Child and family perceptions of satisfaction with neutropenia management in pediatric acute myeloid leukemia.

PURPOSE: Chemotherapy for pediatric acute myeloid leukemia (AML) is very intensive and many, but not all centers, require extended hospitalization until neutrophil recovery. Child and family preferences, beliefs, and experiences around hospitalization have not been systematically assessed. PATIENTS AND METHODS: We recruited children with AML and their parents from nine pediatric cancer centers across the United States for a qualitative interview about their experiences of neutropenia management. Interviews were analyzed using a conventional content analysis approach. RESULTS: Of 116 eligible individuals, 86 (74.1%) agreed to participate. Interviews were conducted with 32 children and 54 parents from 57 families. Of these 57 families, 39 were cared for as inpatients and 18 were managed as outpatients. A very high proportion of respondents in both groups reported satisfaction with the discharge management strategy recommended by the treating institution: 86% (57 individuals) of respondents who experienced inpatient management and 85% (17 individuals) of respondents who experienced outpatient management expressed satisfaction. Respondent perceptions associated with satisfaction related to safety (access to emergency interventions, infection risk, close monitoring) and psychosocial concerns (family separation, low morale, social support). Respondents believed it could not be assumed that all children would have the same experience due to varied life circumstances. CONCLUSION: Children with AML and their parents express a very high degree of satisfaction with the discharge strategy recommended by their treating institution. Respondents saw a nuanced tradeoff between patient safety and psychosocial concerns that was mediated by a child's life circumstances.

Risk of bacterial bloodstream infection does not vary by central-line type during neutropenic periods in pediatric acute myeloid leukemia.

BACKGROUND: Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy. OBJECTIVE: To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML. METHODS: We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics. RESULTS: The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75-1.32) and TIC IRR = 0.83 (95% CI, 0.49-1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar. CONCLUSIONS: In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

Medical Outcomes, Quality of Life, and Family Perceptions for Outpatient vs Inpatient Neutropenia Management After Chemotherapy for Pediatric Acute Myeloid Leukemia.

Importance: Pediatric acute myeloid leukemia (AML) requires multiple courses of intensive chemotherapy that result in neutropenia, with significant risk for infectious complications. Supportive care guidelines recommend hospitalization until neutrophil recovery. However, there are little data to support inpatient over outpatient management. Objective: To evaluate outpatient vs inpatient neutropenia management for pediatric AML. Design, Setting, and Participants: This cohort study used qualitative and quantitative methods to compare medical outcomes, patient health-related quality of life (HRQOL), and patient and family perceptions between outpatient and inpatient neutropenia management. The study included patients from 17 US pediatric hospitals with frontline chemotherapy start dates ranging from January 2011 to July 2019, although the specific date ranges differed for the individual analyses by design and relative timing. Data were analyzed from August 2019 to February 2020. Exposures: Discharge to outpatient vs inpatient neutropenia management. Main Outcomes and Measures: The primary outcomes of interest were course-specific bacteremia incidence, times to next course, and patient HRQOL. Course-specific mortality was a secondary medical outcome. Results: Primary quantitative analyses included 554 patients (272 [49.1%] girls and 282 [50.9%] boys; mean [SD] age, 8.2 [6.1] years). Bacteremia incidence was not significantly different during outpatient vs inpatient management (67 courses [23.8%] vs 265 courses [29.0%]; adjusted rate ratio, 0.73; 95% CI, 0.56 to 1.06; P = .08). Outpatient management was not associated with delays to the next course compared with inpatient management (mean [SD] 30.7 [12.2] days vs 32.8 [9.7] days; adjusted mean difference, -2.2; 95% CI, -4.1 to -0.2, P = .03). Mortality during intensification II was higher for patients who received outpatient management compared with those who received inpatient management (3 patients [5.4%] vs 1 patient [0.5%]; P = .03), but comparable with inpatient management at other courses (eg, 0 patients vs 5 patients [1.3%] during induction I; P = .59). Among 97 patients evaluated for HRQOL, outcomes did not differ between outpatient and inpatient management (mean [SD] Pediatric Quality of Life Inventory total score, 70.1 [18.9] vs 68.7 [19.4]; adjusted mean difference, -2.8; 95% CI, -11.2 to 5.6). A total of 86 respondents (20 [23.3%] in outpatient management, 66 [76.7%] in inpatient management) completed qualitative interviews. Independent of management strategy received, 74 respondents (86.0%) expressed satisfaction with their experience. Concerns for hospital-associated infections among caregivers (6 of 7 caregiver respondents [85.7%] who were dissatisfied with inpatient management) and family separation (2 of 2 patient respondents [100%] who were dissatisfied with inpatient management) drove dissatisfaction with inpatient management. Stress of caring for a neutropenic child at home (3 of 3 respondents [100%] who were dissatisfied with outpatient management) drove dissatisfaction with outpatient management. Conclusions and Relevance: This cohort study found that outpatient neutropenia management was not associated with higher bacteremia incidence, treatment delays, or worse HRQOL compared with inpatient neutropenia management among pediatric patients with AML. While outpatient management may be safe for many patients, course-specific mortality differences suggest that outpatient management in intensification II should be approached with caution. Patient and family experiences varied, suggesting that outpatient management may be preferred by some but may not be feasible for all families. Further studies to refine and standardize safe outpatient management practices are warranted.

Cancer Risk by Attained Age among Children with Birth Defects in Arkansas.

BACKGROUND: Few studies have evaluated associations between birth defects and risk of pediatric cancers by age of attainment. Therefore, we assessed the risk of cancer among children with and without birth defects by age at attainment. METHODS: We examined cancer risk in children ≤14 years with and without birth defects born between 1996 and 2011 by linking data from the Arkansas Reproductive Health Monitoring System, Arkansas Central Cancer Registry, and birth certificates. Age of attainment for cancer was calculated as person-years from birth to cancer diagnosis, death, or end of study period, whichever occurred first. Using Cox proportional hazards models, we evaluated associations by attained age groups (<1, 1-4, 5-9, and 10-14 years) between: (1) groups of birth defects (any, chromosomal, and non-chromosomal) and any cancer; (2) non-chromosomal birth defects by organ system and any cancer; and (3) non-chromosomal birth defects and subtypes of cancer. RESULTS: In the cohort of 629,086 children, 23,341 (3.7%) children had birth defects and 1,037 (0.2%) children had cancer. For children with non-chromosomal birth defects, specifically cardiovascular and genitourinary, highest risk of any cancer was observed in first year of life (Hazard Ratio [HR] 18.5; 95% confidence interval [CI] 10.1-33.8). For children with chromosomal birth defects, increased cancer risk was observed among those 1-4 years-old (HR 20.0; 95% CI 8.3-48.4). CONCLUSION: Overall, cancer risk among children with birth defects was highest among those <5 years-old. Our findings, consistent with previous studies, may inform surveillance strategies for children with birth defects.

Outcomes after bloodstream infection in hospitalized pediatric hematology/oncology and stem cell transplant patients.

BACKGROUND: Pediatric hematology/oncology (PHO) patients receiving therapy or undergoing hematopoietic stem cell transplantation (HSCT) often require a central line and are at risk for bloodstream infections (BSI). There are limited data describing outcomes of BSI in PHO and HSCT patients. METHODS: This is a multicenter (n = 17) retrospective analysis of outcomes of patients who developed a BSI. Centers involved participated in a quality improvement collaborative referred to as the Childhood Cancer and Blood Disorder Network within the Children's Hospital Association. The main outcome measures were all-cause mortality at 3, 10, and 30 days after positive culture date; transfer to the intensive care unit (ICU) within 48 hours of positive culture; and central line removal within seven days of the positive blood culture. RESULTS: Nine hundred fifty-seven BSI were included in the analysis. Three hundred fifty-four BSI (37%) were associated with at least one adverse outcome. All-cause mortality was 1% (n = 9), 3% (n = 26), and 6% (n = 57) at 3, 10, and 30 days after BSI, respectively. In the 165 BSI (17%) associated with admission to the ICU, the median ICU stay was four days (IQR 2-10). Twenty-one percent of all infections (n = 203) were associated with central line removal within seven days of positive blood culture. CONCLUSIONS: BSI in PHO and HSCT patients are associated with adverse outcomes. These data will assist in defining the impact of BSI in this population and demonstrate the need for quality improvement and research efforts to decrease them.

Association Between Birth Defects and Cancer Risk Among Children and Adolescents in a Population-Based Assessment of 10 Million Live Births.

IMPORTANCE: Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. OBJECTIVES: To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. DESIGN, SETTING, AND PARTICIPANTS: This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10 181 074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. EXPOSURES: Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. MAIN OUTCOMES AND MEASURES: Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. RESULTS: Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P < .05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. CONCLUSIONS AND RELEVANCE: Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.

Griscelli Type 2 Syndrome and Hemophagocytic Lymphohistiocytosis: Sisters With the Same Mutation but Different Presentations.

Griscelli syndrome type 2 (GS2) is an autosomal recessive condition associated with the development of hemophagocytic lymphohistiocytosis. GS2 is caused by a gene mutation involving RAB27A, which affects a melanosome anchoring complex in melanocytes and releases cytolytic granules from T cells and natural killer cells. GS2 is known to have immunologic compromise and oculocutaneous albinism. We present the case of 2 sisters who had vastly different phenotypic presentations despite having the same genetic frameshift mutation in the RAB27A gene. Patient 1 presented with seizures and neurological compromise, whereas patient 2 presented with pancytopenia and diarrhea. Both patients developed hemophagocytic lymphohistiocytosis.

Identifying patient- and family-centered outcomes relevant to inpatient versus at-home management of neutropenia in children with acute myeloid leukemia.

Efficacy of therapeutic strategies relative to patient- and family-centered outcomes in pediatric oncology must be assessed. We sought to identify outcomes important to children with acute myeloid leukemia and their families related to inpatient versus at-home management of neutropenia. We conducted qualitative interviews with 32 children ≥8 years old and 54 parents. Analysis revealed the impact of neutropenia management strategy on siblings, parent anxiety, and child sleep quality as being outcomes of concern across respondents. These themes were used to inform the design of a questionnaire that is currently being used in a prospective, multiinstitutional comparative effectiveness trial.

Treatment of neuroblastoma in congenital central hypoventilation syndrome with a PHOX2B polyalanine repeat expansion mutation: New twist on a neurocristopathy syndrome.

Neuroblastoma in patients with congenital central hypoventilation syndrome (CCHS) as part of a neurocristopathy syndrome is a rare finding and has only been associated with paired-like homeobox 2b (PHOX2B) non-polyalanine-repeat-expansion mutations. To the best of our knowledge, we report the first case of a child with CCHS and Hirschsprung disease who had a PHOX2B polyalanine-repeat-expansion mutation (PARM) (genotype 20/33) and developed high-risk neuroblastoma. We further describe his treatment including chemotherapy and therapeutic I(131) -metaiodobenzylguanidine. This case highlights the need to consider neuroblastoma in patients with CCHS and the longest PHOX2B PARMs and to individualize treatment based on co-morbidities.

Standardized process used in the emergency department for pediatric oncology patients with fever and neutropenia improves time to the first dose of antibiotics.

OBJECTIVES: This study aimed to evaluate the effect of a standardized process on time to the first dose of antibiotics in pediatric oncology patients presenting to the emergency department (ED) with fever and neutropenia (F-N). METHODS: A standardized process and order set were created to be used on all pediatric febrile neutropenic patients who presented to the ED of a large academic children's hospital. The order set was used for patients with a known oncologic diagnosis, a fever greater than 38.3°C, and who were presumed or known to be neutropenic. A retrospective chart review was then performed for the 18 months before and the 6 months after implementation of the new process to evaluate if the time to the first dose of antibiotics was significantly reduced. RESULTS: A total of 130 occurrences of F-N were analyzed. This included 100 episodes before the implementation of the new process and 30 episodes afterward. The time to antibiotics being ordered was reduced by over half, with a median time of 72 minutes preprocess and 27 minutes postprocess implementation (P = 0.04). Median time from the arrival in the ED to the administration of the first dose of antibiotics was reduced by almost an hour, taking 154 minutes before the new process compared with 95 minutes after its implementation (P = 0.0001). CONCLUSIONS: The use of a standardized process that uses a standardized order set can reduce the time to the first dose of antibiotics in pediatric oncology patients with F-N.

Biomarkers for risk stratification of febrile neutropenia among children with malignancy: a pilot study.

BACKGROUND: Patients receiving myelosuppressive chemotherapy remain at increased risk for developing febrile neutropenia (FN). For this heterogeneous population, a biomarker based risk stratification of FN patients may be a useful clinical tool. We hypothesized that serum biomarkers during initial presentation of an FN event could be predictive of subsequent clinical outcome. PROCEDURE: Eighty-nine FN events from 36 non-consecutive subjects were analyzed. "High-risk" FN criteria included prolonged hospitalization (≥ 7 days), admission to pediatric intensive care unit (PICU) or a microbiology confirmed bacteremia. Patients with "low risk" FN had none of the above. Biomarkers measured during the first 2 days of FN hospitalization were analyzed and correlated with respective clinical outcome. RESULTS: Of the 89 FN events, 44 (49%) fulfilled pre-defined high-risk criteria and 45 (51%) were low-risk. Procalcitonin level (>0.11 ng/ml) was found to be associated with the high-risk FN outcome with sensitivity of 97%. With an increase in log scale by 1, the odds of being high-risk FN increased twofold. Hs-CRP >100 mg/L had sensitivity of 88% in predicting high-risk FN. The odds of a high-risk FN event increased by approximately 1.8-fold with an increase in the log scale of hs-CRP by 1 (10-fold). In univariate analysis, IL-6, IL-8, and IL-10 were statistically significant and associated with high-risk FN. However, no statistically significant difference was found for IL-1α, sIL-2Ra, IL-3, or TNF-α. CONCLUSIONS: Biomarkers with appropriate critical threshold values may be a useful clinical tool for appropriate risk stratification of children with FN.

Multidisciplinary approach to reduction of central line associated blood stream infections (CLABSI): an institutional experience with collaborative guidelines.

Central line associated blood stream infections (CLABSI) among hematology-oncology patients significantly increase morbidity and mortality and remain a universal challenge. Strategies to decrease risk of CLABSI include adherence to standardized practices for central venous line (CVL) care with sustained long-term compliance on the part of caregivers. In our efforts to reduce CLABSI, a multidisciplinary task force was created to systematically introduce standardized CVL insertion and maintenance care bundles in the hematology-oncology inpatient unit. Data was collected in standardized format according to CDC criteria and compared to historical institutional CLABSI rates. During the first year after implementation of these interventions, our CLABSI rate decreased by 68% and rate reduction has been sustained during following two years. The overall impact (2009-2011) includes 40 CLABSIs prevented, 3 lives saved and institutional health care cost savings in excess of 1 million dollars.

Cardiac myeloid sarcoma: a case report and review of literature.

Myeloid sarcomas are rare extramedullary tumors composed of immature myeloid cells. Most cases are seen in childhood acute myelogenous leukemia (AML). They can develop at many sites, but cardiac involvement is a rare finding. We report the case of a 24-year-old woman who, after being in remission from AML for 10 years, developed an isolated cardiac myeloid sarcoma.

Antibiotic hypersensitivity in CF: drug-induced life-threatening hemolytic anemia in a pediatric patient.

Adverse reactions to antibiotics in patients with cystic fibrosis (CF) are a growing concern. We report the case of a pediatric patient with CF with multiple comorbidities and a history of drug reactions, who developed life-threatening piperacillin-induced immune hemolytic anemia. We review drug-induced hemolytic anemia (DIIHA) in particular, and antibiotic hypersensitivity in CF in general, including the frequency, pathogenesis, and risk factors. Finally, we discuss the treatment options and propose an algorithm for the management of drug-induced hypersensitivity reactions in patients with CF.

Hemophagocytic lymphohistiocytosis secondary to Ehrlichia chaffeensis infection: a case report.

SUMMARY: Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially life-threatening condition that is characterized by fever, splenomegaly, and cytopenia in 2 or more peripheral blood lineages, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis. HLH may be primary or may be triggered by numerous etiologies, including infections. Identification of underlying etiology of HLH is important as proper treatment can completely resolve the disease process. We present a patient whose clinical presentation fulfilled the diagnostic criteria for HLH but whose illness was caused by infection with Ehrlichia chaffeensis, emphasizing the need to explore all possible etiologies during evaluation of patients presenting with illnesses consistent with HLH.