Clonal hemopoiesis a potential marker for therapy-related myeloid neoplasms
medwireNews: Two independent studies published in The Lancet Oncology find that clonal hemopoiesis increases the risk for developing therapy-related myeloid neoplasms in individuals who receive treatment for a primary cancer.
Describing these neoplasms as “an iatrogenic tragedy,” commentator David Steensma (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) says: “Although no method yet exists to reliably eliminate the preleukaemic clones that can give rise to therapy-related myeloid neoplasms, identification of higher risk patients could still affect monitoring practices, such as the frequency of clinical assessments.”
The first study showed that clonal hemopoiesis was more common in peripheral blood samples obtained at the time of primary cancer diagnosis from the 14 patients who went onto develop therapy-related myeloid neoplasms compared with the 54 who did not develop these neoplasms, with a prevalence of 71% and 31%, respectively.
The results were similar in an external cohort of lymphoma patients given the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without melatonin in the context of a randomized controlled trial. Preleukemic clonal hemopoiesis was detected in 80% of the five patients who developed therapy-related myeloid neoplasms, compared with in 16% of the 69 individuals who did not.
Moreover, multivariate analysis demonstrated that individuals with versus without clonal hemopoiesis were significantly more likely to develop therapy-related myeloid neoplasms, with a hazard ratio of 13.7.
Lead author P Andrew Futreal (The University of Texas MD Anderson Cancer, Houston, USA) and colleagues suggest that “[c]lonal haemopoiesis might function as a potential biomarker for risk prediction and early detection of therapy-related myeloid neoplasms and could be considered as a future therapeutic target to prevent the development of therapy-related myeloid neoplasms.”
The second study, by Eric Padron (H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA) and co-workers, included 13 patients aged at least 70 years who developed a myeloid neoplasm after receiving chemotherapy for a primary malignancy and 56 controls – matched for gender, primary tumor type, age at diagnosis, smoking status, chemotherapy drug class, and duration of follow-up – who remained neoplasm-free.
Clonal hemopoiesis was significantly more prevalent among patients with therapy-related myeloid neoplasms than those without, at 62% versus 27%.
And in multivariate analysis, the presence of clonal hemopoeisis was associated with a 5.75-fold increased risk for these neoplasms.
“Future studies are needed to delineate the mutation-specific risk and the usefulness of [clonal haemopoiesis of indeterminate potential] as a biomarker for the development of therapy-related myeloid neoplasms,” the team concludes.
Steensma notes that the “real importance” of the two studies will become evident “when therapies exist that can effectively eradicate nascent clonal haemopoiesis, thereby preventing therapy-related myeloid neoplasm evolution in at-risk patients.”
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