Persisting mutation predominantly comprised DNMT3A (78.7%), TET2 (54.2%) and ASXL1 (51.6%). In 51.4% of patients, researchers detected persisting mutations in bone marrow during morphological complete remission at highly variable variant allele frequencies (range, 0.0002-0.47). Overall, 89.2% (n = 430) of patients had somatic driver mutations present at diagnosis. To establish and subsequently test next-generation sequencing MRD, researching split the cohort into two cohorts - representative training (n = 283) and validation (n = 147) cohorts. Next-generation sequencing (Illumina) evaluated a panel of 54 genes frequently mutated in myeloid malignancies at diagnosis and in bone marrow in morphological complete remission after completion of induction therapy. Patients received two cycles of standard induction chemotherapy followed by consolidation in HOVON-SAKK clinical trials. Grob and colleagues conducted a large comprehensive study detailing the value of molecular MRD detection by next-generation sequencing among 482 patients with newly diagnosed AML aged 65 years or younger. However, persistent mutations may also represent clonal hematopoiesis, analogous to age-related clonal hematopoiesis of indeterminate potential present in healthy individuals.” Residual leukemia-specific mutations in bone marrow in morphological complete remission after induction therapy are supposed to represent the source of relapse. “It allows for the assessment of a broad range of disease-related gene mutations in a single assay. “Next-generation sequencing has an advantage,” Grob said. Further, there is little knowledge regarding the association between persisting somatic mutations after induction therapy and AML relapse. Molecular MRD detection by polymerase chain reaction-based technologies improves relapse prediction, but only for certain genetically defined subsets of AML. Most patients with AML achieve complete morphological remission after induction therapy. “In sensitivity analysis with time-dependent correction for allogeneic stem cell transplantation, next-generation sequencing MRD was applicable in virtually all newly diagnosed adults with AML.” “In our large prospective study including training and validation cohorts, targeted next-generation sequencing minimal residual disease detection was established as a powerful and independent predictor for relapse and survival,” Tim Grob, MD, of the department of hematology at Erasmus University Medical Center in Rotterdam, Netherlands, said during his presentation. If you continue to have this issue please contact to HealioĪTLANTA - Detection of molecular minimal residual disease by next-generation sequencing remained highly prognostic for relapse and survival among patients with newly diagnosed acute myeloid leukemia, according to a prospective analysis presented during the late-breaking abstract session of the ASH Annual Meeting and Exposition.
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