Roswell Park Faculty Present Cutting-Edge Advances in Care of Patients with Blood Disorders at ASH 2016

BUFFALO, N.Y. — Roswell Park Comprehensive Cancer Center physicians and researchers will be among the scientific leaders offering new insights into the causes and treatment of blood disorders during the 58th annual meeting of the American Society of Hematology (ASH) December 3 – 6 in San Diego, California.

Highlights of the Roswell Park-led research selected for oral presentations during this prestigious meeting include identification of new targeted therapies and promising treatment combinations for acute myeloid leukemia (AML).

Details of selected oral presentations are below.

Genetic Differences and Survival after Blood and Marrow Transplantation Not Replicated in New Large Study

Authors: Theresa Hahn, PhD, Professor of Oncology in the Department of Medicine at Roswell Park, is co-senior author with Lara Sucheston-Campbell, PhD, of The Ohio State University colleges of Pharmacy and Veterinary Medicine.

Drs. Hahn and Sucheston-Campbell led a team that examined the association of previously reported genetic markers, single-nucleotide polymorphisms (SNPs) and their relationship to survival outcomes after blood and marrow transplant using data from the DISCOVeRY-BMT study. Their analysis incorporated data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on more than 3,500 patients transplanted between 2000 and 2011 and their matched unrelated donors. While the team used the DISCOVeRY-BMT study to see if they could replicate results from previously published smaller studies of individual SNPs, none of the previously reported SNPs could be replicated in the much larger DISCOVeRY-BMT study population.

“Our ability to genotype patient samples has evolved to be quicker and cheaper than it was even five to 10 years ago. This has allowed us to have a more comprehensive look at patients’ genetic variants in relation to survival after BMT,” says Dr. Hahn, co-senior author of the study. “While we were not able to replicate prior smaller published studies, this may be due to differences in the patient populations and types of BMT donors. Hence, more research is needed.”

Presentation details:
Session 732/abstract no. 71
“Replication of Candidate SNP Survival Analysis and Gene-Based Tests of Association from Survival Outcomes after an Unrelated Donor Blood or Marrow Transplant Results from the Discovery-BMT Study”
Oral Presentation: Saturday, December 3, 8:30 a.m. EST
Seaport Ballroom (Manchester Grand Hyatt San Diego)

CD28 Stimulates Cell Respiration, Supports Survival of Long-Lived Plasma Cells

Authors: Kelvin Lee, MD, Chair of the Department of Immunology at Roswell Park, is the senior author of the study.

CD28 is a key molecule known to regulate the metabolism of T cells and the survival of long-lived plasma cells. In this study, scientists report that this influential molecule regulates the nutrients available to plasma cells, as well as their metabolic fitness. They expect that this understanding will inform more effective design of cancer vaccines and may also offer the opportunity for novel targeted approaches to fight autoimmune responses often exhibited in cancer.

“Our findings indicate that this key molecule may play an important role in the cancer microenvironment. Understanding these mechanisms may lead to novel therapeutic strategies to combat antibody-mediated autoimmunity and achieve better patient outcomes,” says Dr. Lee.

Presentation details:
Session 203/abstract no.128
“CD28 Induces Mitochondrial Respiration through Irf4 for Long-Lived Plasma Cells Survival”
Oral Presentation: Saturday, December 3, 12:15 p.m. EST
Room 33 (San Diego Convention Center)

Novel Genetic Differences Associated with Survival after Blood and Marrow Transplantation

Authors: Qianqian Zhu, PhD, Assistant Professor and Li Yan, PhD, Assistant Professor, both in the Department of Biostatistics and Bioinformatics at Roswell Park, are co-first authors. Theresa Hahn, PhD, Professor of Oncology in the Department of Medicine at Roswell Park, is co-senior author with Lara Sucheston-Campbell, PhD, of The Ohio State University colleges of Pharmacy and Veterinary Medicine.

This large national study analyzed the relationship of genetic markers, single-nucleotide polymorphisms (SNPs), to survival outcomes following blood and marrow transplant (BMT), and is based on data from the DISCOVeRY-BMT study. The team’s analysis incorporated data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on more than 3,500 patients transplanted between 2000 and 2011 and their matched unrelated donors. The researchers studied rare, uncommon SNPs in the DISCOVeRY-BMT study population and found 6 rare variants in the gene OR51D1 were associated with overall survival as well as transplant-related mortality. OR51D1 is an olfactory receptor involved in the sense of smell. However, it has recently been reported that proteins made by this gene are found on some white blood cells involved in the immune response.

“This study found a new unexpected gene associated with survival after unrelated-donor BMT,” says Dr. Zhu, first author of the study. “Our type of study looking for novel genes is needed to advance the field and discover new insights into immune biology.” Drs. Hahn and Sucheston-Campbell will be pursuing additional studies to further understand the role of this gene in relation to survival after BMT.

Presentation details:
Session 732/abstract no. 518
“Exome Array Analyses Identify New Genes Influencing Survival Outcomes after HLA-Matched Unrelated Donor Blood and Marrow Transplantation”
Oral Presentation: Sunday, December 4, 4:45 p.m. EST
Grand Hall D (Manchester Grand Hyatt San Diego)

Preliminary Results Demonstrate Effectiveness of New Chemotherapy Combination for AML

Authors: Eunice S. Wang, MD, Chief of the Leukemia Service at Roswell Park, is lead author and Robert Collins, MD, of the University of Texas Southwestern Medical Center is the senior author.

Acute myeloid leukemia (AML) is an aggressive blood cancer affecting mostly older adults. The standard therapies for this disease have remained unchanged for more than 25 years. Approximately one-third of AML patients harbor a FLT3 gene mutation, which correlates with worse survival. In this study, 26 patients received crenolanib, a potent and specific FLT3 inhibitor, along with standard chemotherapy. The research team reports that the combination was well tolerated and 88% of the patients achieved a complete remission following one cycle of treatment. The overall response rate was 96%. After six months of follow-up, only three patients have relapsed.

“The results from this clinical study are encouraging. These data, although preliminary, are important in that they demonstrate that this novel combination therapy can be safely administered for the treatment of this type of AML,” says Dr. Wang. “Of note, Roswell Park has currently accrued the most patients in the nation to this important clinical trial, reflecting its dedication to providing the most cutting-edge therapeutic treatments for leukemia patients.”

Presentation details:
“Crenolanib, a Type 1 FLT3 TKI, Can be Safely Combined with Cytarabine and Anthracycline Induction Chemotherapy and Results in High Response Rates in Patients with Newly Diagnosed FLT3 Mutant Acute Myeloid Leukemia (AML)”
Oral Presentation: Monday, December 5, 5 p.m. EST
San Diego Ballroom AB (Marriott Marquis San Diego Marina)

Gene Alterations May Be Exploited For Therapeutic Opportunities

Authors: Bora Baysal, MD, PhD, Associate Professor of Oncology in the Department of Pathology and Laboratory Medicine at Roswell Park, is the lead author and Shraddha Sharma, PhD, Research Associate in the Department of Pathology at Roswell Park, is the last author of the study.

Human immunodeficiency virus-1 (HIV-1) infection increases the risk of certain malignant tumors such as cervical cancer and lymphomas. Specific host protein factors including APOBEC3G have the ability to inhibit HIV-1 by altering the genetic materials of the virus. The team led by Dr. Basal reports that this protein also has the ability to alter gene transcripts through a process called RNA editing. The study suggests that RNA editing may be a novel mechanism by which APOBEC3G protein restricts the HIV-1 virus.

“Our findings suggest a previously unrecognized mechanism by which HIV-1 infection might be inhibited. This has the potential to further define specific gene targets, opens new avenues of inquiry on gene functions and offers potential opportunities for therapeutic targets against HIV-1 infection,” says Dr. Baysal.

Presentation details:
 Session 203/abstract no. 547
“The Anti-HIV-1 Cytidine Deaminase APOBEC3G is a Cellular Site-Specific RNA Editing Enzyme.”
Oral Presentation: Monday, December 5, 7 a.m. EST
Room 33 (San Diego Convention Center)

Roswell Park Faculty Leading Scientific/Educational Sessions

Additionally, several Roswell Park faculty members will offer their expertise through participation in educational, training and scientific programs during the meeting. Eunice Wang, MD, and Kara Kelly, MD, will serve as moderators during two separate scientific oral programs. Scott Abrams, PhD, and Kelvin Lee, MD, from the Department of Immunology and Theresa Hahn, PhD, from the Department of Medicine will lead training workshops to encourage and support students as they pursue academic careers in basic, translational and clinical research. And Philip McCarthy, MD, Director of the Blood and Marrow Transplant Center, will lead an education discussion about transplant maintenance.

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About CIBMTR® (Center for International Blood and Marrow Transplant Research®)
A research collaboration between the National Marrow Donor Program® (NMDP)/Be The Match® and the Medical College of Wisconsin, CIBMTR facilitates critical, cutting-edge research that has led to increased survival and an enriched quality of life for thousands of patients. CIBMTR collaborates with the global scientific community to advance hematopoietic cell transplantation and cellular therapy research worldwide. The prospective and observational research is accomplished through scientific and statistical expertise, a large network of transplant centers and clinical database of more than 415,000 transplant recipients.

About Roswell Park Comprehensive Cancer Center
The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Founded in 1898, Roswell Park 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 1-800-ROSWELL (1-800-767-9355) or email AskRoswell@Roswellpark.org. Follow Roswell Park on Facebook and Twitter.