3 big new leukemia research projects advance cutting-edge cell therapies, stem cell transplant

$20M renewal of 4-decade-long federal grant to Hutch scientists
Bone marrow transplant pioneer Dr. Don Thomas and his wife and research partner, Dottie Thomas, are surrounded by a group of survivors at the 2005 Bone Marrow Transplant Reunion.
Bone marrow transplant pioneer Dr. Don Thomas and his wife and research partner, Dottie Thomas, are surrounded by a group of survivors at the 2005 Bone Marrow Transplant Reunion. Fred Hutch file photo

The National Cancer Institute has awarded Fred Hutchinson Cancer Research Center with five years and nearly $20 million in funding for research to develop better therapies for people with blood cancers. The award, announced this month, is the latest renewal of a grant that has been funded continuously for more than 40 years and is the primary source of funding for the Hutch’s marrow transplantation program.

“I am very optimistic that the work that will be supported by this grant will directly translate into continued improvements in cure rates in patients with leukemia, lymphoma and multiple myeloma,” said Fred Hutch Executive Vice President and Deputy Director Dr. Fred Appelbaum in emailed comments. Appelbaum is the principal investigator of the project, called the Adult Leukemia Research Center grant, or ALC grant.

This funding will advance three major areas of research at the Hutch:

First is the development of a genetically engineered T-cell therapy for patients whose leukemia has come back after chemotherapy. This experimental immunotherapy involves reprogramming patients’ disease-fighting T cells to kill cells bearing a molecule called WT1, which is found in high amounts on the cancer cells of many patients with acute myeloid leukemia. This project, led by Dr. Phil Greenberg, will explore ways to improve the strategy’s efficacy and lower its toxicity.

In the second project, a team led by Dr. Damian Green will evaluate the safety and efficacy of an experimental, genetically engineered T cell therapy for patients with multiple myeloma. This strategy aims the T cells of patients with recurrent multiple myeloma at cells bearing a marker called BCMA. The researchers will also be evaluating variations on this strategy that could improve its safety or efficacy.

In the third project, researchers will evaluate novel strategies for preventing a common side effect of bone marrow transplant called graft-vs.-host disease, or GVHD. Under the leadership of Drs. Marie Bleakley and Marco Mielcarek, the team will test two novel approaches to preventing GVHD after transplant: removing certain GVHD-promoting immune cells from the donor tissue before transplant and treating the patient with a certain chemotherapy after transplant. The investigators will compare both approaches to the standard of care to determine which works best for preventing GVHD and staving off cancer relapse.

Besides improving T-cell therapies and eliminating GVHD, the research team’s other major goal is to develop methods to integrate T-cell therapy and donor transplantation.

Dr. Fred Appelbaum
Dr. Fred Appelbaum Fred Hutch file photo

Four decades of lifesaving discoveries

All three of these projects build off decades of discoveries by Hutch researchers that have made transplantation safer and more widely available.

“Don's goal from the start was to create a curative therapy for patients with hematologic malignancies, and that remains the goal of this grant,” Appelbaum said, referring to the PI for the grant’s first 15 years: the late Dr. E. Donnall Thomas, who won a Nobel Prize for the development of bone marrow transplantation. “It is gratifying that when we compare survival rates after transplantation at our institution over each decade … cure rates have continued to improve. Many different investigators have contributed to this work.

“Over that time, with the support of this grant and others that evolved from it, we have met a number of major challenges to transplantation,” said Appelbaum, describing how transplantation was once only used to treat patients under age 40 whose donors were identical twins or matched siblings. “With advances in unrelated and cord blood transplantation, we now can find a donor for almost everyone in need, and by eliminating many of the complications we have made the procedure far safer and tolerable.” (Read more about how bone marrow transplantation has evolved.)

Hutch scientists long ago recognized the importance of donor T cells in killing a patient’s cancer cells, a phenomenon known as the graft-vs.-leukemia effect. With the support of the ALC grant, Fred Hutch researchers have been developing methods to harness this effect, Appelbaum explained. The work of many investigators has now led to the emergence of T-cell therapies, “which we hopefully can use to overcome the remaining major challenge of transplantation, i.e., post-transplant relapse,” Appelbaum said.

The renewed grant also funds several centralized research support services, or cores, whose work will advance all three research projects. One of these is a program to collect long-term follow-up data on the well-being of patients who have received genetically modified T-cell therapy or bone marrow transplant; this work is directed by Dr. Stephanie Lee, who holds the David and Patricia Giuliani/Oliver Press Endowed Chair in Cancer Research. Another is a cell processing and sample collection core led by Dr. Cameron Turtle, and a third is a biostatistics and bioinformatics core led by Dr. Ted Gooley.

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