Grant of Nearly $5.2 Million Supports RPCI-Led Research to Improve Survival After Blood/Marrow Transplant

Largest R01 Research Grant in Institute History

BUFFALO, NY — Even with the best donor match, patients who undergo a lifesaving transplant of blood or bone marrow from an unrelated donor face a one-in-three chance of transplant-related death within a year. The National Institutes of Health (NIH) has awarded a four-year, $5.18 million Research Project Grant (R01) to investigators at Roswell Park Comprehensive Cancer Center (Roswell Park) to support research aimed at improving the survival rate of those patients and making transplant a possibility for more patients.

Theresa Hahn, PhD, of the Department of Medicine at Roswell Park and Lara Sucheston, PhD, of the Department of Cancer Prevention and Population Sciences will serve as Co-Principal Investigators of the project, which is the largest R01 ever awarded to Roswell Park.

Blood or marrow transplantation (BMT) can often cure patients with leukemia or other life-threatening blood diseases. A patient with a sibling who is a compatible donor will have the best chance of success, “but only 30 percent of patients have a matched-sibling donor, so the majority need an unrelated donor,” says Dr. Hahn.

Patients are matched to the best potential donors through “tissue typing,” to lower the risk that the donor’s hematopoietic stem cells will perceive the patient as “foreign” and cause a serious complication called graft-versus-host disease. The tissue-typing test looks at patient/donor compatibility for one set of genes, called the Human Leukocyte Antigen (HLA) system.

Drs. Hahn and Sucheston hypothesize that transplant-related deaths might be due to patient/donor incompatibility at areas in the genome other than the HLA system — for example, in genes that affect how a person’s body responds to drugs or radiation, or that regulate the immune system. They will lead a team of researchers from across the U.S. in an unprecedented effort to identify non-HLA genetic traits that might play a role in transplant-related deaths.

“Over the past 10 to 15 years, survival rates for BMT patients with unrelated donors have really increased,” says Dr. Hahn. “It used to be that half of those patients died within three months, and now a third are dying within a year, so that’s a huge improvement in survival. But we’ve reached the limit of our current knowledge, and we feel we can do better.”

The project involves 2,800 patients (and their HLA-matched unrelated donors, for a total of 5,600 people) who received a transplant at any U.S. BMT center between 2000 and 2008. In all cases, the patients and donors are well matched for HLA compatibility, yet about one-third died of transplant-related causes in the first year. “The primary purpose of the study, then, is to ‘map’ non-HLA genetic variations that are found in individuals who died of treatment-related mortality (TRM) but not in those who survived treatment,” says Dr. Sucheston.

Using data from the same group of individuals, the investigators will also examine how TRM is impacted by the relationship of those genetic variants with different combinations of chemotherapy drugs and radiation used in the transplant process. That relationship has never before been evaluated as a predictor of patient survival in a study this large.

Results derived from the first patient/donor group will be validated with data from an additional group of 1,000 patients and their HLA-matched unrelated donors (2,000 people) who received a transplant between 2009 and 2011.

Information gleaned from the study could be used to introduce routine genetic tests that might help personalize the treatment plans for BMT candidates with unrelated donors, identify the best donors, and improve patient survival. “Sometimes patients have more than one donor you can select from,” explains Dr. Hahn. “It could be that we need to add a few other genetic variants that we test for, in addition to HLA, to choose the best donor for that patient and lower their risk of transplant-related mortality.”

Co-investigators on the project — titled “Genetic Susceptibility to Unrelated Donor Stem Cell Transplant-Related Mortality” — include Philip McCarthy, Jr., MD, Director, Blood and Marrow Transplant Program, Roswell Park; Song Liu, PhD, Bioinformatics and Biostatistics, Roswell Park; Gary Chen, PhD, Biostatistics, Keck School of Medicine, University of Southern California (USC); Thomas Furlani, PhD, Director, Center for Computational Research, University at Buffalo; Christopher Haiman, ScD, Associate Professor, Preventive Medicine, Keck School of Medicine, USC; Kenan Onel, MD, PhD, Director, Pediatric Familial Cancer Clinic, University of Chicago Medical Center; Marcelo Pasquini, MD, MS, Division of Neoplastic Diseases and Related Disorders, Medical College of Wisconsin; Stephen Spellman, Senior Manager, Scientific Services, National Marrow Donor Program, Minneapolis; David Tritchler, ScD, Research Professor, Biostatistics, University at Buffalo; and David Van Den Berg, PhD, Director, Genomics Center, USC Norris Comprehensive Cancer Center.

The NIH awards R01 grants for health-related research and development that reflects the NIH mission and the expertise of the investigator(s). At the conclusion of the project, the data generated will be available on the NIH website to promote future scientific discovery by other researchers in the scientific and medical community.

The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Roswell Park, founded in 1898, was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit Roswell Park’s website at, call 1-800-ROSWELL (1-800-767-9355) or email

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