A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients
Martínez-Cuadrón, David (Centro de Investigación Biomédica en Red de Cáncer)
Gil, Cristina (Hospital General Universitario de Alicante (Alacant, País Valencià))
Serrano, Josefina (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Rodríguez, Gabriela (Hospital General Universitario Gregorio Marañón)
Perez de Oteyza, Jaime (Hospital Universitario HM Sanchinarro (Madrid))
García-Boyero, Raimundo (Consorci Hospitalari Provincial de Castelló)
Jiménez-Bravo, Santiago (Hospital Universitario de Gran Canaria Dr. Negrín)
Vives Polo, Susana (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Vidriales, María Belén (Hospital Universitario de Salamanca)
Lavilla, Esperanza (Hospital Universitario Lucus Augusti (Lugo))
Pérez-Simón, José Antonio (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Tormo, Mar (Hospital Clínic Universitari (València))
Colorado Araujo, Mercedes (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Bergua Burgues, Juan Miguel (Hospital San Pedro de Alcántara)
López, Juan A. (Complejo Hospitalario de Jaén)
Herrera, Pilar (Hospital Universitario Ramón y Cajal (Madrid))
Hernández-Campo, Pilar (Vivia Biotech)
Gorrochategui, Julián (Vivia Biotech)
Primo, Daniel (Vivia Biotech)
Rojas, José Luis (Vivia Biotech)
Villoria, Jesús
Moscardó, Federico (Hospital Universitari i Politècnic La Fe (València))
Troconiz, Iñaki (Universidad de Navarra)
Linares Gómez, María (Hospital Universitario 12 de Octubre (Madrid))
Martínez-López, Joaquín (Hospital Universitario 12 de Octubre (Madrid))
Ballesteros, Joan (Vivia Biotech)
Sanz, Miguel A (Centro de Investigación Biomédica en Red de Cáncer)
Montesinos, Pau (Centro de Investigación Biomédica en Red de Cáncer)
Universitat Autònoma de Barcelona

Date:	2019
Abstract:	Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Acute myeloid leukemia ; Clinical correlation ; Complete remission ; Ex vivo assay ; Pharmacological profile
Published in:	Leukemia Research, Vol. 76 (january 2019) , p. 1-10, ISSN 1873-5835

DOI: 10.1016/j.leukres.2018.11.006
PMID: 30468991

10 p, 2.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles