Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine
Abstract: The prognostic impact of monocytic differentiation in patients with acute myeloid leukemia (AML) receiving venetoclax (Ven) and azacitidine (Aza) remains unclear. In a prospective cohort of 86 newly diagnosed patients with AML treated with Ven-Aza, we used multiparametric flow cytometry (M...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925002332 |
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| author | Lin-Pierre Zhao Typhaine Dumas-Rivero Lauren Barette Lorea Aguinaga Arij Cheffai Clémentine Chauvel Reinaldo Dal Bello Emmanuel Raffoux Emmanuelle Clappier Matthieu Duchmann Pierre Fenaux Pierre Lemaire Stephanie Mathis Marie Sébert Lionel Adès Raphaël Itzykson |
| author_facet | Lin-Pierre Zhao Typhaine Dumas-Rivero Lauren Barette Lorea Aguinaga Arij Cheffai Clémentine Chauvel Reinaldo Dal Bello Emmanuel Raffoux Emmanuelle Clappier Matthieu Duchmann Pierre Fenaux Pierre Lemaire Stephanie Mathis Marie Sébert Lionel Adès Raphaël Itzykson |
| author_sort | Lin-Pierre Zhao |
| collection | DOAJ |
| description | Abstract: The prognostic impact of monocytic differentiation in patients with acute myeloid leukemia (AML) receiving venetoclax (Ven) and azacitidine (Aza) remains unclear. In a prospective cohort of 86 newly diagnosed patients with AML treated with Ven-Aza, we used multiparametric flow cytometry (MFC) to define monoblasts as AML blasts coexpressing ≥2 monocytic markers (CD4, CD36, and CD64) per European LeukemiaNet (ELN) guidelines. Patients with higher monoblasts/CD45+ proportions had lower complete response rates (odds ratio, 0.24; P = .005) and significantly shorter overall survival (OS; 4.0 vs 14.9 months; P = .003). A ≥10% monoblasts/CD45+ threshold, identified via maximally selected rank statistics, stratified patients into monoblasthigh (≥10%) and monoblastlow (<10%) groups. MFC reclassified 20% of French-American-British (FAB) non-M4/5 and 15% of FAB M4/5 cases into monoblasthigh and monoblastlow groups, respectively. Multivariable analysis confirmed monoblasthigh status as an independent adverse prognostic factor for OS (hazard ratio [HR], 1.95; P = .023), with a particularly strong impact in ELN 2024 favorable-risk patients (HR, 2.81; P = .024). Our findings highlight monocytic differentiation, assessed via MFC, as a key predictor of Ven-Aza resistance and poor survival, independent of genetic classification. Given its availability in routine diagnostics, MFC-based monocytic assessment could improve AML risk stratification and treatment decisions in patients eligible for less intensive therapies. This trial was registered at www.clinicaltrials.gov as #NCT05326919. |
| format | Article |
| id | doaj-art-d421be660d114bcfab4ccbc7eb48292c |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-d421be660d114bcfab4ccbc7eb48292c2025-08-20T03:51:29ZengElsevierBlood Advances2473-95292025-07-019143556356510.1182/bloodadvances.2024015734Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidineLin-Pierre Zhao0Typhaine Dumas-Rivero1Lauren Barette2Lorea Aguinaga3Arij Cheffai4Clémentine Chauvel5Reinaldo Dal Bello6Emmanuel Raffoux7Emmanuelle Clappier8Matthieu Duchmann9Pierre Fenaux10Pierre Lemaire11Stephanie Mathis12Marie Sébert13Lionel Adès14Raphaël Itzykson15Université Paris Cité, INSERM UMR 1342, Institut de Recherche Saint-Louis, Paris, France; Leukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Seniors, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceUniversité Paris Cité, INSERM UMR 1342, Institut de Recherche Saint-Louis, Paris, France; Leukemia Institute Paris Saint-Louis, Paris, France; Laboratoire d’Hématologie, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceLeukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Seniors, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceLeukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Seniors, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceLeukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Seniors, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceLeukemia Institute Paris Saint-Louis, Paris, France; Laboratoire d’Hématologie, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceLeukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Adulte, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceLeukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Adulte, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceUniversité Paris Cité, INSERM UMR 1342, Institut de Recherche Saint-Louis, Paris, France; Leukemia Institute Paris Saint-Louis, Paris, France; Laboratoire d’Hématologie, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceUniversité Paris Cité, INSERM UMR 1342, Institut de Recherche Saint-Louis, Paris, France; Leukemia Institute Paris Saint-Louis, Paris, France; Laboratoire d’Hématologie, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceUniversité Paris Cité, INSERM UMR 1342, Institut de Recherche Saint-Louis, Paris, France; Leukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Seniors, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceLeukemia Institute Paris Saint-Louis, Paris, France; Laboratoire d’Hématologie, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceLeukemia Institute Paris Saint-Louis, Paris, France; Laboratoire d’Hématologie, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceUniversité Paris Cité, INSERM UMR 1342, Institut de Recherche Saint-Louis, Paris, France; Leukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Seniors, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceUniversité Paris Cité, INSERM UMR 1342, Institut de Recherche Saint-Louis, Paris, France; Leukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Seniors, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, FranceUniversité Paris Cité, INSERM UMR 1342, Institut de Recherche Saint-Louis, Paris, France; Leukemia Institute Paris Saint-Louis, Paris, France; Service Hématologie Adulte, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, France; Correspondence: Raphaël Itzykson, Service Hématologie Adultes, Hôpital Saint-Louis, 1 Ave Claude Vellefaux, F-75010 Paris, France;Abstract: The prognostic impact of monocytic differentiation in patients with acute myeloid leukemia (AML) receiving venetoclax (Ven) and azacitidine (Aza) remains unclear. In a prospective cohort of 86 newly diagnosed patients with AML treated with Ven-Aza, we used multiparametric flow cytometry (MFC) to define monoblasts as AML blasts coexpressing ≥2 monocytic markers (CD4, CD36, and CD64) per European LeukemiaNet (ELN) guidelines. Patients with higher monoblasts/CD45+ proportions had lower complete response rates (odds ratio, 0.24; P = .005) and significantly shorter overall survival (OS; 4.0 vs 14.9 months; P = .003). A ≥10% monoblasts/CD45+ threshold, identified via maximally selected rank statistics, stratified patients into monoblasthigh (≥10%) and monoblastlow (<10%) groups. MFC reclassified 20% of French-American-British (FAB) non-M4/5 and 15% of FAB M4/5 cases into monoblasthigh and monoblastlow groups, respectively. Multivariable analysis confirmed monoblasthigh status as an independent adverse prognostic factor for OS (hazard ratio [HR], 1.95; P = .023), with a particularly strong impact in ELN 2024 favorable-risk patients (HR, 2.81; P = .024). Our findings highlight monocytic differentiation, assessed via MFC, as a key predictor of Ven-Aza resistance and poor survival, independent of genetic classification. Given its availability in routine diagnostics, MFC-based monocytic assessment could improve AML risk stratification and treatment decisions in patients eligible for less intensive therapies. This trial was registered at www.clinicaltrials.gov as #NCT05326919.http://www.sciencedirect.com/science/article/pii/S2473952925002332 |
| spellingShingle | Lin-Pierre Zhao Typhaine Dumas-Rivero Lauren Barette Lorea Aguinaga Arij Cheffai Clémentine Chauvel Reinaldo Dal Bello Emmanuel Raffoux Emmanuelle Clappier Matthieu Duchmann Pierre Fenaux Pierre Lemaire Stephanie Mathis Marie Sébert Lionel Adès Raphaël Itzykson Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine Blood Advances |
| title | Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine |
| title_full | Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine |
| title_fullStr | Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine |
| title_full_unstemmed | Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine |
| title_short | Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine |
| title_sort | prognostic significance of monocytic like phenotype in patients with aml treated with venetoclax and azacytidine |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925002332 |
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