Comprehensive Care Improvement for Oncologic Fever and Neutropenia from a Pediatric Emergency Department.

Introduction: Rapid time to antibiotics (TTA) for pediatric patients with fever and neutropenia in an emergency department decreases in-hospital mortality. Additionally, national guidelines recommend outpatient antibiotic management strategies for low-risk fever and neutropenia (LRFN). This study had two specific aims: (1) improve the percent of patients with suspected fever and neutropenia who receive antibiotics within 60 minutes of arrival from 55% to 90%, and (2) develop and operationalize a process for outpatient management of LRFN patients by October 2018. Methods: Using Lean methodologies, we implemented Plan-Do-Check-Act cycles focused on guideline development, electronic medical record reminders, order-set development, and a LRFN pathway as root causes for improvements. We used statistical process control charts to assess results. Results: The project conducted from July 2016 to October 2018 showed special cause improvement in December 2016 on a G-chart. Monthly Xbar-chart showed improvement in average TTA from 68.5 minutes to 42.5 minutes. A P-chart showed improvement in patients receiving antibiotics within 60 minutes, from 55% to 86.4%. A LRFN guideline and workflow was developed and implemented in October 2017. Conclusions: Implementation of guidelines, electronic medical record reminders, and order sets are useful tools to improve TTA for suspected fever and neutropenia. Utilizing more sensitive statistical process control charts early in projects with fewer patients can help recognize and guide process improvement. The development of workflows for outpatient management of LRFN may be possible, though it requires further study.

Isobaric Labeling Strategy Utilizing 4-Plex N,N-Dimethyl Leucine (DiLeu) Tags Reveals Proteomic Changes Induced by Chemotherapy in Cerebrospinal Fluid of Children with B-Cell Acute Lymphoblastic Leukemia.

The use of mass spectrometry for protein identification and quantification in cerebrospinal fluid (CSF) is at the forefront of research efforts to identify and explore biomarkers for the early diagnosis and prognosis of neurologic disorders. Here we implemented a 4-plex N,N-dimethyl leucine (DiLeu) isobaric labeling strategy in a longitudinal study aiming to investigate protein dynamics in children with B-cell acute lymphoblastic leukemia (B-cell ALL) undergoing chemotherapy. The temporal profile of CSF proteome during chemotherapy treatment at weeks 5, 10-14, and 24-28 highlighted many differentially expressed proteins, such as neural cell adhesion molecule, neuronal growth regulator 1, and secretogranin-3, all of which play important roles in neurodegenerative diseases. A total of 63 proteins were significantly altered across all of the time points investigated. The most over-represented biological processes from gene ontology analysis included platelet degranulation, complement activation, cell adhesion, fibrinolysis, neuron projection, regeneration, and regulation of neuron death. We expect that results from this and future studies will provide a means to monitor neurotoxicity and develop strategies to prevent central nervous system injury in response to chemotherapy in children.

Association of Immune Thrombocytopenia and T-Lymphoblastic Lymphoma in a Pediatric Patient.

Immune thrombocytopenia (ITP) is characterized by isolated thrombocytopenia of unclear etiology. We present a unique case of an 8-year-old girl with chronic ITP who was subsequently diagnosed with T-lymphoblastic lymphoma at age 11. The clinical course was complicated by the occurrence of nonepileptiform events with bizarre behavior changes following the administration of nelarabine and intrathecal and high-dose systemic methotrexate. This case highlights an unusual co-occurrence of hematologic malignancy and chronic ITP in an otherwise healthy child. We speculate that underlying genetic or immunologic lesions may predispose a subset of pediatric ITP patients to the development of hematologic malignancies.

Burkitt's and Burkitt-like lymphoma in children and adolescents: a review of the Children's Cancer Group experience.

Historically, the survival of children and adolescents with Burkitt's and Burkitt-like lymphoma had been poor. Recently, short and intensive chemotherapy appears to have improved disease outcome. We therefore reviewed the results of four successive Children's Cancer Group trials conducted on 470 children with disseminated Burkitt's and Burkitt-like lymphoma. Of the patients studied, the median age was 8 years (0-21 years), the male:female ratio was 4:1, 58% had lactate dehydrogenase (LDH) > or = 500 IU/l, 23% had M2 or M3 bone marrow (BM), and 12% demonstrated central nervous system involvement. In a multivariate analysis, the 4-year event-free survival (EFS) in patients > or = 15-years-old compared with < 15-year-old was 34 +/- 7 versus 59 +/- 2% (P < 0.05), the 4-year EFS of M2/M3 compared with M1 BM was 38 +/- 5 versus 63 +/- 3% (P < 0.001), and the 4-year EFS with LDH > or = 500 IU/l compared with LDH < 500 IU/l was 49 +/- 3 versus 71 +/- 4% (P < 0.001). Furthermore, patients treated on the most recent protocol, which was short and more intensive, had a significantly improved survival compared with those on previous trials (4-year EFS 80 +/- 6 versus 54 +/- 2%, P < 0.001). In summary, the outcome for childhood Burkitt's and Burkitt-like lymphoma has recently improved with the use of short and intensive B-cell non-Hodgkin's lymphoma-directed therapy.