Persistent leukemia-associated mutations that can be detected in at least 5% of bone marrow cells at 30 days after remission were associated with a significantly increased risk of relapse and reduced overall survival in patients with acute myeloid leukemia (AML), in a study published Aug. 25 in JAMA.
About 20% of adult patients with AML fail to achieve remission following standard initial induction chemotherapy, and approximately half of them will subsequently experience a relapse after achieving complete remission. Currently, tests that predict outcomes for these patients are imprecise, especially for those with intermediate-risk disease.
“The data presented in this report begin to define a genomic method for the risk stratification of patients with AML that places greater emphasis on the clearance of somatic mutations after chemotherapy than the identification of specific mutations at the time of presentation,” wrote Dr. Jeffery M. Klco, Washington University, St Louis, and his colleagues. (JAMA. 2015;314:811-22).
Whole-genome or exome sequencing was performed on samples that were obtained at disease presentation from 71 patients with AML who were treated with standard induction chemotherapy in March 2002, with follow-up through January 2015. A subsequent re-analysis was conducted in a cohort of 50 patients, who had available samples from both presentation and documented remission.
Of this group, 24 (48%) had persistent leukemia-associated mutations in at least 5% of bone marrow cells at remission, while 26 patients had cleared all mutations.
The investigators noted that patients with at least one persistent mutation on day 30 had significantly reduced event-free survival compared with those who had cleared all mutations (median, 6.0 months [95% CI, 3.7-9.6] vs 17.9 months [95% CI, 11.3-40.4], hazard ratio [HR], 3.67 [95%CI, 1.93-7.11], P less than .001).
Findings were similar for overall survival. Median survival was 10.5 months [95% CI, 7.5-22.2] for those with persistent mutations vs 42.2 months [95% CI, 20.6-not estimable] for those without them (HR, 2.86 [95% CI, 1.39-5.88], P = .004).
The results were similar for the 32 patients with intermediate-risk AML, in that persistent mutations were associated with reduced event-free survival as well as overall survival.