Abstract

Abstract Disclosure: M. Tantoush: None. Background: Asparaginase (ASP) is a cornerstone pediatric leukemia and lymphoma therapy. Hyperglycemia following ASP is described, but hypoglycemia is infrequently identified as a complication. Following hypoglycemic events in children receiving ASP therapy, evaluation of associations and outcomes was undertaken. Aim: Evaluate and describe the risk factors, prevalence, duration, severity, recurrence and outcomes of children developing ASP-induced hypoglycemia. Method: Retrospective cohort study using electronic medical records to identify all patients who received ASP (PEGylated or non-PEGylated), and had diagnosis of hypoglycemia between 6/1/2017 and 6/30/22 at Texas Children's Hospital. We defined ASP-induced hypoglycemia as blood glucose (BG) <70 mg/dl 2-8 weeks from ASP administration, without alternative causes. If hypoglycemia evaluation was completed, hyperinsulinism was defined by: BG < 50 mg/dL; insulin > 2 mIU/mL; β-hydroxybutyrate < 1.8 mmol/L; free fatty acids < 1.7 mmol/L; or a post-glucagon BG > 30 mg/dL. Demographic and clinically relevant data were collected. Descriptive analysis was completed. Univariate regression models using Stata16 were analyzed. A p-value <0.05 was statistically significant. Results: Patients receiving ASP totaled 722, with 56 (7.6%) having ASP-induced hypoglycemia. Cancer diagnosis included acute lymphoblastic leukemia (n=50), lymphoblastic lymphoma (n=5) or acute myeloid leukemia (n=1). Median age was 4.4 years (IQR: 2.6 - 8.1), with 46% Hispanic and 59% male. Median BMI z-score was +0.4 (IQR: -0.3 - 1.2). Initial hypoglycemia event was during Induction therapy in 86% (n=48), with median time from ASP to hypoglycemia diagnosis 11 days (IQR: 6-15). Median lowest BG was 51 mg/dL (IQR: 43-57) with median duration 11 days (IQR: 7-19). Treatment included dietary change (52%, n=29), cornstarch (29%, n=16), and continuous feedings (13%, n=7). Continuous BG monitoring was utilized in 9 (16%). A critical sample was obtained in 18 (32%) with all evaluations consistent with hyperinsulinism. Recurrent hypoglycemia with subsequent ASP doses occurred in 42 (74%), with a median duration 14 days (IQR: 8-21; max: 56 days). Overall cancer survival following ASP-induced hypoglycemia was 80% (85% if excluding relapse disease), with 3 years’ median follow up. Severity of hypoglycemia (lowest BG, number of events, or length of events) was not associated with age, sex, ethnicity, or BMI z-score in univariate analysis. Conclusion: ASP-induced hypoglycemia is relatively common, often recurs with subsequent dosing, and may become severe requiring intensive therapy. Prospective screening of patients receiving ASP may be appropriate to prevent and manage events. Patients completed chemotherapy without change in survival at 3 years’ follow-up. Further studies to elucidate prognostic factors of ASP-induced hypoglycemia are needed. Presentation: Saturday, June 17, 2023

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