Infantile systemic juvenile xanthogranuloma case with massive liver infiltration.

Infantile systemic juvenile xanthogranuloma (ISJXG) is an uncommon form of juvenile xanthogranuloma, a non-Langerhans cell proliferation of infancy and early childhood. In a small percentage of patients, the visceral involvement-most commonly to the central nervous system, liver, spleen, or lungs-may be associated with severe morbidity, and eventually fatal outcome. Here we describe the clinical and pathological findings of a 28-day-old girl with ISJXG who died with respiratory distress syndrome. She had few cutaneous lesions but massive liver and spleen infiltration; other affected organs were multiple lymph nodes, thoracic parasympathetic nodule, pleura, pancreas, and kidneys. Additional findings were mild pulmonary hypoplasia and bacteremia. Immunohistochemistry on fixed tissues is the standard for diagnosis. Immunophenotype cells express CD14, CD68, CD163, Factor XIIIa, Stabilin-1, and fascin; S100 was positive in less than 20% of the cases; CD1a and langerin were negative. No consistent cytogenetic or molecular genetic defect has been identified. This case demonstrates that the autopsy is a handy tool, because hepatic infiltration, which was not considered clinically, determined a restrictive respiratory impairment. In our opinion, this was the direct cause of death.

Infantile systemic juvenile xanthogranuloma case with massive liver infiltration

Infantile systemic juvenile xanthogranuloma (ISJXG) is an uncommon form of juvenile xanthogranuloma, a non-Langerhans cell proliferation of infancy and early childhood. In a small percentage of patients, the visceral involvement­most commonly to the central nervous system, liver, spleen, or lungs­may be associated with severe morbidity, and eventually fatal outcome. Here we describe the clinical and pathological findings of a 28-day-old girl with ISJXG who died with respiratory distress syndrome. She had few cutaneous lesions but massive liver and spleen infiltration; other affected organs were multiple lymph nodes, thoracic parasympathetic nodule, pleura, pancreas, and kidneys. Additional findings were mild pulmonary hypoplasia and bacteremia. Immunohistochemistry on fixed tissues is the standard for diagnosis. Immunophenotype cells express CD14, CD68, CD163, Factor XIIIa, Stabilin-1, and fascin; S100 was positive in less than 20% of the cases; CD1a and langerin were negative. No consistent cytogenetic or molecular genetic defect has been identified. This case demonstrates that the autopsy is a handy tool, because hepatic infiltration, which was not considered clinically, determined a restrictive respiratory impairment. In our opinion, this was the direct cause of death.

Cost-Effectiveness of rFVIIa versus pd-aPCC in the Management of Mild to Moderate Bleeds in Pediatric Patients with Hemophilia A with Inhibitors in Mexico.

OBJECTIVE: To compare the costs and clinical consequences of treating mild-to-moderate joint bleeds with recombinant activated factor VII (rFVIIa) versus plasma-derived activated prothrombin complex concentrate (pd-aPCC) in pediatric patients with hemophilia A with inhibitors in Mexico. METHODS: A cost-effectiveness model was developed using TreeAge Pro v14.2.2 software (licensed in the USA) and adapted from a previously published model, with adjustments to reflect local clinical practice. Expert opinion was sought regarding patients' clinical management and resource utilization in Mexico to ensure that the current model was appropriate and relevant. The model compared rFVIIa and pd-aPCC for the treatment of mild-to-moderate joint bleeds in children <14 years old (assumed average weight: 30 kg). The analysis outcome was incremental cost per resolved mild-to-moderate joint bleed. One-way sensitivity analysis and probabilistic sensitivity analysis were used to assess specific assumptions and to address any uncertainty in the model. RESULTS: The cost of treating mild-to-moderate joint bleeds was lower for rFVIIa versus pd-aPCC after 7 days (MX$105,581 vs. MX$132,024), assuming complete bleed resolution. After 48 hours, rFVIIa was associated with an 8% improvement in bleed resolution versus pd-aPCC, resulting in cost savings of MX$16,754. Probabilistic sensitivity analysis indicated that rFVIIa treatment was more cost-effective than pd-aPCC in 67% (at 7 days) and 72% (at 48 hours) of Monte Carlo simulations. CONCLUSION: Accounting for model uncertainty, rFVIIa provided cost savings over pd-aPCC for the Mexican public health care payer in the management of mild-to-moderate joint bleeds in pediatric hemophilia A with inhibitors.

Early mortality in children with acute lymphoblastic leukemia in a developing country: the role of malnutrition at diagnosis. A multicenter cohort MIGICCL study.

The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient's age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08-4.01) was observed in the group of malnourished children with a high-risk ALL.

[Descriptive epidemiology of children with acute myeloid leukemia residing in Mexico City: a report from the Mexican Inter-Institutional Group for Identifying Childhood Leukemia Causes]. / Epidemiología descriptiva de la leucemia mieloide aguda (LMA) en niños residentes de la Ciudad de México: reporte del Grupo Mexicano Interinstitucional para la Identificación de las Causas de la Leucemia en Niños.

INTRODUCTION: Acute myeloid leukemias represent the second most common childhood leukemia subtype. In Mexico, there are few studies on descriptive epidemiology for this disease. AIMS: To report acute myeloid leukemia incidence for children less than 15 years of age in the Metropolitan Area of the Valley of Mexico for a period of five years (2010-2014) and to analyze whether there are differences in the incidence of acute myeloid leukemia by regions. MATERIAL AND METHODS: A descriptive study was conducted in nine public hospitals in Mexico City. The crude annual average incidence rate and adjusted average annual incidence rate were calculated. RESULTS: A total of 190 patients with diagnosis of de novo acute myeloid leukemia were analyzed. Male sex (57.2%) and acute myeloid leukemia-M3 subtype (25.3%) were more frequent. The adjusted average annual incidence rates for Mexico City and for the Metropolitan Area of the Valley of Mexico were 8.18 and 7.74 per million children under 15 years old, respectively. CONCLUSIONS: It seems that childhood acute myeloid leukemia incidence is increasing in Mexico City, which makes the identification of associated risk factors imperative.

Parental Exposure to Workplace Carcinogens and the Risk of Development of Acute Leukemia in Infants. Case-Control Study.

BACKGROUND AND AIMS: Occupational exposure of parents to carcinogens is of great interest in the etiology of leukemias. Evidence of the impact of such exposure on infants or small children is scarce. Here we estimated whether occupational exposure of parents to carcinogens could be a risk factor for leukemias in their children. METHODS: Cases of acute leukemia (AL) in infants ≤24 months old diagnosed in Mexico City (1998-2013) were included in a population-based, case-control study. Each of the 195 cases was matched with at least one healthy child (n = 369). For each of four exposure windows studied, the degree of exposure to carcinogens was determined for both parents by using a validated occupational exposure index. An unconditional logistic regression was carried out. RESULTS: Odds ratios (OR) and the 95% confidence intervals (CI) of the overall occupational exposure for parents during the four exposure windows indicated no association with risk of AL in their children. Pre-conception, the OR by the father 0.77 (0.49-1.21), by the mother 1.03 (0.50-2.11); during pregnancy, father 0.66 (0.38-1.15), mother 1.79 (0.46-6.90); during breastfeeding, father 0.75 (0.43-1.30), mother 0.96 (0.21-4.30); and after birth, father 0.74 (0.45-1.22), mother 0.90 (0.24-3.32). The statistical power of the sample size to identify an OR ≥2 and an exposure of ≥10% among controls was 78%. CONCLUSIONS: These data support the idea that parents' occupational exposure during any of the periods studied was not a risk factor contributing to the etiology of AL in infants ≤24 months of age.

Prevalence of gene rearrangements in Mexican children with acute lymphoblastic leukemia: a population study-report from the Mexican Interinstitutional Group for the identification of the causes of childhood leukemia.

Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010-2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology.

BACKGROUND: Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. METHODS: Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level). RESULTS: Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive correlation between the average number of persons per household and the incidence of the pre-B immunophenotype (Pearson's r, 0.789; P = 0.02). CONCLUSIONS: The frequency of ALL in Mexico City is among the highest in the world, similar to those found for Hispanics in the United States and in Costa Rica.

The age incidence of childhood B-cell precursor acute lymphoblastic leukemia in Mexico City.

The objective of this population-based survey was to assess the peak age of incidence of B-cell precursor acute lymphoblastic leukemia (ALL) in children in Mexico City (MC). All patients were classified according to their immunophenotype, and only B-cell precursor and T-lineage were analyzed. Rates of incidence were calculated x10 children. Of the 364 children from MC who were included in this study, immunophenotyping had been performed for 81.6%. The frequency of B-cell precursor ALL was 76.1%, whereas T lineage ALL showed a frequency of 23.6%. Peak age for ALL was 2 to 3 years of age. B-cell precursor ALL was the major contributor to peak age; T lineage ALL showed a peak among 1 and 3 years of age. We conclude that the age peak for children with ALL in MC is within the ranges reported for developed countries and that B-cell precursor ALL is the main contributor to these peak.

Secuelas neurológicas y psicológicas que deja la radioterapia o el metotresate intratecal en niños con leucemia linfoblástica aguda / Neurogical and psycological sequelae in children with acute lymphoblastic. leukemia who received central nervous system prophylaxis with radiotherapy or intrathecal methrotexate

Comparar las alteraciones neurológicas y psicológicas en niños con leucemia linfoblástica aguda (LLA), quienes habían estado con más de tres años sin tratamiento antineoplásico, y que recibieron profilaxis al sistema nervioso central (SNC) con base a radioterapia (RT), más quimioterapia intratecal (QTT) con metotrexate (Grupo 1) o sólo con QTIT (Grupo 2). En ambos grupos se realizó evaluación neurológica, electroencefalograma (EEG) y tomografía computada de cráneo (TACC). La evaluación psicológica consistió en la medición del coeficiente intelectual y de la función visomotora con la prueba de Bender. Las personas que realizaron cada una de las evaluaciones desconocían a que grupo de pacientes correspondía. Análisis estadístico: prueba exacta de Fisher y U de Mann-Whitnney. Catorce pacientes del grupo 1 y ocho pacientes del grupo 2. En el grupo 1 se encontró coeficiente intelectual significativamente inferior (mediana 83.5) al del segundo (90.5). En un paciente de cada grupo se encontraron alteraciones neurológicas, alteraciones en el EEG en 6 del grupo 1 y en 4 del grupo 2 y en la TACC, sólo en 2 pacientes del segundo grupo, sin tener diferencia estadística. Los niños con LLA quienes recibieron profilaxis al SNC con RT más QTIT, tuvieron mayor alteración en el rendimiento intelectual, en comparación con los tratados con metotrexate intratecal. En los dos grupos se presentaron anormalidades neurológicas, sin diferencia entre uno y otro grupo

Nutritional state alterations in children with acute lymphoblastic leukemia during induction and consolidation of chemotheraphy

The objective of the study was to determine if children with high risk acute lymphoblastic leukemia (ALL) exhibit higher frequency of alterations in nutritional state during the phases ofinduction and consolidation of chemotherapy than children with low risk ALL, based on the arm muscle area. The design was concurrent comparative cohort. It was performed at pediatric hematology service of the Hospital General del Centro Medico Naciona "La Raza" and hematology service of the Hospital de Pediatria del Centro Medico Nacional "Siglo XXI". One hundred-five patients were incorporated into the study: 53 with high risk (HR) ALL and 52 with low risk (LR) ALL. Basal measurements of arm circunference and tricipital skinfold were surveyed monthly (for 3 months) by standardized personnel. Altered nutritional state during follow-up was defined as the loss of 10 percent or more of the arm muscular area (AMA) measured at diagnosis. Statistics of proportion analysis with a significance level of 0.05 and relative risk (RR) was 0.77 (CI 0.31-1.87); the LR group was the most affected. In the second month the RR was 7.31 (CI 1.41-38.03); the most affected group was the HR. In the third month the RR was 1.77 (CI 0.60-4.92); the HR group was the most affected. High-risk patients show a higher frequency of nutritional state alterations reflected in AMA during the second month after diagnosis. This may be caused by the more aggressive chemotherapy received by these patients

Aplasia selectiva congénita de la serie roja: estudio de 13 casos / Congenital pure red cell aplasia: report of 13 cases

Se estudiaron 13 niños con aplasia selectiva congénita de la serie roja (ASCSR); nueve furon del sexo masculino. La mayoría de los pacientes iniciaron sus manifestaciones clínicas antes de los seis meses de edad, caracterizadas principalmente por: palidez; hepatomegalia, soplo cardíaco y malformaciones congénitas diversas. En todos los casos se documentó anemia moderada a severa, con cuenta de reticulocitos baja (promedio 0.6%) y de leucocitos y plaquetas normales. En todos los casos el estudio de médula ósea mostró disminución marcada de los precursores de la serie roja. Tres pacientes presentaron remisión completa de la anemia después del tratamiento con prednisona; en otros seis casos se observó respuesta parcial al tratamiento corticosteroide, requiriendo la administración prolongada de dosis bajas de prednisona. Finalmente, los cuatro pacientes restantes no presentaron respuesta al tratamiento, requiriendo transfusiones frecuentes

Anemia hemolítica autoinmune primaria en niños / Primary autoimmune hemolytic anemia in children

La anemia hemolítica autoinmune primaria (AHAIP) en niños puede ser debida a presencia de anticuerpos de tipo IgG o IgM, que sensibilizan al eritrocito del paciente y condicionan su destrucción en el sistema reticuloendotelial del bazo o del hígado. Clínicamente se caracteriza por la presencia de anemia, ictericia (hiperbilirrubinemia indirecta), hepato o esplenomegalia, reticulocitosis, elevación de los valores de hemoglobina libre en plasma y pruebas de Coombs directa e indirecta positivas. Aunque en algunos casos puede observarse remisión espontánea, en la mayoría de los niños con AHAIP se requiere la administración de corticosteroides para controlar el fenómeno hemolítico. En casos de evolución prolongada puede requerirse la utilización de otros métodos de tratamiento que incluyen: drogas inmunosupresoras, danazol, plasmaféresis y esplenectomía