Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia
Megías-Vericat, Juan Eduardo (Hospital Universitari i Politècnic La Fe (València))
Martínez-Cuadrón, David (Centro de Investigación Biomédica en Red de Cáncer)
López, Joaquín Martínez (Hospital Universitario 12 de Octubre (Madrid))
Bergua Burgues, Juan Miguel (Hospital San Pedro de Alcántara)
Tormo, Mar (Hospital Clínic Universitari (València))
Serrano, Josefina (Hospital Universitario Reina Sofía (Còrdova, Espanya))
González, Ataulfo (Hospital Clínico San Carlos (Madrid))
Perez de Oteyza, Jaime (Hospital Universitario HM Sanchinarro (Madrid))
Vives Polo, Susana (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Vidriales, Belén (Complejo Asistencial Universitario de Salamanca)
Herrera, Pilar (Hospital Universitario Ramón y Cajal (Madrid))
Vera, Juan Antonio (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Martínez, Aurelio López (Hospital Arnau de Vilanova (Lleida, Catalunya))
De La Fuente, Adolfo (MD Anderson Cancer Center, Madrid, Spain)
Amador, Ma Lourdes (Hospital Montecelo)
Hernández Rivas, José Ángel (Hospital Universitario Infanta Leonor)
Fernández, Ma Ángeles (Hospital Xeral-Cíes (Vigo, Galícia))
Cervero, Carlos (Hospital Virgen de La Luz (Cuenca))
Morillo, Daniel (Hospital Universitario Fundación Jiménez Díaz)
Campo, Pilar Hernández (Vivia Biotech, Tres Cantos, Madrid, Spain)
Gorrochategui, Julián (Vivia Biotech, Tres Cantos, Madrid, Spain)
Primo, Daniel (Vivia Biotech, Tres Cantos, Madrid, Spain)
Rojas, José Luis (Vivia Biotech, Tres Cantos, Madrid, Spain)
Guenova, Margarita (Specialized Hospital for Active Treatment of Hematological Diseases, Sofía, Bulgaria)
Ballesteros, Joan (Vivia Biotech, Tres Cantos, Madrid, Spain)
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:	Induction schedules in acute myeloid leukemia (AML) are based on combinations of cytarabine and anthracyclines. The choice of the anthracycline employed has been widely studied in multiple clinical trials showing similar complete remission rates. Using an ex vivo test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone. Bone marrow (BM) samples of 198 AML patients were incubated for 48 hours in 96 well plates, each well containing different drugs or drug combinations at different concentrations. Ex vivo drug sensitivity analysis was made using the PharmaFlow platform maintaining the BM microenvironment. Drug response was evaluated as depletion of AML blast cells in each well after incubation. Annexin V-FITC was used to quantify the ability of the drugs to induce apoptosis, and pharmacological responses were calculated using pharmacokinetic population models. Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC with idarubicin (p=1. 462E-06), whereas the interpatient variability of either drug was large. To identify those cases of selective sensitivity to anthracyclines, potency was compared, in terms of area under the curve. Differences in anthracycline monotherapy potency greater than 30% from 3 pairwise comparisons were identified in 28. 3% of samples. Furthermore, different sensitivity was detected in 8. 2% of patients comparing combinations of cytarabine and anthracyclines. A third of the patients could benefit from the use of this test in the first line induction therapy selection, although it should be confirmed in a clinical trial specifically designed.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Anthracycline ; Ex-vivo test ; Idarubicin ; Daunorubicin ; Mitoxantrone ; Acute myeloid leukemia ; Personalized medicine
Published in:	Mediterranean Journal of Hematology and Infectious Diseases, Vol. 11 (march 2019) , ISSN 2035-3006

DOI: 10.4084/MJHID.2019.016
PMID: 30858954

11 p, 623.1 KB

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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
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Articles > Published articles