Factores relacionados con la mortalidad en niños diagnosticados de leucemia linfoide aguda con insuficiencias orgánicas / High risk factors in pediatric patients diagnosed with acute lymphoid leukemia with organ failur

Introducción: Los pacientes pediátricos con leucemia linfoide aguda se estratifican en tres grupos de riesgo: bajo, intermedio y alto. Hay condiciones predictivas de muerte en este grupo de pacientes que incluyen indicadores clínicos y de laboratorio, que en relación con estos factores desarrollan durante la enfermedad insuficiencias orgánicas. Objetivo: Analizar los factores asociados con la mortalidad en pacientes pediátricos diagnosticados de leucemia linfoide aguda con insuficiencias orgánicas. Métodos: Se realizó una investigación bibliográfico-documental acerca del tema. Se consultó fundamentalmente artículos de los últimos 10 años de las bases de datos de SciELO y PubMed. Análisis y síntesis de la información: Se describe los factores de alto riesgo en pacientes pediátricos graves con insuficiencias orgánicas, desde aquellos ya establecidos en protocolos nacionales e internacionales; así como los propios que se desencadenan en los pacientes con disfunción orgánica y su relación en la evolución desfavorable del paciente. Conclusiones: Se encontró una relación entre los factores de alto riesgo en pacientes pediátricos diagnosticados de leucemia linfoide aguda con el desarrollo de insuficiencias orgánicas como complicaciones y muerte en estos grupos de enfermos.

Introduction: Pediatric patients with acute lymphoid leukemia are stratified into three risk groups: low, intermediate and high. There are conditions predictive of death in this group of patients that include clinical and laboratory indicators, which in relation to these factors develop organ insufficiencies during the disease. Objective: To relate the factors associated with mortality in pediatric patients diagnosed with acute lymphoid leukemia with organ failure. Methods: A bibliographic-documentary research on the subject was carried out. The Scielo and PubMed databases of the last ten years were fundamentally consulted. Analysis and synthesis of information: High-risk factors in severe pediatric patients with organ failure are described, from those already established in national and international protocols; as well as those that are triggered in patients with organic dysfunction and their relationship in the unfavorable evolution of the patient. Conclusions: A relationship was found between high risk factors in pediatric patients diagnosed with acute lymphoid leukemia with the development of organ failure as complications and death in these groups of patients.

Terapias dirigidas a dianas moleculares: perspectiva actual en la leucemia promielocítica / Molecular targeted therapies: current perspectives in acute promyelocytic leukemia

Introducción: La leucemia promielocítica presenta particularidades biológicas y clínicas con respecto al resto de las leucemias mieloides agudas. El descubrimiento de los detalles moleculares de su patogénesis, posibilitó que su tratamiento, constituya una de las mejores representaciones de la investigación traslacional y esto hace que establezca un modelo para el desarrollo de terapias dirigidas a dianas moleculares con enfoque curativo en pacientes con cáncer. Objetivo: Abordar los principales avances en la terapia de la LPM desde el descubrimiento de los agentes diferenciadores hasta su estado actual. Métodos: Se realizó una búsqueda exhaustiva en bases de datos como Scielo, Pubmed, ScienceDirect, Redalyc y se utilizaron como referencias los artículos actualizados publicados principalmente en los últimos cinco años. Análisis y síntesis de la información: Se abordaron los principales avances en la terapia de este tipo de leucemia, desde el descubrimiento de los agentes diferenciadores hasta su estado actual, haciendo énfasis en su mecanismo de acción y nuevas opciones terapéuticas. Conclusiones: Los aportes realizados en el estudio etiopatogénico y molecular de la leucemia promielocítica y su impacto objetivo en la investigación clínica, constituyen uno de los mejores ejemplos de tratamiento dirigido a alteraciones moleculares específicas y representa un modelo de integración biológica, clínica y terapéutica en beneficio de los pacientes afectados con esta enfermedad(AU)

Introduction: Acute promyelocytic leukemia is a biologically and clinically different type from other acute myeloid leukemias. The discovery of molecular details in its pathogenesis enabled its treatment to constitute one of the best examples of translational research and makes a model for the development of targeted therapies with a curative approach in cancer patients. Objective: To analize the main advances in PML therapy from the discovery of differentiating agents to their current state. Methods: An exhaustive search was carried out in the databases as Scielo, Pubmed, ScienceDirect, Redalyc, and updated articles published mainly in the last five years were used as references. Analysis and synthesis of the information: The article addressed the main advances in the therapy of this type of leukemia, from the discovery of differentiating agents to its current state, emphasizing its mechanism of action and new therapeutic options. Conclusions: The contributions made in the etiopathogenic and molecular study of promyelocytic leukemia and its objective impact on clinical research constitute one of the best examples of treatment aimed at specific molecular alterations and represents a model of biological, clinical and therapeutic integration in benefit of patients affected with this disease(AU)

Perfil clínico-epidemiológico e sobrevida hospitalar dos casos de leucemia aguda em um hospital de referência em Rio Branco, Acre, 2007-2014 / Clinical epidemiological profile and survival of hospital cases of acute leukemia in a reference hospital in Rio Branco - Acre, 2007-2014

Resumo Introdução A Unidade de Assistência de Alta Complexidade em Oncologia (UNACON) permite o tratamento de leucemias agudas no Acre. Objetivo Determinar o perfil clínico-epidemiológico e a sobrevida hospitalar de leucemias agudas tratadas na UNACON/Acre entre 2007 e 2014. Método É um estudo longitudinal e retrospectivo de pacientes com leucemias agudas entre 15/06/2007 e 31/12/2014, cujos prontuários médicos forneceram dados para a análise descritiva das variáveis e posterior análise de sobrevida acumulada em 1 ano e 2 anos (método Kaplan-Meier) e comparação das curvas de sobrevida (teste de log-rank). Resultados A sobrevida para leucemias mieloides agudas (LMA) foi de 30% e 32% em 1 e 2 anos, respectivamente, com pior sobrevida para pacientes masculinos, brancos, ≥ 20 anos de idade, leucometria < 20.000 células/mm3, desidrogenase lática ≥ 600 U/dl e subtipo diferente do M3. Para leucemias linfoides agudas (LLA), a sobrevida foi de 59% e 45% em 1 e 2 anos, respectivamente, com pior sobrevida para sexo feminino, ≥ 20 anos de idade e leucometria elevada. Em pacientes abaixo de 20 anos de idade com LLA, a melhor sobrevida foi observada na faixa etária de 2 a 9 anos. Conclusão Trata-se do primeiro estudo epidemiológico de sobrevida realizado no Acre para leucemias agudas com resultados coerentes com a literatura. Contudo, novas pesquisas deverão ser realizadas.

Abstract Background The High Complexity Oncology Unit (Unidade de Assistência de Alta Complexidade em Oncologia - UNACON/Acre) allowed the treatment of acute leukemias in Acre. Objective To determine the clinical-epidemiological profile and hospital survival of acute leukemias treated at UNACON/Acre between 2007 and 2014. Method This is a longitudinal, retrospective study of patients with acute leukemias between 06/15/2007 and 12/31/2014 whose medical records provided data for descriptive analysis of the variables, and subsequent analysis of 1-year and 2-year cumulative survival (Kaplan Meier method) and comparison of survival curves (log-rank test). Results The survival for acute myeloid leukemia (AML) was 30 and 32% at 1 and 2 years, respectively, with a worse survival rate for males, white, age ≥20 years, leukometry <20,000 cells/mm3, lactic dehydrogenase ≥600 U/dl and subtype different from M3. For acute lymphoid leukemias (ALL), survival was 59 and 45% at 1 and 2 years, respectively. Female gender, age ≥20 years, and high leukometry had worse survival. For patients <20 years with ALL, better survival was observed in the age group of 2-9 years. Conclusion This is the first epidemiological study of survival in Acre for acute leukemias with results consistent with the literature. However, new studies should be performed.

Metodología y aplicaciones de la citometría de flujo para el inmunofenotipaje de las leucemias agudas / Methodology and applications of flow cytometry for immunophenotyping of acute leukemias

La citometría de flujo (CMF) es una técnica de avanzada, altamente sensible y automatizada, que se emplea para el inmunofenotipaje de las células normales y leucémicas. En este artículo se muestran los principales aspectos metodológicos a tener en cuenta para un mejor desarrollo e interpretación del inmunofenotipo por CMF, entre los que se encuentran: tipo, cantidad, conservación y transportación de la muestra, uso de anticoagulantes, empleo de anticuerpos monoclonales y fluorocromos, lisado de hematíes, fijación celular, así como la calibración y compensación de la auto-fluorescencia. Finalmente, se exponen las principales aplicaciones de esta metodología para definir el estado de maduración celular leucémico, clasificar las leucemias agudas en distintos subtipos inmunológicos, identificar subgrupos de mal pronóstico y detectar fenotipos aberrantes. Todo lo anterior resulta de gran utilidad para el diagnóstico de la enfermedad mínima residual que permite estratificar a los pacientes en diferentes grupos de riesgo e individualizar el tratamiento antileucémico(AU)

Flow cytometry (FCM) is an advanced, highly sensitive and automated technique used for immunophenotyping of normal and leukemic cells. The main methodological aspects to consider for better development and interpretation of immunophenotyping by FCM are shown in this article. Among them are: type, quantity, storage and transportation of the sample, use of anticoagulants, use of monoclonal antibodies and fluorochromes, erythrocyte lysate, cell attachment, calibration and auto-fluorescence compensation. Finally, the main applications of this methodology are given for defining the state of leukemic cell maturation, acute leukemias rank in different immunological subtypes, poor prognosis subgroups and to identify and detect aberrant phenotypes, which are useful for the diagnosis of minimal residual disease, allowing to stratify patients into different risk groups and thus to identify the anti-leukemic treatment(AU)

Leucemias agudas en ancianos de la provincia de Santiago de Cuba / Acute leukemias in the elderly from Santiago de Cuba province

Se realizó un estudio descriptivo y retrospectivo de 64 pacientes mayores de 60 años con leucemia aguda, atendidos en el Servicio de Hematología del Hospital General Docente "Dr. Juan Bruno Zayas Alfonso" de Santiago de Cuba, durante el quinquenio 2006-2011, para determinar las principales características clínicas y hematológicas en el momento del diagnóstico, así como la supervivencia global de los afectados, aunque los tratamientos administrados no tenían criterio curativo. La edad promedio de los ancianos fue de 70 años, en un rango etario de 60 a 90; en tanto, la variedad no linfoblástica representó 98,4 %, y todos los pacientes presentaron anemia y trombocitopenia como alteraciones hematológicas, con incremento en los requerimientos transfusionales. De igual forma, la presencia de blastos en la sangre periférica se demostró en 50 % y la hiperleucocitosis en 59,4 %, mientras las principales causas de muerte estuvieron relacionadas con la hemorragia cerebral y la progresión de la enfermedad con la infiltración multiorgánica, lo cual condujo a una supervivencia muy corta de los integrantes de la serie...

A descriptive and retrospective study of 64 patients older than 60 years with acute leukemia, assisted in the Hematology Service of "Dr. Juan Bruno Zayas Alfonso" Teaching General Hospital in Santiago de Cuba was carried out during the five year period 2006-2011, to determine the main clinical and hematological characteristics at the moment of diagnosis, as well as the global survival of those affected, although the administered treatments had no healing criterium. The average age of the elderly was 70 years, in an age range of 60 to 90; while the non lymphoblastic variety represented 98.4%, and all the patients presented anemia and thrombocytopenia hematological changes, with increment in the transfusional requirements. Likewise, the blastos presence in the peripheral blood was demonstrated in 50% and the hyperleucocytosis in 59.4%, while the main causes of death were related to the cerebral hemorrhage and the progression of the disease with the multiorganic infiltration, which led to a very short survival of the members of this series...

Frequência de imunofenótipos aberrantes em leucemias agudas: análise de 213 casos diagnosticados na Fundação Hemope / Frequency of aberrant immunophenotypes in acute leukemia: analysis of 213 cases diagnosed in Fundação Hemope

As leucemias agudas (LAs) são doenças clonais do tecido hematopoético caracterizadas por proliferação anômala de progenitores das diferentes linhagens. 0 diagnóstico das LAs se baseia em achados citomorfológicos, citoquimicos e imunofenotipicos em células da Medula Óssea (MO) e/ou Sangue Periférico (SP). Cerca de 30 a 50% das LMAs e LLAs, bem caracterizadas pelo imunofenótipo, exibem expressão de antigenos aberrantes e esta situação deve ser distinguida das leucemias bifenotipicas, que tem atualmente critérios de diagnóstico bem definidos. A detecção dos antígenos aberrantes não parece ter implicação prognóstica, mas é uma importante ferramenta para a detecção de doença residual mínima (DRM). 0 objetivo deste trabalho foi relatar a frequência de Fenótipos Aberrantes (FA) em LAs nos pacientes diagnosticados na Fundação Hemope, correlacionar este achado com a idade e identificar os antígenos aberrantes predominantes. 0 estudo contou com 213 pacientes de ambos os sexos e sem restric;:ao de faixa etária ou raça. A imunofenotipagem utilizou amostras de SP e/ou MO, sendo a análise realizada por citometria de fluxo multiparamétrica. Para as LMAs, LLAs BeLLAs T as frequências de FA encontradas foram de 47%, 40% e 52%, respectivamente. Os antígenos aberrantes predominantes foram CD? e CD56 para as LMAs e CD13 e CD33 para as LLAs. A frequência de antígenos aberrantes (45%) e a predominância de antígenos linfocitários T e NK na LMAs e de antígenos mielóides nas LLAs, condizem com a literatura. Por outro lado, o predomínio de FA entre os adultos parece sugerir mais uma caracteristica da amostra, onde esta faixa etária predominou, que uma caracteristica biológica das leucemias analisadas. Finalmente, este estudo, definindo melhor o perfil imunofenotipico de nossos pacientes, possibilita o uso deste conhecimento na avaliação de DRM.

Acute leukemias (AL) are clonal diseases of the hematopoietic tissue characterized by anomalous proliferation of precursors of different lineage. The diagnosis of AL is based on morphological, citochemical and immunophenotypical findings in cells of Bone Marrow (BM) and/or Peripheral Blood (PB). About 30 to 50% of AML and ALL, well-characterized by immunophenotype, display aberrant expression of antigens and this situation should be distinguished from biphenotipic leukemias, which are currently well-defined criteria for diagnosis. The detection of aberrant antigen does not seem to have prognostic implication, but it is an important tool for the detection of minimal residual disease (MRD). The objective of this study was to report the frequency of aberrant phenotypes (AP) at AL in patients diagnosticated by Funda9iio Hemope, correlate this finding with age and identify the predominant aberrant antigens. The study included 213 patients of both genders and without restriction of age or race. The immunophenotyping used samples of PB and/or BM, being the analysis by multiparametric flow cytometry. For AML, B-ALL and T-ALL the frequencies of FA found were 47%, 40% and 52% respectively. The predominant aberrant antigens for AML were CD7 and CD56 and for ALL were CD33 and CD13. The frequency of aberrant antigens (45%) and the predominance of lymphocyte T and NK antigens in AML and myeloid antigens in ALL, matches with the literature. Moreover, the prevalence of AP among adults, who are the predominant age group, seems to be more suggestive of a characteristic of the sample, than a biological feature of leukemias that were analyzed. Finally, this study, defines better the immunophenotypical profile of our patients and allows the use of this knowledge in the evaluation.

Polimorfismo dos genes NQO1 e PON1 na etiologia das leucemias agudas infantis

As leucemias pediátricas são doenças hetereogêneas, consequentes da combinação de susceptibilidade genética individual e exposições a fatores ambientais. Polimorfismos em genes que codificam enzimas do metabolismo modificam correlações de riscos entre exposições e as leucemias. Baseados nas hipóteses que as leucemias na infância têm origem durante a vida intra-uterina, estudos demonstraram associações de exposições maternas durante a gestação à pesticidas e algumas substâncias medicamentosas. Especulamos se os polimorfismos NQO1C609T, PON1Q192R e PON1L55M poderiam influenciar na etiologia das leucemias infantis. O objetivo principal deste estudo foi determinar a freqüência dos polimorfismos nos genes NQO1 e PON1 em crianças com leucemias agudas e suas mães para avaliar as possíveis associações de riscos entre susceptibilidade genética e exposição ambiental. Foram testadas amostras brasileiras de crianças com diagnóstico de leucemia aguda (578); 393 amostras de crianças saudáveis não-sindrômicas (controles), bem como, amostras das respectivas mães. As genotipagens dos genes NQO1 e PON1 foram realizadas através da técnica de discriminação alélica por PCR em tempo real utilizando sondas TaqMan. O genótipo mutante do polimorfismo NQO1C609T confere um risco para o desenvolvimento de leucemias agudas [OR=2,5; IC95%, 1,05-5,88] às crianças com idade ≥24 meses. Na análise estratificada por subtipo leucêmico, nas leucemias mielóides o genótipo mutante confere um risco elevado [OR=5,44; IC95%, 1,08-27,63] nas crianças entre 13-24 meses de idade. A somatória dos genótipos heterozigoto e homozigoto-mutante do NQO1 apresentou uma tendência de risco 2,0 vezes maior da ocorrência nas leucemias com rearranjos do gene MLL [IC95%, 0,94-4,57]. A presença do alelo polimórfico do NQO1C609T nas mães apresenta risco para leucemias agudas pediátricas [OR=1,76; IC95%, 1,03-3,02]. O polimorfismo PON1L55M apresentou associação de risco para LLA, tanto com o genótipo mutante [OR=3,21; IC95%, 1,21-8,51], quanto com a somatória dos genótipos heterozigoto e homozigoto-mutante [OR= 1,94; IC95%, 1,02-3,68]. Este risco aumenta nas crianças com idade entre 13-24 meses [OR=3,22; IC95%, 1,15-8,99]. Foram realizadas análises de exposição materna a pesticidas, antibióticos e infusões de ervas. O polimorfismo do gene NQO1 não mostrou associação de risco, enquanto os polimorfismos do gene PON1 mostraram associações com as exposições e apresentaram magnitudes de risco independentes do tipo de exposição

Pediatric leukemias are heterogeneous diseases which result from the combination of individual genetic susceptibility factors and environmental exposures. Polymorphisms in genes that codify metabolic enzymes alter the risk associations between exposures and leukemias. Based on the prenatal origin of leukemias, studies have demonstrated association between maternal exposures during pregnancy to pesticides or some medicines and childhood leukemia. We speculated whether the polymorphisms NQO1C609T, PON1Q192R and PON1L55M could influence the etiology of the infant leukemias. The main objective of this study was to determine the frequency of these polymorphisms in children with acute leukemia and their mothers to evaluate the possible risk associations between genetic susceptibility and environmental exposures. Samples from children diagnosed with acute leukemia were tested (cases); samples from health children (controls) as well as samples from the respective mothers of both cases and controls were also tested. The genotyping of NQO1 and PON1 was performed using the allelic discrimination real time PCR assay using TaqMan probes. The NQO1C609T mutant genotype was associated with a higher risk of acute leukemia development [OR=2.5; CI95%, 1.05-5.88] in children ≥24 months-old. In the stratified analysis considering the leukemia subtypes, the group of myeloid leukemias presented an increased risk [OR=5.44; CI95%, 1.08-27.63] in children between 13-24 months-old. The sum of NQO1 heterozygous and mutant homozygous alleles showed a trend of 2-fold higher risk of leukemia occurrence in association with MLL gene rearrangements [CI95%, 0.94-4.57]. The polymorphism NQO1C609T within the mothers’ group was associated with childhood leukemias [OR=1.76; CI95%, 1.03-3.02]. The polymorphism PON1L55M presented a risk association with ALL, both considering the homozygous mutant genotype [OR=3.21; CI95%, 1.21-8.51], as well as considering the sum of the heterozygous and the mutant homozygous genotypes [OR= 1.94; CI95%, 1.02-3.68]. This risk increases in children aged between 13-24 months [OR=3.22; CI95%, 1.15-8.99]. The maternal exposures during pregnancy to pesticides, antibiotics and herbal infusions were analyzed in comparison to the genotypes. While no interaction risk associations were observed with the NQO1 polymorphism, the PON1 polymorphisms showed associations with the exposures and presented magnitudes independent of the type of exposure

Gastrointestinal manifestations as initial presentation of acute leukemias in children and adolescents / Manifestaciones gastrointestinales como presentación de las leucemias agudas en niños y adolescentes

OBJECTIVE: this study aimed to determine the prevalence and characteristics of gastrointestinal manifestations on initial clinical presentation of acute leukemias (AL) in childhood. MATERIAL AND METHODS: this is a retrospective and descriptive study that assessed medical records of 354 patients with AL from January 1995 to December 2004. RESULTS: acute lymphoid leukemia (ALL) was diagnosed in 273 (77.1%) patients and acute non-lymphocytic leukemia (AML) in 81 (22.9%). There were 210 males (59.4%) and 144 females (40.6%). The most common presenting features were: abdominal pain (19.5% in ALL and 11.8% in AML), nausea and vomiting (14.9 in ALL and 14% in AML), abdominal distention (18.5 in ALL and 8.6% in AML; p 0.024), constipation (5% in ALL and 6.5% in AML), diarrhea (3.6% in ALL and 11.8% in AML; p 0.03%), and gastrointestinal bleeding (7.9% in ALL and 9.7% in AML). Ultrasound scanning was made in 61.1% and hepatomegaly was found on 33.6% and esplenomegaly on 28.5% of the patients with AL. Seventy-seven (21.7%) and 15 (4.2%) patients received nonsteroidal anti-inflammatory drugs and glucocorticoids before the diagnostic of AL. An association is well-defined between abdominal symptoms like nausea, vomiting and pain and use of this therapy but this association did not occurred clearly in this study. CONCLUSIONS: gastrointestinal symptoms are not very well-documented as initial manifestation of leukemia in children and should be considered on the differential diagnosis of gastrointestinal symptoms of unknown etiology in children.

Objetivo: el objetivo del estudio fue determinar la prevalencia y las características de las manifestaciones gastrointestinales en la presentación clínica inicial de las leucemias linfoides agudas (LLA) en la infancia. Materialy métodos: se trata de un estudio descriptivo y retrospectivo que evaluó los registros médicos de 354 pacientescon LLA de enero de 1995 a diciembre de 2004. Resultados: la (LLA) ha sido diagnosticada en 273 (77,1%) pacientes y leucemia mieloide aguda (LMA) en 81 (22,9%). Hubo 210 niños (59,4%) y 144 niñas (40,6%). Los síntomas más comunes de presentaciónhan sido los siguientes: dolor abdominal(19,5% en LLA y 11,8% en el LMA), náuseas y vómitos (14,9 en LLA y 14% en LMA, P 0.024), distensión abdominal (18,5 en LLA y 8,6% en LMA, p 0,024), estreñimiento (5% en LLA y 6,5% en LMA), diarrea (3,6% en LLA y 11,8% en LMA, p 0,03%) y hemorragia gastrointestinal (7,9% en LLA y 9,7% enLMA). La ecografía fue realizada en 61,1% de los pacientes encontrándose hepatomegalia en 33,6% y esplenomegalia en 28,5% con LLA. Setenta y siete (21,7%) y 15 (4,2%) pacientes recibieron los fármacos antiinflamatorios no esteroides y glucocorticoides antes del diagnóstico de LLA. Hay una asociación bien definidaentre síntomas abdominales como náuseas, vómitos y dolor y el uso de esta terapia pero esta asociación no seprodujo claramente en este estudio. Conclusiones: las manifestaciones gastrointestinales no están bien documentadas como manifestaciones iniciales de la leucemia en los niños y debe considerarse en el diagnóstico diferencial de los síntomas gastrointestinales de etiología desconocida en estas edades.

Leucemias agudas: primeiros sinais e sintomas em pacientes menores de 20 Anos no Hospital Universitário de Juiz de Fora / Universidade Federal de Juiz de Fora Medical research: how to improve students´ involvement

As leucemias agudas são as causas de câncer mais comuns na infância e seus sinais e sintomas, na maioria dos casos , são inespecíficos no inicío da doença; o que retarda o diagnóstico e consequentemente o tratamento. Este Trabalho visa analisar os prontuários de pacientes com diagnósticos e assim alertar os profissionais de saúde para que estes façam o diagnóstico mais alertar os profissionais da saúde para que estes façam o diagnóstico mais proprecocemente. Dentre os achados mais frequentes encontram-se: palidez (96,4%); febre (82,14%); hepatomegalia (75%); esplenomegalia (71,4%); linfadenomegalia (53,6%); anemia (92,9%); leucocitose (64,3); neutropenia (46,4%);trombocitopenia (88,5%) e blastos (71,43%).