Revolutionizing Treatment for Graft-Versus-Host Disease

Leslie Kean

Dr. Leslie Kean has treated hundreds of children with cancer, but one particular patient is seared on her memory. He was a teenage football star, a popular kid who had the world at his feet until he was struck by leukemia.

Kean guided him through a bone marrow transplant that was supposed to beat his cancer and rebuild his immune system. Instead, the transplanted cells attacked his body and triggered graft-versus-host disease, or GVHD. The disease is one of the two most common causes of death for cancer patients who receive transplants – the other is cancer relapse.

The boy quickly went from the prime of his life to being confined to the hospital with debilitating stomach problems, relying on his mother to care for his most basic needs.

“He was amazing,” Kean says. “He never complained, he just kept hanging in there, even though we feared he wasn’t going to make it.”

As Kean watched GVHD overtake the boy, she resolved to find a way to prevent the devastating disease. This fueled her work at Emory University, where she pioneered new treatments and became a leading GVHD researcher. Kean joined Seattle Children’s Research Institute’s Ben Towne Center for Childhood Cancer Research last summer, drawn by a unique chance to pursue revolutionary cures.

“Transplants are the best treatment we have and I want to make them as safe as possible,” Kean says, “but I also want to create a future where most patients don’t need them at all.”

Testing a Drug That Could Eliminate GVHD

At Emory, Kean broke new ground when she discovered that a rheumatoid arthritis drug could potentially eliminate GVHD. Her team showed that the drug dramatically improves how animal models tolerate transplants. Now Kean is leading a Phase II clinical trial to evaluate whether the drug works in children. It’s the nation’s only multicenter pediatric clinical trial aimed at preventing GVHD.

The trial is partially funded by the FDA, but Kean needs more funding to complete critical, related studies that investigate how the body integrates – and sometimes rejects – transplanted immune cells.

“The biological research may be even more important than the actual clinical trial because it could lead to new insights about the immune system,” Kean says. “Those insights could lay the foundation for the next generation of therapies.”

Unlocking the Mysteries of T Cells

It might seem strange that Kean, who still sees patients as a transplant specialist, came to Seattle to work for someone who wants to put her out of business. After all, one of Dr. Michael Jensen ’s goals as the Ben Towne Center’s director is to replace transplants with immunotherapies that use reprogrammed immune cells to destroy cancer. But there’s a synergy between Jensen and Kean’s research.

The infection-fighting T cells that cause GVHD are the same cells that Jensen uses to destroy cancer. Kean wants to control these T cells so they don’t attack transplant patients. Jensen reprograms them so they recognize cancer cells and wipe them out. Accomplishing either goal requires a sophisticated understanding of these cells, and a way to help the body tolerate them.

Kean also knows there will always be a role for bone marrow transplants. Some cancers simply can’t be treated with immunotherapy. And transplants may always be the best treatment for non-cancerous bone marrow disorders. Kean is determined to make these transplants 100% successful.

Another tie that binds Kean and Jensen is the fact many T-cell therapies are meant to prevent cancer from relapsing in patients who have undergone transplants. If those patients have GVHD, they may be too sick to receive Jensen’s modified T cells.

“We’re thinking about different sides of the same equation,” Kean says, “but our goal is the same: harness the immune system to save patients’ lives.”

Kean left a thriving practice and research lab to come to Seattle Children’s because she thought it was the best place to move toward a future where children won’t suffer from GVHD or transplantation’s other debilitating effects.

“Seattle is the epicenter of transplant research,” Kean says. “It’s a dream come true to be here.”

How You Can Help

To support Kean’s incredible work, please email Mandy Hanousek  or call her at 206-987-0151.