Neutropenia and Infection Prophylaxis in Childhood Cancer.

PURPOSE OF REVIEW: Pediatric oncology patients frequently experience episodes of prolonged neutropenia which puts them at high risk for infection with significant morbidity and mortality. Here, we review the data on infection prophylaxis with a focus on both pharmacologic and ancillary interventions. This review does not include patients receiving hematopoietic stem cell transplantation. RECENT FINDINGS: Patients with hematologic malignancies are at highest risk for infection. Bacterial and fungal prophylaxis decrease the risk of infection in certain high-risk groups. Ancillary measures such as ethanol locks, chlorhexidine gluconate baths, GCSF, IVIG, and mandatory hospitalization do not have enough data to support routine use. There is limited data on risk of infection and role of prophylaxis in patients receiving immunotherapy and patients with solid tumors. Patients with Down syndrome and adolescent and young adult patients may benefit from additional supportive care measures and protocol modifications. Consider utilizing bacterial and fungal prophylaxis in patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. More research is needed to evaluate other supportive care measures and the role of prophylaxis in patients receiving immunotherapy.

Multi-institutional analysis of treatment modalities in basal ganglia and thalamic germinoma.

BACKGROUND: Central nervous system (CNS) germinomas are treatment-sensitive tumors with excellent survival outcomes. Current treatment strategies combine chemotherapy with radiotherapy (RT) in order to reduce the field and dose of RT. Germinomas originating in the basal ganglia/thalamus (BGTGs) have proven challenging to treat given their rarity and poorly defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have all been utilized; however, the best treatment strategy remains unclear. METHODS: Retrospective multi-institutional analysis has been conducted across 18 institutions in four countries. RESULTS: For 43 cases of nonmetastatic BGTGs, the 5- and 10-year event-free survivals (EFS) were 85.8% and 81.0%, respectively, while the 5- and 10-year overall survivals (OS) were 100% and 95.5%, respectively (one patient fatality from unrelated cause). Median RT doses were as follows: CSI: 2250 cGy/cGy(RBE) (1980-2400); WBI: 2340 cGy/cGy(RBE) (1800-3000); WVI: 2340 cGy/cGy(RBE) (1800-2550); focal: 3600 cGy (3060-5400). Thirty-eight patients (90.5%) received chemotherapy. There was no statistically significant difference in the EFS based on initial field extent (p = .84). Nevertheless, no relapses were reported in patients who received CSI or WBI. Chemotherapy alone had significantly inferior EFS compared to combined therapy (p = .0092), but patients were salvageable with RT. CONCLUSION: Patients with BGTGs have excellent outcomes and RT proved to be an integral component of the treatment plan. This group of patients should be included in future prospective clinical trials and the best RT field should be investigated further.

Severe non-hepatic hyperammonaemic encephalopathy in an immunocompromised adolescent with enterocolitis.

Non-hepatic causes of hyperammonaemia are uncommon relative to hepatic aetiologies. An adolescent female was admitted to the hospital with a diagnosis of very severe aplastic anaemia. During her treatment with immunosuppressive therapy, she developed neutropenic enterocolitis, pseudomonal bacteraemia and hyperammonaemia. A combination of intermittent haemodialysis and high-volume continuous veno-venous haemodiafiltration (CVVHDF) was required to manage the hyperammonaemia. Despite a thorough investigation, there were no hepatic, metabolic or genetic aetiologies identified that explained the hyperammonaemia. The hyperammonaemia resolved only after the surgical resection of her inflamed colon, following which she was successfully weaned off from the renal support. This is a novel case report of hyperammonaemia of non-hepatic origin secondary to widespread inflammation of the colon requiring surgical resection in an immunocompromised patient. This case also highlights the role of high-volume CVVHDF in augmenting haemodialysis in the management of severe refractory hyperammonaemia.

Value-Based Care for Healthy Children With First Episode of Febrile Neutropenia.

OBJECTIVES: There is a lack of guidance on the management of febrile neutropenia in otherwise healthy children, including the need for hospitalization and antibiotic administration, leading to significant practice variation in management. The aim of this initiative was to decrease the number of unnecessary hospitalizations and empirical antibiotics prescribed by 50% over a 24-month period for well-appearing, previously healthy patients older than 6 months presenting to the emergency department with a first episode of febrile neutropenia. METHODS: A multidisciplinary team of stakeholders was assembled to develop a multipronged intervention strategy using the Model for Improvement. A guideline for the management of healthy children with febrile neutropenia was created, coupled with education, targeted audit and feedback, and reminders. Statistical control process methods were used to analyze the primary outcome of the percentage of low-risk patients receiving empirical antibiotics and/or hospitalization. Balancing measures included missed serious bacterial infection, emergency department (ED) return visit, and a new hematologic diagnosis. RESULTS: Over the 44-month study period, the mean percentage of low-risk patients hospitalized and/or who received antibiotics decreased from 73.3% to 12.9%. Importantly, there were no missed serious bacterial infections, no new hematologic diagnoses after ED discharge, and only 2 ED return visits within 72 hours without adverse outcomes. CONCLUSIONS: A guideline for the standardized management of febrile neutropenia in low-risk patients increases value-based care through reduced hospitalizations and antibiotics. Education, targeted audit and feedback, and reminders supported sustainability of these improvements.

Peer mentoring for type 2 diabetes prevention in first nations children.

OBJECTIVE: The goal of this study was to assess the efficacy of an after-school, peer-led, healthy living program on adiposity, self-efficacy, and knowledge of healthy living behaviors in children living in a remote isolated First Nation. METHODS: A quasi-experimental trial with a parallel nonequivalent control arm was performed with 151 children in Garden Hill First Nation during the 2010-2011 and 2011-2012 school years. Fourth grade students were offered a 5-month, peer-led intervention facilitated by high school mentors between January and May of each school year; students in the control arm received standard curriculum. The main outcome measures were waist circumference (WC) and BMI z score. Secondary outcome measures included healthy living knowledge and self-efficacy. RESULTS: Fifty-one children (mean ± SD age: 9.7 ± 0.4 years; BMI z score: 1.46 ± 0.84) received the intervention, and 100 children were in the control arm. At baseline, WC (79.8 vs 83.9 cm), BMI z score (1.46 vs 1.48), and rates of overweight/obesity (75% vs 72%) did not differ between arms. After the intervention, the change in WC (adjusted treatment effect: -2.5 cm [95% confidence interval (CI): -4.1 to -0.90]; P = .002) and BMI z score (adjusted treatment effect: -0.09 [95% CI: -0.16 to -0.03]; P = .007) were significantly lower in the intervention arm compared to the control arm. The intervention arm also experienced improvements in knowledge of healthy dietary choices (2.25% [95% CI: -0.01 to 6.25]; P = .02). Self-efficacy was associated with the change in WC after the intervention (ß = -7.9, P = .03). CONCLUSIONS: An after-school, peer-led, healthy living program attenuated weight gain and improved healthy living knowledge in children living in a remote isolated First Nation.