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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2020
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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. |
format | Online Article Text |
id | pubmed-7289527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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