Comparison of efficacy between homoharringtonine, aclarubicin, cytarabine (HAA) and idarubicin, cytarabine (IA) regimens as induction therapy in patients with de novo core binding factor acute myeloid leukemia

Duan, Wenbing; Yang, Sen; Zhao, Ting; Hu, Lijuan; Qin, Yazhen; Jia, Jinsong; Wang, Jing; Lu, Shengye; Jiang, Hao; Zhang, Xiaohui; Xu, Lanping; Wang, Yu; Lai, Yueyun; Shi, Hongxia; Huang, Xiaojun; Jiang, Qian

doi:10.1007/s00277-023-05400-5

Cited by 2 publications

References 26 publications

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Efficacy of venetoclax and azacitidine based therapy in favorable-risk unfit acute myeloid leukemia: a real-world study

Chen,

Wu,

et al. 2024

Preprint

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Venetoclax combined with azacitidine (VA) is a new standard of care for newly diagnosed patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy. We retrospectively analyzed patients who were diagnosed with favorable-risk unfit AML and received VA-based induction regimen between October 2020 and December 2023 in our center. Among 70 patients, 14 had RUNX1::RUNX1T1, 11 had CBFb::MYH11, 14 had CEBPA bzip mutations and 31 had NPM1 mutations. The median age was 60 years (IQR 49–67) and the median follow-up was 18.0 months (IQR 10.9–26.1). The cumulative CR/CRi rate of VA-based induction regimen for all patients was 84.3% (59/70). The median induction course was 1 (range 1–2). The CR/CRi rate for RUNX1::RUNX1T1, CBFb::MYH11, CEBPA bzip and NPM1 mutations was 35.7% (5/14), 90.9% (10/11), 100% (14/14) and 96.8% (30/31), respectively. Twenty patients received long-term VA-based therapy, and 30 received chemotherapy after remission. The MRD negativity rate after two cycle of consolidation therapy was 85.0% (17/20) for VA group and 73.3% (23/30) for chemotherapy group (p = 0.33). There was no significant difference in 2-year OS (p = 0.90) and 2-year EFS (p = 0.58) between VA group (OS: 88.2%; EFS: 41.2%) and chemotherapy group (OS: 83.3%; EFS: 42.8%). The 2-year OS (p = 0.01) and 2-year EFS (p < 0.01) of patients with negative MRD (OS: 89.8%; EFS: 51.4%) were significantly better than those with positive MRD (OS: 65.6%; EFS: 0%). VA-based regimens was an superior option for induction in favorable-risk unfit AML patients who were non-RUNX1::RUNX1T1 positive. Further studies are needed to conform its long-term efficacy.

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Efficacy of venetoclax and azacitidine based therapy in favorable-risk unfit acute myeloid leukemia: a real-world study

Chen,

Wu,

et al. 2024

Preprint

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The Functional Role and Prognostic Significance of TIM-3 Expression on NK Cells in the Diagnostic Bone Marrows in Acute Myeloid Leukemia

Sun,

Shi,

Xie

et al. 2024

Biomedicines

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Background: Compared to other immune checkpoint molecules, T cell immunoglobulin domain and mucin domain-3 (TIM-3) is highly expressed on natural killer (NK) cells, but its functional role and prognostic significance in acute myeloid leukemia (AML) remains unclear. This study aims to evaluate the role of TIM-3 expression on the cytotoxic and killing capacity of NK cells and its prognostic significance in AML. Methods: AML public single-cell RNA sequencing (scRNAseq) data were used to analyze the correlation of transcript levels between HAVCR2 (encoding TIM-3) and cytotoxic molecules in NK cells. NK cells from the bone marrows of seven newly diagnosed AML patients and five healthy donors (HDs) were stimulated in vitro and cell-killing activity was evaluated. A total of one hundred and five newly diagnosed adult AML patients and seven HDs were tested the expression of TIM-3 and cytotoxic molecules on the bone marrow NK cells by multi-parameter flow cytometry (MFC). Results: Both scRNAseq and MFC analysis demonstrated that TIM-3 expression on NK cells was positively related to the levels of perforin (PFP) and granzyme B (GZMB) (all p < 0.05) in AML. It was PFP and GZMB but not the TIM-3 level that was related to NK-cell-killing activity against K562 cells (p = 0.027, 0.042 and 0.55). A high frequency of TIM-3+ NK cells predicted poorer relapse-free survival (RFS) and event-free survival (EFS) (p = 0.013 and 0.0074), but was not an independent prognostic factor, whereas low GZMB levels in TIM-3+ NK cells independently predicted poorer RFS (p = 0.0032). Conclusions: TIM-3 expression on NK cells is positively related to PFP and GZMB levels but has no relation to cell-killing activity in AML, and low GZMB levels in TIM-3+ NK cells in the diagnostic bone marrows predicts poor outcomes. This study lays a theoretical foundation for the clinical application of immune checkpoint inhibitor treatment.

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Comparison of efficacy between homoharringtonine, aclarubicin, cytarabine (HAA) and idarubicin, cytarabine (IA) regimens as induction therapy in patients with de novo core binding factor acute myeloid leukemia

Cited by 2 publications

References 26 publications

Efficacy of venetoclax and azacitidine based therapy in favorable-risk unfit acute myeloid leukemia: a real-world study

Efficacy of venetoclax and azacitidine based therapy in favorable-risk unfit acute myeloid leukemia: a real-world study

The Functional Role and Prognostic Significance of TIM-3 Expression on NK Cells in the Diagnostic Bone Marrows in Acute Myeloid Leukemia

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