Latest Findings on Unrelated-Donor BMT, B-Cell Lymphoma Highlight Roswell Park ASH 2015 Presentations

Four studies selected for podium presentation, including two based on largest genomic study of its kind
Wednesday, December 9, 2015

BUFFALO, N.Y. — More than a dozen Roswell Park Cancer Institute (RPCI) researchers were invited to present findings at the American Society of Hematology (ASH) 57th Annual Meeting & Exposition, a four-day meeting in Orlando, Fla., that concluded yesterday. Among them were four teams invited to deliver podium presentations detailing what they learned from their latest research projects.

Lara Sucheston-Campbell, PhD, gave an oral presentation on a genome-wide association study (GWAS) conducted to determine whether outcomes for patients receiving blood and marrow transplant (BMT) could be improved by identifying genetic factors in both transplant recipients and their unrelated donors. The matching of HLA, or human leukocyte antigen, protein markers is used to find appropriate donors for blood and marrow transplants, but this study sought a way to identify novel genes that are not in the HLA region that might contribute to transplant-related mortality.

This GWAS, named the DISCOVeRY-BMT (Determining the Influence of Susceptibility Conveying Variants Related to One-Year Mortality after BMT) project, is the largest study of its kind and the first GWAS of survival following BMT from an unrelated donor. This effort was supported by the largest Research Project (R01) grant ever awarded to RPCI researchers by the National Institutes of Health and one of its member agencies, the National Heart, Lung, and Blood Institute (grant no. R01HL102278).

“Through this study, we identified gene variants outside the HLA region between unrelated BMT donors and their recipients that significantly impact patients’ risk of transplant-related mortality in the first year after BMT,” explains Dr. Sucheston-Campbell, member and Associate Professor of Oncology in the Department of Cancer Prevention and Control. “This finding could aid in the selection of donors, thus potentially improving long-term survival of leukemia patients treated with transplant as curative therapy.”

That presentation was ASH 2015 abstract 61, “Combined Donor and Recipient Non-HLA Genotypes Show Evidence of Genome Wide Association with Transplant Related Mortality (TRM) after HLA-Matched Unrelated Donor Blood and Marrow Transplantation (URD-BMT) (DISCOVeRY-BMT study).”

A podium presentation by Theresa Hahn, PhD, detailed additional findings from the same DISCOVeRY-BMT GWAS. Dr. Hahn and colleagues examined genotype profiles for thousands of BMT recipients and their unrelated donors.

“While survival outcomes after unrelated-donor blood and marrow transplant have significantly improved over the last two decades, there is still room for improvement,” says Dr. Hahn, Professor of Oncology in the Department of Medicine. “Through our retrospective analysis, we identified several markers that appear to be associated with shorter survival after unrelated-donor BMT, and may indicate patients who need to be treated differently with BMT or another treatment approach.”

Dr. Hahn’s presentation was ASH 2015 abstract 397, “Genome-Wide Association Study of Overall and Progression-Free Survival after HLA-Matched Unrelated Donor Blood and Marrow Transplantation (DISCOVeRY-BMT study).”

Kyle Runckel gave the third oral presentation from Roswell Park at the ASH 2015 meeting, reporting findings from a study in diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma. The addition of rituximab as a frontline treatment for this disease, in combination with other agents, has significantly improved outcomes for patients with relapsed/refractory DLBCL, but drug resistance remains an issue for many patients.

“Our findings indicate that a key protein, XIAP, or x-linked inhibitor of apoptosis protein, is critically important in drug-resistant forms of lymphoma because it promotes tumor cell resistance to chemotherapy,” notes Runckel, a predoctoral trainee in the Department of Immunology. “In a preclinical study, we found that blocking XIAP expression in models of drug-resistant lymphoma increased chemotherapy response to the point where treated laboratory models appear to be fully tumor-free. These findings are preliminary and will need to be confirmed through additional experiments, but these results are exciting and very encouraging.”

His presentation was ASH 2015 abstract 590, “Targeting the X-Linked Inhibitor of Apoptosis Protein (XIAP) Can Promote Tumor Cell Death, and Increase the Cytotoxic Effects of Chemotherapy Agents in in Vitro and In Vivo Models of Rituximab-Resistant Lymphoma.”

Adam Utley, a Predoctoral Trainee in the Department of Immunology, was the fourth presenter from RPCI. His presentation was ASH 2015 abstract 288, “CD28 Induces Mitochondrial Respiration through Slp-76 in Long-Lived Plasma Cells for Reactive Oxygen Species-Dependant Survival.”

CD28 is a key molecule that facilitates survival of multiple myeloma and antibody-producing plasma cells in bone marrow by inducing metabolic fitness.

“By inhibiting CD 28, we can block this survival signal in the myeloma microenvironment and achieve better patient outcomes,” says Utley. “Furthermore, by targeting the same molecule on antibody secreting plasma cells, we may be able to alleviate antibody-mediated disease such as peanut allergy and lupus."

Additional Roswell Park presentations from the meeting are linked below.

Presented by Alyssa Aldridge, an undergraduate student in the lab of Sarah Holstein, MD, PhD:

Presented by Bora Baysal, MD, PhD, Associate Professor of Medicine in the Department of Pathology and Laboratory Medicine:

Presented by Maria Bhatti, MD, Clinical Fellow in the Department of Pediatrics:

Presented by Alyssa Clay, Predoctoral Trainee in the Department of Cancer Prevention and Control:

Presented by Jason Den Haese, PhD, Research Technologist in the Department of Medicine:

Presented by Christopher Dougher, Predoctoral Trainee in the Department of Immunology:

Presented by Elizabeth Griffiths, MD, Associate Professor of Oncology in the Department of Medicine:

Presented by Juan Gu, PhD, Postdoctoral Associate in the Department of Medicine

Presented by Monica Reddy Muppidi, MD, Clinical Fellow in the Department of Medicine:

Presented by Jayakymar Nair, PhD, Scientist with the Department of Immunology:

Presented by Kyle Runckel, Predoctoral Trainee in the Department of Immunology:

Presented by Pallawi Torka, MD, Clinical Fellow in the Department of Medicine

Presented by Eunice Wang, MD, Acting Chief, Leukemia Service, and Associate Professor of Oncology in the Department of Medicine:

Presented by Qunling Zhang, MD, PhD, formerly a visiting physician at Roswell Park:

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The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is 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 www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org. Follow Roswell Park on Facebook and Twitter.

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