Geoffrey Hill, transplantation physician-scientist

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Dr. Geoffrey Hill, transplantation physician-scientist

Revealing the mysteries of graft-vs.-host disease to help patients

July 31, 2018

By Susan Keown / Fred Hutch News Service

Two decades ago, Dr. Geoffrey Hill cared for a man who at the time was not far in age from himself. In normal life, their social circles might have overlapped. But the young man, a promising musician, had relapsed leukemia, and life, for him, was no longer normal. No treatment options were left that had a chance of curing him. Having gone through so much already, he refused to spend any more time in the hospital. So Hill would meet him at a local park or at home to provide palliative care.

Hill couldn’t save the man’s life. But in the years that followed, the doctor realized laboratory research was a powerful way he could save the lives of others.

Now an accomplished physician-scientist at Fred Hutchinson Cancer Research Center, where he holds the José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research, Hill leads field-changing studies on graft-vs.-host disease, or GVHD.

GVHD is an all-too-common complication for patients who receive transplants of potentially lifesaving blood stem cells to treat severe blood diseases like advanced leukemias. In a transplant, the donated immune cells patrol the patient’s body for cancer and destroy it. But too often, they destroy healthy tissue as well. That is GVHD.

The chronic form of GVHD, which is one of Hill’s specialties, develops slowly after transplant but is the greatest cause of illness and debility in transplant survivors. The web of immune-system signals that trigger chronic GVHD is maddeningly complex. So too are its manifestations. The donor immune system can attack anywhere: Patients’ skin can scar and thicken, making movement difficult. Damage to the eyes can reduce vision. It can obstruct the function of the lungs, the liver, the esophagus.

Working with a mouse model of transplant they developed, Hill and his team have painstakingly unraveled the tangled immunologic signals that cause chronic GVHD. The team’s research has “broken down a number of dogmas that were clearly not based in scientific fact,” in this arena, he said — most recently, finding that immune cells that were thought to have a certain role in initiating GVHD actually act in a completely different way.

Most importantly, the Hill Lab’s insights have led to the development of multiple new drugs that target GVHD-triggering immunologic signals, including some that are now routinely used in patient care and others that are in human trials. After so many years of struggling, Hill says, the transplant field has now seen “huge progress” in chronic GVHD.

Hill’s accent traces his origin to his native New Zealand and to Australia, where he has spent most of his career so far. When he arrived in Seattle in 2018, he took on the role of director of Hematopoietic Stem Cell Transplantation at Fred Hutch and Seattle Cancer Care Alliance, the Hutch’s clinical-care partner.

At SCCA, he cares for people with blood cancers. “Being a clinician allows you to understand the problems that you’re dealing with,” Hill said. “And it also allows you to have a clearer understanding of whether what you’re researching in the lab may, or may not, be easily translatable or applicable to the clinic.”

Hill’s research has built a foundation for clinical improvements in areas of transplant care beyond GVHD, from controlling the infections that can bedevil transplant recipients with compromised immune systems to preventing relapse of patients’ cancers. Joined with advances made by colleagues worldwide, Hill’s work has steadily improved transplantation, ensuring that, today, many patients can expect a very different outcome than what that long-ago young man experienced.

“As transplant becomes safer and we can move it forward to earlier in the treatment, the outcomes, especially for things like ALL” — acute lymphoblastic leukemia, the type of cancer Hill’s young patient had — “are quite different,” he said.

With the emergence of drugs for GVHD, thanks to Hill and colleagues’ work, the next big research goal is to identify the right drugs for the right patients, Hill said. Clearly, many more improvements in transplant care are approaching on the horizon.

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