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Reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia

A substantial segment of patients with acute myeloid leukemia (AML) will relapse following an initial response to induction therapy or will prove to be primary refractory. High-dose cytarabine and mitoxantrone (HiDAC/MITO) is an established salvage therapy for these patients. We studied all adult pa...

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Autores principales: Canaani, Jonathan, Nagar, Meital, Heering, Gabriel, Gefen, Chen, Yerushalmi, Ronit, Shem-Tov, Noga, Volchek, Yulia, Merkel, Drorit, Avigdor, Abraham, Shimoni, Avichai, Amariglio, Ninette, Rechavi, Gidi, Nagler, Arnon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289527/
https://www.ncbi.nlm.nih.gov/pubmed/32577167
http://dx.doi.org/10.18632/oncotarget.27618
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author Canaani, Jonathan
Nagar, Meital
Heering, Gabriel
Gefen, Chen
Yerushalmi, Ronit
Shem-Tov, Noga
Volchek, Yulia
Merkel, Drorit
Avigdor, Abraham
Shimoni, Avichai
Amariglio, Ninette
Rechavi, Gidi
Nagler, Arnon
author_facet Canaani, Jonathan
Nagar, Meital
Heering, Gabriel
Gefen, Chen
Yerushalmi, Ronit
Shem-Tov, Noga
Volchek, Yulia
Merkel, Drorit
Avigdor, Abraham
Shimoni, Avichai
Amariglio, Ninette
Rechavi, Gidi
Nagler, Arnon
author_sort Canaani, Jonathan
collection PubMed
description A substantial segment of patients with acute myeloid leukemia (AML) will relapse following an initial response to induction therapy or will prove to be primary refractory. High-dose cytarabine and mitoxantrone (HiDAC/MITO) is an established salvage therapy for these patients. We studied all adult patients with relapsed/refractory (R/R) AML who were treated with HiDAC/MITO in our center between the years 2008-2017. To determine whether responding patients harbored a unique molecular signature, we performed targeted next-generation sequencing (NGS) on a subset of patients. The study cohort consisted of 172 patients with a median age of 54 years (range 18–77). The composite complete remission rate was 58%; 11 patients (6%) died during salvage therapy. Median survival was 11.4 months with a 1-year survival rate of 48%. In multivariate analysis favorable risk cytogenetics [Odds ratio (OR)=0.34, confidence interval (CI) 95%, 0.17–0.68; P = 0.002], and de-novo AML (OR = 0.4, CI 95%, 0.16–0.98; P = 0.047) were independently associated with a favorable response. Patients who attained a complete remission had a median survival of 43.7 months compared with 5.2 months for refractory patients (p < 0.0001). Neither the FLT3-ITD and NPM1 mutational status nor the indication for salvage therapy significantly impacted on the response to HiDAC/MITO salvage. NGS analysis identified 20 different mutations across the myeloid gene spectrum with a distinct TP53 signature detected in non-responding patients. HiDAC/MITO is an effective salvage regimen in R/R AML, however patients with adverse cytogenetics or secondary disease may not benefit as much from this approach.
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spelling pubmed-72895272020-06-22 Reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia Canaani, Jonathan Nagar, Meital Heering, Gabriel Gefen, Chen Yerushalmi, Ronit Shem-Tov, Noga Volchek, Yulia Merkel, Drorit Avigdor, Abraham Shimoni, Avichai Amariglio, Ninette Rechavi, Gidi Nagler, Arnon Oncotarget Research Paper A substantial segment of patients with acute myeloid leukemia (AML) will relapse following an initial response to induction therapy or will prove to be primary refractory. High-dose cytarabine and mitoxantrone (HiDAC/MITO) is an established salvage therapy for these patients. We studied all adult patients with relapsed/refractory (R/R) AML who were treated with HiDAC/MITO in our center between the years 2008-2017. To determine whether responding patients harbored a unique molecular signature, we performed targeted next-generation sequencing (NGS) on a subset of patients. The study cohort consisted of 172 patients with a median age of 54 years (range 18–77). The composite complete remission rate was 58%; 11 patients (6%) died during salvage therapy. Median survival was 11.4 months with a 1-year survival rate of 48%. In multivariate analysis favorable risk cytogenetics [Odds ratio (OR)=0.34, confidence interval (CI) 95%, 0.17–0.68; P = 0.002], and de-novo AML (OR = 0.4, CI 95%, 0.16–0.98; P = 0.047) were independently associated with a favorable response. Patients who attained a complete remission had a median survival of 43.7 months compared with 5.2 months for refractory patients (p < 0.0001). Neither the FLT3-ITD and NPM1 mutational status nor the indication for salvage therapy significantly impacted on the response to HiDAC/MITO salvage. NGS analysis identified 20 different mutations across the myeloid gene spectrum with a distinct TP53 signature detected in non-responding patients. HiDAC/MITO is an effective salvage regimen in R/R AML, however patients with adverse cytogenetics or secondary disease may not benefit as much from this approach. Impact Journals LLC 2020-06-09 /pmc/articles/PMC7289527/ /pubmed/32577167 http://dx.doi.org/10.18632/oncotarget.27618 Text en Copyright: © 2020 Canaani et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Canaani, Jonathan
Nagar, Meital
Heering, Gabriel
Gefen, Chen
Yerushalmi, Ronit
Shem-Tov, Noga
Volchek, Yulia
Merkel, Drorit
Avigdor, Abraham
Shimoni, Avichai
Amariglio, Ninette
Rechavi, Gidi
Nagler, Arnon
Reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia
title Reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia
title_full Reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia
title_fullStr Reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia
title_full_unstemmed Reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia
title_short Reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia
title_sort reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289527/
https://www.ncbi.nlm.nih.gov/pubmed/32577167
http://dx.doi.org/10.18632/oncotarget.27618
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