医学
肿瘤科
威尼斯人
微小残留病
内科学
净现值1
阿扎胞苷
髓系白血病
养生
白血病
慢性淋巴细胞白血病
生物
基因
DNA甲基化
遗传学
基因表达
核型
染色体
作者
Amanda Winters,Mohammad Minhajuddin,Brett M. Stevens,Ajay Major,Grace Bosma,Diana Abbott,Nicholas Miltgen,Jing Yuan,Amy Treece,Bradford Siegele,Mark D. Ewalt,Jonathan A. Gutman,Craig T. Jordan,Daniel A. Pollyea
标识
DOI:10.3324/haematol.2023.283790
摘要
Venetoclax with azacitidine (ven/aza) is a lower-intensity therapeutic regimen that has been shown to improve outcomes in elderly patients with acute myeloid leukemia (AML). Measurable residual disease (MRD) using flow cytometry is a valuable tool for the prediction of relapse in AML using conventional therapies and ven/aza; however, the prognostic value for broad-scale molecular MRD after ven/aza treatment is less clear. We aimed to determine the utility of retrospective assessment using multi-gene molecular MRD by droplet digital PCR (ddPCR). We found this approach correlates with outcomes in a cohort of patients receiving frontline ven/aza for AML. The predictive value of ddPCR MRD persisted when NPM1 mutations were removed from analysis, as well as after adjustment for the impact of stem cell transplant (SCT) on outcomes. Late achievement of MRD negativity, including after SCT, was still associated with superior outcomes compared to persistently detectable MRD. We further explored the impact of ven/aza on the burden of different classes of mutations, and identified the persistence of splicing factor mutations, commonly associated with MDS, as a consistent finding after ven/aza treatment. These data add to our understanding of the effects of ven/aza on AML disease biology and provide details on molecular depth of remission that can guide prospective trials in the future.
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