Asparaginase plays a crucial role in the combined chemotherapy treatment for childhood haematological tumours.However，asparaginase-associated pancreatitis（AAP）is a major challenge for the continuation of asparaginase therapy，which seriously affects the chemotherapy process and results in a lower disease-free survival rate in children with haematological tumours.Currently，the pathogenesis of AAP is still unclear，and its treatment in the acute phase mainly includes nutritional support，fluid resuscitation，and drug therapy.There are no domestic and international guidelines for the prevention of AAP，and the reported preventive methods mainly include low-fat diets，octreotide，vitamin A，as well as galactose and pyruvate.Since prevention of AAP and effective treatment of AAP are important to ensure the safety and sequential application，this article reviews the treatment and prevention methods of AAP.

Objective:To investigate the clinical features and risk factors of second asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL).Methods:In this case-control study, the clinical data of ALL children who were diagnosed with pancreatitis and received asparaginase chemotherapy at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from November 2013 to November 2023 were retrospectively analyzed.Multivariate Logistic regression was used to determine independent risk factors for the occurrence of second AAP.Results:A total of 78 children with AAP were included, of whom 32 were re-exposed to asparaginase.Ten of the 32 cases (31.25%) suffered second AAP, and they were rated at intermediate risk, with an age of (8.26±0.87) years.The number of asparaginase re-exposures before second AAP was (2.10±0.99) times.Second AAP developed during the intensification period in 2 cases and during the re-induction period in 8 cases.There were 3 cases (30.00%) of Grade 1 pancreatitis and 7 cases (70.00%) of Grade 2 pancreatitis.No patient died of second AAP.Two patients (20.00%) experienced AAP-related long-term complications, including chronic pancreatitis and insulin-dependent diabetes mellitus.After 2 children with no clinical data related to the first AAP were excluded, 30 re-exposed children were divided into a control group (22 cases) and a case group (8 cases) according to the presence or absence of second AAP.The univariate analysis showed that there were significant differences in activated partial thromboplastin time (APTT)[(29.80±5.25) s vs.(38.47±1.42) s, t=-0.45, P=0.023] and total bilirubin (TBIL)[18.40 (11.00, 25.53) μmol/L vs.24.30 (19.93, 46.48) μmol/L, Z=-0.32, P=0.020] between the 2 groups.The further multivariate Logistic regression analysis showed that after adjusting for age and immunophenotype, TBIL ( HR=1.115, P=0.048) was an independent risk factor for second AAP.Comparisons of the prognosis revealed that there were no significant differences in long-term complications ( P=0.168) and final survival ( P=0.716) between children with only once AAP (68 cases) and those with second AAP (10 cases). Conclusions:Second AAP mostly occurs after the second dose of asparaginase, and the re-induction period is the peak period of incidence of second AAP.Hyperbilirubinemia may be a risk factor of second AAP.Compared with once AAP, second AAP does not increase the mortality and the incidence of AAP-related long-term complications.

Objective:To investigate the clinical features and risk factors of second asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL).Methods:In this case-control study, the clinical data of ALL children who were diagnosed with pancreatitis and received asparaginase chemotherapy at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from November 2013 to November 2023 were retrospectively analyzed.Multivariate Logistic regression was used to determine independent risk factors for the occurrence of second AAP.Results:A total of 78 children with AAP were included, of whom 32 were re-exposed to asparaginase.Ten of the 32 cases (31.25%) suffered second AAP, and they were rated at intermediate risk, with an age of (8.26±0.87) years.The number of asparaginase re-exposures before second AAP was (2.10±0.99) times.Second AAP developed during the intensification period in 2 cases and during the re-induction period in 8 cases.There were 3 cases (30.00%) of Grade 1 pancreatitis and 7 cases (70.00%) of Grade 2 pancreatitis.No patient died of second AAP.Two patients (20.00%) experienced AAP-related long-term complications, including chronic pancreatitis and insulin-dependent diabetes mellitus.After 2 children with no clinical data related to the first AAP were excluded, 30 re-exposed children were divided into a control group (22 cases) and a case group (8 cases) according to the presence or absence of second AAP.The univariate analysis showed that there were significant differences in activated partial thromboplastin time (APTT)[(29.80±5.25) s vs.(38.47±1.42) s, t=-0.45, P=0.023] and total bilirubin (TBIL)[18.40 (11.00, 25.53) μmol/L vs.24.30 (19.93, 46.48) μmol/L, Z=-0.32, P=0.020] between the 2 groups.The further multivariate Logistic regression analysis showed that after adjusting for age and immunophenotype, TBIL ( HR=1.115, P=0.048) was an independent risk factor for second AAP.Comparisons of the prognosis revealed that there were no significant differences in long-term complications ( P=0.168) and final survival ( P=0.716) between children with only once AAP (68 cases) and those with second AAP (10 cases). Conclusions:Second AAP mostly occurs after the second dose of asparaginase, and the re-induction period is the peak period of incidence of second AAP.Hyperbilirubinemia may be a risk factor of second AAP.Compared with once AAP, second AAP does not increase the mortality and the incidence of AAP-related long-term complications.