5 results on '"Tong, Hongyan"'
Search Results
2. Phosphoproteomic Characterization and Kinase Signature Predict Response to Venetoclax Plus 3+7 Chemotherapy in Acute Myeloid Leukemia.
- Author
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Jin, Jie, Hou, Shangyu, Yao, Yiyi, Liu, Miaomiao, Mao, Liping, Yang, Min, Tong, Hongyan, Zeng, Tao, Huang, Jinyan, Zhu, Yinghui, and Wang, Huafeng
- Subjects
ACUTE myeloid leukemia ,VENETOCLAX ,YOUNG adults ,CANCER chemotherapy ,CLUSTER analysis (Statistics) - Abstract
Resistance to chemotherapy remains a formidable obstacle in acute myeloid leukemia (AML) therapeutic management, necessitating the exploration of optimal strategies to maximize therapeutic benefits. Venetoclax with 3+7 daunorubicin and cytarabine (DAV regimen) in young adult de novo AML patients is evaluated. 90% of treated patients achieved complete remission, underscoring the potential of this regimen as a compelling therapeutic intervention. To elucidate underlying mechanisms governing response to DAV in AML, quantitative phosphoproteomics to discern distinct molecular signatures characterizing a subset of DAV‐sensitive patients is used. Cluster analysis reveals an enrichment of phosphoproteins implicated in chromatin organization and RNA processing within DAV‐susceptible and DA‐resistant AML patients. Furthermore, kinase activity profiling identifies AURKB as a candidate indicator of DAV regimen efficacy in DA‐resistant AML due to AURKB activation. Intriguingly, AML cells overexpressing AURKB exhibit attenuated MCL‐1 expression, rendering them receptive to DAV treatment and maintaining them resistant to DA treatment. Moreover, the dataset delineates a shared kinase, AKT1, associated with DAV response. Notably, AKT1 inhibition augments the antileukemic efficacy of DAV treatment in AML. Overall, this phosphoproteomic study identifies the role of AURKB as a predictive biomarker for DA, but not DAV, resistance and proposes a promising strategy to counteract therapy resistance in AML. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Gilteritinib‐based combination therapy in adult relapsed/refractory FLT3‐mutated acute myeloid leukaemia.
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Chen, Nianci, Pan, Jiajia, Zhou, Yile, Mao, Liping, Lou, Yinjun, Qian, Jiejing, Xu, Gaixiang, Wei, Juying, Zhou, De, Shou, Lihong, Huang, Li, Yan, Minchao, Zeng, Hui, Fan, Cuihua, Wu, Gongqiang, Feng, Weiying, Tong, Hongyan, Jin, Jie, and Wang, Huafeng
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ACUTE myeloid leukemia ,FEBRILE neutropenia ,CYTOPENIA ,LUNG infections ,VENETOCLAX ,PACLITAXEL - Abstract
Summary: Gilteritinib, a potent FMS‐like tyrosine kinase 3 (FLT3) inhibitor, was approved for relapsed/refractory (R/R) FLT3‐mutated acute myeloid leukaemia (AML) patients but still showed limited efficacy. Here, we retrospectively analysed the efficacy and safety of different gilteritinib‐based combination therapies (gilteritinib plus hypomethylating agent and venetoclax, G + HMA + VEN; gilteritinib plus HMA, G + HMA; gilteritinib plus venetoclax, G + VEN) in 33 R/R FLT3‐mutated AML patients. The composite complete response (CRc) and modified CRc (mCRc) rates were 66.7% (12/18) and 88.9% (16/18) in patients received G + HMA + VEN, which was higher compared with that in G + HMA (CRc: 18.2%, 2/11; mCRc: 45.5%, 5/11) or G + VEN (CRc: 50.0%, 2/4; mCRc: 50.0%, 2/4). The median overall survival (OS) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 160.0 days and 231.0 days. The median duration of remission (DOR) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 82.0 days and 77.0 days. Four patients in the G + HMA + VEN group received alloHSCT after remission exhibited prolonged median DOR. The most common grade 3/4 adverse events were cytopenia, febrile neutropenia and pulmonary infection; there were no differences among the three groups. In conclusion, our data demonstrated promising response of G + HMA + VEN combination therapy in R/R FLT3‐mutated AML, and it may be considered an effective therapy bridge to transplantation. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Venetoclax plus daunorubicin and cytarabine in newly diagnosed acute myeloid leukemia patients: A propensity score‐matched analysis.
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Wang, Rong, Zhang, Yi, Chang, Jie, Wang, Huafeng, Lou, Yinjun, Yang, Min, Xu, Gaixiang, Tong, Hongyan, Xie, Wanzhuo, Zhou, De, Wei, Juying, Mai, Wenyuan, Ye, Xiujin, Meng, Haitao, Jin, Jie, and Zhu, Hong‐Hu
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ACUTE myeloid leukemia ,VENETOCLAX ,DAUNOMYCIN ,CYTARABINE ,YOUNG adults - Abstract
Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy (DAV) has shown safety and efficacy in eligible patients with newly diagnosed acute myeloid leukemia (AML). However, there are no direct comparisons between DAV and 3 + 7 daunorubicin and cytarabine chemotherapy (DA) alone. We performed a propensity score‐matched analysis to compare the outcomes of DAV group with historical DA group and identify the clinical and molecular characteristics of patients who might benefit from the DAV regimen. The DAV group had a higher Complete remission (CR) rate than the DA group (90% vs. 55%, p = 0.008). 25 (96%) patients in the DAV group had a higher MRD‐negative CRc rate compared with 13 (62%) patients in the DA group (p = 0.006). After a median follow‐up duration of 19.15 (IQR 17.13–21.67) months, the DAV group had an improved overall survival (p = 0.001) and event‐free survival (p = 0.069), but not disease‐free survival (p = 0.136). Collectively, DAV regimen induced high CR rates and deep MRD‐negative CRc rates after one cycle of induction therapy, as well as prolonged the overall survival, in young adult patients with AML who were eligible for intensive chemotherapy. The addition of venetoclax to intensive chemotherapy should be considered in the future to achieve better survival advantages in eligible AML patients. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Venetoclax plus cytarabine and azacitidine in relapsed/refractory AML: An open-label, single-arm, phase 2 study.
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You, Liangshun, Liu, Yi, Mai, Wenyuan, Xie, Wanzhuo, Zhou, De, Mao, Liping, Chen, Lili, Zhou, Xinping, Ma, Liya, Zheng, Xiaolong, Wei, Juying, Lou, Yinjun, Ye, Xingnong, Tong, Hongyan, Jin, Jie, and Meng, Haitao
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THERAPEUTIC use of antineoplastic agents , *RISK factors of pneumonia , *FLOW cytometry , *ANEMIA , *LEUCOPENIA , *DRUG resistance in cancer cells , *CANCER relapse , *PATIENT safety , *DRUG side effects , *AZACITIDINE , *CLINICAL trials , *ANTINEOPLASTIC agents , *DESCRIPTIVE statistics , *CYTARABINE , *INTRAVENOUS therapy , *DOSE-effect relationship in pharmacology , *THROMBOCYTOPENIA , *DRUG efficacy , *SEPSIS , *SUBCUTANEOUS injections , *SPONTANEOUS cancer regression , *OVERALL survival , *NEUTROPENIA , *EVALUATION , *DISEASE risk factors - Abstract
The outcome of relapsed/refractory (R/R) acute myeloid leukemia (AML) remains extremely poor. Venetoclax (VEN)-based regimens have shown promise in treating R/R AML. This phase 2 study aimed to systematically evaluate the efficacy and safety of the VAA regimen (VEN plus Cytarabine and Azacitidine) in R/R AML patients. Thirty R/R AML patients were enrolled. The study adopted a stepwise ramp-up of VEN dosing, starting with 100 mg on day 1, escalating to 200 mg on day 2, and reaching 400 mg from day 3 to day 9. Cytarabine (10 mg/m2, q12h) was administered intravenously twice daily from days 1 to 10, and Azacitidine (75 mg/m2) was administered via subcutaneous injection once daily from days 1–7. The primary efficacy endpoint was the composite complete remission rate (CRc), including complete response (CR) and complete response with incomplete blood count recovery (CRi). Secondary endpoints included overall survival (OS), duration of response (DOR), and safety analysis. The CRc rate was 63.3% (19/30), with CR in 36.7% of patients and CRi in 26.7%. Notably, 14 (73.7%) of 19 patients achieving CRc showed undetectable measurable residual disease by flow cytometry. With a median follow-up of 10.7 months, the median OS had not been reached, and the median DOR was 18.3 months. The most common grade 3–4 adverse events (AEs) were neutropenia (100%), anemia (96.7%), thrombocytopenia (90.0%), and leukopenia (90.0%). Infections, with pneumonia being the most prevalent (43.3%), were observed, including one fatal case of Pseudomonas aeruginosa septicemia. There were no treatment-related deaths. The VAA regimen is an effective and safe option for patients with R/R AML, demonstrating a high CRc rate and manageable safety profile. • VAA regimen yields 63.3% CRc rate in R/R AML. • Median DOR reached 18.3 months. • High safety profile with manageable AEs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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