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Clofarabine Improves Relapse-Free Survival of Acute Myeloid Leukemia in Younger Adults with Micro-Complex Karyotype
Acute myeloid leukemia (AML) encompasses heterogeneous entities with dismal outcomes. Intermediate and unfavorable-risk AML represent the most difficult-to-treat entities. We recently reported the benefit of the clofarabine-based consolidation (CLARA) regimen compared to the standard high-dose cytar...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017244/ https://www.ncbi.nlm.nih.gov/pubmed/31905904 http://dx.doi.org/10.3390/cancers12010088 |
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author | Fenwarth, Laurène Duployez, Nicolas Thomas, Xavier Boissel, Nicolas Geffroy, Sandrine Marceau-Renaut, Alice Caillot, Denis Raffoux, Emmanuel Lemasle, Emilie Marolleau, Jean-Pierre Berthon, Céline Cheok, Meyling H. Peyrouze, Pauline Pigneux, Arnaud Vey, Norbert Celli-Lebras, Karine Terré, Christine Preudhomme, Claude Dombret, Hervé |
author_facet | Fenwarth, Laurène Duployez, Nicolas Thomas, Xavier Boissel, Nicolas Geffroy, Sandrine Marceau-Renaut, Alice Caillot, Denis Raffoux, Emmanuel Lemasle, Emilie Marolleau, Jean-Pierre Berthon, Céline Cheok, Meyling H. Peyrouze, Pauline Pigneux, Arnaud Vey, Norbert Celli-Lebras, Karine Terré, Christine Preudhomme, Claude Dombret, Hervé |
author_sort | Fenwarth, Laurène |
collection | PubMed |
description | Acute myeloid leukemia (AML) encompasses heterogeneous entities with dismal outcomes. Intermediate and unfavorable-risk AML represent the most difficult-to-treat entities. We recently reported the benefit of the clofarabine-based consolidation (CLARA) regimen compared to the standard high-dose cytarabine (HDAC) regimen in younger AML patients. Here, we aimed at assessing the clinical significance of single-nucleotide polymorphism (SNP)-array alterations and their interactions with chemotherapy regimens. A SNP-array was successfully performed in 187 out of the 221 intent-to-treat patients (CLARA arm: n = 92 patients, HDAC arm: n = 95 patients). The CLARA regimen did not significantly improve relapse-free survival (RFS) among patients who displayed a complex karyotype when compared to the HDAC regimen (4-year RFS (4y-RFS): 36.4% vs. 18.8%, respectively; p = 0.134). Defining micro-complex karyotypes from at least four SNP-array lesions enabled us to refine and enlarge the subset of adverse patients. In such patients, the CLARA regimen significantly improved RFS compared to the HDAC regimen (4y-RFS: 44.4% vs. 13.8%, respectively; p = 0.004). From our study cohort, 8% of patients displayed TP53 mutations, which were associated with an impaired RFS (4y-RFS: 20.0% vs 43.7%; p = 0.029). In a multivariate analysis, micro-complex karyotypes remained the sole poor prognostic factor in the HDAC arm (hazard ratio (HR) = 2.324 (95% confidence interval (CI) = 1.337–4.041), p = 0.003). The SNP array represents a powerful and reproductive approach to refine adverse AML patients that may benefit from alternative consolidation regimens. |
format | Online Article Text |
id | pubmed-7017244 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70172442020-02-28 Clofarabine Improves Relapse-Free Survival of Acute Myeloid Leukemia in Younger Adults with Micro-Complex Karyotype Fenwarth, Laurène Duployez, Nicolas Thomas, Xavier Boissel, Nicolas Geffroy, Sandrine Marceau-Renaut, Alice Caillot, Denis Raffoux, Emmanuel Lemasle, Emilie Marolleau, Jean-Pierre Berthon, Céline Cheok, Meyling H. Peyrouze, Pauline Pigneux, Arnaud Vey, Norbert Celli-Lebras, Karine Terré, Christine Preudhomme, Claude Dombret, Hervé Cancers (Basel) Brief Report Acute myeloid leukemia (AML) encompasses heterogeneous entities with dismal outcomes. Intermediate and unfavorable-risk AML represent the most difficult-to-treat entities. We recently reported the benefit of the clofarabine-based consolidation (CLARA) regimen compared to the standard high-dose cytarabine (HDAC) regimen in younger AML patients. Here, we aimed at assessing the clinical significance of single-nucleotide polymorphism (SNP)-array alterations and their interactions with chemotherapy regimens. A SNP-array was successfully performed in 187 out of the 221 intent-to-treat patients (CLARA arm: n = 92 patients, HDAC arm: n = 95 patients). The CLARA regimen did not significantly improve relapse-free survival (RFS) among patients who displayed a complex karyotype when compared to the HDAC regimen (4-year RFS (4y-RFS): 36.4% vs. 18.8%, respectively; p = 0.134). Defining micro-complex karyotypes from at least four SNP-array lesions enabled us to refine and enlarge the subset of adverse patients. In such patients, the CLARA regimen significantly improved RFS compared to the HDAC regimen (4y-RFS: 44.4% vs. 13.8%, respectively; p = 0.004). From our study cohort, 8% of patients displayed TP53 mutations, which were associated with an impaired RFS (4y-RFS: 20.0% vs 43.7%; p = 0.029). In a multivariate analysis, micro-complex karyotypes remained the sole poor prognostic factor in the HDAC arm (hazard ratio (HR) = 2.324 (95% confidence interval (CI) = 1.337–4.041), p = 0.003). The SNP array represents a powerful and reproductive approach to refine adverse AML patients that may benefit from alternative consolidation regimens. MDPI 2019-12-30 /pmc/articles/PMC7017244/ /pubmed/31905904 http://dx.doi.org/10.3390/cancers12010088 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Report Fenwarth, Laurène Duployez, Nicolas Thomas, Xavier Boissel, Nicolas Geffroy, Sandrine Marceau-Renaut, Alice Caillot, Denis Raffoux, Emmanuel Lemasle, Emilie Marolleau, Jean-Pierre Berthon, Céline Cheok, Meyling H. Peyrouze, Pauline Pigneux, Arnaud Vey, Norbert Celli-Lebras, Karine Terré, Christine Preudhomme, Claude Dombret, Hervé Clofarabine Improves Relapse-Free Survival of Acute Myeloid Leukemia in Younger Adults with Micro-Complex Karyotype |
title | Clofarabine Improves Relapse-Free Survival of Acute Myeloid Leukemia in Younger Adults with Micro-Complex Karyotype |
title_full | Clofarabine Improves Relapse-Free Survival of Acute Myeloid Leukemia in Younger Adults with Micro-Complex Karyotype |
title_fullStr | Clofarabine Improves Relapse-Free Survival of Acute Myeloid Leukemia in Younger Adults with Micro-Complex Karyotype |
title_full_unstemmed | Clofarabine Improves Relapse-Free Survival of Acute Myeloid Leukemia in Younger Adults with Micro-Complex Karyotype |
title_short | Clofarabine Improves Relapse-Free Survival of Acute Myeloid Leukemia in Younger Adults with Micro-Complex Karyotype |
title_sort | clofarabine improves relapse-free survival of acute myeloid leukemia in younger adults with micro-complex karyotype |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017244/ https://www.ncbi.nlm.nih.gov/pubmed/31905904 http://dx.doi.org/10.3390/cancers12010088 |
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