Hutchinson Center researchers seek to keep transplanted immune cells from attacking their new hosts

By Justin Matlick, Hutchinson Center science writer

It’s one of bone marrow transplantation’s most insidious side effects: graft vs. host disease, which strikes when transplanted immune cells turn against a patient’s body and attack its tissues. Around 80 percent of transplant patients will get the disease. Many of these patients will spend months or years taking drugs to fight it off. Some of them will die from it.

But understanding why GVHD affects some people and spares others has been a longstanding scientific puzzle, making it hard to develop ways to prevent the disease. Now, the Hutchinson Center’s Dr. Effie Petersdorf has made a discovery that offers new hope of breaking through these barriers.

To understand what makes someone susceptible to GVHD, Petersdorf took a closer look at the DNA of more than 4,000 transplant patients. “The question I wanted to ask was whether there are genes we don’t know about that could be influencing GVHD risk,” she says.

This led to a key insight: when bone marrow donors and patients have a difference in two key “single-nucleotide polymorphisms” (SNPs) – tiny variations in a person’s DNA – it increases a patient’s risk of suffering GVHD and lowers their odds of survival. Petersdorf is translating this discovery into a new test that could help match patients with donors who have favorable SNP profiles, improving a patients’ chances of avoiding GVHD.

“We’ll be including this test in a new transplant protocol at Seattle Cancer Care Alliance later this year,” Petersdorf says. “It could help us do an even better job of finding donors whose cells will benefit patients the most.”

This could be just the beginning. Petersdorf’s next step is to dig beyond SNPs and identify the actual genes that signal whether a person might suffer GVHD. By improving donor-patient matching even more, this could spare more transplant patients from GVHD, boosting their odds of living longer, happier lives.