Low- vs standard-dose regimens as induction for pediatric AML: a multicenter, randomized noninferiority trial
Abstract
Abstract Intensive chemotherapy is standard for acute myeloid leukemia (AML) but carries high risks of life-threatening complications, particularly in vulnerable patients. We aimed to compare the efficacy and safety of a low-dose chemotherapy (LDC) regimen for induction of AML. A randomized, multicenter, noninferiority trial was conducted in patients with AML aged <18 years. Patients received low-dose cytarabine, mitoxantrone or idarubicin, and granulocyte colony-stimulating factor (G-CSF) or standard-dose chemotherapy (SDC; cytarabine, daunomycin, and etoposide). All patients received postremission consolidation with standard chemotherapy and/or hematopoietic stem cell transplantation. The primary end point was to compare response rates between treatments. The secondary end points were to compare the outcomes, toxicity, and safety of the LDC and SDC regimens. The 2 treatment arms showed no significant differences in outcomes. Complete remission (CR)/CR with incomplete count recovery rates after induction were 95.1% and 95.3% in the LDC and SDC arms, respectively. Measurable residual disease <0.1% after induction II was observed in 87.4% and 87.1% of patients in the LDC and SDC arms, respectively. Median time to neutrophil and platelet recovery was significantly shorter among patients receiving the LDC regimen. Patients in the LDC arm had a 4-year overall survival (OS) of 81.3% vs 83.6% (P = .611), and a 4-year event-free survival (EFS) of 61.5% vs 63.1% (P = .832). In conclusion, the LDC regimen was well tolerated, and was associated with CR, EFS, and OS rates that were not inferior to those of patients treated with the SDC regimen. The trial was registered at www.chictr.org.cn as ChiCTR1800015883.
Article Details
Authors (28)
Li Gao
Xiaowen Zhai
3Department of Hematology and Oncology, Children’s Hospital of Fudan University, Fudan University, Shanghai, China
Ningling Wang
4Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
Ning Liao
5Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, China
Peifang Xiao
1Department of Hematology and Oncology, Children’s Hospital of Soochow University, Soochow University, Suzhou, China
Fang Xu
Key Laboratory of Optoelectronic Chemical Materials and Devices (Ministry of Education), School of Optoelectronic Materials and Technology
Minghua Yang
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy
Xueju Xu
8Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
Qi An
Jixia Luo
10Department of Hematology and Oncology, Kaifeng Children’s Hospital, Kaifeng, China
Liangchun Yang
Xiaojun Yuan
Yunyan He
Yong Zhuang
Hongsheng Wang
Jiangsu Provincial Key Laboratory of Dermatology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College
Linhai Yang
4Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
Weina Zhang
Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control
Yufeng Liu
Key Laboratory of Artificial Structures and Quantum Control (Ministry of Education), School of Physics and Astronomy
Jie Li
Hailong He
Yi Wang
Cheng Cheng
Jun Lu
Hua Jiang
Xiuli Ju
13Department of Pediatrics, Qilu Hospital of Shandong University, Shandong University, Qingdao, China
Qian-Fei Wang
16China National Center for Bioinformation, Beijing, China
Raul C. Ribeiro
Shaoyan Hu