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Homoharringtonine is a safe and effective substitute for anthracyclines in children younger than 2 years old with acute myeloid leukemia

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Abstract

Homoharringtonine (HHT), a plant alkaloid from Cephalotaxus harringtonia, exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s. Trial SCMC-AML-2009 presented herein was a randomized clinical study designed based on our previous findings that pediatric AML patients younger than two years old may benefit from HHT-containing chemotherapy regimens. Patients randomized to arm A were treated with a standard chemotherapy regimen comprising mainly of anthracyclines and cytarabine (Ara-C), whereas patients in arm B were treated with HHT-containing regimens in which anthracyclines in all but the initial induction therapy were replaced by HHT. From February 2009 to November 2015, 59 patients less than 2 years old with de novo AML (other than acute promyelocytic leukemia) were recruited. A total of 42 patients achieved a morphologic complete remission (CR) after the first course, with similar rates in both arms (70.6% vs.72.0%). At the end of the follow-up period, 40 patients remained in CR and 5 patients underwent hematopoietic stem cell transplantation in CR, which could not be considered as events but censors. The 5-year event-free survival (EFS) was 60.2%±9.6% for arm A and 88.0%±6.5% for arm B (P= 0.024). Patients in arm B experienced shorter durations of leukopenia, neutropenia, and thrombocytopenia and had a lower risk of infection during consolidation chemotherapy with high-dosage Ara-C. Consequently, the homoharringtonine-based regimen achieved excellent EFS and alleviated hematologic toxicity for children aged younger than 2 years with de novo AML compared with the anthracycline-based regimen.

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Acknowledgements

This work was partially supported by the National Natural Science Foundation of China (No. 81270623), the Science and Technology Commission of Shanghai Municipality (No. 14411950600), and the Public Health 3-Year Project of Shanghai Children’s Medical Center (No. GWIV-25).

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  1. These authors contributed equally to this article.

Authors and Affiliations

  1. Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China

    Xiaoxiao Chen, Yanjing Tang, Jing Chen, Ru Chen, Longjun Gu, Huiliang Xue, Ci Pan, Jingyan Tang & Shuhong Shen

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  1. Xiaoxiao Chen
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  2. Yanjing Tang
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  3. Jing Chen
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Correspondence to Jingyan Tang or Shuhong Shen.

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Chen, X., Tang, Y., Chen, J. et al. Homoharringtonine is a safe and effective substitute for anthracyclines in children younger than 2 years old with acute myeloid leukemia. Front. Med. 13, 378–387 (2019). https://doi.org/10.1007/s11684-018-0658-4

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  • DOI: https://doi.org/10.1007/s11684-018-0658-4

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