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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.

Se presenta un estudio retrospectivo de las fichas clínicas de 41 niños (59 ojos) con diagnóstico de retinoblastoma tratados por un equipo multidisciplinario en el Hospital Luis Calvo Mackenna, Santiago, Chile, entre los años 1999-2007. Se recolectó información respecto al género, edad al diagnóstico, signos de presentación, lateralidad, diseminación del tumor, tipos de tratamiento y sobrevida. Veintitrés casos (56%) fueron unilaterales y 18 (44%) bilaterales. La edad promedio al momento del diagnóstico fue de 21,6 meses (rango 2-84) y 27 niños (65,9%) fueron hombres. Los signos de presentación más frecuentes fueron leucocoria (51,2%), estrabismo (24,4%) y proptosis (4,9%). Se realizó enucleación en 48 ojos afectados (81,3%), siendo el único tratamiento necesario en 17 niños (41,5%). Los 24 pacientes restantes recibieron tratamientos complementarios locales y/o sistémicos en la modalidad de quimioterapia, terapia focal y radioterapia externa. Durante el período de seguimiento del estudio fallecieron 5 niños, todos ellos con extensión extraocular de la enfermedad hacia la órbita, sistema nervioso central o médula ósea. Conclusiones: No obstante el alto porcentaje de pacientes con retinoblastoma que requieren enucleación como terapia inicial, la tasa de sobrevida con el protocolo actual de tratamiento es comparable a la de paises desarrollados.

Antibiotic treatment in children with High Risk Febrile Neutropenia Background: In children with cancer and high risk febrile neutropenia (HRFN), the initial empiricaltreatment used in our hospital for 5 years includes the association of Cloxacillin + Ceftazidime + Amikacin.There is no chilean literature that reviews the effectiveness of this therapy. Objective: Evaluate the clinicaland microbiological effectiveness of this associated therapy in children with HRFN. Method: A prospective-descriptive study evaluating children with HRFN admitted at Hospital Luis Calvo Mackenna betweenJanuary 2005-August 2006. Results: 100 HRFN episodes were evaluated. In 48% of cases, the antimicrobialtreatment was considered effective, whereas in 52% of episodes the therapy required modifications (15%cases within the first 72 hours). The most frequent diagnoses were fever without clinical focus (51%) andsepsis (13%). 36% had microbiological identification and the most frequently isolated bacteria wereEscherichia coli (9%) and Staphylococcus aureus (9%). Conclusions: A favorable answer with the initialempirical therapy was obtained for 48% of cases; meanwhile in the remaining episodes, 28% requiredantibiotics modifications without justification. This fact remarks the importance of following the establishedguidelines for antimicrobial treatment modification in these patients.(Key words: Cancer, febrile neutropenia, antibiotics, oncology).Rev Chil Pediatr 2008; 79 (4): 381-387RESUMENIntroduccion: En los ninos con cancer y netropenia febril (NF) de alto riesgo, se utiliza en nuestro centrohace 5 anos, como esquema empirico inicial, la asociacion de ceftazidima-amikacina-cloxacilina. No hayliteratura nacional que analice la eficacia de este esquema. Objetivo: Evaluar la eficacia clinica y microbiologicade la asociacion de ceftazidima, amikacina y cloxacilina en ninos con NF de alto riesgo. Metodo: Protocolodescriptivo, prospectivo. Evaluar ninos con NF de alto riesgo hospitalizados en el HLCM entre enero 2005

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.

Background A frontline protocol for newly diagnosed osteosarcoma was conducted simultaneously at St. Jude Children's Research Hospital (sponsor) and Calvo Mackenna Hospital (CMH, partner), a public pediatric hospital and national center for the treatment of bone tumors in Santiago, Chile. Procedure Of 72 eligible patients, 22 (31%) were enrolled and managed in Santiago, without travel to Memphis. Pathology specimens and imaging material were centrally reviewed at St. Jude. Patients received 12 intensive courses of systemic chemotherapy with hematopoietic growth factor support over 35 weeks, and amputation or limb-salvage surgery as indicated for local control. The sponsor assisted the partner site to establish a clinical research infrastructure and obtain hematopoietic growth factor. Communication among medical and nursing teams was maintained throughout the study. Patient-care and protocol issues were discussed frequently between the two centers via scheduled videoconferences and electronic communications. Auditors monitored appropriate study conduct at the international site. Results No major discrepancies were identified in histologic findings, staging, or imaging studies. Preliminary results demonstrated similar outcome and treatment tolerance; the 2-year event-free survival estimate was 78.5% (95% CI, 51–100%) for patients treated at CMH (median follow-up, 1.6 years) and 74.3% (95% CI, 62–87%) for patients treated at St. Jude (median follow-up, 4 years). Overall per-patient costs were significantly lower in Chile. Conclusions Through a twinning mechanism, it is feasible to simultaneously conduct complex front-line osteosarcoma clinical trials at two institutions in countries with different levels of resources. Pediatr Blood Cancer 2008;50:1143–1146. © 2007 Wiley-Liss, Inc.

TPS10079 Background: Large cooperative group studies have shown the efficacy of risk-adapted treatment for Ewing sarcoma (ES). However, validation and local adaptation by national cooperative group...

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

Un paciente de 14 años, portador de leucemia linfoblástica aguda desarrolló una sinusitis subaguda con manifestaciones neurológicas. Mediante biopsia de mucosa nasal y resonancia magnética cerebral se diagnosticó una mucormicosis rinocerebral y basado en un teórico mal pronóstico se decidió efectuar tratamiento conservador: cirugía funcional de la sinusitis y terapia prolongada con anfotericina B deoxicolato completando tras 8,8 meses, 7.700 mg del fármaco. La quimioterapia de la leucemia fue reanudada durante el tratamiento antifúngico alcanzando la remisión oncológica. Tras 31 meses de seguimiento, el paciente está asintomático pero recayó de la leucemia.

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

Background: Pediatric patients in treatment for cancer can have fatal bacterial infections. Thus, in the presence of fever or other signs infection, antimicrobials have to be prescribed empirically. Aim: To know the causative agents of bacteremia in children with cancer, their changes with time and between different hospitals and their patterns of susceptibility. Material and methods: We reviewed the blood cultores of children with cancer in five hospitals of Santiago, from 1994 at 1998. Results: During the study period, 707 agents were isolated. The most frequently isolated species or genus were coagulase negative Staphylococcus (43%), Staphylococcus aureus (16%), Escherichia coli (9%), Klebsiella spp. (8%), Pseudomonas spp. (5%) and Candida spp. (4%). Coagulase negative Staphylococcus was 55% resistant to meticilin and S. aureus was 44% resistant. Enterobacteriae had 15% resistance to gentamicin and amikacin, 2% to imipenem, 26% to ceftriaxone, 21% to cefotaxim and 20% to ceftazidim. Among non fermenting agents resistance was 6% for imipenem, 9% for amikacin 10% for ciprofloxacin, 19% for ceftazidim and 22% for cefoperazone. The resistance of Streptococcus spp. (non pneumoniae) to penicillin reached 50% and that of Enterococcus spp. was of 33%. Conclusions: Treatment for pediatric patients with cancer must be modified and new guidelines including more active medications for patients at risk for bacteremia, should be devised (Rev Méd Chile 2001; 129: 1297-1304)

Thirty-seven patients with Ewing sarcoma were treated in the First National Chilean Trial for Ewing's Sarcoma (1986-1991), which comprised the St. Jude Ewing's 78 Study. All patients received cyclophosphamide, doxorubicin, vincristine, and Dactinomycin for a total treatment period of about 10 months, and all prescribed therapy was administered. Local therapy consisted of irradiation (RT) to the primary tumor, complete surgical resection, or a combination of both surgery and RT. Twenty-nine of these patients had localized tumors, 24% had pelvic primary tumors, 21 were males, and 20 were greater than 10 years of age at diagnosis. Twenty-one patients had tumors that were greater than 8 cm in largest diameter. Fourteen of the 29 patients with localized disease remain disease free at 23 to 91 months from diagnosis. Fourteen patients have died of-tumor-related complications and 1 of a secondary malignancy. Relapse was local only in 4, metastatic in 9, and local plus metastatic in 1. Only 1 of the 8 patients with metastatic disease at presentation remains disease free. Toxicity consisted primarily of myelosuppression and mucositis. We conclude that this form of relative intense multimodal therapy for children/adolescents with localized Ewing sarcoma is curative in about half of affected children as in the original St. Jude study, and that it can be safely given in a developing country, provided that careful attention to supportive care and treatment planning is given. Although these results represent improvement in outcome for our patients, more effective therapy is needed for children with Ewing sarcoma, especially those with metastatic disease at presentation.

10036 Background: Standard treatment of osteosarcoma includes cisplatin and high-dose methotrexate (HD-MTX), but both agents are associated with significant toxicity and MTX administration requires complex pharmacokinetic monitoring. In our previous OS91 trial, the combination of carboplatin and ifosfamide with doxorubicin and HD-MTX yielded outcomes comparable to those of cisplatin-based regimens with less long-term toxicity in localized osteosarcoma. Methods: Between 1999 and 2006, we conducted a multi-institutional trial (OS99) to evaluate the activity of carboplatin, ifosfamide, and doxorubicin without HD-MTX in newly-diagnosed patients with localized osteosarcoma. Treatment comprised 12 cycles of chemotherapy given every 3 weeks: 3 consecutive cycles of carboplatin (dose targeted to AUC 8 mg/ml×min on day 1) and ifosfamide (2.65 g/m2 daily for 3 days) and one cycle of doxorubicin (25 mg/m2 daily for 3 days) followed by definitive surgery (week 12) and 2 additional cycles of carboplatin/ifosfamide and 3 cycles each of ifosfamide/doxorubicin and carboplatin/doxorubicin for a total of 35 weeks. The log rank test was used to compare survival and event-free survival (EFS) distributions. Results: A total of 72 eligible patients were enrolled. The median age was 13.4 years and 41 (57%) were male. The most common tumor site was the femur (n = 46; 64%). The median follow-up for survivors was 4.4 years. Forty of the 66 (60.6%) evaluable patients had good histologic response (tumor necrosis > 90%) to preoperative chemotherapy. There was no difference in EFS or survival distributions between OS99 and OS91. Four-year estimates of EFS were 68.1 ± 6.7% for OS99 compared to 70.2 ± 6.6% for OS91 (p = 0.89). The 4-year OS was 82.4% ± 5.7% for OS99 compared to 74.5% ± 6.3 for OS91 (p = 0.25). Conclusions: OS99 produced outcomes similar to cisplatin or HD-MTX containing regimens and offers an alternative treatment regimen especially for patients with renal compromise and institutions where pharmacokinetic monitoring of MTX is not available. No significant financial relationships to disclose.

ResumenIntroducciónLa respuesta inmune a los antígenos de las vacunas está disminuida en los niños con cáncer. El objetivo de este estudio fue evaluar la seroconversión frente a vacuna ADN recombinante contra hepatitis B al momento del inicio de la quimioterapia y/o remisión en niños con cáncer.Pacientes y métodoEstudio prospectivo, bicéntrico, controlado, no aleatorizado de niños con diagnóstico reciente de cáncer pareados con niños sanos. Los casos fueron vacunados a tiempo 0, 1 y 6 meses, a dosis de 20 y 40μg si eran10 años, respectivamente, con vacuna ADN recombinante contra hepatitis B, en el momento del diagnóstico en el caso de los tumores sólidos y luego de la remisión en el caso de los tumores hematológicos. El grupo control recibió el mismo esquema, con dosis de 10 o 20μg respectivamente. Se midieron anticuerpos séricos anti-HBs a los 2, 8 y 12 meses posvacunación. Seroconversión se definió como títulos anti-HBs>10 mUI/ml al octavo mes.ResultadosUn total de 78 niños con cáncer y 25 controles fueron evaluados con títulos anti-HBs al octavo mes. La tasa de seroconversión fue de 26,9%, en niños con cáncer, sin diferencia por edad, género ni tipo de tumor (p=0,13; 0,29; y 0,44, respectivamente), y de 100% en el grupo control (p10mUI/ml.ConclusionesLa vacunación contra hepatitis B con vacuna ADN recombinante, con esquema reforzado de 3 dosis, en el momento del inicio de la quimioterapia y/o remisión provee una respuesta inmune insuficiente en la mayoría de los niños con cáncer. En esta población debieran evaluarse vacunas de tercera generación, con adyuvantes más inmunogénicos, esquemas reforzados a los 0, 1, 2 y 6 meses, medición de títulos de anticuerpos al octavo y duodécimo mes, eventual uso de refuerzos y reevaluación de inmunogenicidad si correspondiese.AbstractIntroductionImmune 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.Patients and methodProspective, 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 40μg ifthan 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 20μg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as>10 mIU/ml at 8th month of follow up.ResultsA 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 P10 mIU/ml.ConclusionsVaccination 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.