New study may refine predicted survival outcomes and treatment in younger adults with acute leukemia

COLUMBUS, Ohio – The findings of a new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) could refine an important set of prognostic and treatment recommendations for younger adult patients with acute myeloid leukemia (AML.

The retrospective study evaluated the molecular characteristics and outcomes of 863 patients with AML who were treated according to 2017 European LeukemiaNet (ELN) recommendations. The patients were under age 60 with a median age 45 years.

ELN recommendations are internationally used for diagnosing and managing people with AML and other leukemias. AML is a neoplastic disease of the blood that affects about 19,900 Americans and kills nearly 11,200 of them yearly, according to the American Cancer Society. Only 35-40% of AML patients under age 60 achieve long-term survival, the researchers note.

The study, published in the journal Leukemia, found that:

  • 9% of favorable-risk and 53% of intermediate-risk patients should be reclassified as adverse risk;
  • 4% of favorable-risk and 9% of adverse-risk patients should be reclassified as intermediate risk.

“If verified, our findings may refine the ELN risk stratification of younger acute myeloid leukemia patients, which could improve patients’ treatment choices and outcomes,” says first author Ann-Kathrin Eisfeld, MD, an investigator in the OSUCCC – James Leukemia Research Program.

During this study, Eisfeld and her colleagues detected 2,354 mutations, an average of three per patient.

The researchers determined the frequency of mutations additional to those used to define current ELN risk-groups, and mutations in several “functional group” categories: RAS-pathway mutations, kinase and methylation-related mutations, and mutations in genes encoding for spliceosomes, transcription factors and tumor suppressors.

They compared the frequencies of the mutations within each ELN risk group – favorable, intermediate and high – to learn which were associated with better or worse outcomes and might therefore help refine the 2017 ELN classification.

Key findings include:

  • BCOR- or SETBP1-mutated favorable-risk patients with non-core-binding-factor AML and IDH-mutated adverse-risk patients had intermediate-risk outcomes.
  • Outcomes of NPM1/WT1 co-mutated patients and those of ZRSR2-mutated patients resembled outcome of adverse-risk patients.
  • FLT3-ITDhigh allelic ratio conferred adverse risk, rather than intermediate risk, regardless of NPM1 mutation status.
  • DNMT3A mutations signaled very poor survival.

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The Ohio State University joined LeukemiaNet in 2014.

Note: This research paper is dedicated to the memory of the senior author, Clara D. Bloomfield, MD, Distinguished University Professor and Ohio State University Cancer Scholar and Senior Adviser and the William Greenville Pace III Endowed Chair in Cancer Research, who unexpectedly died during completion of the manuscript. Dr. Bloomfield was instrumental in developing the 2017 ELN recommendations, which replaced those issued by the ELN in 2010 that were also co-authored by Bloomfield.

Funding from the National Cancer Institute of the National Institutes of Health (CA180821 CA197734, CA180882, CA233338, CA196171, CA233180, CA189824, CA189850 and CA016058), the Coleman Leukemia Research Foundation, Pelotonia, American Society of Hematology Scholar Award and computing resources from The Ohio Supercomputer Center supported this research.

Other researchers involved in this study were Jessica Kohlschmidt, Alice Mims, Deedra Nicolet, Christopher J. Walker, James S. Blachly, Dimitrios Papaioannou, Albert de la Chapelle, John C. Byrd and Krzysztof Mrózek, The Ohio State University; Andrew J. Carroll, University of Alabama at Birmingham; Jonathan E. Kolitz, Monter Cancer Center, Zucker School of Medicine at Hofstra/Northwell; Bayard E. Powell, Wake Forest Baptist Comprehensive Cancer Center; and Richard M. Stone, Dana-Farber/Partners CancerCare.

About the OSUCCC – James

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 51 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI. As the cancer program’s 356-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet® designation, the highest honor an organization can receive for quality patient care and professional nursing practice. With 21 floors and more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care.

Media Contact
AMANDA HARPER
[email protected]
http://dx.doi.org/10.1038/s41375-020-1007-6

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