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Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia.

Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia.

Authors :
Megías-Vericat JE
Martínez-Cuadrón D
López JM
Bergua JM
Tormo M
Serrano J
González A
de Oteyza JP
Vives S
Vidriales B
Herrera P
Vera JA
Martínez AL
de la Fuente A
Amador ML
Hernández-Rivas JÁ
Fernández MÁ
Cerveró CJ
Morillo D
Campo PH
Gorrochategui J
Primo D
Rojas JL
Guenova M
Ballesteros J
Sanz M
Montesinos P
Source :
Mediterranean journal of hematology and infectious diseases [Mediterr J Hematol Infect Dis] 2019 Mar 01; Vol. 11 (1), pp. e2019016. Date of Electronic Publication: 2019 Mar 01 (Print Publication: 2019).
Publication Year :
2019

Abstract

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.<br />Materials and Methods: 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.<br />Results: Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC <subscript>50</subscript> 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.<br />Discussion: 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.<br />Competing Interests: Competing interests: The authors have declared that no competing interests exist.

Details

Language :
English
ISSN :
2035-3006
Volume :
11
Issue :
1
Database :
MEDLINE
Journal :
Mediterranean journal of hematology and infectious diseases
Publication Type :
Academic Journal
Accession number :
30858954
Full Text :
https://doi.org/10.4084/MJHID.2019.016