RT Journal Article
T1 Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study
A1 Ayala Díaz, Rosa María
A1 Carreño Tarragona, Gonzalo
A1 Barragán, Eva
A1 Boluda, Blanca
A1 Larráyoz, María
A1 Chillón, María Carmen
A1 Carrillo Cruz, Estrella
A1 Bilbao, Cristina
A1 Sánchez García, Joaquín
A1 Bernal, Teresa
A1 Martínez Cuadrón, David
A1 Gil, Cristina
A1 Serrano, Josefina
A1 Rodríguez Medina, Carlos
A1 Bergua, Juan
A1 Pérez Simón, José
A1 Calbacho, María
A1 Alonso Domínguez, Juan Manuel
A1 Labrador, Jorge
A1 Tormo, Mar
A1 Amigo, Maria Luz
A1 Herrera Puente, Pilar
A1 Rapado, Inmaculada
A1 Sargas, Claudia
A1 Vázquez, Iria
A1 Calasanz, María
A1 Gómez Casares, Teresa
A1 García Sanz, Ramón
A1 Sanz, Miguel
A1 Martínez López, Joaquín
A1 Montesinos, Pau
AB 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.
PB MDPI
SN 2072-6694
YR 2022
FD 2022-11-24
LK https://hdl.handle.net/20.500.14352/72316
UL https://hdl.handle.net/20.500.14352/72316
LA eng
NO Instituto de Salud Carlos III
NO Fundación CRIS Contra el Cáncer
NO Instituto de Investigación Hospital 12 de Octubre
NO Unión Europea
DS Docta Complutense
RD 7 abr 2025