Pancreas-related persisting sequelae in ALL survivors with a history of asparaginase-associated pancreatitis: A part of the ALL-STAR study

Objectives: Asparaginase-associated pancreatitis (AAP) occurs in up to 18% of patients treated for acute lymphoblastic leukemia (ALL); however, long-term sequelae are largely unexplored. We aimed to explore pancreatic sequelae among ALL survivors with and without AAP. Methods: We investigated pancreatic sequelae in a national cohort of ALL survivors, aged 1–45 years at ALL diagnosis treated according to the NOPHO-ALL2008 protocol and included sex- and age-matched community controls. Results: We included 368 survivors (median follow-up 6.9 years), including 47 survivors with AAP and 369 controls. The p-lipase and p-pancreas-type amylase levels were lower in AAP survivors compared with both non-AAP survivors (Medians: 23 U/L [IQR 14–32] and 18 U/L [IQR 10–25] versus 29 [IQR 24–35] and 22 [17–28], p <.001 and p =.002) and community controls (28 U/L [IQR 22–33] and 21 U/L [IQR 17–26], both p <.006). Fecal-elastase was more frequently reduced in AAP survivors compared with non-AAP survivors (7/31 vs. 4/144, p =.001). Persisting pancreatic sequelae were found in 15/47 of AAP survivors and 20/323 of non-AAP survivors (p <.001), including diabetes mellitus in 2/39 of AAP survivors and 2/273 of non-AAP survivors. Conclusions: ALL survivors with AAP are at increased risk of persisting pancreatic dysfunction and require special attention during follow-up.