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.

Neurotoxicity prevention with a multimodal program (ATENTO) prior to cancer treatment versus throughout cancer treatment in women newly diagnosed for breast cancer: Protocol for a randomized clinical trial.

A current challenge in breast cancer (BC) patients is how to reduce the side effects of cancer and cancer treatments and prevent a decrease in quality of life (QoL). Neurotoxic side effects, especially from chemotherapy, are present in up to 75% of women with BC, which implies a large impact on QoL. There is a special interest in the preventive possibilities of therapeutic exercise (TE) for these neurological sequelae, and the benefits of TE could be improved when it is combined with vagal activation techniques (VATs). This superiority randomized controlled trial aims to examine the feasibility and efficacy of an 8-week multimodal intervention (ATENTO) based on moderate-vigorous intensity and individualized TE (aerobic and strength exercises) and VAT (myofascial and breathing exercises), on neurotoxicity prevention in women with BC before starting adjuvant chemotherapy (ATENTO-B) versus throughout adjuvant chemotherapy (ATENTO-T). A sample of 56 women newly diagnosed with BC, as calculated with a power of 85%, will be randomly allocated into these two groups. This study could provide an impetus for the introduction of early multimodal intervention methods to prevent neurotoxicity and consequently avoid the QoL deterioration that BC patients presently suffer throughout their treatments.

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.

Efficacy of pre-emptive versus empirical antifungal therapy in children with cancer and high-risk febrile neutropenia: a randomized clinical trial.

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 Clínicos (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 < 0.001), with similar overall mortality (8% in the empirical arm and 5% in the pre-emptive arm, P = 0.47). IFD-related mortality was the same in both groups (3%, P = 0.97), as were the percentage of children with IFD (12%, P = 0.92) and the number of days of fever (9, P = 0.76). The number of days of hospitalization was 19 in the empirical arm and 17 in the pre-emptive arm (P = 0.15) and the need for ICU was 25% in the empirical arm and 20% in the pre-emptive arm (P = 0.47). Conclusions: Pre-emptive antifungal therapy was as effective as empirical antifungal therapy in children with cancer, fever and neutropenia, significantly reducing the use of antifungal drugs.

Results of Therapy for Wilms Tumor and Other Malignant Kidney Tumors: A Report From the Chilean Pediatric National Cancer Program (PINDA).

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.

[Seroconversion in response to a reinforced primary hepatitis B vaccination in children with cancer]. / Seroconversión frente a primovacunación reforzada contra hepatitis B en niños con cáncer.

INTRODUCTION: 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. PATIENTS AND METHOD: 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 if < or > than 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 as > 10 mIU/ml at 8th month of follow up. RESULTS: 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 antibodies > 10 mIU/ml. CONCLUSIONS: 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.

[Characterization of episodes of febrile neutropenia in children with acute myeloid leukemia and acute lymphoblastic leukemia]. / Caracterización de los episodios de neutropenia febril en niños con leucemia mieloide aguda y leucemia linfoblástica aguda.

INTRODUCTION: 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). AIMS: 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. METHOD: 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. RESULTS: 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 a > period of time and had a worse clinical outcome, as evidenced by > hemodynamic instability, > sepsis, CRP > 90 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. CONCLUSIONS: 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.

Incidence and clinical significance of FLT3 and nucleophosmin mutation in childhood acute myeloid leukemia in Chile.

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous disease and approximately one-third of its carriers do not have evident genetic abnormalities. The mutation of specific molecular markers, such as fms-like tyrosine kinase 3 (FTL3) internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) and nucleophosmin (NPM1), are associated with an adverse and favorable prognosis, respectively. OBJECTIVE: The objective was to determine the prevalence of FLT3/ITD and NPM1 in Chilean patients and their association with clinical data and prognosis. METHOD AND RESULTS: Two hundred and thirty-two children were studied between 2011 and 2017, the median being 8.6 years (ranging from 1 to 18 months). Acute promyelocytic leukemia (APL) was diagnosed in 29%. The FLT3/ITD-mutated in non-promyelocytic AML was at 10% (14/133) and the FLT3/TKD, at 3.7% (2/54). In APL, it was at 25.4% (16/63). In non-promyelocytic AML, the FLT3/ITD-mutated was associated with a high leucocyte count, the median being 28.5 x mm3 (n = 14) versus 19.4 x mm3 (n = 119), (p = 0.25), in non-mutated cases. In APL, the median was 33.6 x mm3 (n = 15) versus 2.8 x mm3 (n = 47), (p < 0.001). The five-year overall survival (OS) in non-promyelocytic AML with non-mutated and mutated FLT3/ITD were 62.7% and 21.4%, respectively, (p < 0.001); the 5-year event-free survival (EFS) were 79.5% and 50%, respectively, (p < 0.01). The five-year OS in APL with non-mutated and mutated FLT3/ITD was 84.7% and 62.5%, respectively, (p = 0.05); the 5-year EFS was 84.7% and 68.8%, respectively, (p = 0.122). The NPM1 mutation was observed in 3.2% (5/155), all non-promyelocytic AML with the normal karyotype. CONCLUSION: The FLT3/ITD mutation was observed more frequently in APL and associated with a higher white cell count at diagnosis. However, the most important finding was that the FLT3/ITD mutation was associated with a shorter survival in non-promyelocytic AML.

[Seroprevalence of varicella-zoster virus in children with cancer in six hospitals in Santiago, Chile]. / Seroprevalencia de virus varicela-zoster en niños con cáncer en seis hospitales de Santiago, Chile.

UNLABELLED: 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. AIM: To determine the prevalence of VVZ antibodies in children with cancer who have undergone chemotherapy or have undergone a hematopoietic stem cell transplant. METHODOLOGY: 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). RESULTS: 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%. CONCLUSION: 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.

[Bloodstream infections in children with cancer and high risk fever and neutropenia episodes in six hospitals of Santiago, Chile between 2004 and 2009]. / Agentes causantes de bacteriemia en niños con cáncer y neutropenia febril de alto riesgo en seis hospitales de Santiago, Chile, período 2004-2009.

INTRODUCTION: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

The Role of Polymeric Biomaterials in the Treatment of Articular Osteoarthritis.

Osteoarthritis is a high-prevalence joint disease characterized by the degradation of cartilage, subchondral bone thickening, and synovitis. Due to the inability of cartilage to self-repair, regenerative medicine strategies have become highly relevant in the management of osteoarthritis. Despite the great advances in medical and pharmaceutical sciences, current therapies stay unfulfilled, due to the inability of cartilage to repair itself. Additionally, the multifactorial etiology of the disease, including endogenous genetic dysfunctions and exogenous factors in many cases, also limits the formation of new cartilage extracellular matrix or impairs the regular recruiting of chondroprogenitor cells. Hence, current strategies for osteoarthritis management involve not only analgesics, anti-inflammatory drugs, and/or viscosupplementation but also polymeric biomaterials that are able to drive native cells to heal and repair the damaged cartilage. This review updates the most relevant research on osteoarthritis management that employs polymeric biomaterials capable of restoring the viscoelastic properties of cartilage, reducing the symptomatology, and favoring adequate cartilage regeneration properties.

Monkeypox and HIV in the Canary Islands: A Different Pattern in a Mobile Population.

BACKGROUND: The clinical and epidemiological data of the recent outbreak of monkeypox (MPX) differ from previous reports. One difference is the epidemiological profile; the disease mainly affects a subgroup of MSM (men who have sex with men) with high-risk sexual behaviors, frequently persons living with human immunodeficiency virus (PLHIV). METHODS: In this observational analysis, all patients with PCR (polymerase chain reaction)-confirmed MPX attending an Infectious Diseases and Tropical Medicine Unit in Gran Canaria (Spain) between May and July 2022 were considered. RESULTS: In total, 42 men were included; 88% were identified as MSM, with a median age of 40 years. Only 43% were born in Spain. All the patients had systemic symptoms and skin lesions. The distribution of lesions was more frequent in the genital/anal region, and the involvement of hands and feet was less common. Fever and lymphadenopathies were less frequent than in other series. Other unusual manifestations were proctitis, pharyngitis and penile-scrotal edema. Half of the patients had other associated infections (mainly STIs, sexually transmitted infections), and 60% of the monkeypox patients had PLHIV (People Living with HIV). When comparing the clinical characteristics between HIV-positive and -negative patients, we found three main differences: (i) a higher frequency of perioral lesions, (ii) a higher frequency of pharyngitis and (iii) a higher number of sexually transmitted infections in HIV-positive patients. CONCLUSIONS: The clinical findings in this outbreak of MPX had great variability in presentation. Several clinical differences were found in PLHIV-coinfected patients.

Syncope: a rare presentation of massive pulmonary embolism in a previously healthy girl.

Pulmonary embolism is a very infrequent event in previously healthy children, particularly in the outpatient scenario. This report involves a 7-year-old girl who presented to the emergency room after syncope. A prompt diagnostic workup showed a massive pulmonary embolism. A timely treatment initiation permitted a good and rapid response. She represented a diagnostic and treatment challenge, mainly because of the atypical presentation and the absence of known risk factors. Finally, a thorough study uncovered a nephrotic-range urine protein loss. At the beginning, the patient did not meet the whole nephrotic syndrome diagnostic requirements. The complete thombophilic study was normal. The clinical presentation, epidemiology, diagnostic tools and the treatment of pulmonary embolism are reviewed. We also discuss a recently described risk factor, present in our patient, as a potential role in the development of pulmonary embolism.

Defining a Standardized Information Model for Multi-Source Representation of Breast Cancer Data.

This work aims to define a standardized information model for representation of multiple data sources in breast cancer. A set of data elements has been identified using ICHOM Breast Cancer as the minimum data set and adapting it to the needs of Hospital Universitario 12 de Octubre. With this, an information model has been defined according to ISO 13606 and SNOMED CT standards.

[Clinical characteristics and microbiological profile of viridans group streptococci bacteremia in children with cancer and high-risk febrile neutropenia]. / Caracterización clínica y microbiológica de episodios de bacteriemia por Streptococcus grupo viridans en niños con cáncer y neutropenia febril de alto riesgo.

BACKGROUND: Viridans group streptococci (VGS) has acquired relevance as a microorganism causing febrile neutropenia, associated with significant morbidity. AIM: 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. METHOD: 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. RESULTS: 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 ß lactams. As expected, there were not non-susceptible strains to vancomycin. DISCUSSION: VGS is a relevant microorganism in children with cancer, fever and neutropenia, with a high percentage of sepsis. Resistance to ß lactams is an issue that requires strict epidemiological surveillance in this population.

Predictors of severe sepsis not clinically apparent during the first twenty-four hours of hospitalization in children with cancer, neutropenia, and fever: a prospective, multicenter trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 age > or =12 years [odds ratio (OR): 3.85; 95% confidence interval (CI): 2.41-6.15], admission CRP > or =90 mg/L (OR: 2.03; 95% CI: 1.32-3.14), admission IL-8 > or =200 pg/mL (OR: 2.39; 95% CI: 1.51-3.78), 24-hour CRP > or =100 mg/L (OR: 3.06; 95% CI: 1.94-4.85), and 24-hour IL-8 > or =300 pg/mL (OR: 3.13; 95% CI 1.92-5.08). CONCLUSIONS: Age > or =12 years and admission or 24-hour values of CRP > or =90/100 mg/L and IL-8 > or =200/300 pg/mL are predictors of sepsis not clinically apparent during the first 24 hours of hospitalization.

Incidence and clinical significance of FLT3 and nucleophosmin mutation in childhood acute myeloid leukemia in Chile

Abstract Introduction Acute myeloid leukemia (AML) is a heterogeneous disease and approximately one-third of its carriers do not have evident genetic abnormalities. The mutation of specific molecular markers, such as fms-like tyrosine kinase 3 (FTL3) internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) and nucleophosmin (NPM1), are associated with an adverse and favorable prognosis, respectively. Objective The objective was to determine the prevalence of FLT3/ITD and NPM1 in Chilean patients and their association with clinical data and prognosis. Method and Results Two hundred and thirty-two children were studied between 2011 and 2017, the median being 8.6 years (ranging from 1 to 18 months). Acute promyelocytic leukemia (APL) was diagnosed in 29%. The FLT3/ITD-mutated in non-promyelocytic AML was at 10% (14/133) and the FLT3/TKD, at 3.7% (2/54). In APL, it was at 25.4% (16/63). In non-promyelocytic AML, the FLT3/ITD-mutated was associated with a high leucocyte count, the median being 28.5 x mm3 (n= 14) versus 19.4 x mm3 (n= 119), (p= 0.25), in non-mutated cases. In APL, the median was 33.6 x mm3 (n= 15) versus 2.8 x mm3 (n= 47), (p < 0.001). The five-year overall survival (OS) in non-promyelocytic AML with non-mutated and mutated FLT3/ITD were 62.7% and 21.4%, respectively, (p < 0.001); the 5-year event-free survival (EFS) were 79.5% and 50%, respectively, (p < 0.01). The five-year OS in APL with non-mutated and mutated FLT3/ITD was 84.7% and 62.5%, respectively, (p= 0.05); the 5-year EFS was 84.7% and 68.8%, respectively, (p= 0.122). The NPM1 mutation was observed in 3.2% (5/155), all non-promyelocytic AML with the normal karyotype. Conclusion The FLT3/ITD mutation was observed more frequently in APL and associated with a higher white cell count at diagnosis. However, the most important finding was that the FLT3/ITD mutation was associated with a shorter survival in non-promyelocytic AML.

[Microorganisms isolated from blood cultures in children with cancer and high-risk febrile neutropenia from five hospitals in Santiago, Chile, 2012-2015]. / Microorganismos aislados de hemocultivos en niños con cáncer y neutropenia febril de alto riesgo en cinco hospitales de Santiago, Chile, período 2012-2015.

BACKGROUND: Microorganisms isolated from blood cultures (BC) in patients with febrile neutropenia (NF) vary over time, requiring systematic monitoring to guide appropriate empirical therapy. AIM: To identify microorganisms isolated from BC and their antimicrobial resistance profile in children with cancer and high risk NF. METHOD: 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. RESULTS: 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. DISCUSSION: 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.

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.

Admission clinical and laboratory factors associated with death in children with cancer during a febrile neutropenic episode.

BACKGROUND: Early identification of children with cancer at risk for death during a febrile neutropenic (FN) episode may increase their possibility for survival. Our aim was to identify at the time of admission, clinical and laboratory variables differing significantly among children who survived or died during a FN episode. METHODS: In a prospective, multicenter study, children admitted with a high-risk FN episode were uniformly evaluated at enrollment and managed according to a national consensus protocol. Medical charts of children who died were evaluated to determine whether the death could be associated with an infection. Admission clinical and laboratory variables significantly associated with death were identified. RESULTS: A total of 393 (70%) of 561 FN episodes evaluated from June 2004 to December 2005 were classified as high risk for invasive bacterial infection, of which 14 (3.6%) resulted in an infectious-related death. Deaths occurred from 2 to 27 days after admission, and most dying children were admitted with relapse of acute lymphocytic leukemia (36%), hypotension (71%), and a diagnosis of sepsis (79%), compared with surviving children (16%, 20%, and 5% respectively, P < 0.001). Children who died were admitted with lower absolute neutrophil count (P < 0.001) and absolute monocytes count levels (P = 0.008), higher blood urinary nitrogen (P = 0.03) and C-reactive protein values (P < 0.001), and had more positive cultures (79% versus 32%, P = 0.008). CONCLUSIONS: We identified early clinical and laboratory findings significantly associated with death occurring at a later stage. Routine evaluation of these variables may prove to be useful in the early identification of children with a high-risk FN episode at risk for death.