Background: There is a need to identify clinical parameters for early and effective risk stratification and prediction of bacterial blood stream infections (BSI) in patients with febrile neutropenia (FN). 1,2,3,4 Acetaminophen is used widely to treat fever in FN; however, little research exists on whether fever response to acetaminophen can be used as a predictor of BSIs. Objectives: Investigate the relationship between fever response to acetaminophen and bacteremia in FN. Design/Method: A retrospective review of patients (1-21 years old) presenting with FN and bacteremia at Rady Children’s Hospital (2012-2018) was performed. Demographic information, presenting signs/symptoms, degree of neutropenia (ANC > 500 or < 500 cells/µL), absolute monocyte count (AMC), blood culture results, temperatures 1-, 2-, and 6-hours after acetaminophen, and timing of antibiotic administration were examined. Patients were stratified into three malignancy categories: leukemia/lymphoma, solid tumor, and hematopoietic stem cell transplant (HSCT). Patients were matched with culture negative controls based on sex, age, malignancy category, and degree of neutropenia. Results: Thirty-five cohort-control pairs met inclusion criteria (70 presentations of FN). Mean age of cohort was 10.7 years (± 6.3) vs. 10.0 years (± 5.9) for the controls. Twenty were female (57%). Twenty-three pairs were categorized as leukemia/lymphoma (66%), 8 as solid tumor (23%) and 4 as HSCT (11%). Thirty-four pairs (97%) had a presenting ANC < 500 cells/µL. Higher temperature 1-hour post-acetaminophen was associated with bacteremia (p = 0.04). Logistic regression demonstrated that temperature 1-hour post-acetaminophen had significant predictive value for bacteremia (p = 0.011). Area under the receiver operating characteristic curves (AUC-ROC) for logistic regression and classification and regression tree (CART) analysis were 0.70 and 0.71 respectively. Conclusion: While temperature 1-hour post-acetaminophen was higher among patients with bacteremia and was a significant predictor of bacteremia, fever response in isolation lacks sufficient predictive value to impact clinical decision making. Future studies are needed to assess fever responsiveness as an adjunct to existing modalities of FN risk stratification.

Purpose: Craniospinal irradiation (CSI) has historically treated the entire vertebral body (VB) in growing children. Vertebral body sparing proton craniospinal irradiation (VBSpCSI) is a technique which spares the majority of the VB from significant irradiation. This retrospective study reviews the acute toxicity of VBSpCSI compared to photon CSI. Methods: Pediatric CSI patients treated between 2008 and 2018 were evaluated. Patients were stratified to the VBSpCSI cohort or the photon cohort and analyzed for acute toxicity profile during treatment and disease-free survival (DFS). Statistical analysis was performed using Kaplan-Meier log rank analysis for DFS and Fisher’s exact test for toxicity. Results: Twenty-five patients received VBSpCSI and 13 patients received photon CSI. Mean patient age at treatment was 7.5y (range 2 to 16). The cohorts were well-matched with respect to gender, age, and CSI dose. Two-year DFS was similar between cohorts (81% VBSpCSI vs 61% photon, p=0.18). Patients receiving VBSpCSI had lower rates of grade 2+ GI toxicity (24% vs 76.5%, p=0.005), grade 2+ nausea (24% vs 61.5%, p=0.035), and any-grade esophagitis (0% vs 38%, p=0.0026). Patients treated with VBSpCSI had lower red blood cell transfusion rates (21.7% vs 60%, p=0.049) and grade 4+ lymphopenia (33.3% vs 77.8%, p=0.046). Conclusions: VBSpCSI in children is a volumetric de-escalation from traditional volumes which irradiate the entire vertebral body. Based on our results, VBSpCSI was associated with less acute gastrointestinal and hematologic toxicity. The study adds to the growing body of evidence supporting the use of protons over photons for pediatric CSI.