A new clinical tool may pinpoint which patients with clonal hematopoiesis are at highest risk for cancer progression, according to new findings presented by Weeks et al at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 926).
Background
Clonal hematopoiesis—a recently characterized precancerous condition—is present in roughly 15% of individuals over 65 years, 4% of whom may go on to develop hematologic cancer. Because there is no robust, rigorous way to assess risk, clinicians have struggled to advise patients with clonal hematopoiesis on their prognoses.
“We’ve been able to detect clonal hematopoiesis in patients for years now,” noted lead study author Lachelle D. Weeks, MD, PhD, a Professor of Medicine at Harvard Medical School and a hematologist-oncologist in the Adult Leukemia program at the Dana-Farber Cancer Institute. “But this diagnosis often exposes patients to stress and anxiety because it’s unclear who is at highest risk of developing [hematologic] cancer. Our tool can help change that.”
Methods and Findings
In the new study, Dr. Weeks and her colleagues analyzed data from nearly 200,000 healthy participants, examined exome sequencing data to determine specific genetic mutations associated with clonal hematopoiesis, and combined genetic data with other demographic and laboratory parameters. From this information, the researchers identified several factors that may have been highly predictive of the risk of hematologic cancer in patients with clonal hematopoiesis. These factors included a patient’s age, the type and number of genetic mutations present in blood cells, the fraction of cells in the blood with the clonal hematopoiesis mutation, low blood counts, and factors related to red blood cell volume.
The researchers combined these factors together into a computational algorithm, creating a tool capable of calculating the clonal hematopoiesis risk score—which predicted an individual’s future risk of developing hematologic cancer. The clonal hematopoiesis risk score values defined three distinct groups of patients according to the likelihood of cancer progression—a score of 9.5 or less (low risk), a score ranging from 10 to 12 (intermediate risk); and a score of 12.5 or greater (high risk). While the 10-year risk of blood cancer was less than 1% in the low-risk group, the risk of developing a hematologic cancer such as myelodysplastic syndrome or acute myeloid leukemia was over 50% for the high-risk group.
The team validated their tool using three additional cohorts: a second cohort of roughly 250,000 healthy participants, as well as two cohorts of patients with clonal hematopoiesis evaluated for hematologic conditions.
Conclusions
“This tool allows us to detect the minority of patients with clonal hematopoiesis who are at high-risk for developing [hematologic] cancer,” highlighted Dr. Weeks, concluding that the results were “really exciting for two reasons—now we can not only estimate patients’ risk[s] and help reduce some of their anxiet[ies] and uncertaint[ies], but also take another critical step forward in building out this new field of early detection for [hematologic] cancers.”
The ability to stratify patients with clonal hematopoiesis according to their risk of cancer progression will also help propel clinical trials for potential therapeutic interventions that prevent cancer in high-risk patients. With the new tool for scoring clonal hematopoiesis risk that Dr. Weeks and her colleagues developed, it may be possible to target experimental treatments to those patients who are most likely to benefit from them during a clinical study.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
