Mutation patterns identify adult patients with de novo acute myeloid leukemia aged 60 years or older who respond favorably to standard chemotherapy: an analysis of Alliance studies
Autor: | Sophia E. Maharry, Jonathan E. Kolitz, Jessica Kohlschmidt, Richard Stone, Eunice S. Wang, Bayard L. Powell, James S. Blachly, Clara D. Bloomfield, Christopher J. Walker, Krzysztof Mrózek, Ann-Kathrin Eisfeld, Andrew J. Carroll, Deedra Nicolet, John C. Byrd, Shelley Orwick, Albert de la Chapelle |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Oncology Cancer Research NPM1 medicine.medical_specialty Myeloid Cohesin complex medicine.medical_treatment Article Disease-Free Survival 03 medical and health sciences European LeukemiaNet 0302 clinical medicine Internal medicine medicine Humans Aged Aged 80 and over Chemotherapy business.industry High-Throughput Nucleotide Sequencing Nuclear Proteins Cancer Myeloid leukemia Hematology Middle Aged Prognosis medicine.disease 3. Good health Leukemia Myeloid Acute Leukemia 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Mutation Female business Nucleophosmin |
Zdroj: | Leukemia |
ISSN: | 1476-5551 0887-6924 |
Popis: | Thus far, only 5-15% of AML patients aged ≥60 years are cured with chemotherapy. Identification of patients who are less (more) likely to respond to standard chemotherapy might enable early risk stratification toward alternative treatment regimens. We used a next-generation sequencing panel of 80 cancer- and/or leukemia-associated genes to profile molecularly 423 older patients with de novo AML. Using variables identified in multivariable models and co-occurring mutations in NPM1-mutated AML, we classified the patients into good-, intermediate-, and poor-risk groups for complete remission (CR) attainment, disease-free (DFS), and overall survival (OS). Whereas 81% of good-risk patients (comprising NPM1-mutated patients harboring mutations in chromatin remodeling, cohesin complex, methylation-related, spliceosome, and/or RAS pathway genes, FLT3-TKD, and/or patients without FLT3-ITD) achieved a CR, only 32% of poor-risk patients (with U2AF1, WT1 mutations and/or complex karyotype) did. Intermediate-risk patients had a 50% CR rate. Similarly, using NPM1 co-mutation patterns and SF1 mutation status, we identified patients with favorable DFS and OS 3-year rates of 46% and 45%, respectively. Patients with adverse genetic features had DFS and OS rates of only 2% and 4%. We show that application of our proposed criteria may refine the 2017 European LeukemiaNet classification for older patients treated with chemotherapy. |
Databáze: | OpenAIRE |
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