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Background: Cancer is one of the most significant non-transmissible diseases at public health level, and febrile neutropenia (FN) one of its most serious life threatening complications. Objective: To estimate 5-year survival rates for children with cancer and FN from a referral health center in Santiago, Chile, by clinical-demographic variables. Method: Prognostic and analytic historical cohort survival study. (FONDECYT nº 1090194, 2009-2011). Results: 116 subjects were included, and grouped in three categories, by type of cancer: 1) leukemia/lymphomas (51.7%), 2) osteosarcoma (25.9%) and 3) another type of solid organ tumors (22.4%), the median number of days between chemotherapy and the first episode of FN was 5 days [1-7], 7 [7-8] and 7 [5-8] respectively. The five year overall specific survival rate was 64.7%. There were protective factors identified through Cox Model: age, post cancer comorbidity and average educational level of the caregiver. Risk factors identified were: presence of another type of solid organ tumor (HR 3.43 95% CI 1.64-7.19), sepsis (HR 2.89 95% CI 1.47-5.70), delay in chemotherapy treatment (HR 2.94 95% CI 1.17-7.40) and invasive fungal infection (HR 3.36 95% CI 1.22-9.22). Conclusion: This is the first pediatric study in Chile to analyze prognostic factors in children with cancer and FN. The predictor variables that were identified comply with previous reports from international literature.

The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year.Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners.Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability.Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (

Resumen Introducción: Streptococcus grupo viridans (SGV) ha adquirido relevancia como microorganismo causante de neutropenia febril, asociándose a morbilidad significativa. Objetivo: Caracterizar episodios de bacteriemia causados por SGV en niños con cáncer que desarrollaron neutropenia febril de alto riesgo (NFAR) desde abril de 2004 a junio de 2018 en seis hospitales pediátricos de Santiago, Chile. Pacientes y Métodos: Análisis retrospectivo de bases de datos de cuatro proyectos FONDECYT sucesivos, prospectivos y multicéntricos, registrando características clínicas y de laboratorio de los pacientes, además de patrón de resistencia antimicrobiana de las cepas aisladas. Resultados: Se registraron 95 episodios de bacteriemia asociada a SGV en 91 niños con NFAR. Destacan: leucemia mieloide aguda como enfermedad de base, neutropenia profunda, hospitalización prolongada (15 días), uso extendido de antimicrobianos (14 días), uso de citarabina en esquemas de quimioterapia (86% episodios). Las manifestaciones clínicas más frecuentes fueron respiratoria y gastrointestinal, asociándose en 26% a síndrome de shock por Streptococcus grupo viridans. Hubo elevada resistencia a β lactámicos, sin cepas no susceptibles a vancomicina. Discusión: SGV es un patógeno relevante en niños con cáncer, fiebre y neutropenia en nuestro medio, asociado a casos de sepsis. La resistencia a β lactámicos es un aspecto que requiere vigilancia epidemiológica estricta en esta población.

Viridans group streptococci (VGS) has acquired relevance as a microorganism causing febrile neutropenia, associated with significant morbidity.To characterize episodes of bacteremia caused by VGS in children with cancer who developed high-risk febrile neutropenia (HRFN) during the period from April 2004 to June 2018 in six pediatric hospitals of Santiago, Chile.Database analysis of 4 successive, prospective and multicentric studies recording clinical and laboratory characteristics of patients, as well as antimicrobial susceptibility pattern of isolated strains.95 episodes of VGS bacteremia in 91 children with HRFN were analyzed. It emphasizes acute myeloid leukemia as cancer type, deep neutropenia, prolonged hospitalization (15 days), with extended use of antimicrobials (14 days) and use of cytarabine in chemotherapy schemes (86% episodes). The most frequent clinical manifestations were respiratory and gastrointestinal, associating up to 26% viridans group shock syndrome. There was high resistance to β lactams. As expected, there were not non-susceptible strains to vancomycin.VGS is a relevant microorganism in children with cancer, fever and neutropenia, with a high percentage of sepsis. Resistance to β lactams is an issue that requires strict epidemiological surveillance in this population.

Osteosarcomas are bone tumors that frequently metastasize to the lung. Aberrant expression of the transcription factor, runt-related transcription factor 2 (RUNX2), is a key pathological feature in osteosarcoma and associated with loss of p53 and miR-34 expression. Elevated RUNX2 may transcriptionally activate genes mediating tumor progression and metastasis, including the RUNX2 target gene osteopontin (OPN/SPP1). This gene encodes a secreted matricellular protein produced by osteoblasts to regulate bone matrix remodeling and tissue calcification. Here we investigated whether and how the RUNX2/OPN axis regulates lung metastasis of osteosarcoma. Importantly, RUNX2 depletion attenuates lung metastasis of osteosarcoma cells in vivo. Using next-generation RNA-sequencing, protein-based assays, as well as the loss- and gain-of-function approaches in selected osteosarcoma cell lines, we show that osteopontin messenger RNA levels closely correlate with RUNX2 expression and that RUNX2 controls the levels of secreted osteopontin. Elevated osteopontin levels promote heterotypic cell-cell adhesion of osteosarcoma cells to human pulmonary microvascular endothelial cells, but not in the presence of neutralizing antibodies. Collectively, these findings indicate that the RUNX2/OPN axis regulates the ability of osteosarcoma cells to attach to pulmonary endothelial cells as a key step in metastasis of osteosarcoma cells to the lung.

The treatment of acute lymphoblastic leukemia (ALL) includes the use of asparaginase (ASP), a drug associated with hypersensitivity reactions (HSR) that requires discontinuing its use.To determine the incidence of HSR associated with ASP that require discontinuation of its use and des cribe them, and to verify if there is a relationship between HSR incidence and protocols or survival.Retrospective study. Clinical records of all patients (1-15 years) diagnosed with ALL between January 2010 and December 2015 at the Hospital Luis Calvo Mackenna were reviewed. The incidence of HSR to ASP was determined and classified according to the CTCAE v5.0 severity score. We analyzed the relative risk of HSR using Fisher's test and the survival with the Kaplan-Meier estimator.110 patients were collected. During the first treatment (ALL-IC- BFM), the incidence of HSR to L-ASP was 55%, therefore it was changed to PEG-ASP as second-line treatment, and 44% of them had HSR, and ASP should discontinued in 25% of patients. Of all the HSR to ASP, 77% were anaphylactic (CTCAE 3-5). Patients treated with augmented IB protocol were at higher risk of not completing ASP treatment due to HSR, RR 3.81 (95% CI, 1.98-7.31, p = 0.0001). Patients without HSR in ALL-IC-BFM were at lower risk of relapse, HR 0.29 (95% CI, 0.14-0.62, p = 0.0013). Considering all treatments (ALL-IC-BFM and relapse), patients who completed the ASP treatment had higher overall survival, HR 0.20 (95% CI, 0.07-0.57, p = 0.0026).HSR to ASP that require discontinuation of treatment are frequent in children with ALL, most of them were severe anaphylactic reactions. This study suggests a better prognosis in patients without HSR to ASP.

Purpose Health-related quality of life (HRQOL) improves throughout treatment of patients with nonmetastatic osteosarcoma. We compared HRQOL for patients in the United States and Chile treated on an international trial (OS99) with polychemotherapy and surgery, and we assessed the relationships among HRQOL measures, event-free survival (EFS), and overall survival (OS). Materials and Methods Patients with newly diagnosed, localized osteosarcoma and their parents completed three HRQOL instruments (PedsQL v.4, PedsQL Cancer v.3, and Symptom Distress Scale [SDS]). Data were collected at four time points throughout therapy. Repeated measures models were used to investigate the effect of treatment site on instrument scores. The log-rank test examined the impact of treatment site on survival outcomes, and Cox proportional hazards regression models evaluated baseline HRQOL measures as predictors of EFS and OS. Results Of 71 eligible patients, 66 (93%) participated in the HRQOL studies in the United States (n = 44) and Chile (n = 22). The median age was 13.4 years (range, 5 to 23 years). Clinical characteristics were similar between treatment sites. US patients reported better scores for physical ( P = .030), emotional ( P = .027), and school functioning ( P < .001). Chilean patients reported poorer scores for worry ( P < .001) and nausea ( P = .007). Patient and parent nausea scores were similar between patients treated in the United States and Chile by the end of therapy. Differences in symptom distress were not observed between the countries. Neither HRQOL measures nor treatment site were associated with EFS or OS. Conclusion Although significant differences in HRQOL were observed between countries, outcomes were similar, and HRQOL measures were not associated with prognosis.

Resumen Antecedentes: Los microorganismos aislados de hemocultivos (HC) en pacientes con neutropenia febril (NF) varían en el tiempo, siendo necesaria su vigilancia para orientar una terapia empírica adecuada. Objetivo: Identificar microorganismos aislados de HC y su perfil de resistencia (R) a antimicrobianos en niños con cáncer y NF de alto riesgo. Método: Estudio prospectivo, multicéntrico de episodios de NF de alto riesgo en pacientes bajo 18 años de edad, de cinco hospitales en Santiago de Chile, 2012-2015. Análisis de HC positivos. Resultados: Se analizaron 206 microorganismos en 185 episodios de NF de alto riesgo con HC positivos. Los aislados principales fueron bacilos gramnegativos (BGN) (46,6%) y cocáceas grampositivas (CGP) (45,1%) y los microorganismos más frecuentes Escherichia coli (22,8%), Staphylococcus coagulasa negativa (18,0%) y Klebsiella spp (16,5%). En resistencia (R) a antimicrobianos destaca: E. coli y Klebsiella spp 4,2 y 67,6% R a cefalosporinas de tercera generación (cefotaxima/ceftriaxona) respectivamente, 10,6 y 40,6% R a ciprofloxacina y 2,1 y 26,5% a amikacina, respectivamente. S. coagulasa negativa y S. aureus 86,4% y 22,2% R a oxacilina, Streptococcus grupo viridans 71% R a penicilina. Discusión: Este estudio actualiza la etiología y el perfil de R de microorganismos aislados en HC de niños con cáncer y NF de alto riesgo, herramienta esencial para el adecuado manejo de estos pacientes.

Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population.To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN.Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds.A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04).Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN.

To assess the impact of a structured educational programme for caregivers of children with cancer on their level of knowledge about the disease and patient's clinical outcome.This prospective, non-randomised, experimental study included caregivers of recently diagnosed children at two hospitals in Chile. Caregivers whose children were treated at the first centre were the structured education programme group (EPG), while the second hospital provided the standard care (SCG). We evaluated caregivers' level of knowledge on days 1, 10 and 90 as well as the children's clinical outcomes over 1 year of treatment.A total of 102 caregivers were enrolled between 2014 and 2015. Only the EPG showed a significant increase in knowledge between days 1 and 90. The rate of central venous catheter infections was significantly lower in the EPG versus SCG (7% versus 26%; p = .01). The risk ratio was 0.35 (95% CI = 0.13-0.94), and a log-rank test showed a statistically significant difference between the two groups (p = .018). There were also fewer Emergency Department visits in the EPG for fever episodes.Providing a structured education to caregivers increased their level of knowledge and improved the clinical outcome of their children during the first year of treatment.

Introduction The treatment of acute lymphoblastic leukemia (ALL) includes the use of asparaginase (ASP), a drug associated with hypersensitivity reactions (HSR) that requires discontinuing its use. Objective To determine the incidence of HSR associated with ASP that require discontinuation of its use and des cribe them, and to verify if there is a relationship between HSR incidence and protocols or survival. Patients and method Retrospective study. Clinical records of all patients (1-15 years) diagnosed with ALL between January 2010 and December 2015 at the Hospital Luis Calvo Mackenna were reviewed. The incidence of HSR to ASP was determined and classified according to the CTCAE v5.0 severity score. We analyzed the relative risk of HSR using Fisher's test and the survival with the Kaplan-Meier estimator. Results 110 patients were collected. During the first treatment (ALL-IC- BFM), the incidence of HSR to L-ASP was 55%, therefore it was changed to PEG-ASP as second-line treatment, and 44% of them had HSR, and ASP should discontinued in 25% of patients. Of all the HSR to ASP, 77% were anaphylactic (CTCAE 3-5). Patients treated with augmented IB protocol were at higher risk of not completing ASP treatment due to HSR, RR 3.81 (95% CI, 1.98-7.31, p = 0.0001). Patients without HSR in ALL-IC-BFM were at lower risk of relapse, HR 0.29 (95% CI, 0.14-0.62, p = 0.0013). Considering all treatments (ALL-IC-BFM and relapse), patients who completed the ASP treatment had higher overall survival, HR 0.20 (95% CI, 0.07-0.57, p = 0.0026). Conclusions HSR to ASP that require discontinuation of treatment are frequent in children with ALL, most of them were severe anaphylactic reactions. This study suggests a better prognosis in patients without HSR to ASP.

Introduction: The improvements made in the field of pediatric oncology in the last decades due to the propensity to develop national and international cooperative protocols have not been historically seen for a number of very rare pediatric neoplasms whose common denominator lies in their having been treated as orphan diseases. For several years now, this situation has fortunately been gradually changing, and various projects dedicated to these rare diseases have been developed in several countries.Areas covered: This paper describes the schemes dedicated to rare pediatric tumors in countries with different development levels, with a particular reference to the EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) project.Expert opinion: Experience gained in recent years on rare tumors in childhood underscores the importance of cooperation and networking. Further efforts are now needed to extend research and improve the quality of patients care. The pediatric study groups that have i...

Objectives To compare the efficacy of pre-emptive versus empirical antifungal therapy in children with cancer, fever and neutropenia. Methods This was a prospective, multicentre, randomized clinical trial. Children presenting with persistent high-risk febrile neutropenia at five hospitals in Santiago, Chile, were randomized to empirical or pre-emptive antifungal therapy. The pre-emptive group received antifungal therapy only if the persistent high-risk febrile neutropenia was accompanied by clinical, laboratory, imaging or microbiological pre-defined criteria. The primary endpoint was overall mortality at day 30 of follow-up. Secondary endpoints included invasive fungal disease (IFD)-related mortality, number of days of fever, days of hospitalization and use of antifungal drugs, percentage of children developing IFD, requiring modification of initial treatment strategy and need for ICU. The trial was registered with Registro Brasileiro de Ensaios Clinicos (ReBEC) under trial number RBR-3m9d74. Results A total of 149 children were randomized, 73 to empirical therapy and 76 to pre-emptive therapy. Thirty-two out of 76 (42%) children in the pre-emptive group received antifungal therapy. The median duration of antifungal therapy was 11 days in the empirical arm and 6 days in the pre-emptive arm (P

ResumenLos tumores infrecuentes están definidos como cánceres pediátricos con una incidencia anual

Microorganisms isolated from blood cultures (BC) in patients with febrile neutropenia (NF) vary over time, requiring systematic monitoring to guide appropriate empirical therapy.To identify microorganisms isolated from BC and their antimicrobial resistance profile in children with cancer and high risk NF.Prospective, multicenter study. The analysis included episodes of high-risk FN with positive BC in children under 18 years of age treated in five hospitals in Santiago, Chile, 2012-2015.A total of 206 microorganisms were analyzed in 185 episodes of high-risk FN. The main isolates were Gram negative bacilli (46.6%) and Gram positive cocci (45.1%) and the most frequent microorganisms were Escherichia coli (22.8%), coagulase negative Staphylococcus (18.0%) and Klebsiella spp. (16.5%). Escherichia coli and Klebsiella spp showed 4.2% and 67.6% resistance to third generation cephalosporins (cefotaxime/ceftriaxone), 10.6% and 40.6% resistance to fluoroquinolones (ciprofloxacin) and 2.1% and 26.5% to amikacin, respectively. Coagulase negative Staphylococcus and Staphylococcus aureus had 86.4% and 22.2% resistance to oxacillin, Streptococcus viridans group had 71% resistance to penicillin.This study updates the etiology and resistance profile of microorganisms isolated in BC from children with cancer and high risk FN, an essential tool for the adequate management of these patients.

Following previous metronomic meetings in Marseille (2011), Milano (2014), and Mumbai (2016), the first Latin American metronomic meeting was held in the School of Medical Sciences, National University of Rosario, Rosario, Argentina on 27 and 28 of May, 2016. For the first time, clinicians and researchers with experience in the field of metronomics, coming from different countries in Latin America, had the opportunity of presenting and discussing their work. The talks were organised in three main sessions related to experience in the pre-clinical, and clinical (paediatric and adult) areas. The different presentations demonstrated that the fields of metronomic chemotherapy and repurposing drugs in oncology, known as metronomics, constitute a branch of cancer therapy in permanent evolution, which have strong groups working in Latin America, both in the preclinical and the clinical settings including large, adequately designed randomised studies. It was shown that metronomics offers treatments, which, whether they are combined or not with the standard therapeutic approaches, are not only effective but also minimally toxic, with the consequent improvement of the patient’s quality of life, and inexpensive, a feature very important in low resource clinical settings. The potential use of metronomic chemotherapy was proposed as a cost/effective treatment in low-/middle-income countries, for adjuvant therapy in selected tumours. The fundamental role of the governmental agencies and non-governmental alliances, as the Metronomic Global Health Initiative, in supporting this research with public interest was underlined.

Objectives To determine efficacy and safety of withholding antimicrobials in children with cancer, fever and neutropenia (FN) with a demonstrated respiratory viral infection. Methods Prospective, multicentre, randomized study in children presenting with FN at five hospitals in Santiago, Chile, evaluated at admission for diagnosis of bacterial and viral pathogens including PCR-microarray for 17 respiratory viruses. Children positive for a respiratory virus, negative for a bacterial pathogen and with a favourable evolution after 48 h of antimicrobial therapy were randomized to either maintain or withhold antimicrobials. Primary endpoint was percentage of episodes with uneventful resolution. Secondary endpoints were days of fever/hospitalization, bacterial infection, sepsis, admission to paediatric intensive care unit (PICU) and death. Results A total of 319 of 951 children with FN episodes recruited between July 2012 and December 2015 had a respiratory virus as a unique identified microorganism, of which 176 were randomized, 92 to maintain antimicrobials and 84 to withdraw. Median duration of antimicrobial use was 7 days (range 7–9 days) versus 3 days (range 3–4 days), with similar frequency of uneventful resolution (89/92 (97%) and 80/84 (95%), respectively, not significant; OR 1.48; 95% CI 0.32–6.83, p 0.61), and similar number of days of fever (2 versus 1), days of hospitalization (6 versus 6) and bacterial infections throughout the episode (2%–1%), with one case of sepsis requiring admission to PICU in the group that maintained antimicrobials, without any deaths. Conclusions The reduction of antimicrobials in children with FN and respiratory viral infections, based on clinical and microbiological/molecular diagnostic criteria, should favour the adoption of evidence-based management strategies in this population.

Respiratory viral infections in episodes of fever and neutropenia (FN) in children with cancer are not well characterized. We compared the clinical outcome of infections caused by different respiratory viruses (RVs) and by RV coinfection in this population.Children with cancer and FN at 3 hospitals in Chile were prospectively evaluated by clinical examination, blood cultures and detection of 17 RVs using multiplex polymerase chain reaction (nasopharyngeal samples). Clinical characterization and outcome variables were determined and compared by the type of RV detected.A total of 1044 episodes of FN in 525 children were included. At least 1 RV was detected in 46%. In 350 of 1044 (34%) episodes, we detected only RVs, of which 284 (81%) were classified as a single-RV infection and 66 (19%) as a viral coinfection. Respiratory symptoms were present at admission in 65% of the episodes with any detected RV. Median age was 6 years (interquartile range, 3-10), and 51% were women. The most common RVs detected were rhinovirus, respiratory syncytial virus, parainfluenza, influenza, adenovirus and human metapneumovirus. Episodes caused by different types of RVs had no differences in the clinical outcome (days of hospitalization, days of fever, O2 requirement, admission to the intensive care unit and death) and when comparing single and viral coinfection.To our knowledge, this is the largest report comparing clinical outcome in FN episodes caused by different RVs in children with cancer. A positive polymerase chain reaction for RV at admission was significantly associated with the presence of respiratory symptoms. Our data showed a favorable outcome in all episodes with RV detection, including single and viral coinfections.

Purpose To develop an evidence-based guideline for the empiric management of pediatric fever and neutropenia (FN). Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group composed of experts in pediatric oncology and infectious disease as well as a patient advocate. The Panel was convened for the purpose of creating this guideline. We followed previously validated procedures for creating evidence-based guidelines. Working groups focused on initial presentation, ongoing management, and empiric antifungal therapy. Each working group developed key clinical questions, conducted systematic reviews of the published literature, and compiled evidence summaries. The Grades of Recommendation Assessment, Development, and Evaluation approach was used to generate summaries, and evidence was classified as high, moderate, low, or very low based on methodologic considerations. Results Recommendations were made related to initial presentation (risk stratification, initial evaluation, and treatment), ongoing management (modification and cessation of empiric antibiotics), and empiric antifungal treatment (risk stratification, evaluation, and treatment) of pediatric FN. For each recommendation, the strength of the recommendation and level of evidence are presented. Conclusion This guideline represents an evidence-based approach to FN specific to children with cancer. Although some recommendations are similar to adult-based guidelines, there are key distinctions in multiple areas. Implementation will require adaptation to the local context.

BACKGROUND The role of respiratory viral infections (RVIs) as a cause of overall fever and neutropenia (FN) episodes in children with cancer has been less characterized than bacterial infections. We conducted a study aimed to determine the frequency of RVI in children with low compared with high risk for invasive bacterial infection (IBI) FN episodes and compare the clinical outcome of RVI and mixed RV-bacterial infections. METHODS Prospective, multicenter study in children with cancer and FN admitted to pediatric hospitals in Chile between May 2009 and January 2011. Children were evaluated by clinical examination and laboratory tests, including bacterial cultures and their risk for IBI. Nasopharyngeal sample was obtained for the detection of 17 respiratory viruses using polymerase chain reaction-DNA microarray platform. RESULTS A total of 331 episodes of FN in 193 children were enrolled of whom 55% were male, with the median age of 7 years and 61% had a hematological malignancy. A viral and/or bacterial pathogen was detected in 67% (224/331) episodes. Overall, RVIs were associated with 57% of FN of which one-third were mixed RV-bacterial infections. Bacterial infection was detected in 29% (97/331). Children classified at admission as high risk for IBI had a similar overall proportion of RVI compared with low-risk group. Respiratory syncytial virus (31%) and rhinovirus (23%) were the most frequently detected respiratory viruses, followed by parainfluenza (12%) and influenza A (11%). Children detected with any respiratory virus had fewer days of hospitalization and a significantly lower probability of hypotension and admission to pediatric intensive care unit irrespective of their risk classification status at admission when compared with children with mixed RV-bacterial or bacterial infections (P < 0.05). All children with a sole RVI had favorable outcome. CONCLUSIONS RVIs were the most frequently detected agents irrespective of their initial risk assessment for IBI. The clinical outcome of mixed RVI was similar to sole RVI episodes as well as for bacterial infections compared with mixed viral-bacterial infections. Systematic and early detection of RVI in children with cancer and FN might help to optimize their management by reducing hospitalization and antimicrobial use.

Introduction Lung infections are a serious complication in children with cancer. Bronchoalveolar lavage (BAL) has been demonstrated to be an effective procedure for achieving etiologic diagnosis. Method We did a retrospective analysis of BAL data performed between November 2005 and October 2008 in children with cancer, severe neutropenia and lung infiltrates for assessing its performance, clinical utility and safety. Thirty-seven BAL were evaluated in 35 patients. Results Focal infiltrates were demonstrated in imaging studies associated with 19/37 BAL; in 8 an infectious agent was found. Interstitial pattern was observed in 15/37, in which there were 4 positive studies, proving a higher microbiological performance in BAL associated with focal lesions. BAL yielded significant microbiological findings in 32.4% (12/37). Sixteen microorganisms were identified in the study: bacteria in 8 cases, Mycobacterium tuberculosis (n: 2), Pseudomonas aeruginosa (n: 2), Acinetobacter baumannii (n: 1), A. Iwoffii (n: 1), group viridans Streptococcus (n: 1), Mycoplasma pneumoniae (n: 1); viruses in 3 cases, metapneumovirus (n: 2) cytomegalovirus (n: 1) and fungal infection in 5 cases, Pneumocystis jiroveci (n: 2) Aspergillus fumigatus (n: 1), Aspergillus niger (n: 1), Candida albicans (n: 1). Therapeutic adjustments were done in 6/37 episodes (16.2%). Conclusion BAL has a significant role in the evaluation of pulmonary infiltrates in pediatric oncological patients, requiring a prompt and safe diagnosis, which is crucial for the survival with minimal morbidity. Our results suggest that BAL by fiberbronchoscopy should be considered as an initial diagnostic tool in these patients.

Introducción: Conocer la etiología de los episodios de neutropenia febril de alto riesgo (NFAR) en pacientes con cáncer tiene importancia para implementar tratamientos antimicrobianos ajustados a la epidemiología local, lo que tiene impacto en la morbilidad y mortalidad. Objetivo: Describir la etiología de las bacteriemias en niños con cáncer y NFAR en el período 2004-2009, en la red PINDA de Santiago (Región Metropolitana), Chile, y comparar estos agentes y su susceptibilidad antimicrobiana con un estudio previo realizado en el período 1994-1998. Material y Métodos: Se registraron prospectivamente los agentes causantes de bacteriemia y su susceptibilidad a antimicrobianos de los pacientes bajo 18 años de edad en tratamiento quimioterápico por cáncer, ingresados con diagnóstico de NFAR a los seis hospitales de la red, durante el período 2004-2009. Resultados: De 839 episodios de NFAR, 181 tuvieron hemocultivos positivos, correspondientes a cocáceas grampositivas (56%), bacilos gramnegativos (42%) y levaduras (2%). Los agentes más frecuentemente aislados fueron: Staphylococcus coagula-sa negativa (25%), Escherichia coli (20%), Streptococcus grupo viridans (14%), Staphylococcus aureus (13%) y Pseudomonas spp (9%). Al comparar los dos períodos de tiempo, destacan los siguientes cambios significativos: disminución en frecuencia relativa de Staphylococcus coagulasa negativa (desde 44 a 25%), aumento de Streptococcus spp (desde 4 a 17%), y aumento de la resistencia de Staphylococcus coagulasa negativa a oxacilina (desde 55 a 77%). Conclusiones: Se dan a conocer los principales agentes etiológicos de los episodios de NFAR y la susceptibilidad a antimicrobianos en un período de cinco años. Esto permite racionalizar el manejo antimicrobiano empírico de los episodios de NFAR en esta población.

BACKGROUND: The objective of this study was to prospectively evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early imaging indicator of tumor histologic response to preoperative chemotherapy and as a possible prognostic factor for event-free survival (EFS) and overall survival in pediatric patients with newly diagnosed, nonmetastatic osteosarcoma who were treated on a single, multi-institutional phase 2 trial. METHODS: Three serial DCE-MRI examinations at week 0 (before treatment), week 9, and week 12 (tumor resection) were performed in 69 patients with nonmetastatic osteosarcoma to monitor the response to preoperative chemotherapy. Four DCE-MRI kinetic parameters (the influx volume transfer constant [Ktrans], the efflux rate constant [kep], the relative extravascular extracellular space [ve], and the relative vascular plasma space [vp]) and the corresponding differences (ΔKtrans, Δkep, Δve, and Δvp) of averaged kinetic parameters between the outer and inner halves of tumors were calculated to assess their associations with tumor histologic response, EFS, and overall survival. RESULTS: The parameters Ktrans, ve, vp, and kep decreased significantly from week 0 to week 9 and week 12. The parameters Ktrans, vp, and Δkep at week 9 were significantly different between responders and nonresponders (P = .046, P = .021, and P = .008, respectively). These 3 parameters were indicative of histologic response. The parameter Δve at week 0 was a significant prognostic factor for both EFS (P = .02) and overall survival (P = .03). CONCLUSIONS: DCE-MRI was identified as a prognostic factor for EFS and overall survival before treatment on this trial and was indicative of a histologic response to neoadjuvant therapy. Further studies are needed to verify these findings with other treatment regimens and establish the potential role of DCE-MRI in the development of risk-adapted therapy for osteosarcoma. Cancer 2012. © 2011 American Cancer Society.

Purpose Patients with Ewing sarcoma (ES) with metastases and those who relapse fare poorly and receive therapies that carry significant toxicity. This phase 1/2 study was conducted to evaluate the efficacy of figitumumab in advanced ES. Patients and Methods Patients with sarcoma 10 to 18 years old were enrolled in two dose escalation cohorts (20 and 30 mg/Kg intravenously every 4 weeks) in the phase 1 portion of the study. Patients with ES 10 years old or older were enrolled in the phase 2 portion of the study. The primary phase 2 objective was objective response rate (ORR). Results Thirty-one patients with ES (n = 16), osteosarcoma (n = 11), or other sarcomas (n = 4) were enrolled in the phase 1 portion of the study. Dose escalation proceeded to 30 mg/kg every 4 weeks with no dose-limiting toxicity identified. In the phase 2 portion of the study, 107 patients with ES received figitumumab at 30 mg/kg every 4 weeks for a median of 2 cycles (range, 1 to 16). Sixty three percent of phase 2 patients had received at least three prior treatment regimens. Of 106 evaluable patients, 15 had a partial response (ORR, 14.2%) and 25 had stable disease. Median overall survival was 8.9 months. Importantly, patients with a pretreatment circulating free insulin-like growth factor (IGF) -1 lower than 0.65 ng/mL (n = 14) had a median OS of 3.6 months, whereas those with a baseline free IGF-1 ≥ 0.65 ng/mL (n = 84) had a median OS of 10.4 months (P < .001). Conclusion Figitumumab had modest activity as single agent in advanced ES. A strong association between pretreatment serum IGF-1 and survival benefit was identified.

The standard treatment of osteosarcoma includes cisplatin and high-dose methotrexate (HDMTX); both agents exert significant toxicity, and HDMTX requires complex pharmacokinetic monitoring and leucovorin rescue. In the previous OS91 trial, the treatment of localized disease with carboplatin, ifosfamide, doxorubicin, and HDMTX yielded outcomes comparable to those of cisplatin-based regimens and caused less toxicity. To build on this experience, the authors conducted a multi-institutional trial (OS99) that evaluated the efficacy of carboplatin, ifosfamide, and doxorubicin without HDMTX in patients with newly diagnosed, localized, resectable osteosarcoma.Treatment was comprised of 12 cycles of chemotherapy administered over 35 weeks: 3 cycles of carboplatin (dose targeted to area under the concentration-time curve of 8 mg/mL × min on Day 1) and ifosfamide (at a dose of 2.65 g/m(2) daily ×3 days) and 1 cycle of doxorubicin (at a dose of 25 mg/m(2) daily ×3 days) before surgical resection, followed by 2 additional cycles of the combination of carboplatin and ifosfamide and 3 cycles each of doxorubicin (25 mg/m(2) daily ×2 days) combined with ifosfamide or carboplatin.A total of 72 eligible patients (median age, 13.4 years) were enrolled between May 1999 and May 2006. Forty of the 66 (60.6%) evaluable patients had good histologic responses (90% tumor necrosis) to preoperative chemotherapy. The estimated 5-year event-free survival rate was 66.7% ± 7.0% for the OS99 trial compared with 66.0% ± 6.8% for the OS91 trial (P = .98). The estimated 5-year survival rate was 78.9% ± 6.3% for the OS99 trial and 74.5% ± 6.3% for the OS91 trial (P = .40).The regimen used in the OS99 trial was found to produce outcomes comparable to those of cisplatin-containing or HDMTX-containing regimens. This therapy offers a good alternative for patients, particularly those who demonstrate an intolerance of HDMTX, and for institutions that cannot provide pharmacokinetic monitoring for MTX.

Empiric antifungal treatment has become standard of care in children with cancer and prolonged fever and febrile neutropenia (FN), with the downside that it leads to significant over treatment. We characterized epidemiologic, clinical, and laboratory features of invasive fungal disease (IFD) in children with cancer and FN with the aim to identify risk factors for IFD that can aid in better selecting children who require antifungal treatment.In a prospective, multicenter study, children admitted with FN at high-risk for sepsis, in 6 hospitals in Santiago, Chile were monitored from admission until the end of the FN episode. Monitoring included periodic evaluation of clinical findings, absolute neutrophil count, absolute monocyte count (AMC), serum C-reactive protein (CRP), bacterial cultures, imaging studies, and galactomannan antigen. A diagnosis of proven, probable, and possible IFD was made after episode resolution based on European Organization for Research and Treatment of Cancer classification.A total of 646 high-risk FN episodes were admitted during the study period, of which 604 were enrolled. IFD was diagnosed in 35 episodes (5.8%) of which 7 (1.2%) were proven, 10 (1.6%) probable, and 18 (3.0%) possible. Four variables obtained on day 4 were significantly more common in IFD cases, which were presence of fever, absolute neutrophil countor =500/mm, AMCor =100/mm, and CRPor =90 mg/L. The combination of fever, AMCor =100/mm, and CRPor =90 at day 4 provided a RR for IFD of 5.4 (99% CI, 3.2-9.2) with a sensitivity of 75%, specificity of 87%, positive and negative predictive values of 13% and 99%, respectively.Fever persisting at day 4 of admission, together with AMCor =100 and CRPor =90 significantly increased the risk for IFD in children with cancer.

Background Health-related quality of life (HRQOL) of paediatric patients with osteosarcoma has not been documented longitudinally during treatment. Aims of this prospective study were to assess treatment effects on patients’ HRQOL at diagnosis, during therapy and after completion of therapy, to assess sex- and age-related differences in HRQOL ratings and to assess differences between patients’ and parents’ reports. Patients and methods Sixty-six patients (median age, 13.4 years) with newly diagnosed, localised disease completed three HRQOL instruments, and their parents completed two of the same instruments at diagnosis, before surgery (Week 12), at Week 23 and a median of 20 weeks after treatment completion. Results Significant improvements in most domains and worsening of nausea were reported by patients and parents from diagnosis to Weeks 12 and 23. Symptom distress decreased from diagnosis to Weeks 12 and 23 in 81% and 64% of patients, respectively. There were no sex- and few age-related differences in scores. Scores from patients and parents achieved good agreement. Conclusions The HRQOL of patients improves during aggressive treatment for non-metastatic osteosarcoma, except in the domain of nausea. Clinicians can use these findings to prepare their patients for the distressing symptoms that they will likely experience at certain time points and to provide reassurance that these will significantly improve.

ResumenPropósitoDeterminar el impacto de un programa de educación entregado por la enfermera a los padres de niños con cáncer en el aumento del conocimiento de la enfermedad de sus hijos y disminución de la ansiedad.Pacientes y métodosEstudio prospectivo y aleatorio. Incluyó a los padres de niños con diagnóstico reciente de cáncer, atendidos en el Hospital Dr. Luis Calvo Mackenna. Tras la firma de consentimiento informado se aleatorizó a los padres en 2 grupos, uno que recibió el programa educativo y otro sin intervención. Ambos grupos contestaron una encuesta de riesgo social y 3 evaluaciones de conocimiento y de ansiedad.ResultadosUn total de 96 padres fueron incluidos (julio 2010-noviembre 2011). Al comparar el número de respuestas correctas al día 10 y 90 posterior a la intervención entre ambos grupos, se encontró un aumento significativo en el nivel de conocimiento de los padres del grupo que recibió el programa educativo (p

Los hongos del orden Mucorales causan la mucormicosis, que se presenta habitualmente como una enfermedad fúngica invasora con rápida angioinvasión en pacientes inmunocomprometidos. La presentación rino-cerebral es la más frecuente. Las formulaciones lipídicas de anfotericina B se usan como tratamiento primario en las mucormicosis invasoras; el uso combinado de posaconazol podría permitir reducir la dosis de anfotericina B generando una mejor tolerancia y adherencia al tratamiento. La asociación de caspofungina con anfotericina ha demostrado acción sinérgica in vitro y eficacia en modelos murinos. Se presenta el caso de una niña preescolar que durante el debut de una leucemia linfoblástica aguda evolucionó con una mucormicosis rino-cerebral persistente, que respondió en forma exitosa al tratamiento antifúngico combinado de anfotericina liposomal y caspofungina.

The fungi of the order Mucorales cause mucormycosis, which usually presents as an invasive fungal disease with rapid angioinvasion in immunocompromised patients. Rhinocerebral is the most common presentation. The lipid formulations of amphotericin B are used as primary treatment in invasive mucormycosis; the combined use of posaconazole could allow a reduction in the dose of amphotericin B improving tolerance and adherence to treatment. Caspofungin and amphotericin B association has been shown to be synergistic in vitro and effective in murine models. We present the case of a preschool patient that during the debut of acute lymphoblastic leukemia developed a rhinocerebral mucormycosis successfully responding to antifungal treatment with the combination of liposomal amphotericin and caspofungin.

Purpose To compare outcome and cost of ambulatory versus hospitalized management among febrile neutropenic children at low risk for invasive bacterial infection (IBI). Patients and Methods Children presenting with febrile neutropenia at six hospitals in Santiago, Chile, were categorized as high or low risk for IBI. Low-risk children were randomly assigned after 24 to 36 hours of hospitalization to receive ambulatory or hospitalized treatment and monitored until episode resolution. Outcome and cost were determined for each episode and compared between both groups using predefined definitions and questionnaires. Results A total of 161 (41%) of 390 febrile neutropenic episodes evaluated from June 2000 to February 2003 were classified as low risk, of which 149 were randomly assigned to ambulatory (n = 78) or hospital-based (n = 71) treatment. In both groups, mean age (ambulatory management, 55 months; hospital-based management, 66 months), sex, and type of cancer were similar. Outcome was favorable in 74 (95%) of 78 ambulatory-treated children and 67 (94%) of 71 hospital-treated children (P = NS). Mean cost of an episode was US $638 (95% CI, $572 to $703) and US $903 (95% CI, $781 to $1,025) for the ambulatory and hospital-based groups, respectively (P = .003). Conclusion For children with febrile neutropenia at low risk for IBI, ambulatory management is safe and significantly cost saving compared with standard hospitalized therapy.

To determine the impact of an educational program provided by a nurse to parents of children with cancer to improve the level of knowledge of the disease and to decrease the levels of anxiety.A prospective randomized study was conducted on parents of children recently diagnosed with cancer and treated in the Hospital Luis Calvo Mackenna. After informed consent, parents were randomized in two groups: one receiving the educational program and another without intervention. Both groups completed a questionnaire on social risk, and three tests to assess the levels of knowledge and anxiety.A total of 96 parents were enrolled (July 2010-November 2011). When comparing the number of correct responses on day 10, and day 90 after the intervention, a significant increase was observed in the level of parental knowledge in the group that received the educational program (P.0001). No significant differences were observed in the levels of anxiety (P=.06) between both groups.An educational program provided by nurses to parents of children recently diagnosed with cancer, increased the knowledge of their children's disease. However there was no effect on the levels of anxiety. A feasible educational intervention is proposed that could be implemented at other cancer centers for children.

Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer.Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 μg iforthan 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 μg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as10 mIU/ml at 8th month of follow up.A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P.0001 compared with the cancer group. At month 12 of follow up, just 31.9% of children with cancer achieved anti-HBs antibodies10 mIU/ml.Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12h to evaluate the need for further booster doses.

Introducción: En Chile, la leucemia es el cáncer más frecuente en niños, siendo las dos principales leucemia linfoblástica aguda (LLA) y leucemia mieloide aguda (LMA). Objetivo: Describir los episodios de neutropenia febril (NF) observados en niños con LMA, determinando la frecuencia de infecciones según agente, foco y evolución, comparándolos con episodios de niños con LLA. Método: Estudio prospectivo, multicéntrico. Pacientes < de 18 años con NF que consultaron en uno de los seis hospitales del grupo PINDA de Santiago, Chile (abril de 2004-junio de 2011), enrolados en dos sucesivos proyectos FONDECYT. Se recogió de manera sistemática la información epidemiológica, clínica y de laboratorio relativa a cada episodio de NF; posteriormente se extrajo de la base de datos la información correspondiente a los pacientes con LMA y LLA. Resultados: Se evaluaron 506 episodios de NF en niños con leucemia: 173 en niños con LMA y 333 en niños con LLA. Los episodios de NF en niños con LMA presentaron significativamente mayor duración e intensidad de la neutropenia, se mantuvieron febriles por un mayor período de tiempo y presentaron una peor evolución clínica, evidenciada por mayor inestabilidad hemodinámica, mayor frecuencia de sepsis, PCR > 90 mg/L por un período más prolongado, más días de hospitalización, mayor frecuencia de hospitalización en UCI, mayor presencia de bacteriemia, principalmente por Streptococcus grupo viridans, mayor número de cambio de esquemas antimicrobianos y mayor uso de antifúngicos, particularmente de tipo empírico. Conclusiones: Este estudio demuestra que los episodios de NF en niños con LMA evolucionan en mayor medida en forma desfavorable, comparado con episodios de NF en niños con LLA. Los episodios de NF en niños con LMA requieren un enfoque diagnóstico y terapéutico más agresivo, relacionado a su gravedad.

PURPOSE: To identify clinical and laboratory parameters present at the time of a first evaluation that could help predict which children with cancer, fever, and neutropenia were at high risk or low risk for an invasive bacterial infection. PATIENTS AND METHODS: Over a 17-month period, all children with cancer, fever, and neutropenia admitted to five hospitals in Santiago, Chile, were enrolled onto a prospective protocol. Associations between admission parameters and risk for invasive bacterial infection were assessed by univariate and logistic regression analyses. RESULTS: A total of 447 febrile neutropenic episodes occurred in 257 children. Five parameters were statistically independent risk factors for an invasive bacterial infection. Ranked by order of significance, they were as follows: C-reactive protein levels of 90 mg/L or higher (relative risk [RR], 4.2; 95% confidence interval [CI], 3.6 to 4.8); presence of hypotension (RR, 2.7; 95% CI, 2.3 to 3.2); relapse of leukemia as cancer type (RR, 1.8, 95% CI, 1.7 to 2.3); platelet count less than or equal to 50,000/mm3 (RR, 1.7; 95% CI, 1.4 to 2.2); and recent (≤ 7 days) chemotherapy (RR, 1.3; 95% CI, 1.1 to 1.6). Other previously postulated risk factors (magnitude of fever, monocyte count) were not independent risk factors in this study population. CONCLUSION: In a large population of children, common clinical and laboratory admission parameters were identified that can help predict the risk for an invasive bacterial infection. These results encourage the possibility of a more selective management strategy for these children.

BACKGROUND: We previously created a risk prediction model for severe sepsis not clinically apparent during the first 24 hours of hospitalization in children with high-risk febrile neutropenia (HRFN), which identified 3 variables, age ≥ 12 years, serum C-reactive protein (CRP) ≥ 90 mg/L and interleukin-8 ≥ 300 pg/mL, evaluated at the time of admission and at 24 hours of hospitalization. The combination of these 3 variables identified a risk for severe sepsis ranging from 8% to 73% with a relative risk of 3.15 (95% confidence interval: 1.1-9.06). The aim of this study was to validate prospectively our risk prediction model for severe sepsis in a new cohort of children with cancer and HRFN. METHODS: Predictors of severe sepsis identified in our previous model (age, CRP and interleukin-8) were evaluated at admission and at 24 hours of hospitalization in a new cohort of children with HRFN between April 2009 and July 2011. Diagnosis of severe sepsis, not clinically apparent during the first 24 hours of hospitalization, was made after discharge by a blind evaluator. RESULTS: A total of 447 HRFN episodes were studied, of which 76 (17%) had a diagnosis of severe sepsis. The combination of age ≥ 12 years, CRP ≥ 90 mg/L and interleukin-8 ≥ 300 pg/mL at admission and/or at 24 hours in the new cohort identified a risk for severe sepsis ranging from 7% to 46% with an RR of 6.7 (95% CI: 2.3-19.5). CONCLUSIONS: We validated a risk prediction model for severe sepsis applicable to children with HRFN episodes within the first 24 hours of admission. We propose to incorporate this model in the initial patient assessment to offer a more selective management for children at risk for severe sepsis.

During a 2-year period, all children with cancer, neutropenia, and fever who were admitted to Hospital de Ninos Luis Calvo Mackenna (Santiago, Chile) were enrolled in a study of the safety of stopping antibiotic therapy on day 3 of treatment. Children who met predefined criteria for nonbacterial fever were randomized on day 3 to stop (group A) or continue (group B) antibiotic therapy. A total of 220 children with cancer had 238 episodes of fever and neutropenia; 68 children with 75 episodes met entry criteria for nonbacterial fever (group A, 36; group B, 39). Both groups were comparable in terms of age, gender, oncological disease, chemotherapy status, and initial neutrophil count. Resolution of symptoms occurred in 34 of 36 episodes in group A and 36 of 39 episodes in group B (P > .05). No deaths occurred, and bacterial superinfections were uncommon. For children with cancer as well as episodes of fever and neutropenia without an identifiable bacterial etiology at admission, stopping antibiotic therapy on day 3 was safe and not associated with a higher risk of bacterial superinfections.

Leukemia is the most common cancer in Chilean children. Acute lymphoblastic leukemia (ALL) is more prevalent and longer survival compared to acute myeloid leukemia (AML).To describe episodes of febrile neutropenia (FN) in children with AML, determining frequency of infections as agent, focus and evolution, comparing children with ALL episodes.A prospective multicenter study. Children presenting with FN at six hospitals in Santiago, Chile, were invited to participate in two consecutive FONDECYT projects, from April 2004 to June 2011. All patients were uniformly evaluated, recording epidemiological, clinical and laboratory variables. Information regarding FN episodes of children with LMA and LLA was used to this study.We evaluated 506 episodes of FN in children with leukemia: 173 children with AML and 333 in children with ALL. NF episodes in children with ALML showed significantly greater depth and duration of neutropenia, febrile remained aperiod of time and had a worse clinical outcome, as evidenced byhemodynamic instability,sepsis, CRP90 mg/L for a longer time, more days of hospitalization,frequency of hospitalization in ICU,bacteremia, mainly by Streptococcus viridans group,change of antimicrobial treatment,use of antifungal therapy.This study demonstrates that FN episodes in children with ALML further evolve unfavorably, compared with episodes of FN in children with ALL. FN episodes in children with ALML require a more aggressive diagnostic and therapeutic approach, related to its severity.

Las infecciones por virus varicela-zoster (VVZ) en ninos inmunocomprometidos presentan una alta morbi-mortalidad. Se desconoce la seroprevalencia de VVZ en ninos con cancer en nuestro medio. Objetivo: Determinar la prevalencia de anticuerpos anti VVZ en ninos sometidos a tratamiento por cancer (quimioterapia o trasplante de precursores hematopoyeticos). Metodo: Estudio colaborativo, multicentrico. Se recolectaron muestras de suero de 281 ninos con cancer y episodios de neutropenia febril (NF) en seis hospitales de Santiago, entre junio 2004 y agosto 2006 y almacenadas a -70° Co. Doscientas muestras fueron seleccionadas al azar para determinacion de IgG anti VVZ. Resultados: De las 200 muestras de suero obtenidas se excluyeron 21: 12 por ser muestras de un mismo paciente en diferentes episodios de NF y 9 por falta de informacion. Se analizaron las muestras de 179 ninos, 65% de sexo masculino. Noventa y ocho resultaron positivos (55%), 72 negativos (40%) y 9 indeterminados (5%). Estratificado por edad: 1-4 anos (32%), 5-9 anos (42%), 10-14 anos (78%) y mayores de 15 anos (88%). Conclusion: 40% de los ninos en tratamiento por cancer son seronegativos para VVZ, condicion que disminuye en pacientes con mayor edad. Estos resultados apoyan la adopcion de medidas que eviten la infeccion en esta poblacion de ninos con riesgo de desarrollar una enfermedad grave y eventualmente fatal.

Infections with varicella-zoster virus (VVZ) in immunocompromised children imply a high mortality. There is no data about VVZ seroprevalence in children with cancer in our country.To determine the prevalence of VVZ antibodies in children with cancer who have undergone chemotherapy or have undergone a hematopoietic stem cell transplant.collaborative, multicenter study. Serum samples were collected from 281 children with cancer and episodes of febrile neutropenia from 6 hospitals belonging to the public health network in the Metropolitan Region between June 2004 and August 2006. These samples were stored at -70 ° C, and 200 of them were randomly chosen and analyzed to determine VVZ IgG (ELISA).179 samples from 179 children, 65% male. Ninety eighth/179 (55%) were positive, 72/179 (40%) negative and 9/179 (5%) indeterminate. Stratified by age, seropositive percentage was: 1 to 4 years 32%, 5-9 years 42%, 10-14 years 78%, over 15 years 88%.Forty percent of children treated for cancer are seronegative to VVZ infection, a frequency that decreases with age. These results support the adoption of preventive measures to avoid infection in this population of children at risk of developing a serious and possibly fatal illness.

To determine the etiology of invasive bacterial infection in high risk febrile neutropenia (HRFN) episodes in children with cancer is essential because of the favorable impact on mortality of the early empiric antibiotic treatment.To determine the etiology of bacteremia in pediatric patients with cancer and HRFN in the National Child Program of Antineoplastic Drugs during the 2004-2009 period, and compare these agents and their antimicrobial susceptibility with the period 1994-1998 described in a previous study.The causative agents of bacteremia were prospectively recorded in patients less than 18 years of age receiving chemotherapy for cancer with HRFN and positive blood cultures admitted to one of the six hospitals from the Child Program of Antineoplastic Drugs network during the period 2004-2009.839 episodes of HRFN were identified; 181 blood cultures were positive in the following proportion: gram positive cocci (56%), gram negative bacilli (42%) and yeast (2%).The most common etiologic agents were Staphylococcus coagulase negative (25%), Escherichia. coli (20%), group viridans Streptococcus (14%), Staphylococcus aureus (13%) and Pseudomonas aeruginosa (9%). Comparing the two periods, the relative frequency of Streptococcus spp increased from 4 to 17%, coagulase negative Staphylococcus decreased from 44 to 25%, showing an increase in their resistance to oxacillin from 55% to 77%.We describe the main etiological agents from HRFN episodes in children with cancer in a 5 years period. This information could help for a better approach in the empirical antimicrobial therapy in this population.

Lung infections are a serious complication in children with cancer. Bronchoalveolar lavage (BAL) has been demonstrated to be an effective procedure for achieving etiologic diagnosis.We did a retrospective analysis of BAL data performed between November 2005 and October 2008 in children with cancer, severe neutropenia and lung infiltrates for assessing its performance, clinical utility and safety. Thirty-seven BAL were evaluated in 35 patients.Focal infiltrates were demonstrated in imaging studies associated with 19/37 BAL; in 8 an infectious agent was found. Interstitial pattern was observed in 15/37, in which there were 4 positive studies, proving a higher microbiological performance in BAL associated with focal lesions. BAL yielded significant microbiological findings in 32.4% (12/37). Sixteen microorganisms were identified in the study: bacteria in 8 cases, Mycobacterium tuberculosis (n: 2), Pseudomonas aeruginosa (n: 2), Acinetobacter baumannii (n: 1), A. Iwoffii (n: 1), group viridans Streptococcus (n: 1), Mycoplasma pneumoniae (n: 1); viruses in 3 cases, metapneumovirus (n: 2) cytomegalovirus (n: 1) and fungal infection in 5 cases, Pneumocystis jiroveci (n: 2) Aspergillus fumigatus (n: 1), Aspergillus niger (n: 1), Candida albicans (n: 1). Therapeutic adjustments were done in 6/37 episodes (16.2%).BAL has a significant role in the evaluation of pulmonary infiltrates in pediatric oncological patients, requiring a prompt and safe diagnosis, which is crucial for the survival with minimal morbidity. Our results suggest that BAL by fiberbronchoscopy should be considered as an initial diagnostic tool in these patients.

The objective of this study was to prospectively evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early imaging indicator of tumor histologic response to preoperative chemotherapy and as a possible prognostic factor for event-free survival (EFS) and overall survival in pediatric patients with newly diagnosed, nonmetastatic osteosarcoma who were treated on a single, multi-institutional phase 2 trial.Three serial DCE-MRI examinations at week 0 (before treatment), week 9, and week 12 (tumor resection) were performed in 69 patients with nonmetastatic osteosarcoma to monitor the response to preoperative chemotherapy. Four DCE-MRI kinetic parameters (the influx volume transfer constant [K(trans) ], the efflux rate constant [k(ep) ], the relative extravascular extracellular space [v(e) ], and the relative vascular plasma space [v(p) ]) and the corresponding differences (ΔK(trans) , Δk(ep) , Δv(e) , and Δv(p) ) of averaged kinetic parameters between the outer and inner halves of tumors were calculated to assess their associations with tumor histologic response, EFS, and overall survival.The parameters K(trans) , v(e) , v(p) , and k(ep) decreased significantly from week 0 to week 9 and week 12. The parameters K(trans) , v(p) , and Δk(ep) at week 9 were significantly different between responders and nonresponders (P = .046, P = .021, and P = .008, respectively). These 3 parameters were indicative of histologic response. The parameter Δv(e) at week 0 was a significant prognostic factor for both EFS (P = .02) and overall survival (P = .03).DCE-MRI was identified as a prognostic factor for EFS and overall survival before treatment on this trial and was indicative of a histologic response to neoadjuvant therapy. Further studies are needed to verify these findings with other treatment regimens and establish the potential role of DCE-MRI in the development of risk-adapted therapy for osteosarcoma.

Background: Bacterial isolation using conventional microbiologic techniques rarely surpasses 25% in children with clinical and laboratory findings indicative of an invasive bacterial infection. The aim of this study was to determine the role of real-time polymerase chain reaction (RT-PCR) from whole blood samples compared with automated blood cultures (BC) in detection of relevant microorganisms causing bacteremia in episodes of high-risk febrile neutropenia (HRFN) in children with cancer. Methods: Children presenting with HRFN at 6 hospitals in Santiago, Chile, were invited to participate. Blood samples were obtained at admission for BC, and at admission and 24 hours for RT-PCR targeting DNA of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa causing bacteremia in children with HRFN. Results: A total of 177 HRFN episodes were evaluated from May 2009 to August 2010, of which 29 (16.3%) had positive BC, 9 (5%) positive for 1 of the 3 selected bacterial species: 5 for E. coli, 3 for S. aureus, and 1 for P. aeruginosa. RT-PCR detected 39 bacteria in 36 episodes (20%): 14 E. coli, 20 S. aureus, and 5 P. aeruginosa. The sensitivity, specificity, and positive and negative predictive values of RT-PCR compared with BC were 56%, 80%, 13%, and 97%. The final clinical diagnosis was compatible with an invasive bacterial infection in 30/36 (83%) RT-PCR-positive episodes. Conclusions: In our series, RT-PCR significantly improved detection of the most relevant bacteria associated with HRFN episodes. Large number of patients and close clinical monitoring, in addition to improved RT-PCR techniques will be required to fully recommend RT-PCR-based diagnosis for the routine workup of children with cancer, fever, and neutropenia.

Tumor Related Hypercalcemia: A Review of Three Cases Hypercalcemia is an infrecuent complication in pediatric oncology, with an incidence between 0,5 and 3%. It can occur at diagnosis, during the disease course or at relapse, and it is resolved by treating the underlying pathology, requiring in some cases the use of specifi c therapy such as calcitonin and biphosphonates. This article presents 3 cases of children with cancer and hypercalcemia during their illness, analyzing its clinical presentation, pathophysiology and treatment.( Key words: Tumoral hypercalcemia, pediatric oncology, paraneoplasic syndrome).Rev Chil Pediatr 2010; 81 (4): 347-352 RESUMEN La hipercalcemia es una complicacion infrecuente en ninos con cancer, con una incidencia que oscila entre 0,5 y 3%. Se puede presentar al diagnostico, durante el tratamiento o en la recaida de una neoplasia, se resuelve al tratar la enfermedad de base, pudiendo ademas, requerir el uso de terapia especi fi ca como calcitonina y bifos-fonatos. En el presente articulo se revisan 3 casos clinicos de ninos con cancer que presentaron hipercalcemia en algun momento de su enfermedad, se discute su forma de presentacion, fi siopatologia y manejo.(

Children under oncological therapy are at risk of infection by hepatitis B virus (HBV).To determine the prevalence of infection of HBV in children with cancer who have undergone chemotherapy or have had a hematopoietic stem cell transplant.Collaborative, multi-centric study. Serum samples were collected from 281 children with cancer and episodes of febrile neutropenia, from 6 hospitals belonging to the public health network in the Metropolitan Region, between June 2004 and August 2006. These samples were stored at -70 degrees C. In September 2006, 200 samples were randomly chosen and 170 analyzed to determine hepatitis B virus surface antigen (HBsAg) and anticore total antibodies (anti HBc) by fluorescent ELISA (Enzyme Linked Immunosorbent Assay). In five cases in which a low volume of sample was available, only one marker was studied (HBsAg in two and anti HBc in three).Samples came from children aged 4 months to 18 years, 104 males (61%). They had received an average of 38 transfusions (range 3-107) from 65 donors (range 3-345). Twelve children were found positive for some marker of HBV: HBsAg in three (1.8%) and anti HBc in ten (7%). In 5 patients that had negative HBsAg and positive anti HBc, anti surface antigen antibodies (anti HBs) were determined and resulted positive in four.The prevalence of HBV in this sample was 7% if both serologic markers are considered and 1.8% if only HBsAg is considered.