Prognostic Significance of Monocytic-like Phenotype in AML patients treated with Venetoclax and Azacytidine.

IF 7.4 1区医学 Q1 HEMATOLOGY

Blood advances Pub Date : 2025-04-18 DOI:10.1182/bloodadvances.2024015734

Lin-Pierre Zhao, Typhaine Dumas-Rivero, Lauren Barette, Lorea Aguinaga, Arij Cheffai, Clementine Chauvel, Reinaldo Dal Bello, Emmanuel Raffoux, Emmanuelle Clappier, Matthieu Duchmann, Pierre Fenaux, Pierre Lemaire, Stephanie Mathis, Marie Sébert, Lionel Adès, Raphael A Itzykson

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引用次数: 0

Abstract

The prognostic impact of monocytic differentiation in AML patients receiving Venetoclax (Ven) and azacitidine (Aza) remains unclear. In a prospective cohort of 86 newly diagnosed AML patients treated with Ven-Aza, we used multiparametric flow cytometry (MFC) to define mono-blasts as AML blasts co-expressing ≥2 monocytic markers (CD4, CD36, CD64) per ELN guidelines. Patients with higher mono-blasts/CD45+ proportions had lower complete response rates (OR=0.24, p=0.005) and significantly shorter overall survival (OS, 4.0 versus 14.9 months, p=0.003). A ≥10% mono-blasts/CD45+ threshold, identified via maximally selected rank statistics, stratified patients into mono-blasthigh (≥10%) and mono-blastlow (<10%) groups. MFC reclassified 20% of FAB non-M4/5 and 15% of FAB M4/5 cases into mono-blasthigh and mono-blastlow groups, respectively. Multivariable analysis confirmed mono-blasthigh status as an independent adverse prognostic factor for OS (HR=1.95, p=0.023), with a particularly strong impact in ELN 2024 favorable-risk patients (HR=2.81, p=0.024). 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.

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Venetoclax和阿扎胞苷治疗AML患者单核细胞样表型的预后意义。

单核细胞分化对接受Venetoclax （Ven）和阿扎胞苷（Aza）治疗的AML患者的预后影响尚不清楚。在86名接受Ven-Aza治疗的新诊断AML患者的前瞻性队列中，我们使用多参数流式细胞术（MFC）将单核细胞定义为根据ELN指南共同表达≥2个单核细胞标记物（CD4, CD36, CD64）的AML细胞。单核细胞/CD45+比例较高的患者完全缓解率较低（OR=0.24, p=0.005），总生存期明显较短（OS, 4.0 vs 14.9个月，p=0.003）。≥10%的单胚细胞/CD45+阈值，通过最大选择的秩统计确定，将患者分为单胚高（≥10%）和单胚低(

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来源期刊

Blood advances Medicine-Hematology

CiteScore

12.70

自引率

2.70%

发文量

840

期刊介绍： Blood Advances, a semimonthly medical journal published by the American Society of Hematology, marks the first addition to the Blood family in 70 years. This peer-reviewed, online-only, open-access journal was launched under the leadership of founding editor-in-chief Robert Negrin, MD, from Stanford University Medical Center in Stanford, CA, with its inaugural issue released on November 29, 2016. Blood Advances serves as an international platform for original articles detailing basic laboratory, translational, and clinical investigations in hematology. The journal comprehensively covers all aspects of hematology, including disorders of leukocytes (both benign and malignant), erythrocytes, platelets, hemostatic mechanisms, vascular biology, immunology, and hematologic oncology. Each article undergoes a rigorous peer-review process, with selection based on the originality of the findings, the high quality of the work presented, and the clarity of the presentation.