Gastrointestinal graft-versus-host disease is a common and potentially deadly side effect for patients who undergo an allogeneic stem-cell transplant to treat certain blood cancers.
A research from Fred Hutchinson Cancer Research Center has shown that adding a widely used topical corticosteroid to the standard treatment for GVHD kept the disease in remission and significantly reduces deaths one year after therapy.

A reformulation of Beclomethasone dipropionate ( BDP ) into two different pills specifically releasing the drug into the stomach and mid-small intestine prevented relapse of gastrointestinal GVHD and allowed those patients to be on a shorter treatment course of high-dose Prednisone.
Mortality was reduced by 46 percent a year following the start of treatment in a multi-center Phase III clinical trial, according to findings published in the journal Blood.
The lead author is David M. Hockenbery, at the Hutchinson Center.
Beclomethasone is an anti-inflammatory drug long used to treat a variety of diseases such as asthma and ulcerative colitis.

About 60 percent of patients who receive an allogeneic stem-cell transplant to treat blood cancers such as acute and chronic myelogenous leukemia, acute lymphocytic leukemia and non-Hodgkin's lymphoma develop gastrointestinal GVHD as a major side effect of being infused with donor stem cells. Those who show gastrointestinal symptoms of the disease usually receive a two to four-week course of high-dose systemic Prednisone therapy that is then tapered slowly. However, that drug is a two-edged sword, Hockenbery said. On the one hand it is designed to suppress the donor cells so GVHD can be controlled. But suppressing the immune system also makes patients susceptible to potentially fatal infections.

In the clinical trial, 129 patients were randomized into two groups. One group received a short course of standard prednisone therapy and oral Beclomethasone for 50 days. The other group received a placebo in place of the oral Beclomethasone for the same period.
At day 10, the Prednisone dose was quickly tapered in patients whose symptoms had responded. Fewer patients randomized to Beclomethasone had a subsequent flare-up of GVHD.

After completion of the 50-day treatment period, patients were followed for an additional 30 days to see if the treatment effect would last. Patients randomized to BDP had a significantly more durable response rate compared to those in the placebo group. At one year after treatment, mortality rates had been reduced 46 percent compared to the placebo group.

" Oral Beclomethasone provides much more tailored and targeted control of gastrointestinal GVHD and it allows patients to move away from the side effects of standard prednisone therapy. All of this improves the chances that patients will have a successful outcome," Hockenbery said. " I think this is a very convincing clinical trial because by targeting topical therapy to the areas most affected, we were able to keep symptoms at bay while minimizing systemic immune suppression."

The idea to reformulate Beclomethasone into an oral form for stem-cell-transplant patients belongs to George B. McDonald, one of the study co-authors and a colleague of Hockenbery's at the Hutchinson Center. The goal was to target corticosteroid therapy to the areas of the GI tract affected by GVHD. The anti-inflammatory actions of the two Beclomethasone-containing pills would then be focused on the intestinal lining from top to bottom to suppress GVHD, thus avoiding excessive corticosteroid medication in the bloodstream.

Source: Fred Hutchinson Cancer Research Center, 2007

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