Leukemia study highlights need to standardize testing
Research led by Fralin Biomedical Research Institute scientists found that the usefulness of a widely used measure of acute myeloid leukemia relapse risk depends on who is doing the test.
As a cancer researcher in Fralin Biomedical Research Institute Professor Chris Hourigan’s lab in Washington, D.C., Jesse M. Tettero examined real-world differences in how well tests for measurable residual disease predicted patient outcomes in acute myeloid leukemia. Photo by Lena Ayuk for Virginia Tech.
Multiparametric flow cytometry — a test that is widely accessible, cost-effective, and timely — can find one cancerous cell hidden among thousands of healthy cells following treatment for acute myeloid leukemia.
Identifying those cells helps doctors monitor disease progression, predict relapse risk, and guide treatment. One way to improve care for the estimated 22,720 people in the U.S. diagnosed annually with the rare, aggressive blood cancer is to improve the sensitivity and accuracy of testing.
But a research team led by Virginia Tech scientists from the Fralin Biomedical Research Institute’s Cancer Research Center in Washington, D.C., found that not all test results are created equal. Their findings were published in Haematologica.
In multiparametric flow cytometry, combinations of features on the surface of patient cells can help identify remaining cancer, or measurable residual disease (MRD). Variations of this test are commonly performed clinically, but MRD can be challenging to interpret.
The research team found wide variations in how well the test results predicted patient outcomes in real-world clinical settings. The depth of the data stands out: Much of the prior research involved relatively modest sample sizes from individual clinical trials or local practice patterns. Working with the Center for International Blood and Marrow Transplant Research, this study reviewed the clinical experience of 2,542 patients across 131 U.S. testing centers who received blood-forming stem cell transplants from healthy donors from 2013 to 2019.
“We’ve now shown that on a national level, flow cytometry works in the real world. It’s a test worth doing,” said author Jesse Tettero, who led the study as a researcher at Virginia Tech’s Fralin Biomedical Research Institute. “But it depends on who’s doing the test.”
Their recommendation? Standardization.
Researchers looked at overall survival, death from causes other than AML, disease-free survival, and relapse.
Although patients who tested positive by flow cytometry for measurable residual disease before transplant were more likely to relapse, most relapses overall occurred among the much larger pool of people who had tested negative. This highlights the need for more consistent, more sensitive testing.
“There are sites that are doing a tremendous job, and there are sites that are trying, but something’s not hitting the way that it needs to,” Tettero said. “That makes it particularly important that we establish standards to help ensure patients receive consistently reliable results.”
Tettero led the study while conducting postdoctoral research with Chris Hourigan, a global expert on MRD and director of the institute’s Cancer Research Center in Washington, D.C.
Hourigan advocates for a precision-medicine approach to improve the care of patients with cancer and is focused on measuring remaining leukemia cells by leveraging advanced, highly sensitive, molecular diagnostics, including whole genome DNA-sequencing.
“The work Dr. Tettero has done is very important to benchmark where we currently are in clinical practice, and the scale of the challenge we face if we are going to truly deliver on the promise of personalized medicine,” Hourigan said. “As a physician-scientist, Dr. Tettero understands both the unmet needs of patients suffering from this terrible disease but also the incredible opportunity offered by advanced technological solutions; and why translational research is so important for medical progress.”
Hourigan will deliver the first Maury Strauss Distinguished Public Lecture at 5:30 p.m. Thursday, Sept. 17, at the Fralin Biomedical Research Institute in Roanoke.
Tettero earned his medical and doctoral degrees from the Amsterdam University Medical Center, where he focused on blood cancers. The research was inspired in part by differences between his experience with flow cytometry in Europe and its use in the United States. Tettero completed his postdoctoral research in Washington, D.C., in July and returned to the Netherlands to complete his medical residency at the Amsterdam University Medical Center.
“Centralized testing has improved reproducibility in the European Union, but MRD testing in the United States remains largely decentralized, with varying methodologies and thresholds across laboratories,” Tettero said. While the U.S. Food and Drug Administration has issued guidance on MRD testing, compliance is left to individual testing sites.
“This study did not have the granularity of data to pinpoint the exact problem, but it did show that this is something we want to change,” Tettero said. The next step is a task force that will determine the data required and the guardrails needed to achieve consistency and improve testing.
During his fellowship, Tettero was also a key member of the national clinical protocol MEASURE, run by Hourigan at 18 major U.S. cancer centers, which aims to prospectively validate standardized AML MRD testing using state-of-the-art approaches.
“What we ultimately want is for a test result to mean the same thing, regardless of where a patient is tested. Our findings show we’re not there yet and why initiatives like MEASURE are so important.”
Original study and funding sources: https://doi.org/10.3324/haematol.2026.300764
Other Virginia Tech authors:
- Gege Gui, Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, Washington, D.C.
- Laura W. Dillon, Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, Washington, D.C.
