Hematology · 2 h ago
FLT3-ITD microclones found in 10% of older AML patients receiving less-intensive care
In a single-center study of 201 patients aged 65 years or older with acute myeloid leukemia (AML), ultrasensitive sequencing detected FLT3-ITD microclones in 10.4% of patients previously classified as negative by conventional testing. Microclones were not associated with overall survival in the full cohort; a shorter survival signal appeared in the subgroup receiving best supportive care alone.
- Ultrasensitive sequencing detected microclones in 10.4% of 201 patients.
- Conventional fragment-length analysis detected 28.5% of identified microclones.
- Overall survival was similar in the full cohort.
- A survival difference appeared only in the best-supportive-care subgroup.
Researchers analyzed diagnostic samples from 201 patients aged 65–90 years with AML who were FLT3-ITD negative by conventional fragment-length analysis and received less-intensive treatment or best supportive care. Error-corrected, ultrahigh-sensitivity next-generation sequencing detected FLT3-ITD microclones in 21 patients (10.4%), at a median variant allele frequency of 0.035%. Conventional analysis detected only six of these 21 microclones. Treatment included hypomethylating-agent monotherapy, hypomethylating agents with venetoclax or ivosidenib, or best supportive care alone.
Microclone-positive patients had higher white blood cell counts at diagnosis and more frequent DNMT3A, SMC3 and NRAS mutations. Overall survival did not differ between microclone-positive and -negative patients in the full cohort (p=0.97). Among patients receiving best supportive care alone, microclone positivity was associated with shorter survival (HR 2.8; 95% CI 1.006–7.808; p=0.04); no such difference was observed in either treatment group receiving hypomethylating agents.
The findings suggest conventional fragment-length analysis may miss small FLT3-ITD clones. The survival result was limited to a subgroup and had a wide confidence interval; it does not establish that microclone status should guide treatment. The study was observational and single-center, and follow-up clonal analyses were available for only seven microclone-positive patients.
In practice
For older adults with AML receiving less-intensive therapy, ultrasensitive sequencing identified FLT3-ITD microclones in some patients whose conventional fragment-length testing was negative. This shows that assay sensitivity affects detection, but the study did not demonstrate an overall-survival difference by microclone status. A shorter survival association was seen only among patients receiving best supportive care, in a subgroup with a wide confidence interval. These observational findings do not establish that testing or treatment decisions should change.
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Leukemia: Clinical and molecular characteristics of FLT3-ITD microclones in elderly patients with acute myeloid leukemia receiving less-intensive therapy ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.