Shyam Patel, MD, PhD, Explains the Patterns of Progression from CHIP to Myeloid Neoplasms

Dr. Patel, of UMass Chan Medical School, joins Blood Cancers Today to discuss his study, “Natural History of Clonal Haematopoiesis Seen in Real-World Haematology Settings.”

“Clonal hematopoiesis is thought to be the pathophysiologic hallmark of myeloid neoplasms, and it’s a precursor for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML),” Dr. Patel began.

The average rate of progression for clonal hematopoiesis of indeterminate potential (CHIP) to MDS or AML is about 1% per year, he added.

Dr. Patel and colleagues collaborated with Stanford University and the Dana-Farber Cancer Institute to risk assess patients with CHIP and to illustrate clinical trajectories for patients with various mutational profiles.

A total of 94 patients with a true diagnosis of either CHIP or clonal cytopenia of undetermined significance (CCUS) were divided into two groups: those who had sole DTA mutations (mutations only in DNMT3A, TET2, and ASXL1), and those who had nonsole DTA mutations (mutations in any other cluster that was not purely DNMT3A, TET2, and ASXL1).

“We mapped the clinical trajectories of these two groups from the real-world setting and found that patients with sole DTA mutations did not progress to an obvious myeloid neoplasm in the absence of an additional mutation,” Dr. Patel explained. “A concurrent mutation or mutations were required for progression of sole DTA patients to myeloid neoplasm. In the non-sole group, nonsole DTA mutations were sufficient for progression from CHIP or CCUS to MDS or AML.”

The researchers also validated the Clonal Hematopoiesis Risk Score (CHRS), a prognostic model for CHIP and CCUS, in the real-world setting.

“We found that patients who did progress to myeloid neoplasm generally had high-risk CHRS,” Dr. Patel explained. “There was a great correlation between the CHRS score and true progressors in the real-world setting for patients who had an indication for testing.”

They also found that the RUNX1 mutation carried the strongest risk for progression from CHIP or CCUS to either MDS or AML.

“Overall, our study provides insight into patterns for progression to myeloid neoplasm, and it may be very valuable to use the CHRS in real-world hematology settings,” Dr. Patel concluded.