Impact of FLT3-ITD mutation status and its ratio in a cohort of 2901 patients undergoing upfront intensive chemotherapy: a PETHEMA registry study

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dc.contributor.authorAyala, Rosa
dc.contributor.authorCarreño-Tarragona, Gonzalo
dc.contributor.authorBarragán, Eva
dc.contributor.authorBoluda, Blanca
dc.contributor.authorLarráyoz, María José
dc.contributor.authorChillón, María Carmen
dc.contributor.authorCarrillo-Cruz, Estrella
dc.contributor.authorBilbao, Cristina
dc.contributor.authorSánchez-García, Joaquín
dc.contributor.authorBernal, Teresa
dc.contributor.authorMartínez-Cuadrón, David
dc.contributor.authorGil, Cristina
dc.contributor.authorSerrano, Josefina
dc.contributor.authorRodríguez-Medina, Carlos
dc.contributor.authorBergua, Juan
dc.contributor.authorPérez-Simón, José A.
dc.contributor.authorCalbacho, María
dc.contributor.authorAlonso-Domínguez, Juan M.
dc.contributor.authorLabrador, Jorge
dc.contributor.authorTormo, Mar
dc.contributor.authorAmigo, María Luz
dc.contributor.authorHerrera-Puente, Pilar
dc.contributor.authorRapado, Inmaculada
dc.contributor.authorSargas, Claudia
dc.contributor.authorVázquez Urio, Iria
dc.contributor.authorCalasanz, María José
dc.contributor.authorGómez-Casares, Teresa
dc.contributor.authorGarcía-Sanz, Ramón
dc.contributor.authorSanz, Miguel A.
dc.contributor.authorMartínez-López, Joaquín
dc.contributor.authorMontesinos, Pau
dc.contributor.departmentCienciases_ES
dc.contributor.departmentZientziakeu
dc.date.accessioned2024-11-11T10:11:46Z
dc.date.available2024-11-11T10:11:46Z
dc.date.issued2022-11-24
dc.date.updated2024-11-11T09:54:48Z
dc.description.abstractFLT3-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.en
dc.description.sponsorshipWe 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 2018/001, and by the Instituto de Investigación Hospital 12 de Octubre (IMAS12). A complete list of the institutions and clinicians participating in the PETHEMA epidemiologic registry of acute myeloid leukemia and acute promyelocytic leukemia appears in the Supplementary Material.
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dc.format.mimetypeapplication/zipen
dc.identifier.citationAyala, R., Carreño-Tarragona, G., Barragán, E., Boluda, B., Larráyoz, M. J., Chillón, M. C., Carrillo-Cruz, E., Bilbao, C., Sánchez-García, J., Bernal, T., Martinez-Cuadron, D., Gil, C., Serrano, J., Rodriguez-Medina, C., Bergua, J., Pérez-Simón, J. A., Calbacho, M., Alonso-Domínguez, J. M., Labrador, J., Tormo, M., Amigo, M. L., Herrera-Puente, P., Rapado, I., Sargas, C., Vazquez, I., Calasanz, M. J., Gomez-Casares, T., García-Sanz, R., Sanz, M. A., Martínez-López, J., Montesinos, P. (2022). Impact of FLT3-ITD mutation status and its ratio in a cohort of 2901 patients undergoing upfront intensive chemotherapy: a PETHEMA registry study. Cancers, 14(23), 1-17. https://doi.org/10.3390/cancers14235799.
dc.identifier.doi10.3390/cancers14235799
dc.identifier.issn2072-6694
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/52480
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofCancers (2022), vol. 14, núm. 23, 5799
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F01518/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F00730/ES/
dc.relation.publisherversionhttps://doi.org/10.3390/cancers14235799
dc.rights© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAcute myeloid leukemia (AML)en
dc.subjectDeathen
dc.subjectFLT3-ITD mutation and ratioen
dc.subjectOutcomeen
dc.subjectPrognosisen
dc.subjectReal-world outcomesen
dc.subjectRelapseen
dc.subjectSurvivalen
dc.titleImpact of FLT3-ITD mutation status and its ratio in a cohort of 2901 patients undergoing upfront intensive chemotherapy: a PETHEMA registry studyen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication3762d67a-d18f-4f29-8eee-8b4c20793cd8
relation.isAuthorOfPublication.latestForDiscovery3762d67a-d18f-4f29-8eee-8b4c20793cd8

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