Association of race and ethnicity and incidence and severity of hyperglycemia and clinically-treated hypertension during induction therapy for pediatric acute lymphoblastic leukemia

Abstract

Abstract Background: Anti-cancer therapies used to treat pediatric acute lymphoblastic leukemia (ALL) achieve high cure rates but can cause significant adverse events (AEs), including hyperglycemia and hypertension. Development of these cardiovascular risk factors during therapy may contribute to acute morbidity and have potential long-term implications for cardiotoxicity in survivorship. Prior studies show that non-Hispanic Black survivors of childhood or adult cancer experience higher rates of hypertension and other cardiometabolic complications compared to other racial and ethnic groups. However, there are minimal data regarding the incidence and severity of these AEs during therapy for pediatric ALL and how they vary by race and ethnicity. This study aimed to compare the incidence and severity of hyperglycemia and clinically-treated hypertension during induction therapy for de novo pediatric ALL by race and ethnicity. Methods: This single institution retrospective cohort study included children aged 0-21 years diagnosed and treated for ALL at Children's Healthcare of Atlanta (CHOA) between January 1, 2010 and September 1, 2022. Demographic data were extracted from the electronic health record (EHR) and CHOA Cancer Registry. Incidence, severity (defined as the highest grade of each AE per National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] definitions), and pharmacologic treatment of hyperglycemia and hypertension were manually abstracted from the EHR following a detailed chart abstraction guide. Hypertension AEs were only included if pharmacologic treatment was initiated. Addresses at diagnosis were used to map the Social Deprivation Index (SDI) to census tract areas of patient residence for each year from 2010 to 2022. The SDI was categorized into quintiles with quintile 1 representing the areas of lowest social deprivation and quintile 5 representing the areas of highest social deprivation. Multivariable binary logistic regression evaluated the association of race and ethnicity with AE incidence and severity, as well as with insulin use and antihypertensive treatments (oral, IV, other, or multiple medications), adjusting for SDI quintile, age at diagnosis, sex, and National Cancer Institute (NCI) risk classification. Results: Among the 713 patients in the cohort, 392 (55.0%) patients were male, median age at diagnosis was 5 years (IQR 3,10 years), 341 (47.8%) were non-Hispanic White, 153 (21.5%) were non-Hispanic Black, and 186 (26.1%) were Hispanic. Development of any grade of hyperglycemia (n=702, 98.5%) or clinically-treated hypertension (n=294, 41.2%) was common. Of the patients with hyperglycemia and clinically-treated hypertension, 82 (11.5%) had severe (grade 3+) hyperglycemia and 82 (11.5%) 210 (29.5%) had severe (grade 3+) clinically-treated hypertension. Of the 702 patients with hyperglycemia, 80 (11.5%) required insulin treatment. Of the 294 patients with clinically-treated hypertension, 197 (67.0%) received oral treatment, 93 (31.6%) received IV treatment, and 96 (32.7%) received ≥2 medications. When adjusting for other covariates, Non-Hispanic Black patients had significantly higher odds of grade 3+ hyperglycemia (OR 1.96, 95% CI: 1.05–3.66) and grade 3+ clinically-treated hypertension (OR 1.81, 95% CI: 1.18–2.77) compared to non-Hispanic White patients. Additionally, non-Hispanic Black patients had a 2.28 times higher odds (95% CI: 1.16-4.66) of receiving oral antihypertensive treatment compared to non-Hispanic White patients, after adjusting for other covariates. No differences were observed by race and ethnicity for insulin use, IV antihypertensive treatment, or use of multiple antihypertensive agents.Conclusions: In this cohort, non-Hispanic Black race and ethnicity was an independent risk factor for severe hypertension and hyperglycemia during induction therapy for pediatric ALL. Notably, non-Hispanic Black patients had significantly higher odds of receiving oral antihypertensive treatment, suggesting differences in clinical management that warrant further investigation. These findings highlight a targetable group for early hyperglycemic and hypertension intervention and potential prevention. Racial and ethnic disparities in cardiometabolic toxicity may begin during frontline therapy, which underscores the need for early, tailored interventions to reduce future morbidity and mortality in these vulnerable populations.