Priapismo y leucemia mieloide crónica en adolescente. Debut poco frecuente. Reporte de caso / Priapism and chronic myeloid leukemia in an adolescent. Rare debut presentation. A case report

El priapismo es una erección dolorosa y persistente acompañada o no de estímulo sexual. Una causa poco frecuente de esta anormalidad es la leucemia mieloide crónica. Se han reportado pocos casos de priapismo como manifestación inicial de una leucemia de este tipo en pacientes adolescentes. A continuación, se informa el caso de un paciente de 16 años de edad que presentó priapismo como manifestación inicial de una leucemia mieloide crónica. Durante su evolución, no se realizó aspiración de los cuerpos cavernosos. Se inició tratamiento hematológico específico y, ante la persistencia del priapismo, fue necesario realizar un shunt de cuerpos cavernosos en dos ocasiones, tratamiento a pesar del cual existen altas probabilidades de secuelas.

Priapism is a painful and persistent erection, with or without sexual stimulation. A rare cause of such abnormality is chronic myeloid leukemia. Few cases of priapism as an initial manifestation of this type of leukemia have been reported in adolescent patients. Here we describe the case of a 16-year-old patient who presented with priapism as the initial manifestation of chronic myeloid leukemia. No cavernosal aspiration was performed. A specific hematological treatment was started and, given the persistence of priapism, the patient required 2 corpora cavernosa shunt procedures; despite this treatment, there is a high probability of sequelae.

Construção e validação de História em Quadrinhos para crianças com leucemia linfoide aguda / Construcción y validación de Cómics a niños con leucemia linfocítica aguda / Construction and validation of Comics at children with acute lymphocytic leukemia

Resumo Introdução O câncer tem impacto na vida das crianças e seus familiares. As Histórias em Quadrinhos podem ser uma estratégia de fortalecer o vínculo e a comunicação entre profissional/paciente/família. Objetivo Desenvolver e validar um material instrucional/educativo, no formato de Histórias em Quadrinhos, voltada para crianças hospitalizadas com leucemia linfóide aguda. Metodologia Estudo metodológico desenvolvido em nove etapas: elaboração do projeto de pesquisa; definição e seleção do conteúdo; adaptação da linguagem; inclusão de ilustrações; construção de um material piloto; validação do material; layout; impressão final e disponibilização. A validação ocorreu com 10 especialistas entre março e maio de 2022, utilizando-se o Instrumento de Validação de Conteúdo Educativo em Saúde. Resultados Foram elaboradas 5 Histórias em Quadrinhos, com 6 personagens principais, sendo necessárias 63 horas de trabalho. Elas foram divididas por temáticas (distúrbios gastrointestinais; cistite hemorrágica; problemas relacionados a autoestima e autoimagem; risco de infecção e dor óssea) que obtiveram Índice de Validade de Conteúdo global satisfatório entre 0,78 e 0,87. Conclusões e implicações para a prática As histórias em quadrinhos podem ser utilizadas como fonte atrativa e confiável de informações sobre a doença, servindo como apoio às informações durante a internação hospitalar e o preparo para alta.

Resumen Introducción El cáncer tiene un impacto en la vida de los niños y sus familias. Los cómics pueden ser una estrategia para fortalecer el vínculo y la comunicación entre profesional/paciente/familia. Objetivo Desarrollar y validar un material didáctico/educativo, en formato de Historietas, dirigido a niños hospitalizados con leucemia linfocítica aguda. Metodología Estudio metodológico desarrollado en nueve etapas: elaboración del proyecto de investigación; definición y selección de contenidos; adaptación lingüística; inclusión de ilustraciones; construcción de un material piloto; validación del material; disposición; impresión final y disponibilidad. La validación se realizó con 10 especialistas entre marzo y mayo de 2022, utilizando el Instrumento de Validación de Contenido de Educación en Salud. Resultados Se crearon 5 Comics, con 6 personajes principales, requiriendo 63 horas de trabajo. Fueron divididos por temas (trastornos gastrointestinales; cistitis hemorrágica; problemas relacionados con la autoestima y la autoimagen; riesgo de infección y dolor óseo) que obtuvieron un Índice de Validez de Contenido global satisfactorio entre 0,78 y 0,87. Conclusiones e implicaciones para la práctica Los cómics pueden ser utilizados como una fuente atractiva y confiable de información sobre la enfermedad, apoyando información durante la hospitalización y preparación para el alta.

Abstract Introduction Cancer has an impact on the lives of children and their families. Comics can be a strategy to strengthen the bond and communication between professional/patient/family. Objective To develop and validate an instructional/educational material, in the format of Comics, aimed at children hospitalized with acute lymphocytic leukemia. Methodology Methodological study developed in nine stages: preparation of the research project; content definition and selection; language adaptation; inclusion of illustrations; construction of a pilot material; validation of the material; layout; final printing and availability. Validation took place with 10 specialists between March and May 2022, using the Health Education Content Validation Instrument. Results 5 Comics were created, with 6 main characters, requiring 63 hours of work. They were divided by themes (gastrointestinal disorders; hemorrhagic cystitis; problems related to self-esteem and self-image; risk of infection and bone pain) that obtained a satisfactory global Content Validity Index between 0.78 and 0.87. Conclusions and implications for practice Comics can be used as an attractive and reliable source of information about the disease, supporting information during hospitalization and preparation for discharge.

Barriers to medication adherence by caregivers of children with leukemia: an observational study / Barreiras de adesão medicamentosa por cuidadores de crianças com leucemia: um estudo observacional

ABSTRACT Objective: To identify barriers to adherence to home oral maintenance chemotherapy in children with leukemia treated at a specialized cancer center. Methods: We used the Brief Medication Questionnaire (BMQ) as a tool for screening barriers to adherence. The level of adherence was calculated considering at least one positive response in each BMQ domain, defined as Regimen Screen, Belief Screen, and Recall Screen. A positive screening for belief barriers (PSB) indicates that the caregiver reports not understanding the medication's mechanism of action and adverse effects. Results: Three important barriers to adherence were identified: beliefs, number of children of the caregiver, and age of the caregiver. The primary caregivers included 32 mothers (80%), four fathers (10%), three grandmothers (7.5%), and one unrelated caregiver (2.5 %). Most caregivers with a PSB were mothers. A PSB indicates that the caregiver reports not understanding the medication's mechanism of action and adverse effects. Caregivers with two or more children (median, three) had more barriers to adherence. Caregivers with potential non-adherence tended to be older than those with potential adherence, although without statistical significance (p=0.079, Mann-Whitney U test). Conclusions: The main barriers to adherence to home oral maintenance chemotherapy in children with leukemia identified through interviews with their caregivers, most often mothers, were lack of understanding of the treatment regimen, a greater number of children, and older age.

RESUMO Objetivo: Identificar barreiras de adesão ao tratamento de manutenção da quimioterapia via oral domiciliar, em uma amostra de crianças diagnosticadas com leucemia atendidas em um serviço especializado em oncologia. Métodos: O Brief Medication Questionnaire (BMQ) foi utilizado como instrumento de coleta para a identificação de barreiras de adesão. O nível de adesão foi calculado considerando-se pelo menos uma resposta positiva no domínio do BMQ, definido como regime, crença e recordação. Uma crença positiva mostra que o cuidador reporta não entender o mecanismo de ação e os efeitos adversos. Resultados: Três importantes barreiras de adesão foram identificadas, incluindo crença, o número de filhos do casal e a idade dos cuidadores. A mãe como principal responsável pelo tratamento da criança apresentou frequência maior entre as pessoas com rastreamento positivo para barreiras de crenças (BPC). Crença positiva significa que o cuidador relata não entender o mecanismo de ação dos medicamentos e os efeitos adversos. Quanto ao número de filhos, o estudo mostrou que quanto mais filhos (dois filhos ou mais, mediana=três) maior a barreira de adesão. Houve tendência de responsáveis com potencial não adesão serem mais velhos que os responsáveis com potencial adesão, embora sem significância estatística ao nível de significância de 5% (p=0,079, teste U de Mann-Whitney). Conclusões: As principais barreiras de adesão dos cuidadores de crianças com leucemia ao tratamento medicamentoso de manutenção foram dificuldades relatadas pelos cuidadores, na maioria das vezes as mães, que não entenderam como o medicamento funcionava, o número de filhos — quanto mais filhos menor a adesão — e a idade dos cuidadores. Cuidadores mais velhos aderiram menos ao tratamento prescrito.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles / Avaliação in vivo e in vitro dos efeitos antitumorais de nanopartículas de óxido de ferro e óxido de ferro com núcleo de folato

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Apoptotic effect of Bulbine Natalensis and Chlorophytum Comosum in myelogenous Leukemia K562 cell line / Efeito apoptótico da natalensia bulbina e do clorofito comoso na linhagem celular mielogênea da leucemia K562

Abstract Bulbine natalensis and Chorophytum comosum are potential medicinal source for the treatment of cancers. Chronic myeloid leukaemia is a hematopoietic stem cells disorder treated by tyrosine kinase inhibitors but often cause recurrence of the leukaemia after cessation of therapy, hence require alternative treatment. This study determines the anti-cancer effect of leaf, root and bulb methanolic and aqueous extracts of B. natalensis and C. comosum in chronic human myelogenous leukaemia (K562) cell line by MTT, Hoechst bis-benzimide nuclear and annexin V stain assays. The root methanolic extract of B. natalensis and C. comosum showed a high cytotoxicity of 8.6% and 16.7% respectively on the K562 cell line at 1,000 μg/ml concentration. Morphological loss of cell membrane integrity causing degradation of the cell and fragmentation were observed in the root methanolic extract of both plants. A high apoptosis (p < 0.0001) was induced in the K562 cells by both leaf and root extracts of the C. comosum compared to the B. natalensis. This study shows both plants possess apoptotic effect against in vitro myelogenous leukaemia which contributes to the overall anti-cancer properties of B. natalensis and C. comosum to justify future therapeutic applications against chronic myelogenous leukaemia blood cancer.

Resumo Bulbine natalensis Baker e Chorophytum comosum (Thunb.) Jacques são potenciais fontes medicinais para o tratamento de cânceres. A Leucemia Mieloide Crônica (LMC) é um distúrbio das células-tronco hematopoiéticas que é tratado com inibidores da tirosina quinase, mas frequentemente, causa recorrência da leucemia após a interrupção da terapia, portanto, requer um tratamento alternativo. Este estudo determinou o efeito anticancerígeno de extratos metanólicos e aquosos de folha, raiz e bulbo de B. natalensis e C. comosum na linhagem celular de leucemia mieloide humana crônica (K562) por ensaios de MTT, Hoechst bis-benzimida nuclear e anexina V. O extrato metanólico da raiz de B. natalensis e C. comosum apresentou alta citotoxidade de 8,6% e 16,7% respectivamente, na linhagem celular K562 com a concentração de 1,000 μg / ml. Perda morfológica da integridade da membrana celular causando degradação dos núcleos, citoplasma e encolhimento celular foi observada no extrato metanólico da raiz de ambas as plantas. Uma alta apoptose (p <0,0001) foi induzida nas células K562 por extratos de folhas e raízes de C. comosum em comparação com B. natalensis. Este estudo mostrou que ambas as plantas possuem efeito apoptótico contra leucemia mieloide in vitro que contribui para as propriedades anticâncer gerais de B. natalensis e C. comosum para justificar futuras aplicações terapêuticas contra câncer de sangue de LMC.

Subpoblaciones de linfocitos T en adultos mayores cubanos con leucemia linfoide crónica / Subpopulations of T lymphocytes in Cuban older adults with chronic lymphoid leukemia

Introducción: la inmunosenescencia está asociada con un mayor riesgo de desarrollo de cáncer. Dentro de las hemopatías malignas que afectan a este grupo de edad, está la leucemia linfoide crónica (LLC), caracterizada por trastornos en la inmunidad adaptativa que incluye las subpoblaciones de linfocitos T. Objetivo: Determinar la frecuencia de las subpoblaciones de linfocitos T en los pacientes adultos mayores con leucemia linfoide crónica evaluados en el Instituto de Hematología e Inmunología de Cuba. Métodos: Se realizó un estudio transversal en 30 adultos mayores con leucemia linfoide crónica. Se cuantificaron los linfocitos TCD3+CD4+ y TCD3+CD8+ en sangre periférica por citometría de flujo. Para la lectura y el análisis de los datos se empleó un citómetro de flujo Beckman Coulter Gallios. Se utilizaron los valores porcentuales, la media y la desviación estándar. Se consideró estadísticamente significativo si p≤0.05. Resultados: Hubo un predominio de hombres que representaron el 56,7 por ciento y del grupo de 70-79 años de edad. No se reportó ningún adulto mayor con LLC con valores altos ni normales de linfocitos TCD3+CD4+. Predominaron los hombres con valores bajos porcentuales de linfocitos TCD3+CD4+, TCD3+CD8+ e inversión del índice CD4/CD8 en relación con las mujeres. Conclusiones: Los adultos mayores con LLC presentan alteraciones en el número de las subpoblaciones de linfocitos T. La acción de estas células en relación al crecimiento de células B malignas aún es desconocido y resulta importante determinar si esto puede reflejar un intento de evasión de las células tumorales al control inmunológico(AU)

Introduction: Immunosenescence is associated with an increased risk of cancer development. Among the malignant hemopathies that affect this age group, it is chronic lymphoid leukemia (CLL), characterized by disorders in adaptive immunity, which include subpopulations of T lymphocytes. Objective: To determine frequency of T lymphocyte subpopulations in older adult patients with chronic lymphoid leukemia evaluated at the Institute of Hematology and Immunology of Cuba. Methods: A cross-sectional study was conducted in 30 older adults with chronic lymphoid leukemia. TCD3+CD4+ and TCD3+CD8+ lymphocytes were quantified in peripheral blood by flow cytometry. A Beckman Coulter Gallios flow cytometer was used to read and analyze the data. The percentage values, the mean and the standard deviation were used. It was considered statistically significant if p≤0.05. Results: There was a predominance of men who represented 56.7 percent and the age group of 70-79 years. No older adults with CLL with high or normal values of TCD3+CD4+ lymphocytes were reported. Men predominated with low percentage values of TCD3+CD4+, TCD3+CD8+ lymphocytes and inversion of the CD4/CD8 ratio in relation to women. Conclusions: Older adult with CLL present alterations in the number of T lymphocyte subpopulations. The role of these cells in relation to the growth of malignant B cells it is unknown and it turns out important to determine if this may reflect an attempt to evade tumor cells from immune control(AU)

Hospitalization expenses of adult leukemia patients with relapse based on quantile regression / 公共卫生与预防医学

Objective Based on quantile regression analysis, the influencing factors of relapse hospitalization expenses of adult leukemia patients were analyzed. Methods Analyze the composition and influencing factors of hospitalization expenses for leukemia recurrence patients in our hospital. Results From 2017 to 2022 , the per capita hospitalization cost for leukemia patients with recurrence showed an increasing trend year by year. The results of quantile regression model showed that age, payment method , length of stay, times of stay, operation and complications had an impact on the hospitalization expenses of patients at different quantiles, and the difference between different quantiles was statistically significant (P<0.05). Conclusions The quantile regression method can more clearly reflect the distribution of the variables of each factor , we can reduce the hospitalization expenses of patients by improving the coverage rate of medical insurance and controlling the length of stay.

Apoptotic effect of Bulbine Natalensis and Chlorophytum Comosum in myelogenous Leukemia K562 cell line

Abstract Bulbine natalensis and Chorophytum comosum are potential medicinal source for the treatment of cancers. Chronic myeloid leukaemia is a hematopoietic stem cells disorder treated by tyrosine kinase inhibitors but often cause recurrence of the leukaemia after cessation of therapy, hence require alternative treatment. This study determines the anti-cancer effect of leaf, root and bulb methanolic and aqueous extracts of B. natalensis and C. comosum in chronic human myelogenous leukaemia (K562) cell line by MTT, Hoechst bis-benzimide nuclear and annexin V stain assays. The root methanolic extract of B. natalensis and C. comosum showed a high cytotoxicity of 8.6% and 16.7% respectively on the K562 cell line at 1,000 g/ml concentration. Morphological loss of cell membrane integrity causing degradation of the cell and fragmentation were observed in the root methanolic extract of both plants. A high apoptosis (p 0.0001) was induced in the K562 cells by both leaf and root extracts of the C. comosum compared to the B. natalensis. This study shows both plants possess apoptotic effect against in vitro myelogenous leukaemia which contributes to the overall anti-cancer properties of B. natalensis and C. comosum to justify future therapeutic applications against chronic myelogenous leukaemia blood cancer.

Resumo Bulbine natalensis Baker e Chorophytum comosum (Thunb.) Jacques são potenciais fontes medicinais para o tratamento de cânceres. A Leucemia Mieloide Crônica (LMC) é um distúrbio das células-tronco hematopoiéticas que é tratado com inibidores da tirosina quinase, mas frequentemente, causa recorrência da leucemia após a interrupção da terapia, portanto, requer um tratamento alternativo. Este estudo determinou o efeito anticancerígeno de extratos metanólicos e aquosos de folha, raiz e bulbo de B. natalensis e C. comosum na linhagem celular de leucemia mieloide humana crônica (K562) por ensaios de MTT, Hoechst bis-benzimida nuclear e anexina V. O extrato metanólico da raiz de B. natalensis e C. comosum apresentou alta citotoxidade de 8,6% e 16,7% respectivamente, na linhagem celular K562 com a concentração de 1,000 g / ml. Perda morfológica da integridade da membrana celular causando degradação dos núcleos, citoplasma e encolhimento celular foi observada no extrato metanólico da raiz de ambas as plantas. Uma alta apoptose (p 0,0001) foi induzida nas células K562 por extratos de folhas e raízes de C. comosum em comparação com B. natalensis. Este estudo mostrou que ambas as plantas possuem efeito apoptótico contra leucemia mieloide in vitro que contribui para as propriedades anticâncer gerais de B. natalensis e C. comosum para justificar futuras aplicações terapêuticas contra câncer de sangue de LMC.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Antibiotic prophylaxis in acute childhood leukemia: What is known so far?

ABSTRACT Introduction: The treatment of acute lymphoblastic leukemia (ALL) has evolved in recent decades, reaching an overall survival rate close to 90%. Currently, approximately 4% of patients with ALL die from secondary complications of chemotherapy. Among these complications, the most frequent is febrile neutropenia (FN). The treatment of acute myeloid leukemias (AMLs) is even more aggressive, being consequently related to a considerable amount of treatment-related toxicity with a high risk of severe infection and death. Method: In order to reduce the infection-related risks in these groups of patients, systemic antibacterial prophylaxis has emerged as a possible approach. Results: Antibiotic prophylaxis during neutropenia periods in those undergoing chemotherapy have .already been proven in adults with acute leukemias (ALs). Among the possible available therapeutic options for bacterial prophylaxis in children with cancer, fluoroquinolones emerged with the most amount of evidence. Within this class, levofloxacin became the best choice. Conclusion: Therefore, the use of levofloxacin seems to be indicated in very specific situations: in children who are known to be neutropenic for a long time, secondary to intensive chemotherapy; in children with AL undergoing chemotherapy to induce remission; or in children undergoing hematopoietic stem cell transplantation (HSCT). This article aims to describe recent evidence focusing on antibiotic prophylaxis in children with ALs.

Infections in patients with chronic lymphocytic leukemia

ABSTRACT Introduction: Infection is a major complication in patients with chronic lymphocytic leukemia (CLL). Newly diagnosed patients are at high risk of developing infection caused by encapsulated bacteria, such as Streptococcus pneumoniae and Haemophylus influenzae. Method and Results: However, once treatment is initiated, the spectrum of pathogens causing infection broadens, depending on the treatment regimens. With disease progression, cumulative immunosuppression occurs as a consequence of multiple treatment lines and the risk of infection further increases. On the other hand, the use of targeted therapies in the treatment of CLL have brought new risks of infection, with an increased incidence of invasive fungal diseases, particularly aspergillosis, in patients receiving Bruton kinase inhibitors. Conclusion: In this article, we review the epidemiology of infection in patients with CLL, taking into account the treatment regimen, and briefly discuss the management of infection.

Pediatric and adolescent chronic myeloid leukemia: A follow-up study in Western India

Background: Chronic myeloid leukemia (CML) is relatively rare in pediatric and adolescent age groups. The purpose of this study was to evaluate the clinical, hematopathological, and biochemical parameters of CML in pediatric and adolescent age groups, along with an assessment of the treatment response with first-line tyrosine kinase inhibitors (TKI) and its correlation with the prognostic scoring systems of adults. Materials and Methods: A retrospective study of 44 Breakpoint Cluster Region-Abelson leukemia virus (BCR-ABL1)-positive pediatric and adolescent CML cases registered at our hospital was done. The clinical and laboratory parameters were evaluated using hospital software. The treatment response was monitored and scoring was performed using mathematical calculations. Results: The mean age was 11.6 (±4.7) years. The median hemoglobin was 8.4 g/dL and 63.6% of the cases showed white blood cell (WBC) counts >250,000/?L. The average follow-up was 21 months. A total of 97.7 and 78.1% cases achieved complete hematological response (CHR) and molecular response, respectively, during the treatment course. The maximum number of patients had low Sokal and European treatment and Outcomes Study (EUTOS) scores. Seventy-five per cent of the cases achieved CHR at 3 months, while 73.6 and 78.6% CML-Chronic phase (CP) cases with low Sokal and EUTOS scores achieved CHR at 3 months, respectively. Conclusion: This study revealed that the CML cases in pediatric and adolescent age groups are normally present with higher WBC counts at the time of diagnosis. The association of the prognostic scoring system with treatment response was statistically insignificant. However, a larger cohort study is needed to determine the treatment response of TKI in children and adolescent CML and its correlation with the prognostic scoring systems.

Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B. Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana. Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años. Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/ µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa. Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados, lo que sugiere que no existe afectación de genes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/ cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µΙ is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

Hematologic malignancies of primary bone marrow involvement: a decade's experience in Bahrain

ABSTRACT Introduction: The data on the pattern of primary hematologic malignancies in Bahrain is sparse, although previously published studies suggested rising trends in their incidence. This study aimed to compare with regional and world data and identify any changing trends. Methods: A retrospective cross-sectional chart analysis study was done on all cases of primary hematologic malignancies of bone marrow origin of Bahraini nationals presenting during the 10-year period from January 2005 to December 2014 at the sole oncology referral center in Bahrain during the study period. Results: In a total of 272 cases, the primary hematologic malignancies in decreasing order of frequency with respective median ages at diagnosis were: acute myeloid leukemia (AML; 26.1%, 39 years), acute lymphoblastic leukemia (ALL; 22.8%, 9 years), multiple myeloma (MM, 16.2%, 57 years), chronic myeloid leukemia (CML, 14%, 39.5 years), myelodysplastic syndromes (MDS; 12.5%, 56 years) and chronic lymphocytic leukemia (CLL; 5.5%, 65 years). The overall crude annual incidence rate of these malignancies was 4.8/105 population. Age-specific incidence rates were found to increase dramatically with age, except for ALL, for which it peaked in the pediatric age group. The age-standardized incidence rates (ASIRs) per 105 per year were 1.47 (AML), 1.13 (MM), 0.93 (ALL), 0.85 (MDS), 0.81 (CML) and 0.44 (CLL). Conclusion: The pattern of primary hematologic malignancies in Bahrain shows unique features that distinguish it from trends reported in Eastern and Western world populations.

Acute promyelocytic leukemia in childhood and adolescence: treatment results of a modified AIDA protocol at a Brazilian center

ABSTRACT Introduction: Acute promyelocytic leukemia currently presents an excellent chance of cure with protocols based on all-trans-retinoic acid (ATRA) and anthracycline or only differentiation agents. However, high early mortality rates continue to be reported Methods: Between 2000 and 2018, patients were enrolled and retrospectively analyzed by medical records. A modified AIDA protocol, with a 1-year shortening of the treatment duration, reduction in the number of drugs and a strategy to reduce early mortality by the postponement of the initiation of anthracyclines were employed. Overall and event-free survival rates and toxicity were analyzed Results: Thirty-two patients were enrolled, of whom 56% were female, with a median age of 12 years and 34% belonged to the high-risk group. Two patients had the hypogranular variant and three had another cytogenetic alteration, in addition to the t(15;17). The median start of the first anthracycline dose was 7 days. There were two early deaths (6%) due to central nervous system (CNS) bleeding. All patients achieved molecular remission after the consolidation phase. Two children relapsed and were rescued by arsenic trioxide and hematopoietic stem cell transplantation. The presence of disseminated intravascular coagulation (DIC) at diagnosis (p = 0.03) was the only factor with survival impact. The five-year event-free survival (EFS) was 84% and 5-year overall survival (OS) was 90% Conclusion: The survival results were comparable to those found in the AIDA protocol, with a low rate of early mortality in relation to the Brazilian reality.

Survival benefit of pediatric-based regimen for adults with acute lymphoblastic leukemia: A single-center retrospective cohort

ABSTRACT Introduction: Improving survival of Acute Lymphoblastic Leukemia (ALL) in adult patients has been a challenge. Despite intensive chemotherapy treatment, overall survival is poor. However, several studies demonstrate that young adult patients have better survival when treated with pediatric-based intensive regimens. Considering these results, We decided to treat newly diagnosed ALL patients according to age and risk factors. The goal of this study was to describe the results of this intensive chemotherapy treatment approach for ALL adult patients diagnosed at our institution. Methods: Fifty-eight ALL patients, diagnosed from 2004 to 2013, were included in the analysis. Patients were assigned to either the St. Jude Total Therapy XIIIB high-risk arm (St Jude) or the CALGB 8811 (CALGB). The Kaplan-Meier survival curve was used for the survival analyses and the Cox proportional hazard regression, for multivariable analysis. Results: The overall survival was 22.9% at 10 years. The St. Jude improved survival, compared to the CALGB (p = 0.007), with 32.6% vs. 7.4% survival rate at 10 years. However, no survival benefit was found for patients younger than 20 years old (p = 0.32). The multivariable analysis demonstrated that undetectable minimal residual disease (MRD) and hematopoietic stem cell transplantation (HSCT) had beneficial impact on survival (p = 0.0007 and p = 0.004, respectively). Conclusion: ALL is a disease of poor prognosis for adults. The joint effort to standardize treatment and seek solutions is the way to start improving this scenario.

Outcome of adolescents and young adults with acute lymphoblastic leukemia in a single center in Brazil

ABSTRACT Introduction: Acute lymphoblastic leukemia (ALL) presents a poor prognosis in adults. The adoption of pediatric protocols has been changing this scenario, especially for adolescents and young adults (AYA). Objective and method: We aimed to evaluate a consecutive series of patients treated at the State Institute of Hematology of Rio de Janeiro between 2012 and 2020, focusing on the AYA subgroup. Result: The B-ALL was the most frequent subtype (81.6%) and AYA, the predominant age group (57.7%). The median overall survival (OS) was 9.4 months. High early mortality was observed and sepsis was the main cause of death. Better OS results were noted in AYA, in comparison to over 39y (13.3 × 6.2 months, respectively), the Berlin-Frankfurt-Münster (BFM) being the protocol of choice in this group. Conclusion: The use of the pediatric protocol seems to improve the OS of AYA, however, high rates of deaths from infection were observed, demonstrating the need for advances in the Brazilian public system clinical support.

Prognostic factors and impact of CMV reactivation on acute myeloid leukemia patients after HLA-matched myeloablative allogeneic stem cell transplantation in a high CMV prevalence country

ABSTRACT Introduction: Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) leads to dismal outcomes. This study aimed to identify high-risk patients and explore the effects of cytomegalovirus (CMV) reactivation in a high CMV-seropositive population. Methods: The study involved a single-center retrospective cohort in Thailand, analyzing clinical risk factors and CMV-mediated immune responses, correlated with transplant outcomes in AML patients. Results: Eighty-five patients with AML in complete remission (CR) undergoing HLA-matched myeloablative allo-SCT between 2011 and February 2021 were enrolled. The relapse rate was 27.1% with the median time of 7 months after transplantation. The 3-year relapse-free-survival (RFS) and overall-survival (OS) were 72.2% and 80.8%, respectively. The disease status (>CR1) and absence of chronic graft-versus-host disease (cGVHD) were independently significant adverse prognostic factors of RFS and OS. Ninety-two percent of recipient-donor pairs were both CMV seropositive. The CMV reactivation occurred in 54.1% of the patients. The clinically significant CMV infection rate was 49.4%. No CMV syndrome/disease or CMV-related mortality occurred. One-year cumulative incidence of relapse among CMV-reactivation and non-reactivation groups were 14.3% and 25.6%, respectively, without a statistically significant difference. Transplantation-related mortality was 11.1%. Conclusions: The transplantation beyond CR1 and absence of cGVHD are powerful prognostic factors associated with inferior RFS and OS. In a high CMV prevalence country, there appears to be no impact of CMV reactivation on relapse in AML patients undergoing an allo-SCT.

Economic burden of acute myeloid leukemia on patients in a resource-limited tertiary hospital in the Philippines

ABSTRACT Introduction: The remission induction treatment for acute myeloid leukemia (AML) has remained unchanged in the resource-limited setting in the Philippines. AML treatment consists of induction chemotherapy followed by high dose consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation. In the Philippines, the Filipino household bears the burden of health care cost of hospitalization expenditure. Insights into the treatment costs becomes an essential requirement as these guides the allocation of resources to scheme health programs. Method: This study involved a retrospective cohort analysis of AML patients who underwent treatment for AML. Review of the statements of account per admission per patient during treatment for remission induction, consolidation, relapsed and refractory disease and best supportive care from 2017 to 2019. Of the 251 eligible patients, 190 patients were included. Result: The mean healthcare expenditure for remission induction chemotherapy (Phase 1) was US $2, 504.78 (Php 125,239.29). While 3 to 4 cycles of consolidation chemotherapy cost an average of US $3,222.72 (Php 162,103.20). For patients who had relapsed and refractory disease, an additional mean cost of US $3,163.32 (Php 159,115.28) and US $2, 914.72 (Php 146,610.55) were incurred, respectively. The average cost of palliative care was US $1,687.00 (Php 84,856.59). Conclusion: The cost of chemotherapy and other therapeutics bear most of the weight of the direct healthcare cost. The cost of AML treatment represents a significant economic burden for patients and the institution. The cost increases as patients proceed through subsequent lines of treatment for induction failure. Existing subsidy for health insurance benefits could still be improved for appropriate source allocation of resources.