Recurrent Hypoglycemia Following Asparaginase Therapy for Lymphoid Malignancies in Childhood: The Texas Children's Hospital Experience.

BACKGROUND

Hypoglycemia is a rarely reported complication of asparaginase (ASP) therapy in children with acute lymphoblastic leukemia/lymphoma (ALL/LLy). We sought to identify risk factors and outcomes among patients with ASP-induced hypoglycemia (AIH) at our institution.

METHODS

Retrospective cohort study using electronic medical records to identify all patients who received ASP and had diagnosis of hypoglycemia between June 1, 2017 and June 30, 2022. Demographic and clinically relevant data were collected.

RESULTS

A total of 672 patients received ASP, with 8% having AIH-defined by a measured low blood glucose level within 14 days of ASP administration and other causes of hypoglycemia excluded. Median age at ALL/LLy diagnosis was 4.4 years (inter-quartile range [IQR]: 2.5-7.7) that was younger than a comparison cohort of patients without AIH (median 6.7 years, p value 0.01). Median BMI z-score was 0.50 (IQR: -0.46 to 0.95). Initial hypoglycemia event was during Induction therapy in 71%, with a median of 11 days (IQR: 6-15) from ASP to hypoglycemia diagnosis. Median duration of the hypoglycemia episode was 11 days (IQR: 7-19). Recurrent hypoglycemia with subsequent ASP doses occurred in 84% of patients, with a median duration of 14 days (IQR: 8-21). Overall survival of the AIH cohort was 80% (85% if limited to patients with newly diagnosed ALL/LLy), with 3-year median follow-up. In univariate analysis, hypoglycemia severity was not associated with age, sex, ethnicity, or weight.

CONCLUSION

AIH is relatively common with no clear risk factors besides younger age. It can recur and become more severe with longer duration. AIH screening and management should be implemented.