Clinical analysis of asparaginase-associated pancreatitis in children

To investigate the clinical characteristics, diagnosis, and treatment of asparaginase-associated pancreatitis (AAP) in children to assess the risk factors of AAP and improve its clinical prognosis.

We performed a retrospective analysis of 24 patients with AAP who suffered from acute lymphoblastic leukemia (ALL) and received asparaginase chemotherapy, and who were admitted to the Children's Hospital of Zhejiang University School of Medicine from January 2009 to January 2019. We analyzed the general situation, drug application, clinical manifestations, laboratory tests, imaging findings, treatment, and prognosis.

In 796 patients with ALL who received asparaginase chemotherapy, the incidence of AAP was 3% (24/796). Among these patients, 11 (45.8%) developed AAP during the first application of asparaginase during the induction of remission, six cases developed AAP during the second application of asparaginase, and seven cases developed AAP during the third and above application. The median time from the diagnosis of AAP in 24 patients to the last asparaginase treatment was 8 days (1-18 days), among whom, the main clinical symptoms were abdominal pain, vomiting, nausea, bloating, and fever, which accounted for 95.8%, 37.5%, 33.3%, 20.8%, 4.0%, and 42.7%, respectively. Additionally, seven patients had peritoneal effusion. At initial diagnosis, 62.5% of the patients (15/24) had an increase in blood amylase levels to more than three times the upper limit of normal. The abdominal ultrasound results of 91.7% (22/24) of the patients were consistent with the imaging changes observed in pancreatitis. All 24 patients immediately stopped asparaginase treatment and received symptomatic supportive treatment, including fluid resuscitation, fasting, nutritional support, antibiotics, pancreatin inhibitors, and treatment of complications, as needed. Twenty-three patients were relieved after treatment, and one died. Following the resolution of symptoms in 14 patients with AAP, asparaginase chemotherapy was reintroduced, and 3 patients relapsed with AAP, all of which were mild. Symptoms were relieved 72 h after stopping asparagine chemotherapy.

According to the data from this single-center study, the incidence of AAP in patients with ALL was 3%, most of which occurred during the first or second exposure to asparaginase. Abdominal pain was the most common clinical manifestation. The diagnosis of AAP should be based on clinical manifestations, laboratory tests, and imaging findings. The prognosis of AAP is good, and whether asparaginase treatment can be reintroduced requires an evaluation of the benefits of asparaginase treatment and the risk of recurrence of pancreatitis.