| Title: |
Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study. |
| Authors: |
Ayala, Rosa; Carreño-Tarragona, Gonzalo; Barragán, Eva; Boluda, Blanca; Larráyoz, María J; Chillón, María Carmen; Carrillo-Cruz, Estrella; Bilbao, Cristina; Sánchez-García, Joaquín; Bernal, Teresa; Martinez-Cuadron, David; Gil, Cristina; Serrano, Josefina; Rodriguez-Medina, Carlos; Bergua, Juan; Pérez-Simón, José A; Calbacho, María; Alonso-Domínguez, Juan M; Labrador, Jorge; Tormo, Mar; Amigo, Maria Luz; Herrera-Puente, Pilar; Rapado, Inmaculada; Sargas, Claudia; Vazquez, Iria; Calasanz, María J; Gomez-Casares, Teresa; García-Sanz, Ramón; Sanz, Miguel A; Martinez-Lopez, Joaquin; Montesinos, Pau |
| Contributors: |
Instituto de Salud Carlos III; Unión Europea. Comisión Europea; CRIS contra el Cáncer; Research Institute Hospital 12 de Octubre |
| Publisher Information: |
Multidisciplinary Digital Publishing Institute (MDPI) |
| Publication Year: |
2022 |
| Collection: |
REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| Subject Terms: |
FLT3-ITD mutation and ratio; real-world outcomes; ACUTE MYELOID LEUKEMIA; PROGNOSIS; OUTCOME; DEATH; RELAPSE; SURVIVAL |
| Description: |
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. ; We thank all patients for agreeing to participate in these studies. This study was funded by Instituto de Salud Carlos III (ISCIII) through the project PI19/01518 and PI19/00730 and co-funded by the European Union, the CRIS Against Cancer Foundation, grant ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.3390/cancers14235799; info:fis/Instituto de Salud Carlos III/Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I/Subprograma Estatal de Generación de Conocimiento/PI19 - Proyectos de investigacion en salud (AES 2019). Modalidad proyectos en salud. (2019)/PI19/01518; info:fis/Instituto de Salud Carlos III/Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I/Subprograma Estatal de Generación de Conocimiento/PI19 - Proyectos de investigacion en salud (AES 2019). Modalidad proyectos en salud. (2019)/PI19/00730; Cancers (Basel). 2022;14(23):5799.; http://hdl.handle.net/20.500.12105/16136; Cancers |
| DOI: |
10.3390/cancers14235799 |
| Availability: |
https://hdl.handle.net/20.500.12105/16136; https://doi.org/10.3390/cancers14235799 |
| Rights: |
http://creativecommons.org/licenses/by-nc-sa/4.0/ ; Atribución-NoComercial-CompartirIgual 4.0 Internacional ; open access |
| Accession Number: |
edsbas.E3C00CF4 |
| Database: |
BASE |