Infections and risk factors for infection-related mortality after pediatric allogeneic hematopoietic stem cell transplantation in Mexico: A single center retrospective study.

OBJECTIVE: To identify the type of infections and risk factors for infection-related mortality (IRM) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Retrospective cohort study of patients <16 years of age treated in 2010-2019 was conducted. Unadjusted hazard ratios (HR) and adjusted hazard ratios (aHR) with 95% confidence intervals (95% CIs) were estimated using Cox regression. Cumulative incidence was calculated. RESULTS: Data for 99 pediatric patients were analyzed. The myeloablative conditioning was the most used regimen (78.8%) and the hematopoietic stem cell source was predominantly peripheral blood (80.8%). Primary graft failure occurred in 19.2% of patients. Frequency of acute graft-versus-host disease was 46.5%. Total of 136 infectious events was recorded, the most common of which were bacterial (76.4%) followed by viral infection (15.5%) and then fungal infection (8.1%). The best predictors for infection subtypes where the following: a) for bacterial infection (the age groups of 10.1-15 years: aHR = 3.33; 95% CI: 1.62-6.85 and. >15 years: aHR = 3.34; 95% CI: 1.18-9.45); b) for viral infection (graft versus host disease: aHR = 5.36; 95% CI: 1.62-17.68), however, for fungal infection statistically significant predictors were not identified. Related mortality was 30% (n = 12). Increased risk for infection-related mortality was observed in patients with unrelated donor and umbilical cord stem cells recipients (HR = 3.12; 95% CI: 1.00-9.85). CONCLUSIONS: Frequencies of infections and infection-related mortality appear to be similar to those reported. Unrelated donors and stem cells from umbilical cord recipients were associated with a high risk of mortality.

Pilot study on the effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on body composition in children with acute lymphoblastic leukemia: randomized clinical trial.

BACKGROUND: N-3 polyunsaturated fatty acids (LCPUFA-ω3), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) might have beneficial effects on lean mass and fat mass synthesis. OBJECTIVE: To investigate the effect of LCPUFA-ω3 supplementation on body composition changes in children with acute lymphoblastic leukemia (ALL) at remission and three months (3 mo) after supplementation. METHODS: This randomized controlled trial enrolled 72 children (3-13 y) with newly diagnosed ALL (placebo group [500 mg sunflower oil]: 36 patients; LCPUFA-ω3 group [225 mg DHA, 45 mg EPA]: 36 patients). LCPUFA-ω3 was administered at 0.100 g/kg of body weight/day for 3 mo. Both groups were provided with an oral milkshake supplement. MAIN OUTCOMES AND MEASURES: Body composition was measured at diagnosis, remission, and 3 months after supplementation by dual-energy X-ray absorptiometry (DXA). Red blood cell fatty acid analyses were performed with gas chromatography. Student's t test compared the percentage changes in body weight, total body fat percentage (TBFP), and lean body mass (LBM) between the groups. The Mann-Whitney U test was used to compare the groups, and the Friedman range test and Wilcoxon signed rank test were used for intratreatment comparisons. Spearman correlation coefficients were calculated for LBM and erythrocyte LCPUFA-ω3 content. RESULTS: LBM decreased significantly in both groups. This loss was greater in the placebo group than in the LCPUFA-ω3 group at remission (p = 0.044) and at 3 months of supplementation (p = 0.039). There were significant and progressive increases in DHA and EPA concentrations in the LCPUFA-ω3 group (p < 0.001). LBM at remission was directly correlated with increased DHA (r = 0.487, p = 0.034) and EPA (r = 0.499, p = 0.030) erythrocytes in the LCPUFA-ω3 group. CONCLUSION: At ALL diagnosis and during the first three months of treatment, 100 mg/kg of body weight/d DHA and EPA decreased LBM loss and allowed the incorporation of fatty acids into cell membranes (clinicaltriasl.gov #: NCT01051154).

Effect of long-chain omega-3 polyunsaturated fatty acids on cardiometabolic factors in children with acute lymphoblastic leukemia undergoing treatment: a secondary analysis of a randomized controlled trial.

Introduction: Increased triglycerides (TGs) are a major risk factor for cardiovascular disease. Furthermore, hypertriglyceridemia is commonly associated with a reduction of high-density lipoprotein cholesterol (HDL-C) and an increase in atherogenic small-dense low-density lipoprotein (LDL-C) levels. Studies provide support that polyunsaturated omega-3 fatty acids (ω3-LCPUFAs) are cardioprotective and have antithrombotic and anti-inflammatory effects. The potential effects of ω3-LCPUFAs on cardiometabolic factors and anti-inflammatory actions in children with acute lymphoblastic leukemia (ALL) are limited. This is a secondary analysis of a previous clinical trial registered at clinical trials.gov (# NCT01051154) that was conducted to analyze the effect of ω3-LCPUFAs in pediatric patients with ALL who were receiving treatment.Objective: To examine the effect of supplementation with ω3-LCPUFAs on cardiometabolic factors in children with ALL undergoing treatment. Methods: Thirty-four children (placebo group: 20 patients; ω3-LCPUFAs group: 14 patients) aged 6.7 ± 2.7 years who were newly diagnosed with ALL were evaluated. Children were randomized to receive either ω3-LCPUFAs or placebo capsules (sunflower oil). ω3-LCPUFAs were administered in the form of 500-mg soft capsules. The ω3-LCPUFA capsules contained 225 mg of DHA, 45 mg of EPA, and 20 mg of another ω3-LCPUFAs. The omega-3 dose was administered at a rate of 0.100 g/kg of body weight/day for three months. Main outcomes: Fasting cholesterol, HDL-C, very-low-density lipoprotein (VLDL-C), TGs, atherogenic index of plasma (AIP), android/gynoid ratio (A/GR), IL-6, TNF-α, and percentage of fat mass (DXA) were measured in all patients. Fatty acid analyses in red blood cells were performed with gas chromatography. Results: We found significantly lower levels of TGs (p=0.043), VLDL-C (p=0.039), IL-6 (p=0.025), and AIP (p=0.042) in the ω3-LCPUFAs group than in the placebo group at three months. In contrast, the total cholesterol concentration was higher at 3 months in the ω3-LCPUFAs group than in the placebo group (155 mg/dl vs. 129 mg/dl, p=0.009). The number of children with hypertriglyceridemia (85% vs. 50%; p=0.054) tended to be lower between the time of diagnosis and after 3 months of supplementation with ω3-LCPUFAs. Conclusion: These findings support the use of ω3-LCPUFAs to reduce some adverse cardiometabolic and inflammatory risk factors in children with ALL. Clinical trial registration: ClinicalTrials.gov, identifier NCT01051154.

[Leading causes of death during the induction therapy in pediatric patients with acute lymphoblastic leukemia]. / Principales causas de mortalidad durante la fase de inducción a la remisión en los pacientes pediátricos con leucemia linfoblástica aguda.

BACKGROUND: Leukemias are the leading cause of childhood cancer. In most developed countries 1-2% of patients die during remission induction; however, in developing countries, this figure is higher and the causes of death apparently vary among the populations studied. The aim was to determine the cause of death during remission induction in pediatric patients with acute lymphoblastic leukemia (ALL) in the hospital "Dr. Gaudencio González Garza" of Centro Médico Nacional La Raza from January 1, 2009, to December 31, 2014. METHODS: A retrospective cohort study was carried out and a descriptive statistical analysis was performed. RESULTS: During the study period, a total of 463 patients with ALL were diagnosed, out of which 5.4% died (n = 25). Among the patients who died, 64% (n = 16) were female and 60% had high-risk clinical features at diagnosis. The main causes of death were septic shock and bleeding. CONCLUSIONS: Early mortality was five times higher than the one reported for developed countries, while the causes of death did not differ. Close monitoring is necessary to detect and promptly treat complications secondary to chemotherapy toxicity in Mexican pediatric patients with ALL.

Introducción: las leucemias son la principal causa de cáncer en la infancia. En la mayoría de países desarrollados fallecen entre 1 y 2% de los pacientes durante la inducción a la remisión; sin embargo, en países en vías de desarrollo, esta cifra al parecer es superior y las causas de muerte varían entre las poblaciones estudiadas. El objetivo fue determinar la causa de mortalidad durante la fase de inducción a la remisión en los pacientes pediátricos con diagnóstico de leucemia linfoblástica aguda (LLA) en el Hospital General "Dr. Gaudencio González Garza" del Centro Médico Nacional La Raza del 1 de enero de 2009 al 31 de diciembre de 2014. Métodos: se realizó un estudio de cohorte retrospectivo y se utilizó estadística descriptiva. Resultados: se diagnosticaron un total de 463 pacientes con LLA durante el periodo de estudio, de los cuales falleció el 5.4% (n = 25). Entre los pacientes que fallecieron, el 64% (n = 16) eran del sexo femenino y el 60% tenía características clínicas de alto riesgo al momento del diagnóstico. Entre las principales causas de muerte estuvieron el choque séptico y las hemorragias. Conclusiones: la frecuencia de mortalidad temprana en los pacientes con LLA fue cinco veces más elevada que la reportada para países desarrollados, mientras que las causas de muerte no difieren. Se requiere de una vigilancia estrecha para detectar y tratar oportunamente las complicaciones secundarias a toxicidad por quimioterapia en pacientes pediátricos mexicanos con LLA.

Survival of Mexican children with acute myeloid leukaemia who received early intensification chemotherapy and an autologous transplant.

BACKGROUND: In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. PROCEDURE: This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005-2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999-2004, was treated as Group A, but without the early intensified chemotherapy. RESULTS: Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. CONCLUSIONS: Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

[Opportunistic bacteria and microbial flora in children with leukemia and neutropenic enterocolitis]. / Bacterias oportunistas y microbiota en niños con leucemia y enterocolitis neutropénica.

OBJECTIVE: to determine the prevalence of opportunistic microorganisms and microbial flora in neutropenic enterocolitis in oncohematological pediatric patients. METHODS: a prospective and observational study was done. Patients with diagnosis of acute leukemia and neutropenia were included. Stool cultures were taken to identify microorganisms and microbial flora. A χ(2) test with Yates corrections and Fisher exact test were used in the statistical analysis. RESULTS: 21 patients were included (12 male, 57.1 %). The stool cultures showed that 68 % of microorganisms were Gram-negative. The presence of microorganisms Gram-positive was 20 %, 6 % for Candida sp.; 3 % for Cryptosporidium sp.; and in 3 % were acid fast bacilli. Staphylococcus epidermidis, Enterobacter sp., and Escherichia coli were presented in pure culture. No association was found between Gram-positive and Gram-negative microorganisms with age, white cell count or pure or mixed cultures. CONCLUSIONS: although Gram-negative microorganisms were the most frequent, Gram-positive and other microorganisms that are not detected habitually in feces culture were isolated.

Objetivo: determinar la microbiota y la prevalencia de microorganismos oportunistas en niños con leucemia y enterocolitis neutropénica. Métodos: se realizó un estudio prospectivo observacional en pacientes con leucemia aguda y neutropenia. Se tomaron cultivos de heces para identificar la presencia de bacterias y microbiota. Se aplicó estadística descriptiva para su análisis. Resultados: fueron incluidos 21 pacientes (12 hombres, 57.1 %). En 68 % de los coprocultivos se observó desarrollo de microorganismos gramnegativos. La presencia de microorganismos grampositivos fue de 20 %, 6 % de Candida sp., 3 % de Cryptosporidium sp. y en 3 % se observaron bacilos ácido alcohol resistentes. Staphylococcus epidermidis, Enterobacter sp., y Escherichia coli se observaron en cultivo puro. No se encontró asociación entre microorganismos grampositivos y gramnegativos con la edad, el recuento leucocitario ni el cultivo puro o mixto.Conclusiones: aunque los microorganismos gramnegativos fueron los más frecuentes, se aislaron de manera importante grampositivos y otros que no se buscan de rutina en el coprocultivo.

Frecuencia de hemorragia intracraneana en niños hemofílicos / Intracranial hemmorrhage frequency in patients hemophilic

La hemorragia intracraneana es la principal causa de muerte entre los pacientes hemofílicos. Por esta razón se revisaron 75 expedientes clínicos de pacientes menores de 16 años con el diagnóstico de hemofilia. Se encontraron seis niños con hemorragia intracraneana (HIC). El tiempo de inicio de la sintomatología fue de 12 h hasta cuatro días con una media de 39 h. Los signos y síntomas encontrados fueron: cefalea, vómito, crisis convulsiva, hematoma en el sitio del traumatismo, hemiperesia corporal izquierda, nistagmus, náusea. Se dio tratamiento substitutivo en todos los niños. Cuatro presentaron secuelas neurológicas. La frecuencia de HIC se estimó en 8 por ciento de los hemofílicos. Se concluye que para prevenir la muerte y minimizar las secuelas, una terapia de reemplazo adecuada, ésta debe ser instituida tan pronto como se sospecha el sangrado o inmediatamente después del traumatismo craneoencefálico