Induction Mortality In Pediatric Acute Lymphoblastic Leukemia (ALL): a Retrospective Cohort Analysis From the Pediatric Health Systems Information (PHIS) Database, 1999–2009
Authors: Seif Alix E. , Rheingold Susan R. , Fisher Brian T. , Huang Yuan-Shung V. , Li Yimei , Kersun Leslie S. , Bailey L. Charles , Reilly Anne F. , Aplenc Richard 
Published: October 2019

Abstract
Abstract 3239
We sought to define factors identifying children at increased risk for mortality during the induction phase of chemotherapy for ALL. We identified a cohort of 11,145 pediatric patients with newly diagnosed ALL using PHIS data from 1999–2009. The PHIS database contains de-identified records of all admissions from 42 children's hospitals across the United States, representing 85% of pediatric admissions to freestanding children's hospitals. Data are internally validated by PHIS, and participating hospitals must have an error rate of <2%. Patients were further validated by manual comparison of induction chemotherapy to published ALL induction standards. Information included in the database are patient demographics, ICD-9 codes, and resource utilization codes for pharmacy, radiology and other procedures. Our strategy to identify newly diagnosed ALL patients included all patients from birth to age 18.99 years with an ICD-9 code for ALL (204.xx) who received one of a series of 3- or 4-drug induction chemotherapy regimens based on standard practices for the era studied. Data were analyzed from the first 30 days after initial admission for ALL. Table 1 shows demographic characteristics, as well as clinical characteristics hypothesized to predict increased mortality. There were 172 patients who died during the study period (1.54%; Table 2). Age <1 year was associated with markedly increased mortality compared to ages 1–9.99 years; patients ages 10–18.99 also had increased mortality. Sex, race and Hispanic ethnicity were not predictive of mortality. We hypothesized that Down syndrome, anthracycline exposure and dexamethasone exposure would be risk factors; however, none of these exposures significantly predicted increased mortality compared to patients without these exposures. Certain interventions were strong predictors of mortality, such as intubation, use of pressors, intubation with concomitant pressors, extracorporeal membrane oxygenation (ECMO), and hemodialysis (Table 2). We tabulated the frequency of ICD-9 codes during the admission in which mortality was observed. The most commonly associated diagnoses were: respiratory failure, acidosis, aplastic anemia, pleural effusion, hemorrhagic stroke, renal failure, sepsis, coagulopathy, complications of a vascular device, hyponatremia, hypotension/shock, pneumonia, and seizure. We are in the process of further analyzing these diagnostic codes for prediction of mortality risk. In summary, we present the largest published dataset of induction mortality in pediatric ALL. Additionally, this is the first use of a nationally representative pediatric ALL dataset that includes patients irrespective of clinical trial enrollment. We are currently performing multivariate analyses using ICD-9 discharge, procedure and utilization codes to define risk factors for induction mortality. Using these analyses, we will develop a model that may allow practitioners to intervene against poor outcomes in high-risk patients. Finally, these data can provide national benchmarks for ALL induction mortality and complication rates that will be critically important in this era of increasing emphasis on patient safety.
Table 1: Demographic characteristics of PHIS ALL cohort, 1999–2009 Patient characteristic N (%) Age at diagnosis, median 5.7 years     <1 year 410 (3.68)     1-9.99 years 7543 (67.68)     10-18.99 years 3192 (28.64) Female 4835 (43.38) Race     Caucasian 8430 (75.66)     African American 938 (8.42)     Asian/Pacific Islander 327 (2.93)     Native American 78 (0.70)     Other/unknown 808 (7.25)     Missing 562 (5.04) Hispanic ethnicity 2376 (21.32) Down syndrome 304 (2.73) Anthracycline exposure 4645 (41.68) Dexamethasone exposure 5393 (48.39) Hospitalization data Mean ± SD Median (range) Duration of 1st admission 13.31 ± 14.82 9 (1-283) Number of hospitalizations in 1st 30 days 1.35 ± 0.59 1 (1-5)
Table 2: Risk of mortality by demographics and need for intervention Risk factor Mortality rate, N (%) RR (95% CI) Overall 172 (1.54) – Age at diagnosis     <1 year 23 (5.61) 7.17 (4.48, 11.49)     1-9.99 years 59 (0.78) 1.0     10-18.99 years 90 (2.82) 3.61 (2.60, 4.99) Any Intubation     Yes 99 (26.68) 39.38 (29.64, 52.32)     No 73 (0.68) 1.0 Pressors     Yes 74 (16.34) 17.82 (13.38, 23.74)     No 98 (0.92) 1.0 Any Intubation + pressors     Yes 60 (45.11) 44.36 (34.10, 57.69)     No 112 (1.02) 1.0 ECMO     Yes 6 (75.00) 50.32 (32.81, 77.17)     No 166 (1.49) 1.0 Hemodialysis     Yes 29 (15.59) 11.95 (8.24, 17.33)     No 143 (1.30) 1.0

Disclosures:
No relevant conflicts of interest to declare.