Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.

Jing Li, Ju Gao, Ansheng Liu, Wei Liu, Hao Xiong, Changda Liang, Yongjun Fang, Yunpeng Dai, Jingbo Shao, Hui Yu, Lingzhen Wang, Li Wang, Liangchun Yang, Mei Yan, Xiaowen Zhai, Xiaodong Shi, Xin Tian, Xiuli Ju, Yan Chen, Jing Wang, Leping Zhang, Hui Liang, Sen Chen, Jingrong Zhang, Haixia Cao, Jiao Jin, Qun Hu, Junlan Wang, Yilin Wang, Min Zhou, Yueqin Han, Rong Zhang, Weihong Zhao, Xiaoli Wang, Limin Lin, Ruidong Zhang, Chao Gao, Liting Xu, Yuanyuan Zhang, Jia Fan, Ying Wu, Wei Lin, Jiaole Yu, Peijing Qi, Pengli Huang, Xiaoxia Peng, Yaguang Peng, Tianyou Wang, Huyong Zheng

Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2023;41(31):4881-4892

PMID: 37531592

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Abstract

PURPOSE

Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML.

PATIENTS AND METHODS

This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years.

RESULTS

We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% 73.9%, = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm ( = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm ( = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, = .336).

CONCLUSION

HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

Address: Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.; Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China.; National Key Clinical Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University), Beijing, China.; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China.; West China Second University Hospital, Sichuan University, Chengdu, China.; Key Laboratory of Chronobiology (Sichuan University), National Health Commission of China, Chengdu, China.; Xi'an Children's Hospital, Xian, China.; Children's Hospital of Henan Province, Zhengzhou, China.; Wuhan Children's Hospital, Wuhan, China.; Jiangxi Provincial Children's Hospital, Nanchang, China.; Children's Hospital of Nanjing Medical University, Nanjing, China.; Shandong First Medical University Affiliated Shandong Provincial Hospital, Jinan, China.; Shanghai Children's Hospital, Shanghai, China.; Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.; Affiliated Hospital of Qingdao University, Qingdao, China.; Children's Hospital of Hebei Province, Shijiazhuang, China.; Department of Pediatrics, Xiangya Hospital Central South University, Changsha, China.; The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.; Children's Hospital of Fudan University, Shanghai, China.; Capital Institute of Pediatrics' Children's Hospital, Beijing, China.; Kunming Children's Hospital, Kunming, China.; Qilu Hospital of Shandong University, Jinan, China.; Children's Hospital of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, China.; Children's Hospital of Shanxi Province, Taiyuan, China.; Peking University People's Hospital, Beijing, China.; Women and Children's Hospital, Qingdao University, Qingdao, China.; Tianjin Children's Hospital, Tianjin, China.; Guiyang Children's Hospital, Guiyang, China.; Qinghai Women's and Children's Hospital, Xining, China.; The Affiliated Hospital of Guizhou Medical University, Guiyang, China.; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.; Northwest Women's and Children's Hospital, Xian, China.; Linyi People's Hospital, Linyi, China.; Chengdu Women's and Children's Central Hospital, Chengdu, China.; Children's Hospital of Liaocheng, Liaocheng, China.; Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.; First Hospital, Peking University, Beijing, China.; Yantai Yuhuangding Hospital, Yantai, China.; Second Affiliated Hospital of Shantou University Medical College, Shantou, China.; Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China.; National Key Clinical Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University), Beijing, China.; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China.; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.; Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing, China.; Children's Hospital of Zhejiang University School of Medicine, the Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, China.; Center for Clinical Epidemiology and Evidence-Based Medicine, Beijing Children's Hospital, Capital Medical University, Beijing, China.

DOI: 10.1200/JCO.22.02836

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MeSH Terms: Child, Humans, Antineoplastic Combined Chemotherapy Protocols, Cytarabine, East Asian People, Homoharringtonine, Leukemia, Promyelocytic, Acute, Multicenter Studies as Topic, Remission Induction, Survival Rate, Treatment Outcome, Tretinoin