Risk factors and outcomes of asparaginase-associated pancreatitis in pediatric patients with ALL

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.

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Journal
Blood
Published
2025-08-11
DOI
https://doi.org/10.1182/blood.2025029785
Citations
2
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
3.76
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article

Risk factors and outcomes of asparaginase-associated pancreatitis in pediatric patients with ALL

Lingzhen Wang, Jingyan Tang, Ching‐Hon Pui, Wenjun Deng et al.
2 citations
Blood
Acute Lymphoblastic Leukemia research
3.76
article

Risk factors and outcomes of asparaginase-associated pancreatitis in pediatric patients with ALL

Lingzhen Wang, Jingyan Tang, Ching‐Hon Pui, Wenjun Deng, Shuhong Shen, Jia‐Shi Zhu, Ningling Wang, Xiaowen Zhai, Qun Hu, Changcheng Chen, Ben-Quan Qi, Xin Tian, Jun Yang, Xiuli Ju, Jiaoyang Cai, Shaoyan Hu, Yongjun Fang, Xuedong Wu, Cheng Cheng, Chi Kong Li, Weina Zhang, Ge Zhang, Xiaoyan Wu, Changda Liang, Xia Guo, Fengling Xu
article en
2 citations

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.

BloodVol. 146(20)
Qingdao University (CN), St. Jude Children's Research Hospital (US), Central South University (CN), Chinese University of Hong Kong (HK), Shanghai Jiao Tong University (CN), Anhui Medical University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Sichuan University (CN), Soochow University (CN), Nanjing Children's Hospital (CN), Kunming Children's Hospital (CN), Shanghai Children's Medical Center (CN), Northwest Women's and Children's Hospital (CN), Nanfang Hospital (CN), Guangzhou Women and Children Medical Center (CN), Affiliated Hospital of Qingdao University (CN), Wuhan Union Hospital (CN), Jiangxi Provincial Children's Hospital (CN), Institute of Hematology & Blood Diseases Hospital (CN), Second Affiliated Hospital of Anhui Medical University (CN), Children's Hospital of Suzhou University (CN), Children's Hospital of Fudan University (CN), Shanghai Children's Hospital (CN), Children's Hospital of Chongqing Medical University (CN), Xiangya Hospital Central South University (CN), Tongji Hospital (CN), Qilu Hospital of Shandong University (CN), Union Hospital (CN), Huazhong University of Science and Technology (CN), Southern Medical University (CN), Chongqing Medical University (CN), Guangzhou Medical University (CN)
Good health and well-being
Openalex Percentile: Top 7%
Acute Lymphoblastic Leukemia research
3.76
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