Association of Age with Acuity and Severity of Illness at Initial Presentation in Children, Adolescents, and Young Adults with Leukemia
Authors: Jain Tarun , Ji Xu , Degroote Nicholas , Himes Alexandra , Coxhead Cortland , Khanna Anjali , Cathcart Alexandra , Miller Tamara P. , Blum Kristie A. , Tarquinio Keiko , Mertens Ann C. , Castellino Sharon M. 
Published: December 2023

Background:
Adolescent and Young Adult (AYA) patients, historically defined by the National Cancer Institute as patients between 15-39 years, diagnosed with cancer are at risk for increased mortality compared with younger patients. Age 10 has been an alternate threshold for higher risk of treatment failure in leukemia. Acuity of illness - as defined by intensive care unit (ICU) level resource use at admission - in children with acute myeloid leukemia (AML) was shown in prior data from the Pediatric Health Information System to mediate excess mortality in Black patients (Winestone et al, Am J Hematol., 2017). This study aims to evaluate the acuity and severity of illness in patients presenting with new diagnoses of leukemia and evaluate whether AYAs have a higher acuity and severity of illness compared to younger patients.
Methods:
We performed a retrospective analysis of 771 patients aged 1-21 years with initial presentation of newly diagnosed leukemia at Children's Healthcare of Atlanta (CHOA) between 2010-2018. Exclusion criteria included those who received any treatment at another facility or those for whom information about the first 72 hours following presentation to the hospital was not available. High acuity of illness was defined (yes/no) as any ICU admission or ICU-level resource use - regardless of physical location in the hospital - by organ system (cardiovascular, respiratory, renal, hematologic, and neurologic) on manual chart review. High severity of illness was defined as initial white blood cell (WBC) count ≥ 50,000 cells/microliter or central nervous system (CNS) disease. Both acuity and severity were assessed during the first 72 hours following the point of diagnosis. Multivariable logistic regression was used to examine the association of age at diagnosis with acuity or severity of illness, controlling for sex, race/ethnicity, insurance status, and type of leukemia.
Results:
Among 536 patients with complete data to date, the median age was 6 years (interquartile range 3-12 years, 65.5% aged 1-9 years, 34.5% aged 10-21 years), 53.4% were male, 45.7% were Non-Hispanic White, and 65.7% had private insurance. Diagnoses included B-cell acute lymphoblastic leukemia (ALL) (70.5%), AML (16.4%), T-cell ALL (9.3%), and other leukemias (3.7%) (juvenile myelomonocytic, chronic myeloid, and Burkitt's).
High acuity of illness was seen in 24.2% of patients and was more likely in older patients (10-21 years, 33.5% versus 1-9 years, 19.4%, p &lt;0.01). Figure 1 illustrates involved organ systems by age group. High severity of illness was seen in 31.3% of cases, and although not significant, was also more likely in older patients (10-21 years, 32.5% versus 1-9 years, 27.9%, p=0.06).
In multivariable analysis, compared to patients aged 1-9 years, patients aged 10-21 years had an increased odds of high acuity of illness [odds ratio (OR) 1.69, 95% confidence interval (CI 1.09-2.63)]. Patients with T-ALL also had an increased odds of high acuity of illness [OR 3.40 (CI 1.76-6.54); referent B-ALL]. The odds of high severity of illness did not differ by age [10-21 years OR 1.23 (CI 0.81-1.86)], but was significantly higher by Non-Hispanic Black race [OR 1.83 (CI 1.14-2.94); referent Non-Hispanic White] and type of leukemia [T-ALL OR 3.90 (CI 2.03-7.48); other leukemia OR 3.26 (CI 1.28-8.32); referent B-ALL] (Table 1).
Discussion and Conclusions:
AYA patients had an increased likelihood of high acuity of illness requiring ICU-level care at presentation, indicating a risk for disparities of outcomes from the point of initial presentation. Future directions will examine the association of acuity of illness with mortality in this cohort, as well as the role of race/ethnicity on severity of illness and mortality. This research will ultimately help inform strategies toward narrowing age disparities in outcomes of AYA leukemia.