Vázquez Urio, Iria

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Vázquez Urio

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Iria

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Ciencias

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Author: Calasanz, María José × Subject: Acute myeloid leukemia (AML) ×

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    PublicationOpen Access
    Impact of FLT3-ITD mutation status and its ratio in a cohort of 2901 patients undergoing upfront intensive chemotherapy: a PETHEMA registry study
    (MDPI, 2022-11-24) Ayala, Rosa; Carreño-Tarragona, Gonzalo; Barragán, Eva; Boluda, Blanca; Larráyoz, María José; Chillón, María Carmen; Carrillo-Cruz, Estrella; Bilbao, Cristina; Sánchez-García, Joaquín; Bernal, Teresa; Martínez-Cuadrón, David; Gil, Cristina; Serrano, Josefina; Rodríguez-Medina, Carlos; Bergua, Juan; Pérez-Simón, José A.; Calbacho, María; Alonso-Domínguez, Juan M.; Labrador, Jorge; Tormo, Mar; Amigo, María Luz; Herrera-Puente, Pilar; Rapado, Inmaculada; Sargas, Claudia; Vázquez Urio, Iria; Calasanz, María José; Gómez-Casares, Teresa; García-Sanz, Ramón; Sanz, Miguel A.; Martínez-López, Joaquín; Montesinos, Pau; Ciencias; Zientziak
    FLT3-ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3-ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3-ITD mutations. In multivariate analyses, patients with an FLT3-ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p < 0.001). Among NPM1/FLT3-ITD-mutated patients, median OS gradually decreased according to FLT3-ITD status and ratio (34.3 months FLT3-ITD-negative, 25.3 months up to 0.25, 14.5 months up to 0.5, and 10 months ≥ 0.5, p < 0.001). Post-remission allogeneic transplant (allo-HSCT) resulted in better OS and RFS as compared to auto-HSCT in NPM1/FLT3-ITD-mutated AML regardless of pre-established AR cutoff (≤0.5 vs. >0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3-ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3-ITD status in all patients, and we found that the group of FLT3-ITD-positive patients with AR < 0.44 had similar 5-year OS after allo-HSCT or auto-HSCT (52% and 41%, respectively, p = 0.86), but worse RFS after auto-HSCT (p = 0.01). Among patients with FLT3-ITD AR > 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3-ITD mutations.