Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial

Jin, Jie; Wang, Jianxiang; Chen, Feifei; Wu, Depei; Hu, Jiong; Zhou, Jianfeng; Hu, Jianda; Wang, Jianmin; Li, Jianyong; Huang, Xiao‐Jun; Ma, Jun; Ji, Chunyan; Xu, Xiaoping; Kang, Yu; Ren, Hanyun; Zhou, Yuhong; Yin, Tong; Lou, Yinjun; Ni, Wanmao; Tong, Hongyan; Wang, Huafeng; Mi, Yingchang; Du, Xin; Chen, Baoan; Shen, Yi; Zhu, Chen; Chen, Sai‐Juan

doi:10.1016/s1470-2045(13)70152-9

Cited by 118 publications

(111 citation statements)

References 22 publications

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“…Despite the presence of myelosuppresion in all of the patients in the present study, which resulted in accompanying risks of infectious complications, the induction mortality was notably low (0 by day 30) compared with previous reports in patients with AML who received an HAA regimen (4% to 5.8% by day 30) (11,34). One of the major issues concerned with HHT is cardiovascular complications.…”

Section: Discussioncontrasting

confidence: 60%

“…A previous study showed that a high dose HHT (5-6 mg/m 2 /day) was associated with severe hypotension and cardiovascular collapse (36). The studies using HAA regimen in AML demonstrated that only 2% of patients had toxic cardiac effects (11,34). Collectively, these results support the safety of HAA regimen.…”

Section: Discussionmentioning

confidence: 56%

“…In addition, combination therapy of HHT and low-dose AraC has been demonstrated to be an effective strategy for advanced MDS and RAEBt and CR was observed in 46.9% (32); however, the median OS was shorter (18.2 months). Encouraging results from an open-label, randomized, controlled phase III study using an HAA regimen as an induction therapy in de novo AML patients aged 14-59 years have been reported (34). In that study, 150/206 patients (73%) received HAA regimen achieved CR versus 125/205 (61%) in the patients who were treated with daunorubicin and AraC (DA regimen); 3-year event-free survival was 35.4% versus 23.1% (P=0.0023) (34).…”

Section: Discussionmentioning

confidence: 99%

“…Encouraging results from an open-label, randomized, controlled phase III study using an HAA regimen as an induction therapy in de novo AML patients aged 14-59 years have been reported (34). In that study, 150/206 patients (73%) received HAA regimen achieved CR versus 125/205 (61%) in the patients who were treated with daunorubicin and AraC (DA regimen); 3-year event-free survival was 35.4% versus 23.1% (P=0.0023) (34). These differences appeared to be mainly a consequence of improved outcome in the patients with favorable and intermediate cytogenetics.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of homoharringtonine plus cytarabine and aclarubicin for patients with myelodysplastic syndrome-RAEB

Xiao

Liu

et al. 2015

Oncology Letters

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Abstract. The aim of the present study was to evaluate the treatment outcome of homoharringtonine, cytarabine (AraC) and aclarubicin combination therapy as induction treatment for myelodysplastic syndromes-refractory anemia with excess blasts (MDS-RAEB). A total of 24 patients with MDS-RAEB who were aged between 18 and 66 years were treated with homoharringtonine, AraC and aclarubicin (HAA regimen). The HAA regimen consisted of homoharringtonine (2 mg/m 2 intramuscularly twice daily, days 1-3), AraC (75 mg/m 2 injected subcutaneously twice daily, days 1-7) and aclarubicin (12 mg/m 2 , days 1-7). The overall response rate was 79% with a complete remission rate of 58.3% and partial remission rate of 20.7%. There was no evidence of early mortality in this group of patients. The median overall survival (OS) was 36.2 months (95% confidence interval, 24.6-47.4 months), and the estimated three year overall survival rate was 45.8%. In conclusion, HAA combination therapy is a suitable induction regimen for patients with MDS-RAEB, which may improve the outcome for de novo higher-risk MDS patients, particularly of those with favorable and intermediate cytogenetics.

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Section: Discussioncontrasting

confidence: 60%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of homoharringtonine plus cytarabine and aclarubicin for patients with myelodysplastic syndrome-RAEB

Xiao

Liu

et al. 2015

Oncology Letters

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“…Following the demonstration of the therapeutic efficacy of omacetaxine mepesuccinate (a type of synthetic HBT) for chronic myeloid leukemia (CML) (16,17), the United States Food and Drug Administration approved its use as a tyrosine kinase inhibitor for the treatment of resistant chronic phase or accelerated CML (18). Previous Chinese studies have added HBT as the third drug to the conventional inductive therapy for AML (19)(20)(21)(22), and these studies demonstrated that the treatment of HBT combined with aclarubicin and Ara-c resulted in a complete remission (CR) rate of 83%. As a result, an HBT, Ara-c and aclarubicin-containing chemotherapy regimen has been recommended for the treatment of AML (19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Novel homobarringtonie‑containing therapy for the treatment of patients with primary acute myeloid leukemia that are resistant to conventional therapy

Zhu

et al. 2017

Oncol Lett

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Abstract. The current study investigated the efficacy and safety of a novel treatment regime consisting of homobarringtonie, cytosine arabinoside and etoposide (HCE) for the treatment of primary acute myeloid leukemia (AML). In the present study, 141 patients diagnosed with AML were divided into the HCE (n=47) and the conventional AML therapy, consisting of idamycin combined with cytarabine (IA; n=94), treatment groups. The measured patient outcome parameters were the emission and response rates, as well as medication-induced adverse events, with a median follow-up time of 28 months. There was no significant difference in the 3-year relapse-free survival rate between the HCE and IA treatment groups. The occurrence and severity of hematological or non-hematological toxicity did not differ between the two groups. However, of the 26 patients that demonstrated a poor response to the IA treatment, 19 cases were administered the HCE treatment and 14 of these patients achieved complete remission (CR). Of the 10 patients that demonstrated a poor response to the HCE treatment, 8 patients were administered the IA treatment and 7 of these achieved CR. Therefore, HCE may be an effective treatment regimen for patients with primary AML. As there was no cross-resistance between the HCE and IA regimens, HCE may be an alternative option for patients that respond poorly to IA induction therapy.

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ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3‐ITD

et al. 2023

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Bromodomain-containing protein 4 (BRD4) inhibitors have been clinically developed to treat acute myeloid leukemia (AML), but their application is limited by the possibility of drug resistance, which is reportedly associated with the activation of the WNT/b-catenin pathway. Meanwhile, homoharringtonine (HHT), a classic antileukemia drug, possibly inhibits the WNT/ b-catenin pathway. In this study, we attempted to combine a novel BRD4 inhibitor (ACC010) and HHT to explore their synergistic lethal effects in treating AML. Here, we found that co-treatment with ACC010 and HHT synergistically inhibited cell proliferation, induced apoptosis, and arrested the cell cycle in FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-positive AML cells in vitro, and significantly inhibiting AML progression in vivo. Mechanistically, ACC010 and HHT cooperatively downregulated MYC and inhibited FLT3 activation. Further, when HHT was added, ACC010-resistant cells demonstrated a good synergy. We also extended our study to the mouse BaF3 cell line with FLT3-inhibitorresistant FLT3-ITD/tyrosine kinase domain mutations and AML cells without FLT3-ITD. Collectively, our results suggested that the combination treatment of ACC010 and HHT might be a promising strategy for AML patients, especially those carrying FLT3-ITD.

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Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial

Cited by 118 publications

References 22 publications

Efficacy and safety of homoharringtonine plus cytarabine and aclarubicin for patients with myelodysplastic syndrome-RAEB

Efficacy and safety of homoharringtonine plus cytarabine and aclarubicin for patients with myelodysplastic syndrome-RAEB

Novel homobarringtonie‑containing therapy for the treatment of patients with primary acute myeloid leukemia that are resistant to conventional therapy

ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3‐ITD

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