Hsiu-Hao Chang1, Jia-Feng Wu2, Chi-Bo Chen3, Shu-Wei Chou4, Yung-Li Yang4, Meng-Yao Lu4, Shiann-Tarng Jou4, Huey-Ling Chen4, Yen-Hsuan Ni4, Dong-Tsamn Lin4, Mei-Hwei Chang4. 1. Department of Pediatrics, National Taiwan University Hospital and National Taiwa University, College of Medicine, Taipei, Taiwan. changhh2001@ntu.edu.tw. 2. Department of Pediatrics, National Taiwan University Hospital and National Taiwa University, College of Medicine, Taipei, Taiwan. wjf@ntu.edu.tw. 3. Department of Pediatrics, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan. 4. Department of Pediatrics, National Taiwan University Hospital and National Taiwa University, College of Medicine, Taipei, Taiwan.
Abstract
BACKGROUND: L-Asparaginase (L-Asp) is an important therapeutic for childhood acute lymphoblastic leukemia (ALL). Asparaginase-associated pancreatitis (AAP) is a severe complication of L-Asp related to the dosage. We investigated the incidence of, and risk factors for, AAP in pediatric patients with ALL. METHODS: From January 2002 to December 2018, pediatric patients with ALL treated at National Taiwan University Hospital were enrolled in this study. The diagnosis of AAP was based on the criteria of the Ponte di Legno Toxicity Working Group. RESULTS: Of the 353 patients enrolled in this study, 14 (4.0%) developed AAP. The incidence of AAP in ALL patients was significantly higher after treatment with the 2013 protocol compared with the 2002 protocol of the Taiwan Pediatric Oncology Group (9.5% vs. 1.3%). Multivariate analysis showed that a high peak L-Asp dose intensity (>45,000 U/m2/month) and older age at diagnosis (>6.8 years) were independently predictive of AAP development. CONCLUSIONS: The incidence of acute pancreatitis in childhood ALL was correlated more strongly with the peak dose intensity than with the cumulative dose of L-Asp. These results could be used to reduce the treatment-related complications of ALL. IMPACT: L-Asparaginase is an important therapeutic for childhood acute lymphoblastic leukemia, and the accumulated dosage of L-asparaginase is considered as a major risk factor of asparaginase-associated pancreatitis. This article demonstrated that the incidence of pancreatitis correlates with the dose-intensity of L-asparaginase, but not the accumulated dosage. Identification of patient group with high risk of pancreatitis could lead to early diagnosis and reduce the complication. This finding could aid in developing further new protocol or therapeutic strategy design to reduce treatment-related complications and improve clinical outcomes of childhood acute lymphoblastic leukemia.
BACKGROUND: L-Asparaginase (L-Asp) is an important therapeutic for childhood acute lymphoblastic leukemia (ALL). Asparaginase-associated pancreatitis (AAP) is a severe complication of L-Asp related to the dosage. We investigated the incidence of, and risk factors for, AAP in pediatric patients with ALL. METHODS: From January 2002 to December 2018, pediatric patients with ALL treated at National Taiwan University Hospital were enrolled in this study. The diagnosis of AAP was based on the criteria of the Ponte di Legno Toxicity Working Group. RESULTS: Of the 353 patients enrolled in this study, 14 (4.0%) developed AAP. The incidence of AAP in ALL patients was significantly higher after treatment with the 2013 protocol compared with the 2002 protocol of the Taiwan Pediatric Oncology Group (9.5% vs. 1.3%). Multivariate analysis showed that a high peak L-Asp dose intensity (>45,000 U/m2/month) and older age at diagnosis (>6.8 years) were independently predictive of AAP development. CONCLUSIONS: The incidence of acute pancreatitis in childhood ALL was correlated more strongly with the peak dose intensity than with the cumulative dose of L-Asp. These results could be used to reduce the treatment-related complications of ALL. IMPACT: L-Asparaginase is an important therapeutic for childhood acute lymphoblastic leukemia, and the accumulated dosage of L-asparaginase is considered as a major risk factor of asparaginase-associated pancreatitis. This article demonstrated that the incidence of pancreatitis correlates with the dose-intensity of L-asparaginase, but not the accumulated dosage. Identification of patient group with high risk of pancreatitis could lead to early diagnosis and reduce the complication. This finding could aid in developing further new protocol or therapeutic strategy design to reduce treatment-related complications and improve clinical outcomes of childhood acute lymphoblastic leukemia.
Authors: B L Asselin; M Y Lorenson; J C Whitin; D J Coppola; A S Kende; R L Blakley; H J Cohen Journal: Cancer Res Date: 1991-12-15 Impact factor: 12.701