Cancers (Nov 2022)
Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study
- Rosa Ayala,
- Gonzalo Carreño-Tarragona,
- Eva Barragán,
- Blanca Boluda,
- María J. Larráyoz,
- María Carmen Chillón,
- Estrella Carrillo-Cruz,
- Cristina Bilbao,
- Joaquín Sánchez-García,
- Teresa Bernal,
- David Martinez-Cuadron,
- Cristina Gil,
- Josefina Serrano,
- Carlos Rodriguez-Medina,
- Juan Bergua,
- José A. Pérez-Simón,
- María Calbacho,
- Juan M. Alonso-Domínguez,
- Jorge Labrador,
- Mar Tormo,
- Maria Luz Amigo,
- Pilar Herrera-Puente,
- Inmaculada Rapado,
- Claudia Sargas,
- Iria Vazquez,
- María J. Calasanz,
- Teresa Gomez-Casares,
- Ramón García-Sanz,
- Miguel A. Sanz,
- Joaquín Martínez-López,
- Pau Montesinos
Affiliations
- Rosa Ayala
- Hematology Department, Hospital Universitario 12 de Octubre, i+12, CNIO, CIBERONC, Complutense University, 28041 Madrid, Spain
- Gonzalo Carreño-Tarragona
- Hematology Department, Hospital Universitario 12 de Octubre, i+12, CNIO, CIBERONC, Complutense University, 28041 Madrid, Spain
- Eva Barragán
- Molecular Biology Unit, Hospital Universitari i Politécnic-IIS La Fe, 46026 Valencia, Spain
- Blanca Boluda
- Hematology Department, Hospital Universitari i Politécnic-IIS La Fe, CIBERONC, 46026 Valencia, Spain
- María J. Larráyoz
- CIMA LAB Diagnostics, Universidad de Navarra, 31008 Pamplona, Spain
- María Carmen Chillón
- Hospital Universitario de Salamanca (HUS/IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL-CSIC), 37007 Salamanca, Spain
- Estrella Carrillo-Cruz
- Hospital Universitario Virgen del Rocío, Instituto de Biomedicina (IBIS/CSIC/CIBERONC), Universidad de Sevilla, 41120 Sevilla, Spain
- Cristina Bilbao
- Hospital Universitario de Gran Canaria Dr. Negrín, 35002 Las Palmas de Gran Canaria, Spain
- Joaquín Sánchez-García
- IMIBIC, Hematology, Hospital Universitario Reina Sofía, UCO, 14004 Córdoba, Spain
- Teresa Bernal
- Hospital Universitario Central de Asturias, Instituto de Investigación del Principado de Asturias (ISPA), 33011 Oviedo, Spain
- David Martinez-Cuadron
- Hematology Department, Hospital Universitari i Politécnic-IIS La Fe, CIBERONC, 46026 Valencia, Spain
- Cristina Gil
- Hospital General Universitario de Alicante, 03010 Alicante, Spain
- Josefina Serrano
- IMIBIC, Hematology, Hospital Universitario Reina Sofía, UCO, 14004 Córdoba, Spain
- Carlos Rodriguez-Medina
- Hospital Universitario de Gran Canaria Dr. Negrín, 35002 Las Palmas de Gran Canaria, Spain
- Juan Bergua
- Hospital Universitario San Pedro de Alcántara, 10001 Cáceres, Spain
- José A. Pérez-Simón
- Hospital Universitario Virgen del Rocío, Instituto de Biomedicina (IBIS/CSIC/CIBERONC), Universidad de Sevilla, 41120 Sevilla, Spain
- María Calbacho
- Hematology Department, Hospital Universitario 12 de Octubre, i+12, CNIO, CIBERONC, Complutense University, 28041 Madrid, Spain
- Juan M. Alonso-Domínguez
- Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain
- Jorge Labrador
- Research Unit, Hematology Department, Hospital Universitario de Burgos, Universidad Isabel I, 09006 Burgos, Spain
- Mar Tormo
- Hematology Department, Hospital Clínico Universitario-INCLIVA, 46026 Valencia, Spain
- Maria Luz Amigo
- Hospital Universitario Morales Messeguer, 30008 Murcia, Spain
- Pilar Herrera-Puente
- Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
- Inmaculada Rapado
- Hematology Department, Hospital Universitario 12 de Octubre, i+12, CNIO, CIBERONC, Complutense University, 28041 Madrid, Spain
- Claudia Sargas
- Molecular Biology Unit, Hospital Universitari i Politécnic-IIS La Fe, 46026 Valencia, Spain
- Iria Vazquez
- CIMA LAB Diagnostics, Universidad de Navarra, 31008 Pamplona, Spain
- María J. Calasanz
- CIMA LAB Diagnostics, Universidad de Navarra, 31008 Pamplona, Spain
- Teresa Gomez-Casares
- Hospital Universitario de Gran Canaria Dr. Negrín, 35002 Las Palmas de Gran Canaria, Spain
- Ramón García-Sanz
- Hospital Universitario de Salamanca (HUS/IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL-CSIC), 37007 Salamanca, Spain
- Miguel A. Sanz
- Hematology Department, Hospital Universitari i Politécnic-IIS La Fe, CIBERONC, 46026 Valencia, Spain
- Joaquín Martínez-López
- Hematology Department, Hospital Universitario 12 de Octubre, i+12, CNIO, CIBERONC, Complutense University, 28041 Madrid, Spain
- Pau Montesinos
- Hematology Department, Hospital Universitari i Politécnic-IIS La Fe, CIBERONC, 46026 Valencia, Spain
- DOI
- https://doi.org/10.3390/cancers14235799
- Journal volume & issue
-
Vol. 14,
no. 23
p. 5799
Abstract
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 p 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 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.
Keywords
- FLT3–ITD mutation and ratio
- real-world outcomes
- acute myeloid leukemia (AML)
- prognosis
- outcome
- death