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PurposeLate effects in childhood cancer survivors are a major cause of morbidity and mortality. The objective was to establish knowledge about the disease, late effects, self-care practices, application of health knowledge/education, sources of information, and biopsychosocial impact of cancer, and compare the results of Chile and Croatia. Methodsone hundred and seventy-one, five-year survivors who were treated for leukemia or non-Hodgkins lymphoma responded to a questionnaire (119 in Chile and 52 in Croatia). The questionnaire was reviewed by BFM- ELTEC. Resultshealth knowledge about past diagnosis and general treatment had 96% Chilean and 85% Croatian survivors. Ninety percent of Chilean and 73% of Croatian survivors were unaware of possible late effects, and half did not know which specialist to visit for follow-up. Forty-six percent of Chilean and 35% of Croatian survivors knew about healthy lifestyles, but most did not practice them. The 74% of Chileans and 87% of Croatian survivors recalled having received health education during treatment. About 50% survivors in both groups was afraid or anguish, but it was also a growth experience for 60% of Chilean and 42% Croatian survivors. Eighty-seven percent Chilean and 77% Croatian survivors considered themselves physically independent, while 76% and 75% felt psychologically independent, respectively. ConclusionIt was detected a significant lack of knowledge about the specific treatment, late effects, and future health in both countries. They did not achieve significant learning with the education received. Psychological sequelae were found that are important to prevent.

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.

Objectives Platinum-based chemotherapy is effective against a variety of pediatric malignancies. Unfortunately, the use of cisplatin and carboplatin can lead to permanent and progressive sensorineural hearing loss which can affect the quality of life of cancer survivors. The objectives of this study were to evaluate the incidence of platinum-induced ototoxicity in children and analyze potential risk factors. Methods Prospective cohort study. All pediatric patients receiving chemotherapy with cisplatin and/or carboplatin from 01/2012 until 10/2017 were included. Hearing evaluations were performed before every chemotherapy cycle, and following the end of chemotherapy, with auditory brainstem response, otoacoustic emissions and/or audiometry. Demographics, cumulative doses, cranial irradiation and exposure to other ototoxic agents were analyzed. Results Twenty-eight patients were included, with a mean age of 7.2 years at the beginning of chemotherapy (range 5 months–15 years 2 months); twenty-one patients received cisplatin, four received carboplatin, and three received both agents. Twelve patients had cranial irradiation and seven received another ototoxic medication. The most frequent malignancies were germ cell tumors, medulloblastoma and gliomas. Sensorineural hearing loss occurred in 28.6% of the patients with a mean follow-up period of 21.5 months (range: 1–53 months). All patients evaluated with audiometry had ≥ Chang 2b ototoxicity. Risk factors include age less than 5 years, cranial irradiation, and cisplatin cumulative dose greater than 400 mg/m2. Conclusion Sensorineural hearing loss is a potential side effect of platinum-based chemotherapy. Pediatric patients receiving cisplatin chemotherapy with a cumulative dose exceeding 400 mg/m2, cranial irradiation as well as patients younger than 5 years are at greater risk of developing hearing loss.

OBJECTIVE The aim of this study was to analyze the survival of children with Wilms tumor and other malignant renal tumors treated with the TWPINDA-99 protocol. MATERIALS AND METHODS Between January 1999 and December 2013, 226 patients were registered on this trial, based on National Wilms Tumor Study-5. Patient characteristics and survival were evaluated. RESULTS Two hundred seven patients were diagnosed with Wilms tumor, which represented 91.6% of renal tumors. The male to female ratio was 0.7:1. The median age at diagnosis was 3.3 years. Stage III was the most frequent (39.2%). Metastatic disease was present in 16.7% of the cases. Synchronous bilateral disease was observed in 9.3% of the cases. Favorable histology was diagnosed in 93.6% and anaplastic histology in 6.4% of the patients. Median follow-up was 7.5 years. Ten-year event-free survival and overall survival (OS) for assessable patients with Wilms tumor (n=192) were 82.0% and 89.9%, respectively. OS for patients with stage I was 100% (n=36), stage II: 97.1% (n=35), stage III: 88.6% (n=71), stage IV: 77.9% (n=32), and stage V: 80.8% (n=18). OS for favorable histology (n=180) and anaplastic histology tumors (n=12) were 91.0% and 72.9%, respectively. Other malignant renal tumors had a poorer survival. CONCLUSION Prognosis for patients with Wilms tumor treated on TWPINDA-99 seems to be better than previous national trials and is similar to developed countries.

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.

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.

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.

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.

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 The National Chilean Pediatric Oncology Group, PINDA, reports the first prospective, nonrandomized trial for acute lymphoblastic leukemia (ALL), using a modified version of the Berlin-Frankfurt-Munster protocol (ALL BFM 86). The aim of this study was to classify immunophenotypes, to decrease cranial irradiation, and to assess whether this protocol would improve the survival rate. Procedure From June, 1987, to June, 1992, 444 unselected children were diagnosed with ALL. Of them, 425 were evaluable. Therapy was stratified by risk. Standard-risk (SR) and high-risk (HR) patients received protocols I, M, II, and maintenance therapy. Very-high-risk (VHR) patients received protocol E instead of protocol M. All patients received a prephase treatment consisting of prednisone and intrathecal methotrexate (MTX). HR and VHR patients received cranial irradiation (12–18 Gy). The following changes were made to the ALL BFM 86 protocol: in protocol M, MTX 1 g/m2 instead of 5 g/m2; in protocol E, citarabine 1 g/m2 instead of 2 g/m2; mithoxantrone and ifosfamide were substituted by teniposide and cyclophosphamide. Results Immunophenotypes: pro-B-ALL, 14%; common ALL, 67.4%; pre-B-ALL, 4.3%; T-ALL, 10%; undifferentiated leukemia (AUL), 4.3%. The overall 5-year event-free survival (EFS) rate was 60% ± 2% (SE). The 5-year EFS rate for each risk group was: SR 75%, HR 62%, VHR 28%, with a median follow-up of 6.5 years (range 4.5–9.5 years). The cumulative incidence of central nervous system (CNS) relapse was 5.4%. Conclusions We have been able successfully to perform a nationwide study. Our strategy to adapt the BFM protocol to our population of patients trial was effective in improving the EFS. The immunophenotype distribution is similar to that in other reported series. Med. Pediatr. Oncol. 33:88–94, 1999. © 1999 Wiley-Liss, Inc.

We evaluated the efficacy of a vancomycin solution in the prevention of bacteremia caused by vancomycin-sensitive organisms (VSO) in cancer patients with a tunneled central venous catheter (CVC). Eighty-three patients who had a single lumen CVC were randomized to use a heparin solution (25 U/ml) for daily catheter flush with (HepVan) or without (Hep) vancomycin, 25 mcg/ml. Febrile episodes were recorded, and central and peripheral blood cultures were drawn before beginning antibiotic therapy. Patients participated in follow-up to 16,677 catheter days (8,666 Hep and 8,011 HepVan), and 143 febrile episodes were recorded (82 Hep and 61 HepVan). Forty-four episodes of bacteremia occurred, 23 of them due to VSO (16 occurred in the Hep group and 7 in the HepVan group (P = 0.19). VSO bacteremia occurred in 14 neutropenic (absolute neutrophil count < 500 x 10(9)/l) episodes (7 Hep vs. 7 HepVan) and in 9 non-neutropenic episodes (9 Hep vs. O HepVan; P = 0.013). Vancomycin effectively prevented bacteremia by VSO in non-neutropenic patients, supporting the idea that intraluminal colonization of indwelling CVCs contributes to bacteremia only in these patients.

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.

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.

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.

Background: Children under oncological therapy are at risk of infection by hepatitis B virus (HBV). Aim: To determine the prevalence of infection of HBV in children with cancer who have undergone chemotherapy or have had a hematopoietic stem cell transplant. Material and methods: 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-'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). Results: Samples carne 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 Conclusions: The prevalence of HBV in this sample was 7% if both serologic markers are considered and 1.8% if only HBsAg is considered.

Severe sepsis is not clinically apparent during the first 24 hours of hospitalization in most children with cancer and febrile neutropenia (FN), delaying targeted interventions that could impact mortality. The aim of this study was to prospectively evaluate biomarkers obtained within 24 hours of hospitalization as predictors of severe sepsis before it becomes clinically evident.Children with cancer, admitted with FN at high risk for an invasive bacterial infection in 6 public hospitals in Santiago, Chile, were monitored throughout their clinical course for occurrence of severe sepsis. Clinical, demographic and 6 biomarkers [eg, blood urea nitrogen, serum glucose, lactic dehydrogenase, serum C-reactive protein (CRP), interleukin (IL)-8, and procalcitonin] were obtained at the time of admission and after 24 hours. Biomarkers independently associated with severe sepsis diagnosed after the first 24 hours of hospitalization were identified by logistic regression analysis.A total of 601 high risk FN episodes were enrolled between June 2004 and October 2006; 151 (25%) developed severe sepsis of which 116 (77%) were not clinically apparent during the first 24 hours of hospitalization. Risk factors for severe sepsis were ageor =12 years [odds ratio (OR): 3.85; 95% confidence interval (CI): 2.41-6.15], admission CRPor =90 mg/L (OR: 2.03; 95% CI: 1.32-3.14), admission IL-8or =200 pg/mL (OR: 2.39; 95% CI: 1.51-3.78), 24-hour CRPor =100 mg/L (OR: 3.06; 95% CI: 1.94-4.85), and 24-hour IL-8or =300 pg/mL (OR: 3.13; 95% CI 1.92-5.08).Ageor =12 years and admission or 24-hour values of CRPor =90/100 mg/L and IL-8or =200/300 pg/mL are predictors of sepsis not clinically apparent during the first 24 hours of hospitalization.

Objetivos: Los tumores del Sistema Nervioso Central (TSNC) representan la segunda neoplasia más frecuente en la infancia. Por este motivo se decidió determinar la presentación clínica previa al diagnóstico y la latencia de la primera consulta, el diagnóstico y el inicio del tratamiento. Material y Métodos: Se analizó retrospectivamente la historia clínica de los niños atendidos en la Unidad de Oncología del Hospital Sótero del Río, con diagnóstico de TSNC, entre noviembre del 1994 y julio del 2002. La información se analizó mediante la prueba de t-student. Resultados: Los síntomas más frecuentes fueron cefalea (62,5%) y vómitos (56,2%). La latencia media de la primera consulta fue de 1 semana y los servicios más consultados fueron Consultorio (45,2%) y Urgencia (25,8%). El diagnóstico fue acertado en un 32,2% de las primeras consultas. La latencia media entre la primera consulta y el diagnóstico fue de 4 semanas, con un promedio de 2 consultas. La latencia media entre el diagnóstico y el inicio de tratamiento fue de 6 días para la cirugía, 37 días para la quimioterapia y 42 días para la radioterapia. Discusión: La cefalea y vómitos son los síntomas más frecuentes, su asociación con síntomas neurológicos debiera alertar al profesional de salud. La primera consulta es precoz, demorándose el diagnóstico por la baja sospecha, especialmente en los Consultorios. Respecto al tratamiento, la cirugía fue precoz, pero la radioterapia y quimioterapia sufrieron retrasos. En conclusión, es necesario reforzar la importancia de la sospecha diagnóstica, sobre todo a nivel de la atención primaria, así como también el manejo postoperatorio para no retrasar el inicio del resto del tratamiento Background: CNS tumours represent the second commonest malignancy in childhood. Objective: to describe the presenting symptoms and delay of the first visit to a health centre, time to diagnosis and to the beginning of treatment. Methods and materials: A retrospective study using the records of children with CNS tumours treated at the Sótero del Rio Hospital Oncology Unit, Santiago, Chile between November 1994 and July 2002. The data was analyzed using the t-test. Results: Headache (62.5%) and vomiting (56.2%) were the most frequent symptoms. The median delay to presentation was 1 week, and common presentation was to primary care centers (45.2%) and Emergency (25.8%). The correct diagnosis was made in 32.2% at the first visit. The median delay time between presentation and diagnosis was 4 weeks, with a mean number of presentations of 2. The mean delay between diagnosis and treatment was 6 days for surgery, 37 days for chemotherapy and 42 days for radiotherapy. Discussion: Headache and vomiting are the most frequent presenting symptoms, their association with neurological symptoms must alert medical staff. The first presentation is early, the delay being produced because of a low index of suspicion, especially at primary care centres. Regarding treatment, surgery was performed early, but chemotherapy and radiotherapy were delayed. We conclude that it is necessary to improve the index of suspucion, especially at primary care centres, and also to improve post surgery management, avoiding delays for the remaining therapy

El manejo de los pacientes pediátricos con cáncer y neutropenia febril (NF) requiere de su clasificación en alto o bajo riesgo de adquirir infecciones bacterianas invasoras (IBI), con el fin de implementar estrategias selectivas de tratamiento. Basados en nuestra experiencia y publicaciones internacionales al respecto, proponemos recomendaciones para el diagnóstico y manejo de niños con cáncer y NF, categorizadas según riesgo de IBI. Todos los pacientes pediátricos que presenten episodios de NF deben ser ingresados al hospital por al menos 24 horas. Durante este lapso se efectuará su evaluación clínica y de laboratorio con el objeto de clasificar el riesgo de este episodio y precisar el (los) posible(s) foco(s). Los pacientes de alto riesgo deben continuar internados hasta su recuperación. Los de bajo riesgo pueden ser manejados en forma ambulatoria. La elección de la terapia antimicrobiana inicial y los criterios para su ajuste deberán basarse en el hallazgo o no de focos infecciosos y en los patrones epidemiológicos e institucionales de susceptibilidad. La reevaluación de ambos grupos debe ser periódica (al menos en los días 3, 5 y 7 de evolución), y la respuesta terapéutica será clasificada como favorable o desfavorable según criterios clínicos y parámetros de laboratorio preestablecidos

Invasive fungal infections (IFI) cause prolonged hospitalizations and increase the possibility of death among patients with cancer and febrile neutropenia (FN). Up to 10% of febrile neutropenic episodes may be caused by IFI.To estimate the incidence of IFI among a large group of Chilean children with cancer and FN.Clinical and laboratory information was collected from a data base provided by the "Programa Infantil Nacional de Drogas Antineoplásicas" (PINDA) that included 445 FN episodes occurring in five hospitals in Santiago, Chile. This information was used to identify children that presented with signs and symptoms compatible with an IFI. According to predefined criteria based on a literature review, IFI episodes were categorized as "proven", "probable" or "possible".A total of 41/445 episodes (9.2%) were compatible with an IFI of which 4 (0.9%) were proven, 23 (5.2%) probable, and 14 (3.1%) possible. Hospitalization was longer (27 vs 8 days, p.01), new infectious foci appeared with higher frequency (71 vs 38%, p.01), and mortality was higher (10 vs 1.6%, p.001) in children with IFI compatible episodes, when compared to children who did not have an IFI.The estimated incidence of IFI in Chilean children with cancer and FN ranged between 6-9% depending on the stringency of criteria selection used for classification. This estimate is similar to that reported by other studies. The low detection yield of clinically compatible IFI underscores the need of improved diagnosis of fungal infections in this population.

A risk prediction model for invasive bacterial infection (IBI) was prospectively evaluated among children presenting with cancer, fever, and neutropenia. The model incorporated assessment of 5 previously identified risk factors: serum level of C-reactive protein (CRP) >/=90 mg/L, hypotension, identification of relapse of leukemia as the cancer type, platelet count of

El grupo oncológico pediátrico nacional, PINDA, reporta el primer protocolo prospectivo, no randomizado, para tratamiento de la leucemia linfoblástica (LLA), usando una versión modificada del protocolo de Berlin-Frankfurt-Munster (LLA BFM 86). Los objetivos de este estudio fueron clasificar inmunofenotipos, disminuir radioterapia de cráneo y comprobar si este protocolo podía mejorar la sobrevida de nuestros pacientes. Procedimiento: Desde junio 1987 a junio 1992 se registraron 444 pacientes, no seleccionados; de ellos 425 fueron evaluables. La terapia fue estratificada según riesgo: Riesgo Bajo (RB), Riesgo Alto (RA) y Riesgo Muy Alto (RMA). Los pacientes en RB y RA recibieron inducción con protocolo I, consolidación con protocolo M (RMA usó protocolo E), reinducción con protocolo II y mantención. Todos recibieron tratamiento de prefase con prednisona oral y metotrexato (MTX) intratecal. Radioterapia de cráneo solo en RA y RMA (12-18 Gy). Los siguientes cambios se introdujeron al protocolo LLA BFM 86: en protocolo M 1 g/m2 en vez de 5 g/m2; en protocolo E, 1 g/m2 de citarabina en vez de 2 g/m2, la mitoxantrona e ifosfamida fueron sustituidas por teniposido y ciclofosfamida. Resultados: Inmunofenotipo: LLA común 67,4%, LLA proB 14%, LLA T 10%, LLA preB 4,3%, indiferenciada 4,3%. La frecuencia de sobrevida libre de eventos (SLE) global a 5 años fue 60% ± 2% error standard; según riesgo fue: RB 75%, RA 62%, RMA 28% con una mediana de seguimiento de 6,5 años (rango 4,5 - 9,5 años). La incidencia acumulada de recaída en sistema nervioso central SNC fue 5,4%. Conclusión: Hemos tenido éxito en realizar un estudio a nivel nacional. Nuestra estrategia para adaptar el protocolo BFM fue efectiva para mejorar la SLE. La distribución por fenotipos es similar a otras series Background. The National Chilean Pediatric Oncology Group, PINDA, reports the first prospective, nonrandomized trial for acute lymphoblastic leukemia (ALL), using a modified version of the Berlin-Frankfurt-Munster protocol (ALL BFM 86). The aim of this study was to classify immunophenotypes, to decrease cranial irradiation, and to asses whether this protocol would improve the survival rate. Procedure: From june, 1987, to june, 1992, 444 unselected children were diagnosed with ALL. Of them, 425 were evaluable. Therapy was stratified by risk. Standard-risk (SR) and high-risk (HR) patients received protocols I, M, II, and maintenance therapy. Very-high-risk (VHR) patients received protocol E instead of protocol M. All patients received a prephase treatment consisting of prednisone and intrathecal methotrexate (MTX). HR and VHR patients received cranial irradiation (12-18 Gy). The following changes were made to the ALL BFM 86 protocol: in protocol M, MTX 1 g/m2 intead of 5 g/m2; in protocol E, citarabine 1 g/m2 instead of 2 g/m2; mithoxantrone and ifosfamide were substituted by teniposide and cyclophosphamide. Results: Immunophenotypes: pro-B-ALL, 14%; common ALL, 67.4%; pre-B-ALL, 4.3%; T-ALL, 10%; undifferentiated leukemia (AUL), 4.3%. The overall 5-year event-free survival (EFS) rate was 60% ± 2% (SE). The 5-year EFS rate for each risk group was: SR 75%, HR 62%, VHR 28%, with a median follow-up of 6.5 years (range 4.5-9.5 years). The cumulative incidence of central nervous system (CNS) relapse was 5.4%. Conclusions: We have been able successfully to perform a nationwide study. Our strategy to adapt the BFM protocol to our population of patients trial was effective in improving the EFS. The immunophenotype distribution is similar to that in other reported series

A 6 1/2 years old girl admitted to our hospital with an aplastic crisis, a serious complication of HereditarySpherocytosis (H.S.), motivated a retrospective review of the cases studies in our Hematology Department duringthe last seven years. Ten families were studied finding 20 members with H.S. The diagnosis was made in most ofthem during school age and only in two patients during the neonatal period. Most patients (80%t had objectivefamily history of H.S. Hemolytic crisis represented 80%, aplastic crisis 15% and cholelithiasis 5 % of thecomplications detected among our patients. The relationships that exist between aplastic crisis and viral Infections,specially parvo-virus, is stressed. It is important to point out that two out of three mothers who were not treatedby splenectomy, showed severe hemolitic crisis during their pregnancy. Splenectomy, its indications and posterioranti-infective prophylaxis are discussed.(Keywords: Anemia. Hemolysis. Hereditary Spherocytosis. Aplastic crisis. Splenectomy).