TY - JOUR AU - Megias-Vericat, Juan Eduardo AU - Martínez-Cuadrón, David AU - Martínez López, Joaquin AU - Bergua, Juan Miguel AU - Tormo, Mar AU - Serrano, Josefina AU - González, Ataulfo AU - Pérez de Oteyza, Jaime AU - Vives, Susana AU - Vidriales, Belen AU - Herrera, Pilar AU - Vera, Juan Antonio AU - López Martínez, Aurelio AU - De la Fuente, Adolfo AU - Amador, María Lourdes AU - Hernández-Rivas, José Ángel AU - Fernández, María Ángeles AU - Cerveró, Carlos Javier AU - Morillo, Daniel AU - Hernández Campo, Pilar AU - Gorrochategui, Julián AU - Primo, Daniel AU - Rojas, José Luis AU - Guenova, Margarita AU - Ballesteros, Joan AU - Sanz, Miguel Ángel AU - Montesinos, Pau PY - 2019/02/26 Y2 - 2024/03/29 TI - DIFFERENCES IN EX-VIVO CHEMOSENSITIVITY TO ANTHRACYCLINES IN FIRST LINE ACUTE MYELOID LEUKEMIA JF - Mediterranean Journal of Hematology and Infectious Diseases JA - Mediterr J Hematol Infect Dis VL - 11 IS - 1 SE - Original Articles DO - 10.4084/mjhid.2019.016 UR - https://www.mjhid.org/mjhid/article/view/2019.016 SP - e2019016 AB - <h4>BACKGROUND: 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.</h4><p><strong>MATERIALS AND METHODS:</strong> Using an <em>ex vivo</em> test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone. &nbsp;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. <em>Ex vivo</em> 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.</p><p><strong>RESULTS: </strong>Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC<sub>50</sub> 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.</p><p><strong>DISCUSSION: </strong>A third of the patients could benefit of the use of this test in the first line induction therapy selection, although it should be confirmed in a clinical trial specifically designed.</p> ER -