دورية أكاديمية
Multi-gene measurable residual disease assessed by digital polymerase chain reaction has clinical and biological utility in acute myeloid leukemia patients receiving venetoclax/azacitidine.
| العنوان: | Multi-gene measurable residual disease assessed by digital polymerase chain reaction has clinical and biological utility in acute myeloid leukemia patients receiving venetoclax/azacitidine. |
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| المؤلفون: | Winters AC; Center for Cancer and Blood Disorders, Department of Pediatrics, University of Colorado, Aurora. amanda.winters@childrenscolorado.org., Minhajuddin M; Division of Hematology, Department of Medicine, University of Colorado, Aurora., Stevens BM; Division of Hematology, Department of Medicine, University of Colorado, Aurora., Major A; Division of Hematology, Department of Medicine, University of Colorado, Aurora., Bosma G; Department of Biostatistics and Informatics, University of Colorado, Aurora., Abbott D; Department of Biostatistics and Informatics, University of Colorado, Aurora., Miltgen N; Molecular Diagnostics, Children's Hospital Colorado, Aurora., Yuan J; Molecular Diagnostics, Children's Hospital Colorado, Aurora., Treece AL; Pediatric Pathology, Children's of Alabama, Birmingham., Siegele BJ; Department of Pathology, University of Colorado, Aurora., Ewalt MD; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York., Gutman JA; Division of Hematology, Department of Medicine, University of Colorado, Aurora., Jordan CT; Division of Hematology, Department of Medicine, University of Colorado, Aurora., Pollyea DA; Division of Hematology, Department of Medicine, University of Colorado, Aurora. |
| المصدر: | Haematologica [Haematologica] 2024 Jun 01; Vol. 109 (6), pp. 1766-1778. Date of Electronic Publication: 2024 Jun 01. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Ferrata Storti Foundation Country of Publication: Italy NLM ID: 0417435 Publication Model: Electronic Cited Medium: Internet ISSN: 1592-8721 (Electronic) Linking ISSN: 03906078 NLM ISO Abbreviation: Haematologica Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : Pavia, Italy : Ferrata Storti Foundation Original Publication: Pavia [etc.] |
| مواضيع طبية MeSH: | Leukemia, Myeloid, Acute*/genetics , Leukemia, Myeloid, Acute*/drug therapy , Leukemia, Myeloid, Acute*/therapy , Leukemia, Myeloid, Acute*/diagnosis , Neoplasm, Residual*/diagnosis , Nucleophosmin* , Sulfonamides*/therapeutic use , Sulfonamides*/administration & dosage , Bridged Bicyclo Compounds, Heterocyclic*/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic*/administration & dosage , Azacitidine*/therapeutic use , Azacitidine*/administration & dosage , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Mutation*, Humans ; Aged ; Male ; Female ; Middle Aged ; Polymerase Chain Reaction/methods ; Prognosis ; Aged, 80 and over ; Retrospective Studies ; Adult ; Treatment Outcome |
| مستخلص: | 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 broadscale 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 polymerase chain reaction (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 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. |
| معلومات مُعتمدة: | I01 BX004768 United States BX BLRD VA; K08 CA279762 United States CA NCI NIH HHS; R35 CA242376 United States CA NCI NIH HHS |
| المشرفين على المادة: | N54AIC43PW (venetoclax) 117896-08-9 (Nucleophosmin) 0 (Sulfonamides) 0 (Bridged Bicyclo Compounds, Heterocyclic) 0 (NPM1 protein, human) M801H13NRU (Azacitidine) |
| تواريخ الأحداث: | Date Created: 20231218 Date Completed: 20240604 Latest Revision: 20240816 |
| رمز التحديث: | 20240817 |
| مُعرف محوري في PubMed: | PMC11141685 |
| DOI: | 10.3324/haematol.2023.283790 |
| PMID: | 38105738 |
| قاعدة البيانات: | MEDLINE |
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