Prognostic and therapeutic implications of measurable residual disease levels during remission induction of childhood ALL
Abstract
Abstract We evaluated the prognostic and therapeutic significance of measurable residual disease (MRD) during remission induction in pediatric patients with acute lymphoblastic leukemia (ALL). In the Chinese Children Cancer Group ALL 2015 protocol, 7640 patients were categorized into low-, intermediate-, or high-risk groups based on clinical and genetic features. Final risk classification was determined by assessing MRD using flow cytometry on days 19 and 46 of remission induction with additional intensified chemotherapy for day 19 MRD ≥1%. Patients with B-ALL with negative MRD (<0.01%) on day 19 or day 46 had significantly better 5-year event-free survival (EFS) than those with MRD of between 0.01% and 0.99% who, in turn, had better EFS than patients with MRD of ≥1%. Provisional low-risk patients with day 19 MRD ≥1% but negative day 46 MRD who were reclassified as intermediate risk had a 5-year EFS that was comparable with that of low-risk patients with day 19 MRD of 0.3% to 0.99% and negative day 46 MRD (82.5% vs 83.0%) and better EFS than provisional low-risk patients with MRD on both days (83.0% vs 72.6%; P < .001). Similarly, patients with provisional intermediate-risk B-ALL with day 19 MRD ≥1% but negative day 46 MRD who received additional therapy had better 5-year EFS than those with day 19 MRD between 0.3% and 0.99% (70.7% vs 53.0%; P < .001). Among low-risk patients with negative day 46 MRD, those with negative day 19 MRD had superior EFS than those with positive day 19 MRD (91.7% vs 86.1%; P < .001). Optimal use of day 19 MRD could improve individualized treatment and outcomes. This trial was registered at www.chictr.org.cn as #ChiCTR-IPR-14005706.
Article Details
Authors (29)
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
Jiaoyang Cai
1Department of Hematology/Oncology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, National Health Committee Key Laboratory of Pediatric Hematology and Oncology, Shanghai, China
Xiang Wang
Yani Ma
2Department of Hematology/Oncology, Key Laboratory of Pediatric Hematology and Oncology of China Ministry of Health, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, National Children’s Medical Center, Shanghai, China
Xiaofan Zhu
Jie Yu
Peifang Xiao
1Department of Hematology and Oncology, Children’s Hospital of Soochow University, Soochow University, Suzhou, China
Ju Gao
Yongjun Fang
12Department of Hematology/Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China
Changda Liang
14Department of Hematology/Oncology, Jiangxi Provincial Children's Hospital, Nanchang, China
Xue Li
Fen Zhou
Xiaowen Zhai
3Department of Hematology and Oncology, Children’s Hospital of Fudan University, Fudan University, Shanghai, China
Xiaoxiao Xu
Xin Tian
Wuya College of Innovation
Aiguo Liu
14Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Department of Pediatrics, Wuhan, China
Ningling Wang
4Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
Jiashi Zhu
16Department of Hematology/Oncology, Children's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
Lingzhen Wang
Frankie Wai-Tsoi Cheng
18Department of Pediatrics, Hong Kong Children’s Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
Liangchun Yang
Ge Zhang
Cheng Cheng
Jun J. Yang
Department of Pharmacy and Pharmaceutical Sciences
Shuhong Shen
1Department of Hematology/Oncology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, National Health Committee Key Laboratory of Pediatric Hematology and Oncology, Shanghai, China
Chi-kong Li
13Department of Pediatrics, Hong Kong Children’s Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
Benshang Li
2Department of Hematology/Oncology, Key Laboratory of Pediatric Hematology and Oncology of China Ministry of Health, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, National Children’s Medical Center, Shanghai, China
Hua Jiang
Ching-Hon Pui