Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia
| Autor: | Megías-Vericat, Juan Eduardo, Martínez-Cuadrón, David, López, Joaquín Martínez, Bergua, Juan Miguel, Tormo, Mar, Serrano, Josefina, González, Ataulfo, de Oteyza, Jaime Pérez, Vives Polo, Susana, Vidriales, Belén, Herrera, Pilar, Vera, Juan Antonio, Martínez, Aurelio López, de la Fuente, Adolfo, Amador, Ma Lourdes, Hernández-Rivas, José-Ángel, Fernández, Ma Ángeles, Cerveró, Carlos Javier, Morillo, Daniel, Campo, Pilar Hernández, Gorrochategui, Julián, Primo, Daniel, Rojas, José Luis, Guenova, Margarita, Ballesteros, Joan, Sanz, Miguel, Montesinos, Pau, Universitat Autònoma de Barcelona |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Anthracycline Daunorubicin Pharmacology 03 medical and health sciences 0302 clinical medicine Medicine Idarubicin Potency ex-vivo test Mitoxantrone Acute myeloid leukemia business.industry lcsh:RC633-647.5 Myeloid leukemia Hematology lcsh:Diseases of the blood and blood-forming organs Ex-vivo test Personalized medicine 030104 developmental biology Infectious Diseases 030220 oncology & carcinogenesis Cytarabine Original Article business Ex vivo medicine.drug |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Mediterranean Journal of Hematology and Infectious Diseases Mediterranean journal of hematology and infectious diseases r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname Mediterranean Journal of Hematology and Infectious Diseases, Vol 11, Iss 1, Pp e2019016-e2019016 (2019) r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| ISSN: | 2035-3006 |
| Popis: | 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. 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. RESULTS: 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. DISCUSSION: 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. |
| Databáze: | OpenAIRE |
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