Annual Report 2013
Last year, doctors performed the world's one millionth bone marrow transplant – a staggering illustration of how Fred Hutchinson Cancer Research Center breakthroughs revolutionize cancer treatment and save lives worldwide.
Led by Dr. E. Donnall Thomas, the Center's scientists pioneered the procedure and have spent decades refining and improving it as a curative treatment for blood disorders, including leukemia. Now, Fred Hutch researchers are at the forefront of investigating how bone marrow transplantation can be extended to help treat a growing number of other diseases, including Crohn's disease and HIV infection.
Dr. George McDonald and his colleagues recently opened a clinical trial that looks at whether transplants can eradicate severe Crohn's disease, an inflammatory bowel disease that occurs when an abnormal immune system reacts to bacteria that have penetrated the lining of the gastrointestinal tract. McDonald's research builds on a serendipitous discovery: When patients with leukemia and Crohn's disease underwent transplants to treat their cancer, the procedure wiped out their Crohn's disease for as long as 15 years.
McDonald made that observation in the 1990s, but balked at using transplants on Crohn's patients because the procedure was too dangerous to be applied to a disease that wasn't life-threatening. Then Fred Hutch's Dr. Rainer Storb developed reduced-intensity transplants that are less toxic and result in fewer side effects. That led McDonald to rethink transplants as a Crohn's therapy. His new study will examine bone marrow transplants as a potential treatment for Crohn's patients who do not have leukemia.
"Instead of giving massive-dose chemotherapy to kill the bone marrow, Dr. Storb's reduced-intensity method of transplant can suppress the immune system and let the donor bone marrow take over," McDonald said. "It's a different concept and it's much safer than traditional transplants."
The research might not have been possible without private philanthropy. McDonald is using a grant from the Los Angeles-based Broad Foundation to build the study's infrastructure. The funds allow him to collect blood and tissue samples and also pay for a research coordinator and a research nurse. These two key staff members have screened more than 500 potential clinical trial participants and performed other key tasks related to FDA and FHCRC regulatory issues.
"The Broad Foundation has been essential – they gave us seed money that we can use to generate the results we need to apply for larger grants," McDonald said.
In another example of how Fred Hutch scientists are teaming up with private organizations and individuals to extend bone marrow transplantation's lifesaving power, Drs. Keith Jerome and Hans-Peter Kiem are investigating how the procedure can lead to new treatments for patients with HIV/AIDS. Jerome, of the Vaccine and Infectious Disease Division and Kiem, of the Clinical Research Division, are building on the remarkable success story of Timothy Ray Brown – the first person cured of HIV.
Brown was diagnosed with the virus in 1995 and used antiretroviral therapy to control it. Then, in 2007, he received a bone marrow transplant to combat acute myeloid leukemia. The cells came from a donor who carried a rare gene mutation that made the donor naturally immune to HIV.
These transplants eradicated Brown's cancer and transferred the genetic variation to his immune system, curing him of both diseases. The Fred Hutch-led team, called defeatHIV, is exploring this breakthrough as a possible blueprint for new curative therapies. The goal is to take blood cells from a patient with HIV, insert genetic instructions into those cells that allow them to resist the virus, and then put the cells back into the patient.
"Timothy Ray Brown was a watershed case – he showed us that an HIV cure is possible," Jerome said. "That never would have happened without bone marrow transplantation."
Funding for Dr. George McDonald's Crohn's Disease study comes from the Broad Medical Research Program of The Broad Foundation.