Scientific Reports (Oct 2021)
Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens
- Tamara Castaño-Bonilla,
- Juan M. Alonso-Dominguez,
- Eva Barragán,
- Rebeca Rodríguez-Veiga,
- Claudia Sargas,
- Cristina Gil,
- Carmen Chillón,
- María B. Vidriales,
- Raimundo García,
- Joaquín Martínez-López,
- Rosa Ayala,
- María J. Larrayoz,
- Eduardo Anguita,
- Rebeca Cuello,
- Alberto Cantalapiedra,
- Estrella Carrillo,
- Elena Soria-Saldise,
- Jorge Labrador,
- Isabel Recio,
- Lorenzo Algarra,
- Carlos Rodríguez-Medina,
- Cristina Bilbao-Syeiro,
- Juan A. López-López,
- Josefina Serrano,
- Erik De Cabo,
- María J. Sayas,
- María T. Olave,
- Joaquín Sánchez-García,
- Mamen Mateos,
- Carlos Blas,
- Jose L. López-Lorenzo,
- Daniel Lainez-Gonzalez,
- Juana Serrano,
- David Martínez-Cuadrón,
- Miguel A. Sanz,
- Pau Montesinos
Affiliations
- Tamara Castaño-Bonilla
- Hematology Department, Hospital Universitario Fundación Jiménez Díaz
- Juan M. Alonso-Dominguez
- Hematology Department, Hospital Universitario Fundación Jiménez Díaz
- Eva Barragán
- Hematology Department, Hospital Universitario La Fe de Valencia
- Rebeca Rodríguez-Veiga
- Hematology Department, Hospital Universitario La Fe de Valencia
- Claudia Sargas
- Hematology Department, Hospital Universitario La Fe de Valencia
- Cristina Gil
- Hematology Department, Hospital General de Alicante
- Carmen Chillón
- Hematology Department, Hospital Universitario de Salamanca
- María B. Vidriales
- Hematology Department, Hospital Universitario de Salamanca
- Raimundo García
- Hematology Department, Hospital General de Castellón
- Joaquín Martínez-López
- Hematology Department, Hospital Universitario Doce de Octubre, Complutense University, CNIO
- Rosa Ayala
- Hematology Department, Hospital Universitario Doce de Octubre, Complutense University, CNIO
- María J. Larrayoz
- Molecular Biology Department, Cimalab Diagnosis, Clínica Universitaria de Navarra
- Eduardo Anguita
- Hematology Department, Hospital Universitario Clínico San Carlos, Medicine Department, UCM
- Rebeca Cuello
- Hematology Department, Hospital Universitario de Valladolid
- Alberto Cantalapiedra
- Hematology Department, Hospital Universitario Río Hortega
- Estrella Carrillo
- Hematology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CISC/CIBERON)
- Elena Soria-Saldise
- Hematology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CISC/CIBERON)
- Jorge Labrador
- Hematology Department, Hospital Universitario de Burgos
- Isabel Recio
- Hematology Department, Hospital Ntra. Sra. de Sonsoles de Ávila-Complejo Asistencial Ávila
- Lorenzo Algarra
- Hematology Department, Hospital General de Albacete
- Carlos Rodríguez-Medina
- Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrín
- Cristina Bilbao-Syeiro
- Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrín
- Juan A. López-López
- Hematology Department, Hospital General Ciudad de Jaén
- Josefina Serrano
- UGC de Hematologia, Hospital U. Reina Sofia, IMIBIC, UCO, Cordoba
- Erik De Cabo
- Hematology Department, Hospital Comarcal del Bierzo
- María J. Sayas
- Hematology Department, Hospital Universitario Doctor Peset
- María T. Olave
- Hematology Department, Hospital Clínico Universitario Lozano Blesa
- Joaquín Sánchez-García
- UGC de Hematologia, Hospital U. Reina Sofia, IMIBIC, UCO, Cordoba
- Mamen Mateos
- Hematology Department, Complejo Hospitalario de Navarra
- Carlos Blas
- Hematology Department, Hospital Universitario Fundación Jiménez Díaz
- Jose L. López-Lorenzo
- Hematology Department, Hospital Universitario Fundación Jiménez Díaz
- Daniel Lainez-Gonzalez
- Instituto de Investigación Sanitaria (IIS-FJD), Hospital Universitario Fundación Jiménez Díaz
- Juana Serrano
- Instituto de Investigación Sanitaria (IIS-FJD), Hospital Universitario Fundación Jiménez Díaz
- David Martínez-Cuadrón
- Hematology Department, Hospital Universitario La Fe de Valencia
- Miguel A. Sanz
- Hematology Department, Hospital Universitario La Fe de Valencia
- Pau Montesinos
- Hematology Department, Hospital Universitario La Fe de Valencia
- DOI
- https://doi.org/10.1038/s41598-021-00050-x
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 10
Abstract
Abstract FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.
