Treatment-Related Hyperglycemia in Children with Acute Lymphoblastic Leukemia: Management and Long-Term Metabolic Outcomes – A Retrospective Cohort Study

Abstract Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with treatment typically involving multidrug chemotherapy regimens that may have hyperglycemia as a well-recognized adverse effect. There are limited data on the management and long-term outcomes of hyperglycemia during ALL therapy in children. The aim of the study is to describe hyperglycemia management during ALL treatment in children, identify associations with its development, and evaluate long-term outcomes. A retrospective chart review of patients with ALL aged 1 to 18 years who developed hyperglycemia during treatment from January 2014 to December 2024 was conducted. Twenty-seven of 880 children (3%) treated for ALL developed hyperglycemia. Of the 27, five (18%) had diabetic ketoacidosis (DKA), four (15%) had diabetic ketosis, and 18 (66%) had hyperglycemia without ketoacidosis. Twenty-three children were treated with insulin, and four needed only hydration. The mean insulin dose was 0.86 units/kg/d (SD = 0.554) and was given for a median of 10 days (interquartile range [IQR] 15.5, range: 2–60 days). None needed HDU/ICU care or had symptomatic hypoglycemia. Hyperglycemia occurred more frequently in children >10 years old (p <0.001). Seventy-four percent of children developed hyperglycemia during the induction phase, with a median duration of 10 days (IQR 10; range, 2–27) between steroid initiation and hyperglycemia. There was no difference in the occurrence of hyperglycemia between intermediate- and high-risk ALL. Forty-four percent (N = 12) developed infections during hyperglycemia, more often in children on high-risk than on intermediate-risk protocols (N = 9 vs. 3, respectively; OR 13.75, p = 0.003). Seven percent (N = 2) had pancreatitis. Sixteen children (59%) with hyperglycemia were followed up for a median duration of 4 years (IQR 4.3 years, range, 1.5–9 years) after ALL therapy. All except one remained euglycemic. An adolescent female diagnosed during the induction phase continued to have insulin-dependent diabetes even at 19.5 years of age. Thirty-three percent were overweight/obese at diagnosis compared to a significant increase to 56% at follow-up (p <0.001). The prevalence of hyperglycemia was 3%, with induction-phase chemotherapy and older age (>10 years) as associated factors. Hyperglycemia was transient and managed successfully with short-term insulin therapy in all but one patient with persistent insulin-dependent diabetes. There was a significant increase in body mass index after ALL treatment, which may be a risk factor for future metabolic complications.