دورية أكاديمية
The Mutational Landscape of Acute Myeloid Leukaemia Predicts Responses and Outcomes in Elderly Patients from the PETHEMA-FLUGAZA Phase 3 Clinical Trial
| العنوان: | The Mutational Landscape of Acute Myeloid Leukaemia Predicts Responses and Outcomes in Elderly Patients from the PETHEMA-FLUGAZA Phase 3 Clinical Trial |
|---|---|
| المؤلفون: | Ayala, Rosa, Rapado, Inmaculada, Onecha, Esther, Martínez-Cuadrón, David, Carreño-Tarragona, Gonzalo, Bergua, Juan, Vives, Susana, Lorenzo Algarra, Jesús, Tormo, Mar, López Martínez, Pilar, Serrano, Josefina, Herrera, Pilar, Ramos, Fernando, Salamero, Olga, Lavilla, Esperanza, Gil, Cristina, López Lorenzo, José Luis, Vidriales, Maria Belén, Labrador, Jorge, Falantes-González, José Francisco, Sayas, María-José, Paiva, Bruno, Barragán. Eva, Prosper, Felipe, Sanz, Miguel Ángel, Martínez-López, Joaquín, Montesinos, Pau |
| المساهمون: | Centro de Investigación Biomédica en Red Cáncer (España), Instituto de Salud Carlos III, Fundación CRIS contra el Cáncer, Instituto de Investigación Hospital 12 de Octubre, European Commission, Cancer Research UK, Fundación Científica Asociación Española Contra el Cáncer, Associazione Italiana per la Ricerca sul Cancro |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute |
| سنة النشر: | 2021 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | This article belongs to the Collection The Biomarkers for the Diagnosis and Prognosis in Cancer. ; [Simple Summary] Mutational profiling using a custom 43-gene next-generation sequencing panel revealed that patients with mutated DNMT3A or EZH2, or an increase in TET2 VAF and lower TP53 VAF showed a higher overall response. NRAS and TP53 variants were associated with shorter overall survival (OS), whereas only mutated BCOR was associated with a shorter relapse-free survival (RFS). Subgroup analyses of OS according to biological and genomic characteristics showed that patients with low–intermediate cytogenetic risk and mutated NRAS benefited from azacytidine therapy and patients with mutated TP53 showed a better RFS in the azacytidine arm. In conclusion, differential mutational profiling might anticipate the outcomes of first-line treatment choices (AZA or FLUGA) in older patients with AML. ; [Abstract] We sought to predict treatment responses and outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) from our FLUGAZA phase III clinical trial (PETHEMA group) based on mutational status, comparing azacytidine (AZA) with fludarabine plus low-dose cytarabine (FLUGA). Mutational profiling using a custom 43-gene next-generation sequencing panel revealed differences in profiles between older and younger patients, and several prognostic markers that were useful in young patients were ineffective in older patients. We examined the associations between variables and overall responses at the end of the third cycle. Patients with mutated DNMT3A or EZH2 were shown to benefit from azacytidine in the treatment-adjusted subgroup analysis. An analysis of the associations with tumor burden using variant allele frequency (VAF) quantification showed that a higher overall response was associated with an increase in TET2 VAF (odds ratio (OR), 1.014; p = 0.030) and lower TP53 VAF (OR, 0.981; p = 0.003). In the treatment-adjusted multivariate survival analyses, only the NRAS (hazard ratio (HR), 1.9, p = 0.005) and ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | Publisher's version; http://dx.doi.org/10.3390/cancers13102458Test; Sí; e-issn: 2072-6694; Cancers 13(10): 2458 (2021); http://hdl.handle.net/10261/262043Test; http://dx.doi.org/10.13039/501100005010Test; http://dx.doi.org/10.13039/501100000289Test; http://dx.doi.org/10.13039/501100004587Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/501100002704Test |
| DOI: | 10.3390/cancers13102458 |
| DOI: | 10.13039/501100005010 |
| DOI: | 10.13039/501100000289 |
| DOI: | 10.13039/501100004587 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100002704 |
| الإتاحة: | https://doi.org/10.3390/cancers13102458Test https://doi.org/10.13039/501100005010Test https://doi.org/10.13039/501100000289Test https://doi.org/10.13039/501100004587Test https://doi.org/10.13039/501100000780Test https://doi.org/10.13039/501100002704Test http://hdl.handle.net/10261/262043Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.469CB440 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cancers13102458 |
|---|