Hyperglycemia requiring insulin during acute lymphoblastic leukemia induction chemotherapy is associated with increased adverse outcomes and healthcare costs

Abstract

Background Hyperglycemia is a complication of induction chemotherapy in 10%‐50% of pediatric patients with acute lymphoblastic leukemia (ALL). Though hyperglycemia in ALL patients is usually transient, it may be associated with adverse health outcomes. However, the risk factors for and consequences of hyperglycemia are poorly understood. We hypothesized that hyperglycemia significant enough to require insulin therapy during induction chemotherapy would be associated with increased morbidity and mortality in pediatric ALL patients during induction chemotherapy and in subsequent care. Methods We abstracted clinical and resource utilization data from the Pediatric Health Information System (PHIS) database utilizing ICD‐9 codes and medication charges. We used logistic regression analysis to predict the development of hyperglycemia. The effects of hyperglycemia on binary and count adverse outcomes following induction chemotherapy were modeled using mixed‐effect regression models. Results An increased risk of hyperglycemia requiring insulin was associated with older age, female sex, higher risk group and trisomy 21. Patients on insulin for hyperglycemia had increased mortality following induction chemotherapy. These patients were more likely to have subsequent infectious complications, need for bone marrow transplant, and risk of disease relapse. They also had greater length of inpatient stay, higher cost of care, and were more likely to require intensive care unit admission during induction chemotherapy. Conclusions Hyperglycemia requiring insulin during induction chemotherapy in pediatric ALL is associated with an increased risk of short‐term and long‐term complications. Prospective studies are needed to analyze formal screening, preventive measures, and optimal management practices for hyperglycemia during ALL induction chemotherapy.

Racial and Economic Differences in the Risk of Hyperglycemia in Children Hospitalized With Acute Lymphoblastic Leukemia

“…Children residing in areas with a median household income in the lower two quartiles faced greater odds of developing hyperglycemia compared to those living in the highest quartile. These findings differ from the secondary analysis of administrative data conducted by McCormick et al (2020) which did not show an association between annual household income and hyperglycemia during ALL treatment. However, in that study, there was no adjustment for the co-morbidity of obesity, a strong predictor of hyperglycemia (McCormick et al, 2020).…”

“…These findings differ from the secondary analysis of administrative data conducted by McCormick et al (2020) which did not show an association between annual household income and hyperglycemia during ALL treatment. However, in that study, there was no adjustment for the co-morbidity of obesity, a strong predictor of hyperglycemia (McCormick et al, 2020).…”

“…We found older children and adolescents between 10 and 20 years to be at greater risk for the development of hyperglycemia than those under the age of 10 years. This finding is consistent with previous research of children with ALL and is likely due to the natural rise in insulin resistance that occurs during puberty (Amiel, et al, 1986; Gatzioura et al, 2016; Koltin et al, 2012; McCormick et al, 2020; Tsai et al, 2015; Zhang et al, 2014). It should be noted that the incidence of ALL is highest among children between the ages of 2 and 5 years, therefore the mean age of 8.8 years potentially reflects an overrepresentation of older children and adolescents in our sample (Hunger & Mullighan, 2015).…”

“…However, the association for Hispanic children was attenuated with the addition of other contributing factors. Previous studies that included race as a predictor did not find differences in their samples (McCormick et al, 2020; Pui et al, 1981; Roberson et al, 2009; Sonabend et al, 2009; Williams et al, 2019).…”

“…Hyperglycemia is a common toxicity affecting between 16% and 24% of children undergoing treatment of acute lymphoblastic leukemia (ALL) during the induction, or initial, phase of treatment (Gatzioura et al, 2016; Tsai et al, 2015; Zhang et al, 2014). Hyperglycemia is associated with diabetic ketoacidosis and increased risk for life-threatening infections in children receiving ALL treatment (Dare et al, 2013; McCormick et al, 2020; Roberson et al, 2008). Children who develop hyperglycemia during treatment may be at increased risk for type 2 diabetes mellitus as survivors (Williams et al, 2019).…”