Acute myeloid leukemia (AML) with core-binding factor (CBF) chromosomal rearrangements carries a poorer prognosis in therapy-related cases than it does when arising de novo, according to a study in the American Journal of Hematology.

Clinical records from patients with AML who had t(8;21) or inv(16) chromosomal alterations were evaluated in this retrospective, multicenter analysis associated with the Bone Marrow Pathology Group. Patients had either therapy-related (69 individuals) or de novo (282 individuals) CBF-AML, and their records were evaluated for genetic, cytogenetic, and survival characteristics. The median follow-up duration was 27.0 months.

Secondary cytogenetic changes, such as sex chromosome loss, trisomy 8, or trisomy 22, were associated with improved overall survival (OS). The median OS was 190 months in patients with secondary cytogenetic changes, compared with 87 months for patients without such changes (log-rank P =.021).

Secondary cytogenetic changes we observed in over half of the patients with de novo CBF-AML but in fewer than half of those with therapy-related disease (P =.026). Patients with de novo disease had a longer OS than therapy-related disease (190 months vs 69 months; log-rank P =.038).

Among 165 patients who were evaluated by genetic sequencing, 75.7% carried pathogenic mutations, the most common of which were N/KRAS mutations in 37.0% of patients. In patients with t(8;21) AML, N/KRAS mutations showed a positive association with OS (log-rank P =.01). TET2 mutations were present in 4.9% of patients, and were associated with lower OS (log-rank P =.012).

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In multivariate analysis, shorter OS showed links to advanced age and a lack of secondary cytogenetic changes across the overall population. Shorter OS was also found with lower hemoglobin levels in patients with therapy-related CBF-AML. In patients with de novo CBF-AML, a higher peripheral blood eosinophil count was linked to shorter OS.

The researchers concluded that patients with therapy-related CBF-AML had higher mortality rates and worse survival outcomes than patients with de novo CBF-AML.

“However, only older age and absence of secondary cytogenetic abnormalities were the significant variables impacting overall survival in multivariate analysis in this cohort,” the researchers concluded.

Reference

Rogers HJ, Wang X, Xie Y, et al. Comparison of therapy-related and de novo core binding factor acute myeloid leukemia: a Bone Marrow Pathology Group study [published online April 6, 2020]. Am J Hematol. doi: 10.1002/ajh.25814