Oral Mucositis in Children with Leukemia Undergoing Chemotherapy: A Case Series

ABSTRACT Objective: To report nine cases of pediatric patients with Acute Lymphoid Leukemia (ALL) or Acute Myeloid Leukemia who developed severe oral mucositis (SOM) at the first week of chemotherapy. Material and Methods: The cases were selected from a sample of 105 children followed for 10 consecutive weeks. Hematological and personal data were obtained from the patient's medical records. The oral cavity was examined weekly using the modified Oral Assessment Guide. Results: More of the patients were male (55.6%), had black/brown skin (55.6%), with ALL (66.7%), and the mean age was 5.55. Two patients had values below normal for leukocytes, platelets, and creatinine over the follow-up. However, all patients showed changes in the normality of hematological data in most weeks. The most used chemotherapeutic agents were aracytin, etoposide, and methotrexate, known for their high stomatotoxic potential. Patients had 2 to 6 (mean of 4) episodes of SOM and 4 to 7 (mean of 5.5) episodes of OM. One patient at week 7, one patient at week 5, and one patient at weeks 2 and 10 did not have OM. Saliva (84 times) and lips (44 times) were the most affected items. Conclusion: The patients showed oscillations in the severity of oral mucositis and hematological parameters over the follow-up. All patients were exposed to stomatotoxic drugs during the initial phase of cancer treatment.

Clinical features and prognosis of high hyperdiploid childhood acute lymphoblastic leukemia: a multicenter retrospective analysis in Fujian Province, China / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features and prognosis of high hyperdiploid (HHD) childhood acute lymphoblastic leukemia (ALL).@*METHODS@#A retrospective analysis was performed on the medical data of 1 414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020. According to karyotype, they were divided into two groups: HHD (n=172) and non-HHD (n=1 242). The clinical features and treatment outcome were compared between the two groups, and the factors influencing the prognosis were further explored.@*RESULTS@#Among the 1 414 children with ALL, 172 (12.16%) had HHD. Compared with the non-HHD group, the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis (age of onset ≥10 years or <1 year, white blood cell count ≥50×109/L, and T-cell phenotype) or positive fusion genes (TEL-AML1, BCR-ABL1, E2A-PBX1, and MLL gene rearrangement) (P<0.05). The HHD group had a significantly higher proportion of children with minimal residual disease (MRD) <0.01% at the end of induction chemotherapy (P<0.05). The 10-year event-free survival (EFS) rate and overall survival (OS) rate in the HHD group were significantly higher than those in the non-HHD group (P<0.05). The univariate analysis showed that the number of chromosomes of 58-66, trisomy of chromosome 10, trisomy of chromosome 17, bone marrow MRD <1% on day 15 or 19 of induction chemotherapy, and bone marrow MRD <0.01% on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate (P<0.05), and trisomy of chromosome 10 was associated with a higher OS rate (P<0.05). The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate (P<0.05).@*CONCLUSIONS@#The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis. The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.

Síndrome hipotalámico como presentación inusual de recaída en el sistema nervioso central de leucemia linfoblástica aguda en niños: reporte de 4 casos / Hypothalamic syndrome as an unusual presentation of CNS relapse of acute lymphoblastic leukemia in children: report of 4 cases

La leucemia linfoblástica aguda (LLA) es la patología oncológica más frecuente en pediatría, y corresponde al 23% de las neoplasias en menores de 15 años. Alrededor del 20% de los pacientes con LLA presentan recaídas, en la mayoría de los casos, en la médula ósea. Las recaídas extramedulares son inusuales y las dos localizaciones más frecuentes son el sistema nervioso central (SNC) y los testículos. Cuando las recaídas ocurren en el SNC, suelen manifestarse con un síndrome meníngeo. El síndrome hipotalámico se define como la presencia de hiperfagia, obesidad y/o cambios en el estado de ánimo, y es una forma de presentación clínica inusual de las recaídas en el SNC y debe alertar al pediatra para mantener un alto índice de sospecha.Se describen cuatro casos que se presentaron con síndrome hipotalámico al momento de desarrollar una recaída de LLA en el SNC

Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, corresponding to 23% of cancer in children younger than 15 years old. About 20% of ALL cases will relapse, commonly in the bone marrow. Extramedullar relapses are unusual, and the two most frequent locations are CNS and testicles. ALL relapses, when diagnosed in the CNS, frequently present with clinical features of a meningeal syndrome. The hypothalamic syndrome, consisting of hyperphagia, obesity and / or behavior disturbances, corresponds to an unusual presentation of relapses in this location and should alert pediatricians to suspect it.We describe 4 ALL cases of hypothalamic syndrome at the time of CNS relapse

Ultraconserved long non-coding RNA uc 112 is highly expressed in childhood T versus B-cell acute lymphoblastic leukemia

ABSTRACT Aberrant expression of long non-coding RNAs (lncRNAs) has been detected in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped on transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated by quantitative real-time PCR in bone marrow samples from children with T-ALL (n = 32) and common-ALL/pre-B ALL (n = 30). In pediatric ALL, higher expression levels of uc.112 were found in patients with T-ALL, compared to patients with B-ALL. T-cells did not differ significantly from B-cells regarding uc.112 expression in non-tumor precursors from public data. Additionally, among B-ALL patients, uc.112 was also found to be increased in patients with hyperdiploidy, compared to other karyotype results. The uc.122, uc.160, and uc.262 were not associated with biological or clinical features. These findings suggest a potential role of uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

Allergic reactions to asparaginase: retrospective cohort study in pediatric patients with acute lymphoid leukemia

ABSTRACT Introduction: To assess the frequency of allergic reactions to asparaginase (ASP) and possible risk factors for reactions in a cohort of pediatric patients. Method: The study was performed based on retrospective data from patients under acute lymphoid leukemia treatment in a general university hospital located in southern Brazil. Information on patients who used ASP from 2010 to 2017 was collected. Allergic reactions were identified in electronic medical records. Results: Among the 98 patients included in the study, 16 (16.3 %) experienced an allergic reaction to native l-asparaginase (L-ASP). Of the 22 patients (22.4 %) that received only intravenous (IV) administration of l-ASP, 10 (62.5 %) had allergic reactions, while 48 patients (49 %) received intramuscular (IM) administration and 28 (28.6 %) received IV and IM administrations. The occurrence of allergic reactions differed between the groups (p < 0.001), and IV administration was associated with allergic reactions. Association was also observed between the severity of the reaction and the route of administration, with the IM route associated with grade 2 and IV route associated with grade 3. Occurrence of allergic reactions was higher when the commercial formulation of l-ASP, Leuginase®, was used (p = 0.0009 in the analysis per patient and p = 0.0003 in the analysis per administration). Conclusions: The IV administration and commercial Leuginase® presentation were associated with more allergic reactions in the study population, which corroborates the findings in the literature. The IV route was also associated with higher severity of reactions in the present study.

Alterações retinianas em pacientes com leucemia linfocítica aguda (lla): discussão de tema a partir de relato de caso / Retinal changes in patients with acute lymphocytic leukemia (all): discussion of topic from a case report

RESUMO A Leucemia Linfocitica Aguda (LLA) é uma doença caracterizada por uma alta taxa de sobrevida, porém o número absoluto de crianças que morrem por ela representa uma grande parcela dos casos de óbitos infantis por câncer. A morbidade decorrente de seu tratamento pode deixar sequelas em pessoas com grande expectativa de vida, tornando-se extremamente necessário o entendimento da patogênese desta doença, possibilitando o desenvolvimento de novos tratamentos e diminuição de sequelas provocadas pela doença. O diagnóstico precoce é importante para se evitar complicações oculares que possam levar a baixa de acuidade visual em longo prazo e para avaliação de recaídas de tratamento sendo determinante no direcionamento de condutas.

ABSTRACT The Acute Lymphocytic Leukemia (ALL) is a disease characterized by a high survival rate, but the absolute number of children who die from it represents a large proportion of cases of infant deaths from cancer. The morbidity resulting from its treatment can leave sequelae in people with high life expectancy, making it extremely necessary to understand the pathogenesis of this disease, enabling the development of new treatments and reduction of sequelae caused by the disease. This early diagnosis is important to avoid ocular complications that may lead to low long-term visual acuity and to evaluate treatment relapses and determine the conducts.

Validación de los instrumentos para medir factores que influyen en el diagnóstico leucemia linfoblástica en niños / Validation of instruments to measure factors that influence the diagnosis of lymphoblastic leukemia in children

La leucemia linfoide aguda (LLA) es el cáncer más frecuente en niños. A nivel mundial se estima que cerca del 30% corresponde a la totalidad de las neoplasias malignas que se presentan en niños y de estas, más del 75% son LLA. Por esto, nos vimos en la necesidad de elaborar un instrumento para medir factores que influyen en el diagnóstico. Porque un diagnóstico oportuno contribuye a mejorar la tasa de vida de estos pacientes. Objetivo: Validar instrumentos para medir los factores que influyen diagnóstico leucemia linfoblástica en niños. Metodología: Esta es una investigación mixta, corte transversal de tipo exploratorio. Diseño descriptivo no experimental. Para validar el instrumento cuantitativo se utilizó una muestra piloto con 15 padres de familia o representes de niños diagnosticados con leucemia linfoblástica aguda, seleccionado y elegido de forma aleatoria probabilística. Para el instrumento cualitativo se utilizó a una sola madre de un niño diagnosticado con leucemia, validado por juicio de cinco expertos, tres oncólogos con experiencia y 2 enfermeras magistradas con experiencia en oncología infantil y alfa de Cronbach. Resultados: Después de la revisión y validación de los instrumentos cuantitativo y cualitativos por los 5 expertos, la calificación obtenida es una puntuación de muy confiable 94,9 para el instrumento cuantitativo y una puntación de muy confiable de 96 puntos, para el instrumento cualitativo. Los puntajes alcanzados dan la seguridad para estructura y proceso, por medio del Coeficiente Alfa de Cronbach y validez de contenido y de constructo. Conclusión: estos instrumentos, quedan validados por juicio de expertos como herramientas muy confiables para obtener datos que se requieran para la investigación científica(AU)

Acute lymphoid leukemia (ALL) is the most common cancer in children. Worldwide, it estimated that about 30% corresponds to all malignant neoplasms that occur in children and of these, more than 75% are ALL. For this reason, we saw the need to develop an instrument to measure factors that influence the diagnosis. Because a timely diagnosis contributes to improving the life rate of these patients. Objective: To validate instruments to measure the factors that influence lymphoblastic leukemia diagnosis in children. Methodology: This is a mixed investigation, exploratory cross-section. Descriptive non-experimental design. A pilot sample used to validate the quantitative instrument, with 15 parents or representatives of children diagnosed with acute lymphoblastic leukemia, selected and chosen in a probabilistic random way. For the qualitative instrument, a single mother of a child diagnosed with leukemia was used, validated by the judgment of five experts, three experienced oncologists and two magistrate nurses with experience in childhood oncology and Cronbach's alpha. Results: After the review and validation of the quantitative and qualitative instruments by the five experts, the score obtained is a very reliable score of 94.9 for the quantitative instrument and a very reliable score of 96 points for the qualitative instrument. The scores achieved provide security for structure and process, through Cronbach's Alpha Coefficient and content and construct validity. Conclusion: Expert judgment validated these instruments as very reliable tools to obtain data required for scientific research(AU)

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)

Expressão da L-asparaginase II de Saccharomyces cerevisiae recombinante extracelular com glicosilação humanizada em Pichia pastoris / Extracellular expression of Saccharomyces cerevisiae's L-asparaginase II in Pichia pastoris with humanized glycosylation

L-asparaginase é um inibidor eficiente do crescimento tumoral, usado em sessões de quimioterapia contra a Leucemia Linfoblástica Aguda (LLA), resultando na remissão completa da doença em 90% dos pacientes tratados. A L-asparaginase II de Saccharomyces cerevisiae (ScASNaseII) tem alto potencial de superar os efeitos adversos da L-asparaginase de bactéria, porém sua produção endógena resulta em uma proteína hipermanosilada e, consequentemente, imunogênica. A cepa de Pichia pastoris Glycoswitch tem a maquinaria para expressar e secretar altas quantidades de enzima com glicosilação humanizada. Nesse trabalho, descrevemos o processo genético para expressar a ScASNaseII no meio extracelular pela P. pastoris Glycoswitch, e também os parâmetros bioquímicos, perfil cinético, citotoxicidade contra células leucêmicas e a interferência da glicosilação na atividade da enzima obtida. Nossos dados mostram que a cepa aplicada foi capaz de expressar ScASNaseII no meio extracelular passível de purificação de proteínas contaminantes com apenas um passo cromatográfico. A atividade específica para asparagina foi 218,2 UI/mg e a atividade glutaminásica representou 3,1% da atividade asparaginásica. Os parâmetros cinéticos foram KM = 120,5 µM e a eficiência catalítica de 3,8 x 105 M-1s-1. Análises por meio de gel nativo sugerem uma conformação tetramérica de aproximadamente 150 kDa. Essa é uma nova estratégia de produzir essa enzima de forma extracelular, com mais facilidade de purificação e com melhores propriedades biotecnológicas

L-asparaginase is an efficient inhibitor of tumor development, used in chemotherapy sessions against acute lymphoblastic leukemia (ALL) tumor cell; its use results in 90% complete remission of the disease in treated patients. Saccharomyces cerevisiae's L-asparaginase II (ScASNaseII) has a high potential to overcome the side effects of bacteria L-asparaginase, but the endogenous production of it results in hypermannosylated immunogenic enzyme. However, Pichia pastoris Glycoswitch strain has the machinery to express and secrete high quantity of the enzyme and with humanized glycosylation. Here we describe the genetic process to acquire the ScASNaseII in the extracellular medium expressed by P. pastoris Glycoswitch, and the biochemical properties of the resultant enzyme, kinetic profile, cytotoxicity against ALL cell line and the interference of glycosylation in its activity. Our data show that the strain employed is able to express extracellular asparaginase active and possible to be purified of contaminant proteins using a single chromatographic step. The specific activity using asparagine was 218.2 IU.mg-1 and the glutaminase activity represents 3.1% of its asparaginase activity. The kinetics parameters were KM=120.5 µM and a catalytic efficiency of 3.8x105 M-1s-1. The Native-PAGE suggested a tetrameric protein conformation, with approximately 150 kDa. This is a novel strategy to produce this enzyme extracellularly, easier to purify and with better biotechnological properties

Apresentação Atípica de Leucemia Linfoide Aguda em Criança: Relato de Caso / Atypical Presentation of Acute Lymphoid Leukemia in Child: Case Report / Presettación Atípica de Leucemia Linfoide Aguda en Niño: Relato de Caso

Introdução: A leucemia linfoblástica aguda (LLA) é a neoplasia maligna mais comum em crianças e a principal causa de morte por câncer nessa faixa etária. A hipercalcemia associada a lesões osteolíticas francas é uma rara apresentação da LLA. Relato do Caso: Paciente de 9 anos, sexo masculino, 37kg, apresentava cefaleia, dor e impotência funcional em membro inferior direito há 15 dias. Exames laboratoriais evidenciaram elevação de velocidade de hemossedimentação e proteína C reativa com hipercalcemia. Nos exames de imagem, apresentava desmineralização óssea e lesões osteolíticas difusas. Aspirado de medula óssea (MO) evidenciou 10% de blastos, o que não caracterizou leucemia. Pela melhora do quadro clínico, o paciente seguiu com investigação diagnóstica ambulatorialmente. Biópsia de lesão lítica em quadril e novo aspirado de MO detectaram maior número de blastos e confirmaram o diagnóstico de LLA. Iniciou tratamento com protocolo do Grupo Brasileiro de Tratamento de Leucemias na Infância, 2009. Após dois anos, estava bem e sem doença. Conclusão:A hipercalcemia está associada a apenas 0,6% a 4,8% dos casos de LLA. O paciente em questão apresentava apenas dores ósseas difusas e hipercalcemia, sem a sintomatologia habitual, o que torna seu quadro clínico ainda mais raro, sendo tal apresentação muito escassa na literatura. Apesar de incomuns, hipercalcemia e lesões osteolíticas difusas podem ser as primeiras e únicas manifestações de LLA na faixa pediátrica. O presente relato torna-se importante ao auxiliar a formulação de diagnósticos precoces da leucemia infantil, mesmo na vigência de um quadro clínico atípico.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignant neoplasm in children and the leading cause of cancer death in this age group. Hypercalcemia associated with frank osteolytic lesions is a rare presentation of ALL. Case Report: 9-year-old male, 37 kg, presented with headache, pain and functional impotence in the lower right leg for 15 days. Laboratory tests showed elevation of erythrocyte sedimentation rate and C-reactive protein with hypercalcemia. Imaging studies revealed bone demineralization and diffuse osteolytic lesions. Bone marrow aspiration showed 10% of blasts, which did not characterize leukemia. Due to the improvement of his clinical condition, the patient continued the clinical investigation as an outpatient. Biopsy of lytic lesion in the hip and new bone marrow aspirations detected higher number of blasts and confirmed the diagnosis of ALL. Treatment was initiated, following the protocol of the Brazilian Group of Treatment of Leukemia in Childhood, 2009. After two years, he was well and without disease. Conclusion: Hypercalcemia is associated with only 0.6% to 4.8% of all ALL cases. The patient presented only diffuse bone pain and hypercalcemia, without the usual symptoms, which makes his clinical condition even rarer, with such presentation being very scarce in the literature. Although uncommon, hypercalcemia and diffuse osteolytic lesions may be the first and only manifestations of ALL in the pediatric range. The present report is important in helping to formulate early diagnosis of childhood leukemia, even in the presence of an atypical clinical condition.

Introducción: La leucemia linfoblástica aguda (LLA) es la neoplasia maligna más común en los niños y principal causa de muerte por cáncer en ese grupo de edad. La hipercalcemia asociada a lesiones osteolíticas francas es una rara presentación de LLA. Relato del Caso: Paciente de 9 años, masculino, 37kg, presentaba cefalea, dolor e impotencia funcional en miembro inferior derecho hace 15 días. Los exámenes de laboratorio evidenciaron elevación de velocidad de sedimentación globular y proteína C reactiva con hipercalcemia. En los exámenes de imagen, presentaba esmineralización ósea y lesiones osteolíticas difusas. Aspirado de médula ósea (MO) evidenció el 10% de blastos, lo que no caracterizó la leucemia. Debido a la mejora del cuadro clínico, el paciente siguió la investigación diagnóstica ambulatoriamente. La biopsia de lesión lítica en cadera y nuevo aspirado de MO detectaron mayor número de blastos y confirmaron el diagnóstico de LLA. Se inició tratamiento con protocolo del Grupo Brasileño de Tratamiento de Leucemias en la Infancia, 2009. Conclusión: La hipercalcemia está asociada a sólo 0,6% a 4,8% de los casos de LLA. El paciente en cuestión presentaba sólo dolores óseos difusas e hipercalcemia, sin la sintomatología habitual, lo que hace el cuadro clínico del paciente aún más raro, siendo tal presentación muy escasa en la literatura. A pesar de inusual, hipercalcemia y lesiones osteolíticas difusas pueden ser las primeras y únicas manifestaciones de LLA en niños. El presente relato se vuelve importante al ayudar a la formulación de diagnósticos precoces de la leucemia infantil, incluso en la vigencia de un cuadro clínico atípico.

Caracterización biológica del marcador CD66c y su importancia clínica en la leucemia linfoide aguda / Biological characterization of the CD66c marker and its clinical importance in acute lymphoid leukemia

Las leucemias son un grupo heterogéneo de hemopatías con diversa etiología, patogenia, historia natural y pronóstico en las que se desencadena una proliferación clonal. La leucemia linfoblástica aguda (LLA) es el tipo de cáncer más común en los niños, se caracteriza por la infiltración de células neoplásicas del sistema hematopoyético a la médula ósea, sangre y otros tejidos. Fue considerada fatal hasta hace 30 años, hoy, la tasa de sobrevida a los 5 años supera el 70 por ciento, lo que implica que la mayoría de los pacientes puede curarse; sin embargo, la situación es diferente para la población infantil de los países en desarrollo. Se estima que la supervivencia al cáncer es entre 10 y 20 por ciento menor que para los infantes en países desarrollados. Uno de los marcadores de inmunofenotipo que ha cobrado mayor relevancia en los últimos años en el diagnóstico de LLA-B y seguimiento de la enfermedad mínima residual es el CD66c, este es una glicoproteína miembro de la familia del antígeno carcinoembrionario con función de adhesión celular y ampliamente utilizado como marcador tumoral que fue descubierto por SvenBerg a finales de los años 1970. Este antígeno se expresa en la superficie de los granulocitos y está implicado en varias funcionesbiológicas, que incluyen la adhesión celular, la migración, la transducción de señales y la regulación de la expresión génica. Este antígeno se presenta frecuentemente en varios tipos de cáncer y su sobrexpresión se asocia a menudo con pobre respuesta al tratamiento y disminución de la supervivencia de los pacientes. Diversos estudios evidencian que este marcador se relaciona con la presencia de diversas alteraciones cromosómicas como BCR-ABL, CRLF2, hiperdiploidía, que permiten orientar al pronóstico de la enfermedad(AU)

Leukemias are a heterogeneous group of blood diseases with a diverse etiology, pathogenesis, natural history and prognosis in which a clonal proliferation may be triggered. Acute lymphoid leukemia (ALL) is one of the most common types of cancer in children, it is characterized by the infiltration of neoplastic cells from the haematopoietic system to the bone marrow, blood and other tissues. Until 30 years ago, it was considered fatal; nowadays, the five-year survival rate exceeds 70 percent, which implies that most patients may heal. Nevertheless, in developing countries the situation might be different for pediatric population; it is estimated that cancer survival rate ranges between 10 and 20 percent less than those children living in developed countries. One of the immunophenotype markers that has been relevant in the last few years in the diagnosis of B-ALL and the follow-up of the minimal residual disease is CD66c. This is a member of the glycoprotein family from the carcinoembryonic antigen with a cellular adhesion function that has been widely used as a tumor marker as discovered by Sven Berg in the late 1970's. This antigen has been identified as a superficial protein expressed on the granulocytes and it is also involved in several biological functions, including cellular adhesion, migration, signal transduction and regulation of gene expression. This antigen is frequently presented in several types of cancer and its overexpression is often associated with a poor response to treatment and a decrease of survival rates for patients. Several studies have evidenced that this marker is relatedwith the presence of several chromosomal abnormalities, such as: BCR-ABL, CRLF2, and hyperdiploidy, which may help in the disease prognosis(AU)

Características de la leucemia linfoblástica aguda y neutropenia febril en niños y adolescentes atendidos en un hospital de Guayaquil, Ecuador / Characteristics of acute lymphoblastic leukemia and febrile neutropenia in children and adolescents cared for in a hospital in Guayaquil, Ecuador

RESUMEN Con el objetivo de caracterizar clínicamente a los niños y adolescentes con leucemia linfoblástica aguda y neutropenia febril en un hospital de Ecuador se realizó un estudio de serie de casos revisando historias clínicas de pacientes atendidos en el Hospital de la Sociedad de Lucha Contra el Cáncer de la ciudad de Guayaquil durante enero 2014 y abril 2016. De los 101 pacientes 51,5% eran mujeres, la edad promedio fue 5,5±2,1 años, el 72,3% tenían riesgo alto de infección bacteriana invasora, el foco de origen infeccioso más frecuente fue el respiratorio con 47,5%, el 18,8% de los microorganismos aislados en hemocultivos fueron Gram-positivos. El 25,7% de los pacientes fallecieron, siendo la refractariedad a la quimioterapia uno de los factores asociados (p<0,001). En conclusión, la mortalidad en niños y adolescentes, con leucemia linfoblástica aguda y neutropenia febril fue elevada; siendo la refractariedad a la quimioterapia uno de los principales factores asociados.

ABSTRACT With the objective of performing a clinical characterization of children and adolescents with acute lymphoblastic leukemia and febrile neutropenia in a hospital in Ecuador, a case series study was carried out, which involved reviewing the clinical records of patients receiving care at "Hospital de la Sociedad de Lucha Contra el Cancer" in Guayaquil between January 2014 and April 2016. Out of the 101 patients, 51.5% were female; mean age was 5.5±2.1 years old; 72.3% were at high risk for invasive bacterial infection; the most common infections were respiratory with 47.5%; 18.8% of bacteria isolated in blood cultures were Gram-positive. Finally, 25.7% of patients died, with chemotherapy resistance as one of the associated factors.

Necessidades de saúde de familiares de crianças com leucemia: conversas e metáforas no itinerário de cuidados / Health Needs of Family Members of Children with Leukemia: conversations and methaphores in the care itinerary

A família pode ser uma aliada importante na suspeição da leucemia ao narrar as manifestações dos primeiros sinais de adoecimento da criança para o profissional de saúde que a acompanha regularmente. Para evitar antecipações geradoras de pânico, sofrimento, angústias e desesperança, é preciso monitorar mais restritamente as necessidades da família e das crianças menores de cinco anos, por meio de uma comunicação terapêutica qualificada e construção de vinculo no território do cuidado. Investigaram-se como objeto de estudo as necessidades de familiares de crianças com leucemia linfoide aguda (LLA) no itinerário de cuidados em saúde, a partir dos primeiros sinais de adoecimento. Os objetivos foram: a) descrever o itinerário percorrido por familiares ou não para atender as necessidades da criança, quando perceberam os primeiros sinais de adoecimento; b) identificar, na narrativa dos familiares, aqueles sinais associados à suspeição, investigação e definição do diagnóstico de LLA; c) compreender a comunicação da notícia do diagnóstico; e d) analisar o itinerário do tratamento e a construção das redes na resolutividade do adoecimento da criança e da família. Método: Pesquisa qualitativa implementada com o método narrativo. Participaram sete familiares cuidadores de cinco crianças com LLA, entre junho e setembro de 2016, em cenários da comunidade de livre escolha dos residentes nas cidades do Rio de Janeiro e São Bernardo do Campo. As entrevistas narrativas, presenciais (6/7) e virtuais (1/7), foram mediadas pelas técnicas de criatividade e sensibilidade Mapa Falante e Corpo Saber. Pesquisa aprovada pelo Comitê de Ética em Pesquisa com o Parecer nº 1.517.322. A análise de conversação resultou em cinco unidades de análise: sinais de adoecimento; itinerário da suspeição ao diagnóstico; a comunicação da notícia; itinerário do tratamento e intercorrências; redes social e de apoio no itinerário de cuidados. Resultados: A memória dos primeiros sinais de adoecimento da criança os relacionou às doenças mais comuns na infância, sem associação inicial com a LLA. As boas condições de vida, acesso aos serviços privados x de saúde e tecnologia de investigação diagnóstica, vínculo da criança com um profissional de saúde de referência e autonomia contribuíram para que houvesse a suspeição e se iniciasse a investigação diagnóstica. A integralidade do cuidado foi determinante para que o diagnóstico e tratamento da LLA ocorressem em tempo oportuno. A comunicação da notícia do diagnóstico foi marcada pelo despreparo profissional. As redes de apoio e social contribuíram para a superação das adversidades e o impacto da doença na vida dos familiares e das crianças com LLA no itinerário de cuidados. Conclusão: As narrativas das famílias indicam a necessidade da realização de exame físico completo, comunicação e escuta terapêutica dos familiares, construção de vínculo e confiança com o enfermeiro e o médico; e monitoramento restrito da criança com LLA, em todo o curso da doença, do tratamento e na fase de monitoramento da sobrevivência.(AU)

Leucemia linfoblástica aguda con grave alteración hepática como manifestación inicial: presentación de dos casos y revisión de la literatura / Acute lymphoblastic leukemia causing hepatic failure: report of two cases

Hematological diseases may cause acute hepatic failure and are seldom sought. We report two cases illustrating this situation. A 16-year-old male presented with an acute liver failure: a bone marrow biopsy showed complete infiltration with lymphoid type blasts. A flow cytometry confirmed the presence of an acute lymphoblastic leukemia. The patient died days later. A 20-year-old female presented with acute liver failure: due to a pancytopenia, a bone marrow biopsy was performed, which confirmed the presence of an acute lymphoblastic leukemia. Chemotherapy was started immediately. The patient had a favorable evolution.

Omics techniques and biobanks to find new biomarkers for the early detection of acute lymphoblastic leukemia in middle-income countries: a perspective from Mexico / Técnicas ómicas y biobancos para el hallazgo de nuevos biomarcadores para la detección temprana de leucemia linfoblástica aguda en países de ingresos medios: una perspectiva mexicana

Abstract: Acute lymphoblastic leukemia (ALL) affects the quality of life of many children in the world and particularly in Mexico, where a high incidence has been reported. With a proper financial investment and with well-organized institutions caring for those patients, together with solid platforms to perform high-throughput analyses, we propose the creation of a Mexican repository system of serum and cells from bone marrow and blood samples derived from tissues of pediatric patients with ALL diagnosis. This resource, in combination with omics technologies, particularly proteomics and metabolomics, would allow longitudinal studies, offering an opportunity to design and apply personalized ALL treatments. Importantly, it would accelerate the development of translational science and will lead us to further discoveries, including the identification of new biomarkers for the early detection of leukemia.

Resumen: La leucemia linfoblástica aguda (LLA) afecta la calidad de vida de una gran cantidad de individuos en edad pediátrica en todo el mundo; particularmente en México, donde se ha reportado una alta incidencia. Con un apropiado fondo de inversión financiera, así como instituciones adecuadamente organizadas al cuidado de los pacientes con LLA, en conjunto con plataformas sólidas para llevar a cabo análisis globales y de alto rendimiento, se propone la creación de un repositorio para la conservación de suero y células provenientes de médula ósea y sangre derivadas de pacientes pediátricos con LLA al diagnóstico. Estos recursos, en combinación con las tecnologías ómicas, en particular la proteómica y la metabolómica, podrían permitir el establecimiento de estudios longitudinales y ofrecer una oportunidad para el diseño y aplicación de tratamientos personalizados para la LLA. Esta estrategia permitiría acelerar el desarrollo de la ciencia traslacional, favoreciendo el hallazgo de importantes descubrimientos, incluyendo la identificación de nuevos biomarcadores para la detección temprana de la leucemia.

Guía de práctica clínica para la detección, tratamiento y seguimiento de leucemias linfoblástica y mieloide en población mayor de 18 años. Guía completa / Clinical practice guideline for the detection, treatment and monitoring of lymphoblastic and myeloid leukemias in a population over 18 years of age

La guía relaciona el diagnóstico y el tratamiento en población adulta de la leucemia linfoblástica aguda (LLA) y la leucemia mieloide aguda (LMA), como el diagnostico, el tratamiento y el seguimiento en población adulta de la leucemia mieloide crónica (LMC).

Perfil epidemiológico, incidência, mortalidade e sobrevida de crianças e adolescentes com leucemias em Pernambuco / Epidemiological Profile, Incidence, Mortality, and Survival of Children and Adolescents Diagnosed with Leukemia in Pernambuco, Brazil

Introdução: Leucemia é o câncer mais comum em crianças e a principal causa de óbito relacionada ao câncer na infância. A sobrevida das crianças com leucemia tem melhorado de forma significativa, entretanto, ainda permanece abaixo de 50% na maioria dos países com recursos limitados. Objetivo: Descrever o perfil epidemiológico, incidência, mortalidade, sobrevida das leucemias agudas e os fatores de risco para o óbito em crianças e adolescentes com leucemia mieloide aguda (LMA) em Pernambuco. Metodologia: a) coorte retrospectiva com crianças e adolescentes (0-19 anos), a partir das informações do Registro de Câncer de Base populacional (RCBP) do Recife (período de 1998 - 2007). As tendências da incidência e da mortalidade foram avaliadas utilizando-se o método Joinpoint. A sobrevida relativa foi calculada, utilizando-se a tábua completa de mortalidade disponível no Instituto Brasileiro de Geografia Estatística (IBGE) para o Brasil em 2010. b) Foram analisados o risco cumulativo de óbito precoce (até 6 semanas do diagnóstico) e a sobrevida global (SG) e livre de eventos (recidiva, segunda neoplasia ou óbito) pelo método de Kaplan Meier para leucemia promielocítica aguda (LPA), LMA da síndrome de Down (LMA-SD) e outros subtipos (exceto LMASD e LPA) e os fatores preditivos para o óbito, por características do diagnóstico utilizando-se a regressão multivariada de Cox, distintamente para leucemia promielocítica aguda (LPA) e para outros subtipos de LMA a partir de uma coorte de crianças diagnosticadas entre 2000-2014 com LMA e acompanhadas no Instituto de Medicina Integral Prof. Fernando Figueira (IMIP). Resultados: a) o estudo de base populacional envolveu 175 casos. A taxa de incidência para leucemias foi de 41,1/milhão de habitantes menores de 20 anos, com pico de incidência de 78,3/milhão na faixa de 1 a 4 anos....

Introduction Leukemia is the most common cancer in children and the leading cause of cancerrelateddeath in childhood, with a variable incidence worldwide. The survival rates for children with leukemia have significantly improved. However, it remains below 50% in most countries with limited resources. Objective The aim of the study was to describe the epidemiological profile, incidence,mortality, survival, and risk factors for death in children and adolescents with acute myeloid leukemia (AML) in Pernambuco, Brazil. Methodology Two studies were conducted. a) The first study included a retrospective cohort of children and adolescents aged 0–19 years, based on the data obtained fromthe population-based cancer registry in Recife (1998–2007). Joinpoint method was used to evaluate the incidence and mortality trends. The relative survival was calculated using the complete mortality table available at the Instituto Brasileiro de Geografia e Estatística for Brazil in 2010. b) The second study included a cohort of children who were diagnosed with AML between 2000 and 2014 and treated at the Instituto de Medicina Integral Prof. Fernando Figueira - IMIP. The cumulative risk ofearly death (until 6 weeks of diagnosis), overall survival (OS), and event-free survival (EFS) considered as recurrence, second neoplasia, or death for acute promyelocytic leukemia (APL), AML with Down syndrome (AML-DS), and other subtypes (except AML-DS and APL) were analyzed using the Kaplan-Meier method. Cox multivariate regression model was used to identify factors predictive of death, by the characteristics of the diagnosis, distinctly for APL and for the othersubtypes of AML...

Frequency and Clinical Characteristics of Intrachromosomal Amplification of Chromosome 21 in Korean Childhood B-lineage Acute Lymphoblastic Leukemia

BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21) is known to be associated with poor prognosis in B-cell ALL (B-ALL). To determine the frequency and clinical characteristics of iAMP21 in Korean B-ALL patients, we performed FISH and multiplex ligation-dependent probe amplification (MLPA) analyses. METHODS: A total of 102 childhood B-ALL patients were screened with ETV6-RUNX1 FISH probes (Abbott Molecular, USA). The presence of an iAMP21 was confirmed by using MLPA P327 iAMP21-ERG probemix (MRC Holland, The Netherlands). RESULTS: iAMP21 was detected in one of the screened B-ALL patients (1/102 patients, 1.0%) who presented the ALL immunophenotype and complex karyotype at initial diagnosis. The patient relapsed twice after bone marrow transplantation. MLPA showed 12.5-Mb and 4.28-Mb regions of amplification and deletion, respectively. CONCLUSIONS: The frequency of iAMP21 is considerable in Korean pediatric patients. Our report suggests that iAMP21 in childhood B-ALL has very unfavorable impact on patient's prognosis. Additional methods such as MLPA analysis is essential to rule out patients with equivocal interphase FISH results.

t(12;17)(p13;q12)/TAF15-ZNF384 Rearrangement in Acute Lymphoblastic Leukemia

No abstract available.