Tamara P. Miller

Neurobehavioral side effects of corticosteroids during active treatment for acute lymphoblastic leukemia in children are age-dependent: report from Dana-Farber Cancer Institute ALL Consortium Protocol 00-01.

Although corticosteroids remain a mainstay of treatment for acute lymphoblastic leukemia (ALL), they can cause troublesome neurobehavioral changes during active treatment, especially in young children. We evaluated acute neurobehavioral side effects of corticosteroid therapy in preschool versus school‐age children by obtaining structured reports weekly for 1 month.

Accuracy of Adverse Event Ascertainment in Clinical Trials for Pediatric Acute Myeloid Leukemia

PURPOSE Reporting of adverse events (AEs) in clinical trials is critical to understanding treatment safety, but data on AE accuracy are limited. This study sought to determine the accuracy of AE reporting for pediatric acute myeloid leukemia clinical trials and to test whether an external electronic data source can improve reporting. METHODS Reported AEs were evaluated on two trials, Childrens Oncology Group AAML03P1 and AAML0531 arm B, with identical chemotherapy regimens but with different toxicity reporting requirements. Chart review for 12 AEs for patients enrolled in AAML0531 at 14 hospitals was the gold standard. The sensitivity and positive predictive values (PPV) of the AAML0531 AE report and AEs detected by review of Pediatric Health Information System (PHIS) billing and microbiology data were compared with chart data. RESULTS Select AE rates from AAML03P1 and AAML0531 arm B differed significantly and correlated with the targeted toxicities of each trial. Chart abstraction was performed on 204 patients (758 courses) on AAML0531. AE report sensitivity was < 50% for eight AEs, but PPV was > 75% for six AEs. AE reports for viridans group streptococcal bacteremia, a targeted toxicity on AAML0531, had a sensitivity of 78.3% and PPV of 98.1%. PHIS billing data had higher sensitivity (> 50% for nine AEs), but lower PPV (< 75% for 10 AEs). Viridans group streptococcal detection using PHIS microbiology data had high sensitivity (92.3%) and PPV (97.3%). CONCLUSION The current system of AE reporting for cooperative oncology group clinical trials in pediatric acute myeloid leukemia underestimates AE rates. The high sensitivity and PPV of PHIS microbiology data suggest that using external data sources may improve the accuracy of AE reporting.

Comparison of in-patient costs for children treated on the AAML0531 clinical trial: A report from the Children's Oncology Group.

A better understanding of drivers of treatment costs may help identify effective cost containment strategies and prioritize resources. We aimed to develop a method for estimating inpatient costs for pediatric patients with acute myeloid leukemia (AML) enrolled on NCI‐funded Phase III trials, compare costs between AAML0531 treatment arms (standard chemotherapy ± gemtuzumab ozogamicin (GMTZ)), and evaluate primary drivers of costs for newly diagnosed pediatric AML.

Comparison of administrative/billing data to expected protocol-mandated chemotherapy exposure in children with acute myeloid leukemia: A report from the Children's Oncology Group

Recently investigators have used analysis of administrative/billing datasets to answer clinical and pharmacoepidemiology questions in pediatric oncology. However, the accuracy of pharmacy data from administrative/billing datasets have not yet been evaluated. The primary objective of this study was to determine the concordance of Pediatric Health Information System (PHIS) administrative/billing chemotherapy data with Childrens Oncology Group (COG) protocol‐mandated chemotherapy and to assess the implications of this level of concordance for further PHIS research.

A comparison of resource utilization following chemotherapy for acute myeloid leukemia in children discharged versus children that remain hospitalized during neutropenia.

Comparisons of early discharge and outpatient postchemotherapy supportive care in pediatric acute myeloid leukemia (AML) patients are limited. We used data from the Pediatric Health Information System on a cohort of children treated for newly diagnosed AML to compare course‐specific mortality and resource utilization in patients who were discharged after chemotherapy to outpatient management during neutropenia relative to patients who remained hospitalized. Patients were categorized at each course as early or standard discharge. Discharges within 3 days after chemotherapy completion were considered “early”. Resource utilization was determined based on daily billing data and reported as days of use per 1000 hospital days. Inpatient mortality, occurrence of intensive care unit (ICU)‐level care, and duration of hospitalization were compared using logistic, log‐binomial and linear regression methods, respectively. Poisson regression with inpatient days as offset was used to compare resource use by discharge status. The study population included 996 patients contributing 2358 treatment courses. Fewer patients were discharged early following Induction I (7%) than subsequent courses (22–24%). Across courses, patients discharged early experienced high readmission rates (69–84%), yet 9–12 fewer inpatient days (all P < 0.001). Inpatient mortality was low across courses and did not differ significantly by discharge status. The overall risk for ICU‐level care was 116% higher for early compared to standard discharge patients (adjusted risk ratio: 2.16, 95% confidence interval: 1.50, 3.11). Rates of antibiotic, vasopressor, and supplemental oxygen use were consistently elevated for early discharge patients. Despite similar inpatient mortality to standard discharge patients, early discharge patients may be at greater risk for life‐threatening chemotherapy‐related complications, including infections.

The Role of Acuity of Illness at Presentation in Early Mortality in Black Children with Acute Myeloid Leukemia.

Black patients with acute myeloid leukemia (AML) experience higher mortality than White patients. We compared induction mortality, acuity of illness prior to chemotherapy, and insurance type between Black and White patients to assess whether acuity of presentation mediates the disparity. Within a retrospective cohort of 1,122 children with AML treated with two courses of standard induction chemotherapy between 2004 and 2014 in the Pediatric Health Information System (PHIS) database, the association between race (Black versus White) and inpatient mortality during induction was examined. Intensive Care Unit (ICU)‐level resource utilization during the first 72 hours following admission for initial AML chemotherapy was evaluated as a potential mediator. The total effect of race on mortality during Induction I revealed a strong association (unadjusted HR 2.75, CI: 1.18, 6.41). Black patients had a significantly higher unadjusted risk of requiring ICU‐level resources within the first 72 hours after initial presentation (17% versus 11%; RR 1.52, CI: 1.04, 2.24). Mediation analyses revealed the indirect effect of race through acuity accounted for 61% of the relative excess mortality during Induction I. Publicly insured patients experienced greater induction mortality than privately insured patients regardless of race. Black patients with AML have significantly greater risk of induction mortality and are at increased risk for requiring ICU‐level resources soon after presentation. Higher acuity amongst Black patients accounts for a substantial portion of the relative excess mortality during Induction I. Targeting factors affecting acuity of illness at presentation may lessen racial disparities in AML induction mortality.

A comparison of discharge strategies after chemotherapy completion in pediatric patients with acute myeloid leukemia: a report from the Children’s Oncology Group

Abstract While most children receive acute myeloid leukemia (AML) chemotherapy as inpatients, there is variability in timing of discharge after chemotherapy completion. This study compared treatment-related morbidity, mortality and cumulative hospitalization in children with AML who were discharged after chemotherapy completion (early discharge) and those who remained hospitalized. Chart abstraction data for 153 early discharge-eligible patients enrolled on a Children’s Oncology Group trial were compared by discharge strategy. Targeted toxicities included viridans group streptococcal (VGS) bacteremia, hypoxia and hypotension. Early discharge occurred in 11% of courses post-Induction I. Re-admission occurred in 80–100%, but median hospital stay was 7 days shorter. Patients discharged early had higher rates of VGS (adjusted risk ratio (aRR) = 1.67, 95% CI = 1.11–2.51), hypoxia (aRR = 1.92, 95% CI = 1.06–3.48) and hypotension (aRR = 4.36, 95% CI = 2.01–9.46), but there was no difference in mortality. As pressure increases to shorten hospitalizations, these results have important implications for determining discharge practices in pediatric AML.

Using electronic medical record data to report laboratory adverse events

Despite the importance of adverse event (AE) reporting, AEs are under‐reported on clinical trials. We hypothesized that electronic medical record (EMR) data can ascertain laboratory‐based AEs more accurately than those ascertained manually. EMR data on 12 AEs for patients enrolled on two Childrens Oncology Group (COG) trials at one institution were extracted, processed and graded. When compared to gold standard chart data, COG AE report sensitivity and positive predictive values (PPV) were 0–21·1% and 20–100%, respectively. EMR sensitivity and PPV were >98·2% for all AEs. These results demonstrate that EMR‐based AE ascertainment and grading substantially improves laboratory AE reporting accuracy.

Low rates of pregnancy screening in adolescents before teratogenic exposures in a national sample of children's hospitals.

Adolescents with cancer engage in sexual behaviors and are exposed to teratogenic chemotherapy. There are no data regarding pregnancy screening patterns for adolescents before chemotherapy exposure.

Opioid utilization among pediatric patients treated for newly diagnosed acute myeloid leukemia

Purpose A cohort of pediatric patients with AML treated at hospitals contributing to the Pediatric Health Information System was used to evaluate differences in opioid utilization by sex, age, race, and insurance. Methods Billing data were used to compute the prevalence of opioid exposure and to quantify rates of utilization among those exposed to opioids as days of use per 1000 inpatient days. Multivariable regressions were used to compare opioid prevalence, and rates of utilization among those exposed. Results On average across courses, 95.2% of patients were exposed to analgesics, 84.7% were exposed to non-opioid analgesics and 77.7% were exposed to opioids. The proportion of opioid-exposed patients increased with age, but did not differ by gender, race, or insurance status. Analyses limited to patients exposed to opioids revealed modest differences in days of opioid use among female patients (adjusted rate ratio (aRR) = 1.19, 95% CI: 1.11, 1.28), patients <1 year (aRR = 1.37, 95% CI: 1.21, 1.55) or ≥10 years of age (aRR = 1.63, 95% CI: 1.46, 1.82), whereas Asian patients received fewer days of opioids compared with white patients (aRR = 0.76, 95% CI: 0.61, 0.95). There was moderate hospital-level variability in both the prevalence of opioid utilization overall and preference for specific opioid medications. There was greater inconsistency in practice concerning choices for supplemental and alternative opioids than in first-line opioid utilization. Conclusion Additional work is needed to discern whether observed differences in opioid utilization by age and race reflect a difference in treatment or a difference in the experience of pain. Future studies should also explore the factors which guide decisions on opioid selections in an attempt to explain the variability across institutions.