Cytokine and chemokine profiles in episodes of persistent high-risk febrile neutropenia in children with cancer.

BACKGROUND: In children with cancer and persistent high-risk febrile neutropenia (HRFN), cytokines/chemokines profiles can guide the differentiation of febrile neutropenia (FN) due to infections and episodes of unknown origin (FN-UO). METHODS: A prospective, multicenter study in Santiago, Chile included patients ≤ 18 years with cancer and HRFN. Clinical and microbiological studies were performed according to validated protocols. Serum levels of 38 cytokines/chemokines were determined on day 4 of persistent HRFN. We performed comparisons between i) HRFN episodes with a detected etiological agent (FN-DEA) and FN-UO, and ii) bacterial versus viral infections. ROC curves were used to assess the discriminatory power of the analytes. RESULTS: 110 HRFN episodes were enrolled (median age 8 years, 53% female). Eighty-four patients were FN-DEA: 44 bacterial, 32 viral, and 8 fungal infections. Twenty-six cases were categorized as FN-UO. Both groups presented similar clinical and laboratory characteristics. Nineteen out of 38 analytes had higher concentrations in the FN-DEA versus FN-UO group. G-CSF, IL-6, and Flt-3L showed the highest discriminatory power to detect infection (AUC 0.763, 0.741, 0.701). Serum levels of G-CSF differentiated bacterial infections and IP-10 viral agents. A combination of G-CSF, IL-6, Flt-3L, and IP-10 showed an AUC of 0.839, 75% sensitivity, and 81% specificity. CONCLUSION: A specific immune response is present on day four of persistent HRFN in children with cancer. We propose a combined measure of serum concentrations of G-CSF, IL-6, IP-10, and Flt-3L, in order to predict the presence of an infectious agent as compared to an episode of FN with unknown origin.

Usefulness of serum galactomannan in initiating and modifying antifungal therapy in children with cancer and persistent high-risk febrile neutropenia.

BACKGROUND: 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. OBJECTIVES: To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN. PATIENTS/METHODS: 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. RESULTS: 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). CONCLUSIONS: Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN.

[Microorganisms isolated from blood cultures and resistance profile in children with cancer and high-risk febrile neutropenia. Red PINDA, Chile, 2016-2021]. / Microorganismos aislados de hemocultivos y su perfil de resistencia en niños con cáncer y neutropenia febril de alto riesgo. Red PINDA, Chile, 2016-2021.

Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN). OBJECTIVE: To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group. METHOD: Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021. RESULTS: 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04). CONCLUSION: VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.

Clinical Outcome in Children With Cancer With Two or More Microorganisms Isolated From Blood Cultures During Episodes of Fever and Neutropenia.

BACKGROUND: Bacterial bloodstream infections are a major cause of morbidity and mortality in children with cancer and episodes of fever and neutropenia (FN). The aim of this study was to evaluate the clinical outcome in children with cancer with 2 or more microorganisms isolated from blood cultures during their episodes of FN. METHODS: Between 2016 and 2021, children presenting with high-risk FN, admitted to any of the 6 participating hospitals in Santiago, Chile, were included in this study if they have positive blood cultures. We compared the clinical outcome of children with 2 or more microorganisms versus those with single agent isolation. RESULTS: A total of 1074 episodes of high-risk FN were enrolled in the study period, of which 27% (298) had positive blood cultures and 3% (32) had 2 or more microorganisms isolated from blood cultures. The most frequent identified agents were Viridans group streptococci and Escherichia coli in 20%, followed by Coagulase negative staphylococci in 14%. Children with 2 or more microorganisms presented more days of fever (7 vs. 4 days, P = 0.02), needed longer courses of antimicrobial therapy (16 vs. 14 days, P = 0.04) and had higher mortality at day 30 (13% vs. 1%, P = 0.003). CONCLUSIONS: Children with cancer and FN with 2 or more microorganisms isolated from blood cultures had a worse clinical outcome than children with single agent isolation.

[Management of episodes of febrile neutropenia in children with cancer. Consensus of the Latin American Society of Pediatric Infectious Diseases 2021]. / Manejo de los episodios de neutropenia febril en niños con cáncer. Consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021.

The Committee for Infections in Immunocompromised Children of Sociedad Latinoamericana de Infectología Pediátrica, presents this Consensus document, titled "Management of episodes of febrile neutropenia in children with cancer. Consensus of the Sociedad Latinoamericana de Infectología Pediátrica 2021". The document includes recommendations on prevention, prediction, diagnosis, treatment and prognosis of episodes of fever and neutropenia, including specific recommendations on: Analysis at admission; evaluation, adjustments and duration of antimicrobial therapies; diagnosis and management of invasive fungal infection; analysis of the main clinical source of infections; environmental conditions necessary for hospitals caring for children with cancer and chemoprophylaxis. Special emphasis has been placed on providing the best recommendations to optimize the management of episodes of fever and neutropenia in children with cancer, with equity and excellence through all the centers that treat these patients in Latin America.

[Humoral immune response induced by influenza vaccine in children with acute lymphoblastic leukemia]. / Respuesta inmune humoral inducida por la vacuna influenza en niños con diagnóstico de leucemia linfoblástica aguda.

BACKGROUND: Patients with acute lymphoblastic leukemia (ALL) have high risk of severe influenza infection and vaccination is highly recommended. The immunogenicity and effectiveness of vaccination are lower than in healthy people. AIM: To evaluate the immune response induced by influenza vaccine in children with ALL and observe effectiveness. METHOD: Children with ALL in maintenance phase and healthy children were recruited. Blood samples were taken at vaccination day (D0) and at day 28 (D28). Humoral response was evaluated by hemaglutination inhibition test (HAI) against H1N1. Patients were followed up for one year, clinical data and influenza episodes were recorded. RESULTS: 34 children with ALL and 9 healthy children were included. Concerning HAI on D28, 12/34 patients and 5/8 healthy children had titers ≥ 1/40, with seroprotection rates of 35 and 63% respectively. Seroprotected children were older than non-seroprotected ones. During follow-up, only 3 patients non seroprotected, presented influenza infection, without oxygen supplementation or critical care support. DISCUSSION: Children with ALL had a lower seroprotection rate than healthy children. Nevertheless, none of the seroprotected children presented influenza infection, reinforcing the annual vaccination recommendation.

Infecciones fúngicas invasoras en niños con cáncer y portadores de aplasia medular severa en nueve hospitales de la red PINDA, Chile. 2016-2020 / Invasive fungal infections in children with cancer and severe aplastic anemia in nine hospitals from PINDA Network, Chile. 2016-2020

INTRODUCCIÓN: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa. OBJETIVO: Describir la epidemiología de la IFI desde el año 2016 al 2020 en niños con cáncer y AM para evaluar la necesidad de profilaxis antifúngica. MÉTODOS: Estudio retrospectivo, multicéntrico, en pacientes pediátricos con cáncer y AM severa. Se incluyeron IFI probables y probadas. RESULTADOS: Se diagnosticaron 57 casos de IFI, mediana de edad 9 años, 70% probadas y 30% probables. Hubo 42% de infecciones por levaduras y 56% por hongos filamentosos. Los sitios de infección más frecuentes fueron pulmón 38%, sangre 36% y rinosinusal 21%. La frecuencia global fue 5,4%; de ellas 21% en AM severa, 10% en leucemia mieloide aguda (LMA), 6,9% en recaída de LMA, 5,4% en recaída de leucemia linfática aguda (LLA), 3,8% en LLA. Las infecciones por hongos filamentosos predominaron en LMA, recaída de LMA. y AM severa. La mortalidad en pacientes con IFI fue de 11%. CONCLUSIÓN: La frecuencia de IFI concuerda con la literatura médica. Recomendamos profilaxis antifúngica contra hongos filamentosos en pacientes con AM severa, LMA y recaída de LMA. Considerar en recaída de LLA de alto riesgo en etapa de inducción.

BACKGROUND: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). AIM: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. METHODS: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. RESULTS: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. CONCLUSION: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.

Manejo de los episodios de neutropenia febril en niños con cáncer: consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021 / Management of episodes of febrile neutropenia in children with cancer: consensus of the Latin American Society of Pediatric Infectious Diseases 2021

Resumen El Comité de Infecciones en el Niño Inmunocomprometido de la Sociedad Latinoamericana de Infectología Pediátrica, entrega este documento de Consenso, llamado "Manejo de los episodios de neutropenia febril en niños con cáncer. Consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021". El documento contiene recomendaciones sobre aspectos de prevención, predicción, diagnóstico, tratamiento y pronóstico de los episodios de fiebre y neutropenia, incluyendo recomendaciones específicas sobre: Análisis de ingreso; evaluación, ajustes y duración de terapias antimicrobianas; diagnóstico y manejo de infección fúngica invasora; análisis de los principales focos clínicos de infección; condiciones ambientales necesarias para hospitales que atienden niños con cáncer y quimioprofilaxis. Se ha puesto especial énfasis en entregar las mejores recomendaciones para optimizar el manejo de los episodios de fiebre y neutropenia en niños con cáncer, buscando la equidad y la excelencia a través de todos los centros que atienden estos pacientes en América Latina.

Abstract The Committee for Infections in Immunocompromised Children of Sociedad Latinoamericana de Infectología Pediátrica, presents this Consensus document, titled "Management of episodes of febrile neutropenia in children with cancer. Consensus of the Sociedad Latinoamericana de Infectología Pediátrica 2021". The document includes recommendations on prevention, prediction, diagnosis, treatment and prognosis of episodes of fever and neutropenia, including specific recommendations on: Analysis at admission; evaluation, adjustments and duration of antimicrobial therapies; diagnosis and management of invasive fungal infection; analysis of the main clinical source of infections; environmental conditions necessary for hospitals caring for children with cancer and chemoprophylaxis. Special emphasis has been placed on providing the best recommendations to optimize the management of episodes of fever and neutropenia in children with cancer, with equity and excellence through all the centers that treat these patients in Latin America.

Respuesta inmune humoral inducida por la vacuna influenza en niños con diagnóstico de leucemia linfoblástica aguda / Humoral immune response induced by influenza vaccine in children with acute lymphoblastic leukemia

Resumen Introducción: Los pacientes con leucemia linfoblástica aguda (LLA) tienen alto riesgo de influenza grave y la vacunación es altamente recomendada. La inmunogenicidad y efectividad de la vacuna es menor comparada a los sujetos sanos. Objetivo: Evaluar la respuesta inmune inducida por vacuna anti-influenza en niños con LLA y observar su efectividad. Métodos: Se reclutaron niños con LLA en terapia de mantención y niños sanos. Se tomaron muestras de sangre el día de la vacuna (D0) y al día 28 (D28), y se realizó test de inhibición de hemaglutinación (IHA) contra H1N1. Los pacientes fueron seguidos por un año, registrando datos clínicos y episodios de influenza. Resultados: Se incluyeron 34 niños con LLA y 9 niños sanos. Respecto al IHA en D28, 12/34 pacientes y 5/8 niños sanos presentaron títulos ≥ 1/40, resultando una tasa de seroprotección de 35 y 63%, respectivamente. Los niños seroprotegidos eran significativamente mayores. Durante el seguimiento, sólo tres pacientes, no seroprotegidos, presentaron infección por influenza, ninguno requirió oxigeno o cuidados intensivos. Discusión: Los niños con LLA alcanzaron una tasa seroprotección más baja que la observada en niños sanos. Sin embargo, ninguno de los niños seroprotegidos presentó infección por influenza, reforzando la recomendación de vacunación anual.

Abstract Background: Patients with acute lymphoblastic leukemia (ALL) have high risk of severe influenza infection and vaccination is highly recommended. The immunogenicity and effectiveness of vaccination are lower than in healthy people. Aim: To evaluate the immune response induced by influenza vaccine in children with ALL and observe effectiveness. Method: Children with ALL in maintenance phase and healthy children were recruited. Blood samples were taken at vaccination day (D0) and at day 28 (D28). Humoral response was evaluated by hemaglutination inhibition test (HAI) against H1N1. Patients were followed up for one year, clinical data and influenza episodes were recorded. Results: 34 children with ALL and 9 healthy children were included. Concerning HAI on D28, 12/34 patients and 5/8 healthy children had titers ≥ 1/40, with seroprotection rates of 35 and 63% respectively. Seroprotected children were older than non-seroprotected ones. During follow-up, only 3 patients non seroprotected, presented influenza infection, without oxygen supplementation or critical care support. Discussion: Children with ALL had a lower seroprotection rate than healthy children. Nevertheless, none of the seroprotected children presented influenza infection, reinforcing the annual vaccination recommendation.

Melanoma infantil / Childhood melanoma

El melanoma en niños es poco frecuente, pero está aumentado aceleradamente, y es de mal pronóstico de no ser reconocido a tiempo. Es una entidad de difícil diagnóstico clínico y patológico, que debe considerarse en el diagnóstico diferencial de toda lesión pigmentada de la infancia. El tratamiento debe ser agresivo, y la resección quirúrgica del melanoma localizado es el único tratamiento potencialmente curativo. El manejo de la enfermedad diseminada es complejo y la quimioterapia e inmunoterapia son las principales armas terapéuticas en la actualidad.

Síndromes mielodisplásticos en pediatría / Pediatric myelodysplastic syndromes

Los síndromes mielodisplásticos (SMD) son desórdenes clónales de las células madres hematopoyéticas caracterizados por hematopoyesis inefectiva, citopenia periférica y riesgo variable de transformación a leucemia mieloide aguda (LMA). Los SMD son relativamente raros en niños, representando aproximadamente el 3 por ciento de las neoplasias hematológicas pediátricas. Se han descrito numerosos subtipos de SMD en niños, no existiendo actualmente una clasificación de consenso. Existen desórdenes genéticos que predisponen al desarrollo de SMD en niños, como el síndrome de Down, la neurofibromatosis tipo I y síndrome de falla medular hereditarios; por otro lado, la exposición a agentes quimioterapéuticos y radiaciones ionizantes, aumenta el riesgo de desarrollar SMD tanto en niños como en adultos. Los SMD infantiles usualmente tienen un curso clínico agresivo y son de difícil manejo, siendo el trasplante de médula ósea alogénico el único tratamiento curativo conocido actualmente.

Púrpura trombocitopénico idiopático / Idiopathic thrombocytopenic purpura

El púrpura trombocitopénico idiopático (PTI) es una enfermedad autoinmune caracterizada por recuento bajo de plaquetas y hemorragias mucocutáneas, sin alteraciones en la médula ósea y en ausencia de otras causas de trombocitopenia. En niños suele ser autolimitada, y puede ser precedida por una infección viral o una inmunización.

Neutropenia en la infancia / Neutropenia in childhood

Neutropenia se define como la disminución en el número absoluto de neutrófilos circulantes, describiéndose etiologías y cursos clínicos diversos. Los casos más severos debutan con infecciones graves de riesgo vital, sin embargo, la mayoría se diagnostica en forma casual como hallazgo en exámenes de laboratorio en pacientes con escasa sintomatología. En esta revisión se presentan los conceptos generales y principales etiologías de las neutropenias en la infancia, así como las características clínicas y de laboratorio de las distintas entidades. Se describen además, las líneas generales del enfrentamiento diagnóstico, manejo del paciente y tratamiento de las principales etiologías.