Appelbaum: $21 million grant renewal for transplantation

The Hutchinson Center's Adult Leukemia Research Center, a large group of researchers studying bone marrow transplants for patients with blood and bone marrow cancers, has received a $21 million renewal from the National Cancer Institute.

Led by Clinical Research Division Director Dr. Fred Appelbaum, the next five-year period of the grant will explore ways to increase the number of people who can receive transplants, reduce risk of relapse following transplantation, and make the procedure safer and more powerful.

Appelbaum has run the research center since 1991, when he took over for the late Dr. E. Donnell Thomas, who first initiated the grant in 1968, making it one of the Center's longest-running grants.

Since Thomas first invented bone marrow transplantation as a cure for leukemia, Appelbaum and many others at Fred Hutch have been working to increase the number of transplants that can be given and the effectiveness of the procedure. In 2010, more than 54,000 people died of blood cancers in the U.S., making it the second leading cause of cancer-related death after lung cancer, but only 8,000 people received transplants.

A donor for every patient

"There are many barriers to transplantation. Some of the barriers are social and economic, and some are scientific and medical," Appelbaum said. "If everyone had a donor, that would definitely expand the availability of transplantation. One of the major goals of this grant is to identify a donor that can be used safely for every patient."

Despite the procedure's ability to cure several types of blood cancers, many cancer patients, especially minorities, in need of a transplant are unable to find a matched donor. Twenty million people are registered as potential bone marrow donors in the U.S. but only 60 percent to 70 percent of Caucasian, 40 percent of Hispanic and 20 percent of African American patients can find a match in that registry.

The Clinical Research Division's Dr. Effie Petersdorf has found a new way to match donors to patients based on their evolutionary similarities rather than the traditional set of markers. This approach may both increase the number of people who can receive transplants and diminish harmful post-transplant effects. Petersdorf will conduct trials to test these findings in the new grant period.

Harnassing power of immunotherapy

Appelbaum's group is also conducting several other studies testing different drugs with the potential to reduce cancer relapse immediately following transplant, before the transplanted blood cells have established themselves, and in the area of immunotherapy to improve transplants' overall success rates.

"I've always felt that one of the greatest potentials of transplantation is the potent immune response against the tumor that comes from the donor, and we've never been able to adequately harness that," Appelbaum said.

This anti-tumor immune response, also called the graft-vs.-leukemia effect, is confounded by the related graft-vs.-host-disease, where the donor immune cells also attack the patient's healthy tissue. Suppressing GVHD has always led to similarly suppressing the beneficial graft-vs.-leukemia effect, Appelbaum said. Now, his group, in studies led by Drs. Stan Riddell and Phil Greenberg, is testing several immunotherapy approaches to transplantation where host immune cells are specifically engineered in the lab to recognize tumor cells but not healthy cells.

Along with the scientific projects, the Adult Leukemia Research Center comprises several Shared Resource Cores that support transplant medicine research, including biostatistics, microbiology and virology, cell processing and storage, and long-term follow up.