Screening for Preleukemic Mutations Could Identify Patients Likely to Develop Therapy-Related Myeloid Neoplasms

Author’s Perspective

Lead author Koichi Takahashi, MD: “Since many cancer patients are now living longer, t-MNs are an increasing concern for cancer survivors. Genetic mutations that are present in t-MN leukemia samples actually could be found in blood samples obtained at the time of the original cancer diagnosis. The data suggest potential approaches of screening for clonal hematopoiesis in cancer patients that may identify patients at risk of developing t-MNs.”

The presence of clonal hematopoiesis at the time of diagnosis of unrelated cancers identifies patients with an increased risk of developing secondary, therapy-related myeloid neoplasms (t-MNs), according to results from a case-control study published in the Lancet Oncology. Koichi Takahashi, MD, and co-authors from the University of Texas MD Anderson Cancer Center in Houston also found that t-MNs can occur years after patients complete cancer treatment.

The authors identified 14 patients who developed t-MNs and 54 controls who did not develop t-MNs after at least five years of follow-up. They then compared paired samples of peripheral blood (PB) and bone marrow (BM) at the time of primary cancer diagnosis and t-MN diagnosis.

Using molecular targeted gene sequencing and molecular barcode sequencing, the authors detected pre-leukemic driver mutations or clonal hematopoiesis in 10 cases (71%) and 17 controls (31%).

The cumulative incidence of t-MNs at five years was significantly higher in patients with clonal hematopoiesis than in patients without: 30 percent (95% CI 16-51) versus 7 percent (95% CI 2-21; p=0.015).

These results were validated in a cohort of 74 patients with lymphoma: After a median follow-up of 14.8 years, five of these patients (7%) developed t-MNs, of whom four (80%) had clonal hematopoiesis. Eleven of the 69 patients who did not develop t-MNs (16%) had clonal hematopoiesis. The incidence of t-MNs at 10 years also was significantly higher in patients with clonal hematopoiesis, compared with patients without (29% [95% CI 12-59] vs. 0%; p=0.001).

“Our results suggest that clonal hematopoiesis could be used as a predictive marker to identify patients with cancer who are at risk of developing t-MNs,” the authors concluded, adding that these results need to be confirmed in a larger, prospective trial.

The study is limited by its case-control design. In addition, the denominator of patients with other cancers is unknown, thus this cannot be recommended as screening of all patients with cancer who are about to embark on chemotherapy or radiation therapy.

Source: Takahashi K, Wang F, Kantarjian HM, et al. Preleukaemic clonal haemopoiesis and risk of therapy-related myeloid neoplasms: a case-control study. Lancet Oncol. 2017;18:100-11.