Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783497157710446592
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
work_keys_str_mv AT fenwarthlaurene clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT duployeznicolas clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT thomasxavier clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT boisselnicolas clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT geffroysandrine clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT marceaurenautalice clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT caillotdenis clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT raffouxemmanuel clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT lemasleemilie clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT marolleaujeanpierre clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT berthonceline clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT cheokmeylingh clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT peyrouzepauline clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT pigneuxarnaud clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT veynorbert clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT cellilebraskarine clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT terrechristine clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT preudhommeclaude clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype
AT dombretherve clofarabineimprovesrelapsefreesurvivalofacutemyeloidleukemiainyoungeradultswithmicrocomplexkaryotype