The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation has awarded a $500,000 grant to Fred Hutchinson Cancer Research Center to support a clinical trial to improve the use of umbilical cord blood as a treatment for leukemia.
Principal investigator Dr. Filippo Milano, associate director of Fred Hutch’s Cord Blood Program, and program director Dr. Colleen Delaney will use the two-year grant to examine a new cord-blood transplant regimen that could not only improve treatment outcomes but lower cost.
Currently, doctors at the Hutch use a total of three cord-blood units for the majority of patients undergoing cord-blood transplantation. Two of these are from a public cord- blood bank and are matched to the patient. One is not. The third, an unmatched unit, is made available “off-the-shelf” after a laboratory process pioneered by Delaney that expands the limited number of cord-blood stem cells.
The researchers now want to eliminate the need for a second cord-blood unit from a public blood bank by using the expanded, off-the-shelf cell unit to provide an initial wave of early recovery until the long-term matched donor cells engraft. In this case, less is more.
"We already know the expanded units are very good,” Milano said. “Now let’s see if the expanded unit can be used in a setting where we use only one matched cord-blood unit along with the unmatched, expanded unit.”
The goal is to reduce early transplant-related mortality while taking advantage of cord-blood stem cells’ anti-leukemia effects after transplantation, leading to improved long-term survival.
“This is a very important step in the clinical development of this universal donor cell therapy, which has been under clinical investigation since the first trial in 2006,” Delaney said.
The Phase 2 clinical trial, which is expected to begin next year, will involve 15 patients. Half of them will be treated at Seattle Cancer Care Alliance, Fred Hutch’s clinical care partner; the other half will undergo treatment at Memorial Sloan Kettering Cancer Center in New York, a collaborator on the trial.
Milano expects promising results. Already, a pilot study has generated strong data on the preliminary efficacy of this therapy, and he is enthusiastic about future work.
“First of all, I’m a big fan of easy things,” Milano said, adding that he hopes to simplify the three-unit approach. “So, going down to two [units] is better. Especially going down to two, when one is already off the shelf, which you can give to everyone as a universal donor product, is going to be very exciting.”
Cord-blood donors are currently considered an alternative to traditional adult hematopoietic stem cell donors. With traditional bone marrow or peripheral blood stem cell transplants, the donors must be “matched” to a patient’s unique genetic background to minimize the risk of graft-vs.-host-disease, or GVHD. This complication occurs when newly transplanted donor cells attack the organs and tissues of the transplant recipient, regarding them as foreign.
Since the donor cells in cord blood come from a baby whose immune system is naïve, the cells can adapt and don’t have to be a complete match to the patient. This is a particularly viable option for leukemia patients of mixed-race ancestry who often can’t find a matched donor in the stem cell registry.
According to Milano, doctors can find suitable cord-blood donors for about 95 percent of patients. The approach also makes lifesaving use of cord blood that would otherwise be discarded as medical waste.
Based in San Antonio, Texas, the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation has a particular interest in funding medical and basic science research, as well as conservation, community services, arts and humanities, wildlife, conservation and animal science.
Note: Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.
— Fritz Freudenberger / Fred Hutch News Service
The American Society of Hematology has selected Dr. Sarah Buckley, a senior fellow in the Clinical Research Division at Fred Hutch, as a recipient of its Research Training Award for Fellows. She is among 12 fellows to receive the award, which is designed to encourage careers in academic hematology by providing protected research time during training.
She will use her $70,000, one-year ASH award to continue pursuing her research into quality of life, or QOL, in patients with acute myeloid leukemia, or AML.
Quality of life concerns all emotional, social and physical aspects of a person’s life. Health-related QOL is an assessment of how the patient’s well-being may be affected over time by a disease, disability or disorder.
“Despite advances in supportive care, AML remains difficult to treat, and long-term survival requires aggressive therapy,” she said. “In such a disease, there is value in incorporating QOL measurement into clinical trials and using this metric as one measure of treatment success.”
A barrier to measuring QOL in AML patients is that they often face unique challenges based on their disease and treatment, so standard instruments may not adequately measure markers of their well-being. For example, Buckley said, most QOL instruments were developed for patients treated in an outpatient setting, but many AML patients spend much of their time in the hospital, where their day-to-day life, concerns and expectations are different than they would be in the outpatient setting. In addition, AML treatment causes a unique array of side effects, which are not adequately measure on generic QOL instruments.
Buckley’s ASH-supported project aims to create a QOL measurement tool that is specific to the AML patient population.
“The ultimate goal of this project is to develop an instrument that could be used in clinical and research settings to help determine optimal treatment strategies based on patient-centered results,” said Buckley, whose primary mentor is transplant physician-scientist Dr. Stephanie Lee and co-mentor is Dr. Roland Walter, both researchers in the Clinical Research Division at Fred Hutch. “I am very grateful to have received the ASH award.”
— Kristen Woodward / Fred Hutch News Service