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

Eur J Haematol. 2024 Jun;112(6):944-956. doi: 10.1111/ejh.14189. Epub 2024 Feb 13.

Abstract

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.

Keywords: acute lymphoblastic leukemia; chemotherapy; long‐term cancer survivors; pediatric hematology/oncology; sequelae; treatment outcome.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / adverse effects
  • Asparaginase* / adverse effects
  • Asparaginase* / therapeutic use
  • Cancer Survivors
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Pancreas / drug effects
  • Pancreas / pathology
  • Pancreatitis* / chemically induced
  • Pancreatitis* / diagnosis
  • Pancreatitis* / epidemiology
  • Pancreatitis* / etiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Survivors
  • Young Adult

Substances

  • Asparaginase
  • Antineoplastic Agents