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2025 ; 16
(ä): 20406207251349261
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The clinical utility and prognostic value of next-generation sequencing for
measurable residual disease assessment in acute myeloid leukemia
#MMPMID40585520
Liu Y
; Cheng H
; Sun M
; Gong T
; Ma J
Ther Adv Hematol
2025[]; 16
(ä): 20406207251349261
PMID40585520
show ga
BACKGROUND: Next-generation sequencing (NGS) offers a method for measurable
residual disease (MRD) assessment by detecting leukemia-associated genetic
mutations. OBJECTIVE: This study aimed to evaluate the clinical implications and
prognostic value of NGS-based MRD assessment in acute myeloid leukemia (AML).
DESIGN: Sixty-nine adult AML patients were included for NGS (targeted sequencing
of AML-related 47 genes), of which 56 patients at initial diagnosis, 69 patients
in the first day of consolidation therapy (C1D1), and 51 patients during 2-year
MRD monitoring (detection following the C1D1) were enrolled. METHODS: Mutation
data were categorized into gene mutations, somatic mutations and somatic
mutations excluding clonal hematopoiesis of indeterminate potential (CHIP) for
analysis. The study also integrated multiparameter flow cytometry (MFC) and NGS
data at C1D1 to evaluate the prognostic significance of combining the two MRD
techniques. RESULTS: Mutation detection rates were 98.21%, 69.57%, and 84.31% for
AML patients at initial diagnosis, C1D1 stage, and MRD monitoring, respectively,
identified by targeted sequencing. During MRD monitoring, the ETV6 mutation
frequency was significantly higher in relapsed patients than in non-relapsed
patients (p < 0.05). The mean variant allele frequency (VAF) was significantly
higher in the 2-year MRD monitoring period (0.160 ± 0.155) compared to the C1D1
period (0.058 ± 0.087; p < 0.05) in relapsed patients. Survival analysis revealed
that patients with a mean VAF (somatic mutations excluding CHIP) ?0.004 in the
C1D1 stage and ?0.020 during MRD monitoring had a better prognosis. Furthermore,
the combination of MFC and NGS-based MRD (somatic mutations excluding CHIP) at
C1D1 stage showed that patients who were negative for two tests had longer
survival than those who were negative for only one. CONCLUSION: The combined
assessment of MFC-MRD and NGS-MRD status provides a refined prognostic
stratification, with the absence of somatic mutations and MFC-MRD negativity
correlating with improved progression-free survival, which is expected to improve
clinical prognostic assessment of AML patients.