Venous thromboembolism in children with acute lymphoblastic leukemia in China: a report from the Chinese Children's Cancer Group-ALL-2015 / 医学前沿

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.

Caracterización de las leucemias en niños en Cuba (2006-2015) / Characterization of leukemias in Cuban children (2006-2015)

Introducción: La leucemia es el cáncer más frecuente en edades pediátricas. La leucemia linfoide aguda (LLA) representa el 23 por ciento de los diagnósticos de cáncer en niños menores de 15 años y el 75 por ciento de todas las leucemias. Más del 90 por ciento de las leucemias mieloides agudas (LMA) en la niñez son agudas y el resto son crónicas. Objetivo: Caracterizar las leucemias agudas de la edad pediátrica en Cuba. Métodos: Estudio descriptivo, longitudinal y retrospectivo. La muestra fue de 799 niños de toda Cuba, los cuales fueron atendidos en los siete hospitales pediátricos acreditados en el país para el tratamiento de leucemias agudas, entre enero 2006 y diciembre de 2015. Como medida de resumen para las variables cuantitativas se utilizaron la media y desviación estándar. Para todas las variables cualitativas se calcularon los porcentajes de cada grupo. Resultados: Las tasas de incidencia fueron de 2,9 x 100 000 niños. El 95 por ciento fueron leucemias agudas (70,6 por ciento linfoides), con el 34,9 por ciento de leucemia promielocíticas (LPM) en las LMA. Predominó el sexo masculino y la edad promedio al diagnóstico fue de 7,1 años. El porcentaje de remisión completa en las LLA fue de 91 por ciento y en las LMA, de 66,7 por ciento. La frecuencia de recaídas de la enfermedad fue de 25,1 por ciento en las LLA, 13,7 por ciento en las LPM y 45 por ciento en las otras mieloides. La sobrevida global y libre de eventos fue de 89 por ciento y 63 por ciento en los niños con LLA, 64 por ciento y 62 por ciento en la LPM, 38 por ciento y 36 por ciento en la LMA no promielocítica, respectivamente. Conclusiones: La frecuencia y distribución etaria de las leucemias en niños cubanos son similares a lo descrito a nivel. Los resultados del tratamiento en las leucemias agudas de manera general pueden considerarse como buenos(AU)

Introduction: Leukemia is the most frequent cancer in pediatric ages. Acute lymphoid leukemia (ALL) accounts for 23 percent of cancer diagnoses in children at ages under 15 years and 75 percent of all leukemias. More than 90 percent of childhood acute myeloid leukemias (AML) are acute and the rest are chronic. Objective: To characterize acute leukemias in pediatric age in Cuba. Methods: Descriptive, longitudinal and retrospective study. The sample was 799 children from all over Cuba, who were treated in any of the country's seven pediatric hospitals accredited for the treatment of acute leukemias, between January 2006 and December 2015. As a summary measure for the quantitative variables, the mean and standard deviation were used. For all qualitative variables, the percentages of each group were calculated. Results: Incidence rates were 2.9 per 100,000 children. 95 percent were acute leukemias (70.6 percent lymphoid), with 34.9 percent corresponding to promyelocytic leukemia (PML) in AML. The male sex predominated and the average diagnosis age was 7.1 years. The percentage of complete remission in ALL was 91 percent, and 66.7 percent in AML. The frequency of disease relapse was 25.1 percent in ALL, 13.7 percent in LPM, and 45 percent in other myeloid leukemias. Overall and event-free survival was 89 percent and 63 percent in children with ALL, 64 percent and 62 percent in LPM, 38 percent and 36 percent in non-promyelocytic AML, respectively. Conclusions: Frequency and age distribution of leukemias in Cuban children are similar to that described worldwide. The results of treatment in acute leukemias in general can be considered as good(AU)

Sobrevida das leucemias linfoides agudas em crianças no Município de São Paulo, Brasil / Survival from acute lymphocytic leukemia in children in the city of São Paulo, Brazil / Supervivencia de niños con leucemias linfoides agudas, municipio de São Paulo, Brasil

Resumo: Este estudo visa analisar as taxas de sobrevida da leucemia linfoide aguda na infância no Município de São Paulo, Brasil, no período de 1997 a 2013, segundo sexo, faixa etária e região administrativa. Trata-se de um estudo longitudinal para calcular as taxas de sobrevida. Os dados dos casos novos de leucemia na faixa etária de 0 a 14 anos foram coletados na base de dados do Registro de Câncer de Base Populacional do Município de São Paulo. Os dados populacionais e de mortalidade foram obtidos do Departamento de Informática do SUS. Foram incluídas crianças de 0 a 14 anos, diagnosticadas com leucemia no período de 1997 a 2013, residentes no Município de São Paulo. As variáveis analisadas foram sexo, faixa etária e Coordenadorias Regionais de Saúde. Na análise de sobrevida, foi calculado o estimador produto-limite de Kaplan-Meier, foram comparadas as curvas de sobrevida pelo teste de log-rank e ajustou-se o modelo de riscos proporcionais de Cox. A maioria estimada dos casos novos eram do sexo masculino, de 0 a 4 anos de idade, diagnosticados entre 2000 a 2004 e residentes na regional Sudeste do Município de São Paulo. A taxa de incidência geral estimada foi de 34,7 casos novos por 1 milhão, e a taxa de mortalidade foi de 9,0 óbitos por 1 milhão. A probabilidade geral de sobrevida por leucemia linfoide aguda em crianças em até 60 meses foi de 68%. Houve diferença estatisticamente significativa segundo década diagnóstica (p = 0,026), especificamente, ocorreu piora das taxas de sobrevida ao longo dos anos, sendo que o pior prognóstico foi nos anos de 2005-2009.

Abstract: This study aims to analyze survival rates in acute lymphocytic leukemia in the city of São Paulo, Brazil, from 1997 to 2013, according to sex, age bracket, and administrative region. This was a longitudinal study to calculate survival rates. Data on new cases of leukemia in the age bracket 0 to 14 years of age were collected from the database in the Population-Based Cancer Registry of the city of São Paulo. Population and mortality data were obtained from the Brazilian Health Informatics Department. The sample included children 0 to 14 years of age diagnosed with leukemia from 1997 to 2013, living in the city of São Paulo. The variables were sex, age bracket, and Regional Health Divisions. The survival analysis calculated the Kaplan-Meier product limit estimator and compared the survival curves through the log-rank test, and the Cox proportional risks model was adjusted. The estimated majority of new cases were males, 0 to 4 years of age, diagnosed from 2000 to 2004, and living in the southeast regional division of the city of São Paulo. The estimated overall incidence rate was 34.7 new cases per million, and the mortality rate was 9.0 deaths per million. The overall five-year survival of children from acute lymphocytic leukemia was 68%. There was a statistically significant difference according to decade of diagnosis (p = 0.026), and specifically the survival rates decreased over the years, with the worst prognosis in the years 2005-2009.

Resumen: El objetivo de este estudio es analizar las tasas de supervivencia de niños con leucemia linfoide aguda en el municipio de São Paulo, Brasil, durante el período de 1997 a 2013, según sexo, franja de edad y región administrativa. Se trata de un estudio longitudinal para calcular las tasas de supervivencia. Los datos de los casos nuevos de leucemia en la franja de edad de 0 a 14 años se recogieron en la base de datos del Registro de Cáncer de Base Poblacional del municipio de São Paulo. Los datos poblacionales y de mortalidad se obtuvieron del Departamento de Informática del Sistema Único de Salud. Se incluyeron niños de 0 a 14 años, diagnosticados con leucemia durante el período de 1997 a 2013, residentes en el municipio de São Paulo. Las variables analizadas fueron sexo, franja de edad y Coordinaciones Regionales de Salud. En el análisis de supervivencia, se calculó el estimador del producto-límite (Kaplan-Meier), se compararon las curvas de supervivencia a través del test de log-rank, y se ajustó el modelo de riesgos proporcionales de Cox. La mayoría estimada de casos nuevos eran de sexo masculino, de 0 a 4 años de edad, diagnosticados entre 2000 a 2004 y residentes en la regional Sudeste del municipio de São Paulo. La tasa de incidencia general estimada fue de 34,7 casos nuevos por 1 millón y la tasa de mortalidad fue de 9,0 óbitos por 1 millón. La probabilidad general de supervivencia por leucemia linfoide aguda en niños de hasta 60 meses fue de un 68%. Hubo una diferencia estadísticamente significativa según la década del diagnóstico (p = 0,026), específicamente, se produjo un empeoramiento de las tasas de supervivencia a lo largo de los años, donde el peor pronóstico fue durante los años de 2005-2009.

CD45 y leucemia linfoide aguda pediátrica / CD45 and childhood acute lymphoblastic leukemia

Introducción: El CD45 se expresa en las células hematopoyéticas, su determinación es indispensable para la clasificación inmunofenotípica de la leucemia linfoide aguda (LLA). Objetivo: Evaluar la expresión del antígeno CD45 en los blastos de pacientes pediátricos con LLA y su relación con las características biológicas, morfológicas y clínicas al inicio de la enfermedad, la respuesta al tratamiento y la supervivencia global (SG) de los enfermos. Métodos: Se estudiaron 160 pacientes con LLA entre diciembre del 2012 y diciembre del 2017, tratados con el protocolo ALL-IC BFM-SG 2009. El inmunofenotipaje celular de la médula ósea se realizó por citometría de flujo. Resultados: El fenotipo B CD45+ predominó en los menores de seis años de edad y en los mayores de diez, el fenotipo T CD45+. Se encontró diferencia significativa entre la ausencia de adenopatías mediastínicas, el fenotipo leucémico y la ausencia de CD45 (p=0.004); entre la respuesta a la prednisona en sangre periférica al día ocho, el fenotipo leucémico y la ausencia de CD45 (p=0.001). Se encontraron diferencias significativas entre la respuesta a la prednisona en sangre periférica el día ocho y la respuesta en médula ósea el día 33, según fenotipo leucémico (p=0.009) y la presencia en los blastos del antígeno CD45 (p=0.02). Se encontró diferencia significativa entre la SG de los enfermos, según fenotipo leucémico y la ausencia del antígeno CD45 (p=0.017). Conclusión: La expresión o ausencia del antígeno de CD45 en los blastos tiene relación con la respuesta al tratamiento y la SG de pacientes pediátricos con LLA(AU)

Introduction: CD45 is expressed in hematopoietic cells, its determination is essential for the immunophenotypic classification of acute lymphoid leukemia (ALL). Objective: To evaluate the expression of the CD45 antigen in the blasts of pediatric patients with ALL and its relationship with the biological, morphological and clinical characteristics at the onset of the disease, the response to treatment and the overall survival (OS) of the patients. Methods: 160 patients with ALL were studied between December 2012 and December 2017, treated with the ALL-IC BFM-SG 2009 protocol. Bone marrow cellular immunophenotyping was performed by flow cytometry. Results: Patients with the CD45 + B phenotype predominated in those under six years of age, while those with a CD45 + T phenotype in those older than ten. A significant difference was found between the absence of mediastinal lymph nodes, the leukemic phenotype and the absence of CD45 (p = 0.004). A significant difference was found between the response to prednisone in peripheral blood at day eight, the leukemic phenotype and the absence of CD45, p = 0.001. Significant differences were found between the response to prednisone in peripheral blood on day eight and the response in bone marrow on day 33, according to leukemic phenotype and the presence in blasts of the CD45 antigen (p = 0.009 and p = 0.02, respectively). A significant difference was found between the OS of patients, according to leukemic phenotype and the absence of the CD45 antigen, p = 0.017. Conclusion: The expression or absence of the CD45 antigen in blasts is related to the response to treatment and OS of pediatric patients with ALL(AU)

Cesariana, condições pré-natal e pós-natal e leucemia linfoblástica aguda na infância / Cesarean section, prenatal and post-natal conditions and acute lymphoblastic leukemia in childhood

Introdução: A leucemia linfoblástica aguda (LLA) é a neoplasia pediátrica com maior incidência no mundo. Sua etiologia é resultante de múltiplas interações entre herança genética e exposição a agentes ambientais potencialmente carcinogênicos nos períodos pré-natal, nascimento e pós-natal. O parto cesáreo tem sido apontado como fator de risco para LLA em crianças. No Brasil, país com altas taxas de cesariana, são poucos os estudos que avaliaram a associação de cesariana com LLA na infância. Objetivos: Investigar a associação de cesariana e condições pré-natal e pós-natal com LLA em crianças nascidas no estado de São Paulo. Métodos: Estudo caso-controle de base populacional. Os casos de LLA, crianças nascidas no estado de São Paulo a partir de 1999, foram recrutados em oito hospitais de 2003 a 2009. Os controles foram emparelhados com os casos por sexo, idade e cidade de nascimento. As informações utilizadas nesse estudo foram obtidas em entrevistas com as mães ou responsáveis pelas crianças por meio de questionário estruturado. Informações adicionais foram adquiridas no banco de Declarações de Nascidos Vivos (DNV), que integra o Sistema de Informações de Nascidos Vivos (SINASC) da Secretaria Municipal de Saúde de São Paulo e do Ministério da Saúde. Após o linkage probabilístico dos bancos de dados, a amostra final comporta 133 casos e 459 controles, relação de 3,4 controles por caso. Análises de regressão logística não condicional e condicional foram conduzidas para estimar a associação entre cesariana, condições pré-natal e pós-natal e LLA, com estimava dos odds ratios (OR) e respectivos intervalos de 95% de confiança (IC 95%). Três modelos de regressão logística foram elaborados: 1) ajuste por idade e sexo da criança, idade e escolaridade da mãe; 2) ajuste pelas variáveis anteriores, mais raça e número de consultas; 3) ajuste por todas as variáveis anteriores e a inclusão de idade e a inclusão de idade gestacional e peso ao nascer. Resultados: A análise de regressão logística não condicional, com base no Modelo 2, revelou discreto risco de LLA na exposição à cesariana (OR=1,10; IC95% 0,71-1,70), proteção na condição de mãe com 12 ou mais anos de escolaridade (OR=0,46; IC95% 0,24-0,89) e idade da criança de 6 a 8 anos no diagnóstico (OR=0,30; IC95% 0,13-0,67). Resultados similares foram observados na análise de regressão logística condicional no Modelo 2: cesariana (OR=1,18; IC95% 0,69-2,00), mães com 12 ou mais anos de escolaridade (OR=0,56; IC95% 0,25-1,24). Conclusões: Há uma tênue associação entre cesariana e LLA na infância, sem significância estatística. Alta escolaridade da mãe e crianças na faixa etária entre 6 e 8 anos foram fatores de proteção para LLA. Crianças com síndrome de Down apresentaram seis vezes o risco de LLA. Os resultados obtidos por análise regressão logística condicional foram similares aos da regressão logística não condicional.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common pediatric neoplasia worldwide. Its etiology results from multiple interactions between genetic inheritance and exposure to potentially carcinogenic environmental agents during the prenatal, birth, and postnatal periods. Cesarean section has been identified as a risk factor for ALL in children. In Brazil, a country with high Cesarean section rates, few studies have evaluated the association of Cesarean section with ALL in childhood. Objectives: To investigate the association of Cesarean section, prenatal and postnatal conditions with ALL in children born in the state of São Paulo. Methods: Population-based case-control study. The cases of ALL, children born in the state of São Paulo from 1999, were recruited in eight hospitals from 2003 to 2009. Controls were matched with cases by sex, age and city of birth. The information used in this study were obtained through interviews with mothers or guardians of the children, using a structured questionnaire. Additional information were get from the Live Births Database, stored in the Live Birth Information System at the São Paulo Municipal Health Department and at the Brazilian Ministry of Health. After the databases probabilistic linkage, the final sample entails 133 cases and 459 controls, 3.4 controls per case ratio. Non-conditional and conditional logistic regression analyzes were conducted to estimate the association between cesarean section, pre- and postnatal conditions, and ALL with estimation of odds ratios (OR) and respective 95% confidence intervals (95% CI). Three models of logistic regression were elaborated: 1) adjustment by age and sex of the child, age and schooling of the mother; 2) adjustment for the previous variables, more race and number of queries; 3) adjustment for all previous variables and the inclusion of gestational age and birth weight. Results: The nonconditional logistic regression analysis, based on Model 2, revealed a slight risk of ALL on cesarean section exposure (OR = 1.10, 95% CI 0.71-1.70), protection on the condition of mothers with 12 or more years of schooling (OR = 0.46, 95% CI 0.24-0.89), and age of child from 6 to 8 years at diagnosis (OR = 0.30, 95% CI, 0.13-0, 67). In the conditional logistic regression analysis in Model 2, similar results were observed: cesarean (OR = 1.18, 95% CI 0.69-2.00), mothers with 12 or more years of schooling (OR = 0.56, 95% CI, 0.25-1.24). Conclusions: There is a weak association between cesarean section and ALL in childhood, with no statistical significance. Mother with high education level and children in the age range between 6 and 8 years were protective factors for ALL. Children with Down syndrome had a six-fold risk of ALL. The results obtained by conditional logistic regression analysis were similar to those of non-conditional logistic regression

Leucemia linfoblástica aguda en niños con síndrome de Down: análisis comparativo con pacientes sin síndrome de Down / Acute lymphoblastic leukemia in children with Down syndrome: Comparative analysis versus patients without Down syndrome

Introducción: Los niños con síndrome de Down (SD) tienen mayor frecuencia de leucemia linfoblástica aguda (LLA) y menor supervivencia que pacientes sin síndrome de Down (NSD). Analizamos las características clínicas, demográficas-biológicas y respuestas al tratamiento en SD-LLA versus NSD-LLA. Pacientes y métodos: Pacientes (0-19 años) con LLA desde enero de 1990 a noviembre de 2016. Se compararon características demográficas biológicas y respuestas al tratamiento con chi cuadrado y Wilcoxon rank sum. La supervivencia global y el intervalo libre de eventos (ILE) se analizaron con Kaplan-Meier y el test log-rank. Resultados: Se incluyeron 1795 pacientes, 54 con SD. Los SD-LLA presentaron edad mayor (p= 0,0189). T odos inmuno fenotipo precursor-B, con menor incidencia de anomalías recurrentes (p < 0,0001). Demostraron mejor tasa de respuesta a prednisona (p= 0,09) y mayor mortalidad en inducción y remisión completa (p < 0,0001). Todas las muertes de los SD-LLA fueron relacionadas con el tratamiento. La sobrevida libre de eventos en niños SD-LLA vs.NSD-LLA fue 47 (± 8)% vs. 73 (± 1)% (p= 0,006) y el ILE de los SD-LLA vs. NSD-LLA fue 54 (± 9)% vs. 75 (± 1)% (p= 0,0297). La tasa de recaídas fue similar en ambos grupos (p= 0,6894). El ILE de los SD-LLA fue menor en el grupo de 6-9 años: 39 (± 19)% (p= 0,7885). Conclusiones: Los niños de 6-9 años con SD-LLA años presentó menor sobrevida. Aunque estos niños presentaron una mejor respuesta temprana, la sobrevida libre de eventos e ILE fueron menores debido a la mortalidad relacionada con el tratamiento.

Introduction. Children with Down syndrome (DS) more commonly have acute lymphoblastic leukemia (ALL) and a lower survival rate than those without Down syndrome (WDS). We analyzed the clinical, demographic, and biological characteristics and treatment response of children with DS-ALL versus those WDS-ALL. Patients and methods: Patients with ALL between January 1990 and November 2016. The demographic and biologic characteristics and treatment response were compared using the χ² and Wilcoxon rank-sum tests. The overall survival and event-free interval (EFI) were analyzed using the Kaplan-Meier and log-rank tests. Results. 1795 patients were included; 54 had DS. Patients with DS-ALL were older (p= 0.0189). All had B-cell precursor immunophenotype and a lower incidence of recurrent abnormalities (p < 0.0001). They showed a better response rate to prednisone (p= 0.09) and a higher mortality in induction and complete remission (p < 0.0001). All deaths of patients with DS-ALL were treatment-related. The event-free survival (EFS) was 47% (± 8%) versus 73% (± 1%) (p= 0.006) and the EFI was 54% (± 9%) versus 75% (± 1%) (p= 0.0297) among patients with DS-ALL versus those WDS-ALL, respectively. The rate of relapse was similar in both groups (p= 0.6894). The EFI of patients with DS-ALL was lower in the group aged 6-9 years: 39% (± 19%) (p= 0.7885). Conclusions. A lower survival was observed among children aged 6-9 years with DS-ALL. Although these children showed a better early response, their EFS and EFI were lower due to treatment-related mortality.

Comparative study of quality of life of adult survivors of childhood acute lymphocytic leukemia and Wilms’ tumor / Estudo comparativo da qualidade de vida de adultos sobreviventes de leucemia linfocítica aguda e tumor de Wilms na infância

Abstract Objective To analyze and compare the health-related quality of life of adult survivors of acute lymphocytic leukemia and Wilms’ tumor amongst themselves and in relation to healthy participants. Methods Ninety participants aged above 18 years were selected and divided into three groups, each comprising 30 individuals. The Control Group was composed of physically healthy subjects, with no cancer history; and there were two experimental groups: those diagnosed as acute lymphocytic leukemia, and those as Wilms’ Tumor. Quality of life was assessed over the telephone, using the Medical Outcomes Study 36-Item Short Form Health Survey. Results Male survivors presented with better results as compared to female survivors and controls in the Vitality domain, for acute lymphocytic leukemia (p=0.042) and Wilms’ tumor (p=0.013). For acute lymphocytic leukemia survivors, in Social aspects (p=0.031), Mental health (p=0.041), and Emotional aspects (p=0.040), the latter also for survivors of Wilms’ tumor (p=0.040). The best results related to the Functional capacity domain were recorded for the experimental group that had a late diagnosis of acute lymphocytic leukemia. There were significant differences between groups except for the Social and Emotional domains for self-perceived health, with positive responses that characterized their health as good, very good, and excellent. Conclusion Survivors of acute lymphocytic leukemia showed no evidence of relevant impairment of health-related quality of life. The Medical Outcomes Study 36-Item Short Form Health Survey (via telephone) can be a resource to access and evaluate survivors.

Resumo Objetivo Analisar e comparar a qualidade de vida relacionada à saúde de sobreviventes adultos de leucemia linfocítica aguda e tumor de Wilms entre si, e em relação a participantes sadios. Métodos Foram selecionados noventa participantes, acima de 18 anos, os quais foram divididos em três grupos, sendo cada um com 30 sujeitos: Grupo Controle, que contou com indivíduos fisicamente saudáveis, sem histórico oncológico; grupo experimental formado por pacientes que tiveram diagnóstico de leucemia linfocítica aguda; e grupo experimental formado por pacientes que tiveram diagnóstico de Tumor de Wilms. A avaliação da qualidade de vida foi realizada por telefone e utilizou o Medical Outcomes Study 36-Item Short Form Health Survey. Resultados Os sobreviventes do sexo masculino apresentaram melhores resultados em relação aos do sexo feminino e controles no Aspecto vitalidade, para leucemia linfocítica aguda (p=0,042) e tumor de Wilms (p=0,013). Para os sobreviventes de leucemia linfocítica aguda nos Aspectos sociais (p=0,031), Saúde mental (p=0,041) e Aspectos emocionais (p=0,040), neste último também para as sobreviventes de Tumor de Wilms (p=0,040). Os melhores resultados relacionados ao domínio Capacidade funcional foram registrados para o grupo experimental de pacientes que tiveram diagnóstico tardio de leucemia linfocítica aguda. Observaram-se diferenças significativas entre os grupos, exceto para os domínios Aspectos sociais e emocionais para a percepção da própria saúde, que teve respostas de cunho positivo, que qualificavam a própria saúde como boa, muito boa e excelente. Conclusão O grupo experimental de pacientes que tiveram diagnóstico de leucemia linfocítica aguda não apresentou evidências de comprometimento relevante da qualidade de vida relacionada à saúde. O Medical Outcomes Study 36-Item Short Form Health Survey (via telefone) pode ser um recurso de acesso e avaliação de sobreviventes.

NRAS Mutations in de novo acute leukemia: Prevalence and clinical significance.

The activating mutations of the Ras gene or other abnormalities in Ras signaling pathway lead to uncontrolled growth factor-independent proliferation of hematopoietic progenitors. Oncogenic mutations in NRAS gene have been observed with variable prevalence in hematopoietic malignancies. In the present study, NRAS mutations were detected using bidirectional sequencing in 264 acute leukemia cases — 129 acute lymphocytic leukemia (ALL) and 135 acute myeloid leukemia (AML) and 245 age- and gender-matched controls. Missense mutation was observed only in the 12th codon of NRAS gene in 4.7% of AML and 3.16% of ALL cases. The presence of NRAS mutation did not significantly influence blast % and lactate dehydrogenase (LDH) levels in AML patients. When the data were analyzed with respect to clinical variables, the total leukocyte count was elevated for mutation positive group, compared to negative group. In AML patients with NRAS mutations, 60% failed to achieve complete remission (CR), as compared to 34.8% in mutation negative group. These results indicated that NRAS mutations might confer poor drug response. In AML, disease free survival (DFS) in NRAS mutation positive group was lesser, compared to mutation negative group (9.5 months vs. 11.68 months). In ALL patients, DFS of NRAS mutation positive group was lesser than mutation negative group (9.2 months vs. 27.5 months). The CR rate was also lower for mutation-positive patients group, compared to mutation-negative group. In conclusion, these results suggested that presence of NRAS mutation at 12th codon was associated with poor response and poorer DFS in both ALL and AML.

Infection and childhood leukemia: review of evidence / Infeccao e leucemia infantil: revisao das evidencias / Infeccion y leucemia infantil: revision de las evidencias

OBJECTIVE : To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS : A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors “childhood leukemia” and “infection” and later searching for the words “childhood leukemia” and “maternal infection or disease” or “breastfeeding” or “daycare attendance” or “vaccination” resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers’ or infants’ to infections (or proxy of infection), and risk of leukemia. RESULTS : Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS : Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology. .

OBJETIVO : Analisar estudos que avaliaram o papel de infecções e de medidas indiretas de exposição às infecções no risco de leucemia infantil, principalmente da leucemia linfocítica aguda. MÉTODOS : A busca nas bases de dados Medline, Lilacs e SciELO utilizando-se inicialmente os descritores “leucemia infantil” e “infecção” e, posteriormente, pesquisando-se as palavras “leucemia infantil” e “infecção ou doença materna” ou “aleitamento materno” ou “frequência à creche” ou “vacinação” recuperou 62 publicações que atenderam aos seguintes critérios de inclusão: amostra composta por sujeitos com idade inferior ou igual a 15 anos; análise específica de casos diagnosticados com leucemia linfocítica aguda ou todas as leucemias; avaliação de exposição materna ou infantil a infecções (ou medidas indiretas de exposição à infecção) e risco de leucemia. RESULTADOS : Globalmente, os 23 estudos que avaliaram infecções nas crianças suportam a hipótese de que a ocorrência de infecções no início da infância reduz o risco de leucemia, mas existem discordâncias intra e entre estudos. A avaliação por meio das medidas indiretas de exposição à infecção mostrou evidências de redução do risco de leucemia associado principalmente com frequência à creche. Mais de 50,0% dos 16 estudos que avaliaram exposição materna à infecção observaram aumento do risco de leucemia associado com episódios de gripe, pneumonia, varicela, herpes zoster, infecção do trato genital inferior, doença de pele, doenças sexualmente transmissíveis, vírus Epstein-Barr ...

OBJETIVO : Analizar estudios que evaluaron el papel de infecciones y de medidas indirectas de exposición a las infecciones en el riesgo de leucemia infantil, principalmente de la leucemia linfocítica aguda. MÉTODOS : Se realizó búsqueda en las bases de datos Medline, LILACS y SciELO utilizándose inicialmente los descriptores “leucemia infantil” e “infección” y, posteriormente, investigándose las palabras “leucemia infantil” e “infección o enfermedad materna” o “lactancia materna” o “frecuencia en guardería” o “vacunación” recuperó 62 publicaciones que atendieron los siguientes criterios de inclusión: muestra compuesta por individuos con edad inferior o igual a 15 años; análisis específica de casos diagnosticados con leucemia linfocítica aguda o todas las leucemias; evaluación de exposición materna o infantil a infecciones (o medidas indirectas de exposición a la infección) y riesgo de leucemia. RESULTADOS : Globalmente, los 23 estudios que evaluaron infecciones en los niños soportan la hipótesis de que la ocurrencia de infecciones en el inicio de la infancia reduce el riesgo de leucemia, pero existen discordancias intra y entre estudios. La evaluación por medio de las medidas indirectas de exposición a la infección mostró evidencias de reducción de riesgo de leucemia asociado principalmente con frecuencia a la guardería. Más de 50% de los 16 estudios que evaluaron exposición materna a la infección observaron aumento de riesgo de leucemia asociado con episodios de gripe, neumonía, varicela, herpes zoster, infección del tracto genital inferior, enfermedad de la piel, enfermedades sexualmente transmisibles, virus Epstein-Barr (EBV) y Helicobacter pylori. CONCLUSIONES : A pesar ...

Leucemia linfoblástica aguda em lactentes: 20 anos de experiência / Acute lymphoblastic leukemia in infants: 20 years of experience

OBJETIVO: Analisar pacientes com menos de dois anos de idade com leucemia linfoblástica aguda atendidos no período de 1990 a 2010, em um centro de referência estadual. MÉTODOS: Estudo clínico, epidemiológico, transversal, descritivo e observacional. Pacientes incluídos tinham menos de dois anos de idade, com leucemia linfoblástica aguda, tratados no período de 1990 a 2010 na unidade de oncologia pediátrica de um centro de referência estadual, totalizando 41 casos. RESULTADOS: Todos os pacientes eram Caucasianos e 60,9% eram do sexo feminino. Com relação à idade, 24,38% tinham menos de seis meses, 17,07% tinham entre seis meses e um ano e 58,53% mais do que um ano de idade. A idade de seis meses foi estatisticamente significante para o desfecho de óbito. Os sinais e sintomas predominantes foram febre, hematomas e petéquias. Uma contagem de leucócitos superior a 100.000 foi observada em 34,14% dos casos; hemoglobina inferior a 11 em 95,13% e contagem de plaquetas inferior a 100.000, em 75,61% dos casos. Infiltração do sistema nervoso central estava presente em 12,91% dos pacientes. Em relação à linhagem, a linhagem B predominou (73%), mas a linhagem de células T foi estatisticamente significativa para o óbito. Trinta e nove por cento dos pacientes tiveram recorrência da doença. Em relação ao estado vital, 70,73% dos pacientes morreram, sendo choque séptico a principal causa. CONCLUSÕES: leucemia linfoblástica aguda em crianças tem uma alta taxa de mortalidade, principalmente em crianças menores de um ano e linhagem derivada de células T.

OBJECTIVE: To analyze patients younger than 2 years with acute lymphoblastic leukemia, treated in the period between 1990 and 2010 in a state reference center. METHODS: This was a clinical-epidemiological, cross-sectional, observational, and descriptive study. It included patients younger than 2 years with acute lymphoblastic leukemia, treated in the period of 1990 to 2010 in a pediatric oncology unit of a state reference center, totaling 41 cases. RESULTS: All patients were white ethnicity, and 60.9% were females. Regarding age, 24.38% were younger than 6 months, 17.07% were between 6 months and 1 year, and 58.53% were older than 1 year. The age of 6 months was statistically significant for the outcome of death. Predominant signs and symptoms were fever, bruising, and petechiae. A leukocyte count > 100,000 was found in 34.14% of cases, hemoglobin count < 11 in 95.13%, and platelet count < 100,000 in 75.61. Infiltration of central nervous system was present in 12.91% of patients. According to the lineage, B-cell lineage predominated (73%), but the T-cell line was statistically significant for death. 39% of patients had disease recurrence. In relation to vital status, 70.73% of the patients died; septic shock was the main cause. CONCLUSIONS: Acute lymphoblastic leukemia in infants has a high mortality rate, especially in children under 1 year and those with T-cell derived lineage.

Leucemia linfoblástica aguda en pacientes portadores de síndrome de Down / Acute lymphoblastic leukemia in children with Down's syndrome

Background: Children with Down's Syndrome (DS) present a higher incidence of Acute Lymphoblastic Leukemia (ALL) with more complications and shorter survival than healthy children. Objective: To describe clinical characteristics, laboratory and treatment results in patients with DS and ALL. Patients and Method: Retrospective analysis of 42 DS and ALL patients treated in three consecutive trials (1992,1996,2002) from the Pediatric National Cancer Program (PINDA). Clinical data, immunophenotype, cytogenetics and treatment results were analyzed. Results: There was no difference by age or gender, no patient presented LLA-T, t (9;22) o t (4;11). Of the 42 patients, 38 patients went into remission, 10 relapsed (26,3 percent, 11 died because of infection, none died from other toxicity. Survival at 5 years was 35 +/- 9 percent (median of follow-up was 50 mo), similar for all protocols (p = 0,61). Conclusion: The group of patients with ALL and DS evaluated was not associated with classic treatment resistance factors. The relapse rate was not increased, if compared with non DS ALL patients; in this group the infections were the determinant factor for a lower survival. These patients can be treated with the current trials but they require a detailed infection care.

Los niños con Síndrome de Down (SD) tienen mayor incidencia de leucemia linfoblástica aguda (LLA) con más complicaciones y menor sobrevida que los niños sin SD. Objetivo: Describir características clínicas, de laboratorio y resultados de tratamiento en niños con SD y LLA. Pacientes y Método: Análisis retrospectivo de 42 pacientes con LLA y SD tratados en 3 protocolos consecutivos (1992, 1996 y 2002) del Programa Nacional de Cáncer Infantil (PINDA). Se analizaron datos clínicos, de laboratorio, inmunofenotipo, citogenética y resultados de tratamiento. Resultados: La distribución por género o grupo etario no mostró diferencias, ningún paciente presentó LLA-T, t (9;22) o t (4;11). De los 38 pacientes que remitieron, 10 recayeron (26,3 por ciento), fallecieron por infección 11/42 (26,2 por ciento). Ninguno falleció por otra toxicidad. La sobrevida libre de eventos global a 5 años fue 35 +/- 9 por ciento (mediana de seguimiento 50 meses), siendo similar en los diferentes protocolos usados (p = 0,61). Conclusión: Los pacientes evaluados con SD y LLA no presentaron factores clásicos de resistencia a tratamiento. No se observó mayor frecuencia de recaída respecto a los pacientes con LLA sin SD y la menor sobrevida en este grupo fue determinada por infecciones. Estos pacientes pueden ser tratados con los protocolos actuales pero requieren un manejo precoz e intensivo de las infecciones.

Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% ( 3.6%) and 58.8% ( 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis > 50 x 10(9)/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 10(9)/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. CONCLUSIONS: These results suggest that a leukocyte count > 50 x 10(9)/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

Immunophenotypic characterization of acute leukemia at a public oncology reference center in Maranhão, northeastern Brazil / Caracterização imunofenotípica das leucemias agudas em um centro oncológico de referência público no Maranhão, Nordeste do Brasil

CONTEXT AND OBJECTIVES: The incidence of acute leukemia (AL) subtypes varies according to geographical distribution. The aim here was to determine the incidence of morphological and immunophenotypic AL subtypes in the state of Maranhão, Brazil, and to correlate the expression of aberrant phenotypes in children with acute lymphoblastic leukemia (ALL) with prognostic factors. DESIGN AND SETTING: Single prospective cohort study at a public oncology reference center in Maranhão. METHODS: Seventy AL cases were diagnosed between September 2008 and January 2010. For the diagnosis, complete blood cell counts, myelograms (at diagnosis and at the end of the induction phase), cytochemical analysis and immunophenotyping were performed. RESULTS: Among adult patients (n = 22), the incidence of AL types was: ALL (22.7 percent) and acute myeloid leukemia (AML) (77.3 percent). The subtype AML M0 occurred most frequently (29.4 percent). In children (n = 48), the types were: AML (18.7 percent), most frequently subtype AML M4 (33.4 percent); biphenotypic acute leukemia (BAL) (4.2 percent); and ALL (77.1 percent), including the subtypes B-ALL (72.9 percent) and T-ALL (27.1 percent). Among the children with ALL, there were no statistically significant differences between patients with and without aberrant phenotypes, in relation to hematological parameters and treatment response. CONCLUSION: This work demonstrates that the frequencies of AML M0 cases among adults and T-ALL cases among children in Maranhão were high. This suggests that there may be differences in AML subtype incidence, as seen with ALL subtypes, in different regions of Brazil. No association was found between the expression of aberrant phenotypes and prognostic factors, in children with ALL.

CONTEXTO E OBJETIVOS: A incidência dos subtipos de leucemias agudas (LA) tem mostrado variações em relação à distribuição geográfica. Objetivou-se determinar a incidência dos subtipos morfológicos e imunofenotípicos de LA no estado do Maranhão, Brasil, e relacionar a expressão de fenótipos aberrantes em crianças com leucemia linfoblástica aguda (LLA) com fatores prognósticos. TIPO DE ESTUDO E LOCAL: Estudo de coorte único prospectivo em um centro oncológico de referência público no Maranhão. MÉTODOS: Diagnosticaram-se 70 casos de LA no período de setembro de 2008 a janeiro de 2010. No diagnóstico, realizaram-se hemogramas, mielogramas (no diagnóstico e ao final da fase de indução), citoquímica e imunofenotipagem. RESULTADOS: Nos pacientes adultos (n = 22), as incidências dos tipos de LA foram: LLA (22,7 por cento) e leucemia mieloide aguda (LMA) (77,3 por cento), sendo o subtipo LMA M0 mais frequente (29,4 por cento). Em crianças (n = 48): LMA (18,7 por cento), subtipo LMA M4 mais frequente (33,4 por cento), leucemia bifenotípica aguda (BAL) (4,2 por cento) e LLA (77,1 por cento), sendo os subtipos LLA-B (72,9 por cento) e LLA-T (27,1 por cento). Na LLA, em crianças, não se encontrou diferença estatisticamente significante entre pacientes com e sem fenótipos aberrantes, em relação aos parâmetros hematológicos e resposta ao tratamento. CONCLUSÃO: Esta pesquisa demonstra elevada frequência de casos de LMA M0 em adultos, bem como das LLA-T em crianças no Maranhão, sugerindo que podem haver diferenças na incidência dos subtipos das LMA, assim como dos subtipos de LLA, em diferentes regiões do Brasil. Não foi encontrada associação entre a expres de fenótipos aberrantes e fatores prognósticos em crianças com LLA.

Time trend in frequency of occurrence of major immunophenotypes in paediatric acute lymphoblastic leukemia cases as experienced by Cancer Institute, Chennai, south India during the period 1989-2009.

Background: Pediatric acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease and socioeconomic and environmental factors are considered to be an important determinant of its immunophenotype. The aim of this analysis is to study the time trend in the immunophenotype of pediatric acute lymphoblastic leukemia (ALL) cases in our geographic setting. Materials and Methods: A total of 639 new pediatric ALL cases immunophenotyped during 1989-2009 forms the basis of this analysis. Representative bone marrow or peripheral blood of these patients was immunophenotyped flowcytometrically using an extensive panel of monoclonal antibodies. Results: During early phase of our study we noticed a relative excess of T-ALL and a paucity of common acute lymphoblastic leukemia (C-ALL) in contrast to western data. Over a period of 20 years we witnessed a gradual reduction in pediatric T-ALL cases and a proportionate increase in C-ALL cases. Conclusion: We find that this change of pattern is synchronizing with the socioeconomic and industrial development prevailing in our geographic setting and suggest a possible link between the predominant immunophenotype of pediatric ALL cases and the environmental and socioeconomic factors prevailing in that locality.

Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL). The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

Frequency and type of chromosomal abnormalities in childhood acute lymphoblastic leukemia patients in Kuwait: a six-year retrospective study

To characterize the frequency of genetic profiles in pediatric acute lymphoblastic leukemia [ALL] patients in Kuwait. This review presents the general cytogenetic characteristics of 164 pediatric patients diagnosed as having ALL in a 6-year period. Chromosomal and fluorescence in situ hybridization studies were made on bone marrow aspirates at diagnosis and during different stages of the disease. Recurring aberrations, observed in 123 [75%] patients, included hyperdiploidy [n = 68, 41%], tetraploidy [n = 12, 7.3%], hypodiploidy [n = 2, 1.2%], TEL-AMU fusion [n = 11, 7%], mixed-lineage leukemia rearrangement [n - 6, 3.6%], t[9;22] [n - 4, 2.4%], t[1;19] [n - 3, 1.8%], t[8;14] or t[8;22] [n = 2, 1.2%], +21 [n - 2, 1.2%], del[6] [n = 2,1.2%] and miscellaneous abnormalities [n = 9,5%].The highest observed numerical chromosome abnormality was high hyperdiploidy in 89 patients [54%] with abnormal karyotype while the TEL-AML fusion was the highest observed structural abnormality. This study showed that clonal anomalies detected in pediatric ALL have shown correlations between specific abnormalities and clinicobiological characteristics of the patients

Magnetic fields and acute lymphoblastic leukemia in children: a systematic review of case-control studies / Campos magnéticos e leucemia linfocítica aguda em crianças: revisão sistemática de estudos caso-controle

Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure to non-ionizing radiation generated by low frequency magnetic fields with childhood leukemia. The current article reviews the case-control studies published on this subject. Of 152 articles tracked in different databases, ten studies from North America, Asia, and Europe met the defined selection criteria, with patients diagnosed from 1960 to 2004. Methodological limitations were observed in these articles, including difficulties with the procedures for assessing exposure. An association may exist between exposure to low frequency magnetic fields and acute lymphoblastic leukemia in children, but this association is weak, preventing the observation of consistency in the findings. Future studies from a wider range of geographic regions should focus on the analysis of acute lymphoblastic leukemia, which is the subtype with the greatest impact on the increasing overall incidence of childhood leukemia.

A incidência de leucemias em crianças tem aumentado nas últimas décadas no mundo, com influência predominante da leucemia linfocítica aguda, principal subtipo em crianças. Estudos têm relacionado a exposição às radiações não-ionizantes geradas pelos campos magnéticos de baixa freqüência com leucemia infantil. Neste artigo foram revisados os estudos caso-controle publicados sobre essa questão. Dos 152 artigos localizados em diferentes bases de dados, dez estudos da América do Norte, Ásia e Europa preencheram os critérios de seleção, comportando pacientes diagnosticados entre 1960 e 2004. Algumas limitações metodológicas foram observadas como dificuldades nos procedimentos de avaliação da exposição. É possível a existência de associação entre exposição a campos magnéticos de baixa freqüência e leucemia linfocítica aguda em crianças, porém, a força desta associação é tênue, impedindo observar consistência entre os resultados. Futuros estudos, com maior diversidade de regiões, deveriam concentrar-se na análise da leucemia linfocítica aguda, pois é o subtipo com maior influência na incidência crescente da leucemia infantil.

Acute leukemia in early childhood

Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months) has detected TEL/AML1+ve (N = 9), E2A/PBX1+ve (N = 4), PML/RARA+ve (N = 4), and AML1/ETO+ve (N = 2) cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95 percentCI = 1.05-2.07), OR = 2.27 (95 percentCI = 1.56-3.31) and OR = 9.08 (95 percentCI = 2.95-27.96)], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

Acute childhood leukemias and exposure to magnetic fields generated by high voltage overhead power lines - a risk factor in Iran.

Many investigators have studied the effects of Extremely Low Frequency-Magnetic Fields generated by ordinary and domestic power lines, as a risk factor in acute leukaemias of children, but there are limited information available regarding very high voltage overhead power lines. Children in developing countries sometimes live very close to such structures and we have registered several patients with acute leukaemias appearing in clusters. In the present study we have analyzed 60 consecutively diagnosed patients with acute leukaemias, and 59 matched controls in a provincial capital city in North-Western Iran. After provision of consent, a detailed form was filled in, and a visit to the present (or previous) residential areas of both groups was arranged. The locations of the very high voltage power lines (123, 230, 400 kilo volts), were noted in each area, if present, and their distances from the houses under study were detected. The expected intensities of the Magnetic Fields (B) were calculated having the mean intensity of the electrical current and other line characteristics, by means of relevant equations. Fourteen patients in the case group (23.5%) were living near the high voltage power lines in distances < or = 500 meters. (Mean B = 0.6 microTeslas, microT). In the control group at the same distance, the figure was 2 children (3.3%) (Mean B = 0.35 microT). Statistically, the likelihood of leukaemia was increased considerably in this distance (Odds ratio (OR) = 8.67, 95% Confidence Interval (CI) = 1.74- 58.4, P value= 0.001). On the other hand 15 pts (25 %) in the leukaemia group were experiencing Magnetic fields above 0.45 microT in comparison to 5 in the control group ( 8.5% )(OR = 3.60, 95% CI = 1.11-12.39, P = 0.01). More children in developing countries like Iran live close to very high voltage lines, and they experience relatively more harmful effects from the Magnetic Fields, in comparison with children in developed countries. Residence near very high voltage overhead power lines, in distances < or = 500 meters, and Magnetic Fields >0.45 microT, should be considered a risk factor for the pathogenesis of acute leukaemias in children.