Risk factors and outcomes of asparaginase-associated pancreatitis in pediatric patients with ALL
Abstract
Abstract Asparaginase-associated pancreatitis (AAP) is a significant complication in pediatric acute lymphoblastic leukemia (ALL) therapy, often leading to treatment delays or discontinuation. This study aimed to identify AAP risk factors, assess outcomes after first and second episodes, and evaluate the impact of asparaginase rechallenge. We retrospectively analyzed 7640 patients (aged 1 month to 18 years) treated under the Chinese Children Cancer Group ALL 2015 protocol. Patients were stratified as low risk (LR), intermediate risk (IR), or high risk (HR) based on clinical features and measurable residual disease (MRD). AAP was categorized as early or late onset depending on treatment phase. Older age and IR/HR status were independent risk factors for AAP. The cumulative AAP incidence was 2.2% in LR and 5.8% in IR/HR groups. Among 298 patients who developed AAP, 92 were rechallenged with asparaginase; second episodes occurred in 20.8% of LR and 33.8% of IR/HR patients, with no increase in severity. Lack of rechallenge and day 46 MRD of ≥0.01% were independently associated with inferior event-free survival (EFS). Among patients with early-onset AAP, those who were rechallenged had superior 5-year EFS than those who were not rechallenged (80.1% vs 60.2%; P = .003). Similarly, among IR/HR group, those who were rechallenged had better 5-year EFS than those who were not rechallenged (82.4% vs 60.6%; P = .004). IR/HR patients with early-onset AAP who were not rechallenged had especially poor outcomes (5-year EFS, 53.3%). These findings support considering asparaginase rechallenge in IR/HR patients with early-onset AAP when alternative therapies are limited. This trial was registered at www.chictr.org.cn as #ChiCTR2000032211.
Article Details
Authors (26)
Changcheng Chen
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
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
Xuedong Wu
Qun Hu
Xiaoyan Wu
Xia Guo
Shenzhen Campus of Sun Yat-sen University
Shaoyan Hu
Xiaowen Zhai
3Department of Hematology and Oncology, Children’s Hospital of Fudan University, Fudan University, Shanghai, China
Benquan Qi
8Department of Pediatrics, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 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
Ningling Wang
4Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
Fengling Xu
11Department of Hematology/Oncology, Chongqing Medical University Affiliated Children's Hospital, Chongqing, China
Yongjun Fang
12Department of Hematology/Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China
Chi-kong Li
13Department of Pediatrics, Hong Kong Children’s Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
Changda Liang
14Department of Hematology/Oncology, Jiangxi Provincial Children's Hospital, Nanchang, China
Lingzhen Wang
Jiashi Zhu
16Department of Hematology/Oncology, Children's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
Wenjun Deng
Xin Tian
Wuya College of Innovation
Xiuli Ju
13Department of Pediatrics, Qilu Hospital of Shandong University, Shandong University, Qingdao, China
Ge Zhang
Jingyan Tang
State Key Laboratory of Molecular Engineering of Polymers
Cheng Cheng
Jun Yang
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
Ching-Hon Pui