RESUMO

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.

Assuntos

RESUMO

BACKGROUND: In Mexico City, the incidence of childhood acute lymphoblastic leukemia (ALL) is one of the highest in the world; epidemiologic evidence suggests that infectious agents could be involved in the genesis of this disease. Early transmitted oncogenic retroviruses infecting lymphocytes are important candidates. METHODS: PCR-based assays were used to screen viral genomic sequences of human T-cell lymphotrophic virus, type 1 (HTLV1) and mouse mammary tumor virus (MMTV)-like virus (MMTV-LV) in leukemic cells from 67 pediatric patients with ALL. RESULTS: Viral genomic sequences were not detected in any sample by neither standard nor nested PCR. CONCLUSIONS: Because of the methodologic strictness and high statistical power of the study, these results suggest that HTLV1 and MMTV-LV are not involved in the genesis of childhood ALL in Mexican children. IMPACT: To our knowledge, this is the first work exploring the direct participation of HTLV1 and MMTV-LV retroviruses in childhood ALL development.

Assuntos

RESUMO

Introducción. El diagnóstico de infección bacteriana en el paciente con cáncer, fiebre y neutropenia se dificulta debido a una pobre respuesta inflamatoria. Se han realizado evaluaciones con reactantes de fase aguda, como la proteína C reactiva, con resultados variables. El objetivo de este trabajo fue calcular la sensibilidad, especificidad, valores predictivos positivos y negativos y razones de verosimilitud de la proteína C reactiva para el diagnóstico de infección bacteriana en pacientes con cáncer y neutropenia febril. Métodos. Se realizó el estudio de la prueba diagnóstica. Se incluyeron pacientes pediátricos con cáncer, y neutropenia (<500 NA/mm³). La proteína C reactiva se cuantificó por nefelometría. Los episodios se clasificaron en cuatro grupos: grupo I, infección microbiológicamente documentada; grupo II, infección clínicamente documentada; grupo III, fiebre por otras causas; y grupo IV, pacientes con neutropenia sin fiebre. Se realizó el cálculo de sensibilidad, especificidad, valores predictivos positivos y negativos, curvas operantes del receptor y razones de verosimilitud. Para la comparación de variables cuantitativas se emplearon la U de Mann-Whitney y Kruskal-Wallis y para variables cualitativas, χ². Resultados. Se incluyeron 127 episodios que se distribuyeron en: 29, 47, 20 y 31 episodios para los grupos I, II, III y IV, respectivamente. Las medianas de la proteína C reactiva fueron 282 mg/L para el grupo I, 205 mg/L grupo II, 27.3 mg/L grupo III y 5.1 mg/L para el grupo IV (p < 0.001). Con la proteína C reactiva de 60 mg/L se obtuvo una sensibilidad de 94%, especificidad de 94%, valor predictivo positivo 96% y valor predictivo negativo 92%; razón de verosimilitud para un resultado positivo 15.6 y de 0.06 para resultado negativo. Conclusiones. La proteína C reactiva es una prueba útil y económica para el diagnóstico de infección bacteriana en el paciente con cáncer, fiebre y neutropenia.

Background. Diagnosis of bacterial infection in the patient with cancer, fever and neutropenia is difficult due to the poor inflammatory response. Several evaluations of acute phase reactants such as C-reactive protein (C-RP) have been performed with diverse results. The aim of this study was to calculate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and likelihood ratios (LR) for C-RP in the diagnosis of bacterial infection of patients with cancer, neutropenia and fever. Methods. We carried out a diagnostic test study. Pediatric patients with cancer and neutropenia (<500 NA/mm³) were selected. C-RP was determined by nephelometry. Episodes were classified into the following groups: group I: microbiologically documented infection; group II: clinically documented infection; group III: fever of unknown origin; group IV: patients with neutropenia without fever. Sensitivity, specificity, PPV, NPV, receiving operating curves (ROC) and LR were calculated. Mann-Whitney U test and Kruskal-Wallis test were used for comparison of quantitative variables. For qualitative variables, χ2 test was used. Results. There were 127 episodes distributed as follows: 29, 47, 20 and 31 for groups I, II, III and IV, respectively. Median of C-RP values were 282 mg/L for group I, 205 mg/L group II, 27.3 mg/L group III and 5.1 mg/L group IV (p <0.001). With a C-RP value of 60 mg/L, we obtained a sensitivity of 94%, specificity 94%, PPV 6% and NPV 92%. LR for a positive test was 15.6 and LR for a negative test was 0.06. Conclusions. C-RP is a useful and economically feasible test for diagnosis of bacterial infection in patients with cancer, neutropenia and fever.

RESUMO

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.

Assuntos

RESUMO

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.

Assuntos

RESUMO

BACKGROUND: Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL) in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. METHODS: From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR) of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s). In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI) was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an expert's opinion. RESULTS: The adjusted ORs and 95% confidence intervals (CI) were 1.69 (0.98, 2.92) during the preconception period; 1.98 (1.13, 3.45) during the index pregnancy; 2.11 (1.17, 3.78) during breastfeeding period; 2.17 (1.28, 3.66) after birth; and 2.06 (1.24, 3.42) for global exposure. CONCLUSION: This is the first study in which an OEI was used to assess a father's occupational exposure to carcinogenic agents as a risk factor for the development of childhood AL in his offspring. From our results, we conclude that children whose fathers have been exposed to a high level of carcinogenic agents seem to have a greater risk of developing acute leukemia. However, confounding factors cannot be disregarded due to an incomplete control for confounding.

Assuntos

RESUMO

BACKGROUND: There are very few studies that report the incidence of acute leukemias in children in Latin America. This work assesses the incidence of acute leukemias, between 1996 and 2000, in children from 0-14 years old who were attended at the Mexican Social Security Institute in Mexico City and in children from 0-11 years old in El Salvador. DESIGN: Population-based data. Hospitals: In San Salvador, El Salvador, Hospital Nacional de Niños "Benjamin Bloom", the only center in El Salvador which attends all children, younger than 12 years, with oncologic disease. The Pediatric Hospital and the General Hospital of the Mexican Social Security Institute in Mexico City, the only centers in Mexico City which attend all those children with acute leukemia who have a right to this service. DIAGNOSIS: All patients were diagnosed by bone marrow smear and were divided into acute lymphoid leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and unspecified leukemias (UL). The annual incidence rate (AIR) and average annual incidence rate (AAIR) were calculated per million children. Cases were stratified by age and assigned to one of four age strata: 1) <1 year; 2) 1-4 years; 3) 5-9 years, or 4) 10-14 or 10-11 years, for Mexico City and El Salvador, respectively. RESULTS: The number of cases was 375 and 238 in El Salvador and Mexico City, respectively. AAIRs in Mexico City were 44.9, 10.6, 2.5, 0.5, and 58.4 per million children for ALL, AML, CML, UL, and total leukemias, respectively. The AAIRs in El Salvador could not be calculated because the fourth age stratum in El Salvador included children only from 0-11 years old. The incidence rates for the Salvadorian group of 0-11 year olds were 34.2, 7.1, 0.6, 0.2, and 43.2 per million children for ALL, AML, CML, UL, and total leukemias, respectively. CONCLUSION: Reported AIRs for each age group in El Salvador were similar to those from other American countries. The AAIR of ALL in Mexico City is one of the highest reported for North America.

Assuntos

RESUMO

Objetivo. Medir la tasa de incidencia de las leucemias agudas (LA) en las diferentes delegaciones políticas del Distrito Federal y evaluar si existe una tendencia significativa en dichos padecimientos en tales delegaciones. Material y métodos. Estudio longitudinal descriptivo realizado en seis hospitales de la ciudad de México, los que atienden a cerca de 97.5 por ciento de todos los niños con cáncer de esta ciudad. Los datos se capturaron de 1995 a 1996, y se analizaron en 1999, en el Hospital de Pediatría del Centro Médico Nacional Siglo XXI, del Instituto Mexicano del Seguro Social. Para cada delegación se cal-cularon la tasa de incidencia anual promedio, la tasa es-tandarizada y la razón estandarizada de morbilidad (REM) con intervalos de confianza al 95 por ciento (IC 95 por ciento). La tendencia se evaluó con la tasa de cambio promedio. Re-sultados. Se observó una tendencia al incremento en la incidencia de la leucemia aguda linfoblástica (LAL) en cinco delegaciones: Alvaro Obregón, Cuauhtémoc, Gustavo A. Madero, Izta-calco y Venustiano Carranza. En la leucemia aguda mieloblás-tica (LAM) no se notificaron cambios estadísticamente signi-ficativos en la incidencia en ninguna delegación política. Sólo con LAM se encontró una REM significativa y co-rrespondió a la delegación Alvaro Obregón (REM= 2.91, IC 95 por ciento 1.63 - 4.80). Las REM más altas se encontraron en el sur y suroeste de la ciudad. Conclusiones. Sólo se observó incremento en la incidencia de LAL en cinco delegaciones políticas. La incidencia más alta de LAM se encontró en la delegación Alvaro Obregón.

Assuntos

RESUMO

Background. Previous reports have shown that undernourished children with acute lymphoblastic leukemia (ALL) have a poorer long-term survival as compared withchildren with normal nourishment status. It has been shown that both the relapse and mortality rates of undernourished children with ALL are higher during the continuation phase of the chemotherapy and are apparently related to a poor tolerance of ablative chemotherapy. No previous artichles have analyzed the aerly mortality rate of these patients. Methods. We carried out a case-control study, and have studied the effect of severe malnutrition on the mortality of 17 children with ALL during the initial induction-to-remission phase of the treatment. These 17 cases were compared with 76 controls who had survived at least the phases of induction and consolidation. Results. It was found that the chance of dying during the initial phase of the treatment was 2.6 times higher (confidence interval 95 percent: 0.55-11.89) in undernourished children with ALL than in those children with normal nourishment status. The risk of death increades with the severity of undernorisment (p= 0.04). Conclusions. These data confirm the prognostic value of malnutrition in children with ALL and suggest that undernourishment may also influence aerly mortality during the induction-to-remission phase of the treatment

Assuntos

RESUMO

Background. The use of combinations of antibiotics has been the cornerstone of therapy for febrile patients with cancer and severe neutropenia. Each empirical regimen should be selected according to the epidemiology and susceptibility patterns in each center. We describe here the experience wtih empirical antimicrobiial treatments in pediatric patients with cancer, fever and severe neutropenia, and identify the risk factors associated with treatment failure. Methods. This is a prospective study including 145 patients with cancer, and 171 episodes of neutropenia and fever. Blood cultures were taken before initiating empirical treatment: a)carbenicillin (400 mg/kg/day) plus amikacin (21 mg/kg/day) (Cb/ak), and b) ceftazidime (100 mg/kg/day), plus amikacin at the same dosage (Cz/ak). Results. The overall response rate was 54.9 percent and 56.3 percent for Cb/ak and Cz/ak, respectively. Fifty-seven episodes (33.3 percent) were microbiologically documented, gram-positive isolated in 38 percent and gram-negative in 49 percent. Risk factors associated significantly with treatment failure were acute mywlocytic leukemia (AML) (RR 2.59, CI 95 percent 1.42-4.7, p=0.003); bacteriological identification (RR= 4.41, CI 95 percent 2.21 - 8.8, p<0.001), and the presence of two or more sites of infection (RR= 2.89, CI 95 percent 1.03 - 8.11, p=0.03). Conclusions. The rates of response are similar to the combinations used in the hospital (Cb/ak, Cz/ak). The risk factors associated with treatment failure were AML diagnosis, bacteriological identification, and the presence of two or more sites of infection

Assuntos