Is asparaginase-associated pancreatitis dependent on the age of patients with acute lymphoblastic leukemia?

This study evaluated whether the risk and severity of asparaginase-associated pancreatitis (AAP) depend on the age of patients with acute lymphoblastic leukemia (ALL). The main finding was that the AAP risk was higher in adolescents and adults compared to younger children.

Asparaginase (ASP; Oncaspar) is an important treatment for ALL. AAP is a major side-effect of this treatment and a common reason why patients stop treatment. AAP involves the inflammation and damage of the pancreas. Stopping treatment early reduces cure rates and many patients experience a second AAP if re-exposed to ASP.

Adolescence is considered as a risk factor for short-term pancreatitis. Adults are increasingly receiving ALL treatments inspired by pediatric regiments. However, the severity of AAP and the risk of cancer relapse have not been compared among children and adults with ALL.

2448 patients with ALL were included in this study. Every patient received a recommended treatment for ALL which included ASP. Patients were divided into three age groups – younger children (1.0-9.9 years), adolescents (10.0-17.9 years) and adults (18.0-45.9 years). They were followed up for 245 days on average.

168 patients had AAP. The frequency of AAP was 7.0% among younger children, 10.1% among adolescents and 11.0% among adult patients. The risks of developing persisting health complications related to AAP were higher in adolescents and adults, compared to young children. However, adolescents were 5.2-times more likely than young children to develop short-term complications related to AAP such as death, short-term need for insulin, admission to the intensive care unit, and accumulation of fluid with pancreatic juices in the abdomen.

Out of 168 patients with AAP, 34 were re-exposed to ASP. 44% of these patients experienced a second AAP after an average of 2 doses. 21 patients with AAP experienced leukemia relapse and ASP was stopped in 17 of them. Neither AAP nor stopping ASP was associated with a higher risk of relapse.

The authors concluded that adolescent and adult patients with ALL had higher risks of AAP compared to younger children. They also concluded that severity was higher in adolescent patients.