoietic stem cells is curative for a large variety of hematological malignancies otherwise lethal. The curative potential of transplant is actually immune mediated, and the reaction comes from donor mature T cells. Unfortunately, this type of reaction can also affect normal body tissues and organs. This reaction is called graft-versus-host disease when it affects the skin, liver, gastrointestinal tract, and lungs.

The incidence of graft-versus-host disease is roughly 50%. Fifty percent of patients are affected, and a quarter of them actually die of acute graft-versus-host disease—complications of acute graft-versus-host disease, infections, organ failure, or evolution in the chronic graft-versus-host disease.

With expansion of the donor pool for transplantation, the incidence of graft-versus-host disease has also increased. However, the way we treat it has actually not changed that much. The key elements for treatment of established graft-versus-host disease remain with systemic glucocorticoids—prednisone or analogues.

If graft-versus-host disease involves less than 50% of the body surface area of skin, we just use topical steroids. If graft-versus-host disease involves the stomach without diarrhea, we can use beclomethasone. This is also non-absorbable. But if diarrhea is involved, the liver is involved, and more than 50% of the skin is involved, then we have to use systemic glucocorticoids—prednisone or others.

In patients who have a good performance status, we can actually use an outpatient regimen of oral prednisone—1 mg/kg per day to 1.25 mg/kg per day in 1 or 2 divided doses. But in patients who have a compromised performance status because of diarrhea, dehydration, concurrent infections, we keep them in the hospital. These patients usually have more aggressive graft-versus-host disease, for which we use intravenous formulations of glucocorticoids, predominantly methylprednisolone at the dose of 2 mg/kg in 2 divided daily doses.

After the treatment starts, we hold the dose steady for a minimum of 7 days and up to 3 weeks to assure that the patient is continuing to improve before we taper the prednisone or methylprednisolone doses. The taper is usually started at 10% of the initial dose, and continues on a weekly schedule after the patient is assessed and we assure that continuation of improvement is observed. We do this before we taper the glucocorticoid dose to the next lower notch.

Transcript edited for clarity.