RT Journal Article
T1 Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia.
A1 Megías-Vericat, Juan Eduardo
A1 Martínez-Cuadrón, David
A1 López, Joaquín Martínez
A1 Bergua, Juan Miguel
A1 Tormo, Mar
A1 Serrano, Josefina
A1 González, Ataulfo
A1 de Oteyza, Jaime Pérez
A1 Vives, Susana
A1 Vidriales, Belén
A1 Herrera, Pilar
A1 Vera, Juan Antonio
A1 Martínez, Aurelio López
A1 de la Fuente, Adolfo
A1 Amador, Ma Lourdes
A1 Hernández-Rivas, José-Ángel
A1 Fernández, Ma Ángeles
A1 Cerveró, Carlos Javier
A1 Morillo, Daniel
A1 Campo, Pilar Hernández
A1 Gorrochategui, Julián
A1 Primo, Daniel
A1 Rojas, José Luis
A1 Guenova, Margarita
A1 Ballesteros, Joan
A1 Sanz, Miguel
A1 Montesinos, Pau
K1 Acute myeloid leukemia
K1 Anthracycline
K1 Daunorubicin
K1 Idarubicin
K1 Mitoxantrone
K1 Personalized medicine
K1 ex-vivo test
AB 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 EC50 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.
SN 2035-3006
YR 2019
FD 2019-03-01
LK https://hdl.handle.net/10668/27685
UL https://hdl.handle.net/10668/27685
LA en
DS RISalud
RD Apr 18, 2025