RT Journal Article
T1 Improving the prediction of acute myeloid leukaemia outcomes by complementing mutational profiling with ex vivo chemosensitivity
A1 Onecha, Esther
A1 Ruiz‐Heredia, Yanira
A1 Martínez‐Cuadrón, David
A1 Barragán, Eva
A1 Martínez Sánchez, María Del Pilar
A1 Linares Gómez, María
A1 Rapado, Inmaculada
A1 Perez‐Oteyza, Jaime
A1 Magro, Elena
A1 Herrera, Pilar
A1 Rojas, José Luis
A1 Gorrochategui, Julián
A1 Villoria, Jesús
A1 Boluda, Blanca
A1 Sargas, Claudia
A1 Ballesteros, Joan
A1 Montesinos, Pau
A1 Martínez López, Joaquín
A1 Ayala Díaz, Rosa María
AB Refractoriness to induction therapy and relapse after complete remission are the leading causes of death in patients with acute myeloid leukaemia(AML). This study focussed on the prediction of response to standard induction therapy and outcome of patients with AML using a combinedstrategy of mutational profiling by next-generation sequencing (NGS, n = 190) and ex vivo PharmaFlow testing (n = 74) for the 10 most widelyused drugs for AML induction therapy, in a cohort of adult patients uniformly treated according to Spanish PETHEMA guidelines. We identifiedan adverse mutational profile (EZH2, KMT2A, U2AF1 and/or TP53 mutations) that carries a greater risk of death [hazard ratio (HR): 3 29,P < 0 0001]. A high correlation was found between the ex vivo PharmaFlow results and clinical induction response (69%). Clinical correlation analysis showed that the pattern of multiresistance revealed by ex vivo PharmaFlow identified patients with a high risk of death (HR: 2 58). Patients with mutation status also ran a high risk (HR 4 19), and the risk was increased further in patients with both adverse profiles (HR 4 82). We have developed a new score based on NGS and ex vivo drug testing for AML patients that improves upon current prognostic risk stratification and allows clinicians to tailor treatments to minimise drug resistance.
SN 0007-1048
SN 1365-2141
YR 2020
FD 2020-02-18
LK https://hdl.handle.net/20.500.14352/102749
UL https://hdl.handle.net/20.500.14352/102749
LA eng
NO Instituto de Salud Carlos III
NO CRIS against Cancer foundation
NO Spanish Ministry of Economy and Competitiveness
DS Docta Complutense
RD 9 abr 2025