Riesgo de mortalidad en infecciones invasivas por Mucor SPP. en niños con enfermedades hemato-oncológicas: revisión sistemática / Mortality risk of invasive Mucor spp. infections in children with cancer: A systematic review

Los estudios sobre la infección fúngica invasiva (IFI) por Mucor spp. en pacientes pediátricos con patología hematooncológica, son de baja solidez científica, lo que dificulta conocer en profundidad sus características y evolución. Con el objetivo de analizar la evolución fatal de esos pacientes, se llevó a cabo esta revisión sistemática (RS). Material y métodos: La búsqueda bibliográfica se realizó con fecha 23 de marzo de 2023, en las principales bases de datos (Medline (a través de Pubmed), Embase (a través de Embase-Elsevier), The Cochrane Library (a través de Wiley), Cinahl (a través de Ebsco HOST), SCI-EXPANDED, SciELO (a través de la WOS) y Scopus (a través de Scopus-Elsevier), libre (mediante el motor Google) y revisando las citas de los artículos incluidos. Resultados: Se rescataron 1393 artículos, de los cuales se descartaron 1386 por diversas razones. Mediante el análisis de los textos completos, finalmente se incluyeron 7 estudios. Todos los estudios eran series de casos (nivel 4). La mediana de la frecuencia de muerte observada fue de 36,6% (Q1 20% - Q347%). Conclusiones: Esta RS mostró en niños con patología hemato-oncológica, que la mortalidad por IFI por Mucor spp. alcanzó a casi un tercio de los pacientes (AU)

Studies on invasive fungal infection (IFI) by Mucor spp. in pediatric patients with cancer have a low level of evidence, which makes it difficult to elucidate its characteristics and progression. To analyze the fatal outcome of these patients, this systematic review (SR) was conducted. Material and methods: A literature search was carried out on March 23, 2023, in the following main databases (Medline (via Pubmed), Embase (via Embase-Elsevier), The Cochrane Library (via Wiley), Cinahl (via Ebsco HOST), SCI-EXPANDED, SciELO (via the WOS) and Scopus (via Scopus-Elsevier). Additionally, a complementary search was carried out using free search engines (such as Google) and by reviewing the references of the included articles. Results: A total of 1393 articles were retrieved, of which 1386 were excluded for various reasons. After a thorough analysis of the full-text articles, 7 studies were ultimately included in the review. All studies were case series (level 4). The median observed death rate was 36.6% (IQR, 20% - 47%). Conclusions: This SR showed that in children with hematological-oncological disease, mortality due to IFI by Mucor spp. affected almost one third of the patients (AU)

Perfil de liberación de biomarcadores miocárdicos en pacientes con enfermedades hemato-oncológicas que reciben trasplante de progenitores hematopoyéticos / Profile or myocardial biomarkers release in patients with hemato-oncological diseases who receive hematopoietic stem cell transplantation / Perfil de liberação de biomarcadores miocárdicos em pacientes com doenças hemato-oncológicas que recebem transplante de células-tronco hematopoéticas

Introducción: las enfermedades cardiovasculares (CV) son la primera causa de muerte en quienes sobreviven al cáncer. Aunque el trasplante de progenitores hematopoyéticos (TPH) se asocia con grados variables de cardiotoxicidad, estas complicaciones han sido escasamente caracterizadas. Objetivo: analizar el perfil de liberación de biomarcadores miocárdicos como potenciales indicadores subclínicos de cardiotoxicidad en pacientes sometidos a TPH. Material y método: estudio descriptivo, analítico, prospectivo transversal y unicéntrico, reclutando pacientes derivados a la policlínica de cardio-oncología, con indicación de TPH en octubre de 2018-marzo de 2020. Se realizaron controles clínicos, ECG, bioquímicos (troponina I TnI y péptido natriurético del tipo BBNP) e imagenológicos según algoritmo de seguimiento. Las variables discretas se presentan como n (%) y las continuas mediante media ± DE o mediana RIQ. Los valores evolutivos de biomarcadores séricos se compararon mediante test de Friedman. La fracciónde eyección del VI (FEVI) basal se comparó con la de los 3 meses del TPH mediante test de Wilcoxon. Resultados: se incluyeron 19 pacientes, 37% mujeres, de 43,8 ± 15,7 años. No se detectaron modificaciones significativas de la FEVI en los controles evolutivos. En ningún caso se observó aumento de la TnI. Los valores de BNP aumentaron en 6 pacientes (32%), con diferencias significativas al mes postrasplante (basal: 13,6 1;6,1-30,9 vs. primer mes: 38,9 16,3-120,0 pg/ml, p = 0,036); con una mayor elevación en aquellos pacientes que recibieron antimetabolitos vs. otros fármacos (basal: 13,6 1;6,1-30,9 vs. al primer mes: 67,0 ;21,3-174,9 pg/ml, p = 0,039). El aumento de BNP no se asoció con el riesgo CV. Conclusión: la liberación de BNP posterior al TPH es un fenómeno frecuente (32% de los pacientes), alcanza un máximo al mes, independientemente de la FEVI. El subgrupo de pacientes que recibió antimetabolitos presentó una mayor liberación precoz de BNP.

Introduction: cardiovascular (CV) diseases are the leading cause of death in those who survive cancer. Although hematopoietic stem cell transplantation (HSCT) is associated with diverse grades of cardiotoxicity, these complications have been poorly characterized. Objective: to analyze the release profile of myocardial biomarkers as a potential subclinical marker of cardiotoxicity in patients undergoing HSCT. Material and method: descriptive, analytical, prospective, cross-sectional, single-center study, recruiting patients referred to the cardio-oncology polyclinic, with indication for HSCT in October 2018-March 2020. Clinical, ECG, biochemical and imaging controls were performed according to the algorithm of follow-up. The evolutionary values of serum biomarkers were compared using the Friedman test. Baseline LVEF was compared with that of 3 months after HSCT using the Wilcoxon test. Results: 19 patients were included, 37% women, aged 43.8 ± 15.7 years. No changes in LVEF were detected. In no case was an increase in TnI observed. BNP values increased in 6 patients (32%), with significant differences one month after transplantation (baseline: 13.6 ;6.1-30.9 vs. first month: 38.9 ;16.3-120.0, p = 0.036), detecting a greater elevation in those patients who received antimetabolites vs. other rugs (baseline: 13.6 ;6.1-30.9 vs. at the first month: 67.0 21.3-174.0, p = 0.039). The increase in BNP was not associated with CV risk. Conclusion: BNP release after HSCT is frequent (32% of our patients), reaching a maximum at one month, regardless of LVEF. The subgroup of patients who received antimetabolites had a greater early release of BNP.

Introdução: as doenças cardiovasculares (CV) são a principal causa de morte em pessoas que sobrevivem ao câncer. Embora o transplante de células-tronco hematopoéticas (TCTH) esteja associado à diverso grado de cardiotoxicidade, essas complicações têm sido mal caracterizadas. Objetivo: analisar o perfil de liberação de biomarcadores miocárdicos como potenciais marcadores subclínicos de cardiotoxicidade em pacientes submetidos ao TCTH. Material e método: estudo descritivo, analítico, prospectivo, transversal, unicéntrico, com recrutamento de pacientes encaminhados à policlínica de cardio-oncologia, com indicação de TCTH de outubro de 2018 a março de 2020. Foram realizados controles clínicos, eletrocardiográficos, bioquímicos e de imagem de acordo com o algoritmo de acompanhamento. Os valores evolutivos dos biomarcadores séricos foram comparados pelo teste de Friedman. A FEVE basal foi comparada com a de 3 meses após o TCTH usando o teste de Wilcoxon. Resultados: foram incluídos 19 pacientes, 37% mulheres, com idade de 43,8 ± 15,7 anos. Nenhuma mudança na LVEF foi detectada. Em nenhum caso foi observado um aumento de TnI. Os valores de BNP aumentaram um mês após o transplante (linha de base: 13,6 6,1-30,9; vs. primeiro mês: 38,9 16,3-120,0, p = 0,036), se detectou uma maior elevação nos pacientes que receberam antimetabólitos vs. outros medicamentos (linha de base: 13,6 ;6,1-30,9; vs. no primeiro mês: 67,0 ;21,3-174,0;, p = 0,039). O aumento do BNP não foi associado ao risco CV. Conclusão: a liberação do BNP após o TCTH é frequente (32% de nossos pacientes), podendo chegar a no máximo um mês, independente da FEVE. O subgrupo de pacientes que recebeu antimetabólitos apresentou maior liberação precoce de BNP.

Doxorubicin cardiotoxicity and Camellia sinensis cardioprotection determined by speckle-tracking echocardiography

Abstract Doxorubicin (Dox) is a medication used in the treatment of cancerous tumors and hematologic malignancies with potentially serious side effects, including the risk of cardiotoxicity. Flavonoids are plant metabolites with antioxidant properties and can be extracted from Camellia sinensis (CS). The aim of this study is to evaluate the possible cardioprotective effect of CS against injuries induced by Dox in rats. A total of 32 animals were distributed into four groups: (1) control - intraperitoneal injection (I.P.) of 0.5 mL saline weekly and 1.0 mL water by gavage daily; (2) CS - 0.5 mL saline I.P. weekly and 200 mg/kg CS by gavage daily; (3) Dox - 5.0 mg/kg Dox I.P. weekly and 1.0 mL water by gavage daily; and (4) Dox+CS -5.0 mg/kg Dox I.P. weekly and 200 mg/kg CS by gavage daily. Clinical examinations, blood profiles, electrocardiograms, echocardiograms, and histological analyses of hearts were performed over 25 days. The animals in the Dox group showed changes in body weight and in erythrogram, leukogram, electrocardiography, and echocardiography readings. However, animals from the dox+CS group had significantly less change in body weight, improved cardiac function, and showed more preserved cardiac tissue. This study demonstrated that CS prevents dox-induced cardiotoxicity, despite enhancing the cytotoxic effect on blood cells

Comparative analysis between cytomorphology and flow cytometry methods in central nervous system infiltration assessment in oncohematological patients

ABSTRACT Introduction Oncohematological patients require the evaluation for possible infiltration of the central nervous system (CNS) by neoplastic cells at diagnosis and/or during the monitoring of the chemotherapeutic treatment. Morphological analysis using conventional microscopy is considered the method of choice to evaluate the cerebrospinal fluid (CSF) samples, despite technical limitations. Objective This study aimed to compare the performance of the cytomorphology and flow cytometric immunophenotyping (FC) in the detection of CNS infiltration. Method We evaluated 520 CSF samples collected from 287 oncohematological patients for whom the detection of neoplastic cells was simultaneously requested by cytomorphology and FC. Results Laboratory analyses revealed 435/520 (83.7%) conclusive results by the two methods evaluated, among which 385 (88.5%) were concordant. Discordance between the methods was observed in 50/435 (11.5%) samples, 45 (90%) being positive by FC. Furthermore, the FC defined the results in 69/72 (95.8%) inconclusive samples by cytomorphology. The positivity of FC was particularly higher among hypocellular samples. Among 431 samples with a cell count of < 5/μL, the FC identified neoplastic cells in 75 (17.4%), while the cytomorphology reported positive results in 26 (6%). Among the samples that presented adequate cell recovery for evaluation by both methods (506/520), the comparative analysis between FC and cytomorphology revealed a Kappa coefficient of 0.45 (CI: 0.37-0.52), interpreted as a moderate agreement. Conclusion The data showed that the CSF analysis by FC helps in the definition of CNS infiltration by neoplastic cells, particularly in the cases with dubious morphological analysis or in the evaluation of samples with low cellularity.

Cytogenetic abnormalities in patients with hematological malignancies in Lahore city, Pakistan / Anormalidades citogenéticas em pacientes com neoplasias hematológicas na cidade de Lahore, Paquistão

Hematological and hematopoietic cells malignancies of the genes and hematopoietic cells are associated with the genetic mutation, often at the chromosomal level. The standard cytogenetic study is widely accepted as one of the main diagnostics and prognostic determinants in patients. Therefore, the current descriptive and cross sectional study sought to determine the cytogenetic analysis of frequent hematological malignancies in Pakistan. A total of 202 peripheral bone marrow or blood samples from patients with benign and malignant hematological malignancy were taken using a conventional G-banding technique. Among enrolled patients, the mean age was 21.5 years ± 23.4, and gender-wise distribution showed a marked predominance of the male 147 (73%) population compared to the female 55 (27%). Patients in the age group (2-10 years) had the highest frequency, 48 (24%), of hematological neoplasms, followed by age (11-20 years) with 40 (20%). Normal karyotypes (46, XX/46, XY) was found in 51% (n=103) patients. Furthermore, the frequency of complex karyotype was 30 (15%), while normal was seen in 171 (85%) patients. Pre-B Acute Lymphoblastic Leukemia (Pre-B ALL) was the most prevalent malignancy of 66 (33%), followed by Chronic Myelogenous Leukemia (CML) of 41 (20%) and Acute Lymphocytic Leukemia of 29 (14%). Translocation was the most prevalent 50 (25%), followed by hypotriploidy 14 (7%) and monosomy 8 (4%) on chromosome aberration analysis. In addition, t(9:22) translocation was found to be 20 (10%) in CML, with the majority in the age group (31-40 years). This study recommends that karyotyping should be tested frequently in hematological conditions because it may provide insight into the relative chromosomal changes associated with particular malignancies.

As neoplasias hematológicas e de células hematopoiéticas dos genes e as células hematopoiéticas estão associadas à mutação genética, geralmente em nível cromossômico. O estudo citogenético padrão é amplamente aceito como um dos principais determinantes diagnósticos e prognósticos em pacientes. Portanto, o presente estudo descritivo e transversal buscou determinar a análise citogenética de neoplasias hematológicas frequentes no Paquistão. Um total de 202 amostras de medula óssea periférica ou sangue de pacientes com malignidade hematológica benigna e maligna foi coletado usando uma técnica convencional de banda G. Entre os pacientes inscritos, a média de idade foi de 21,5 anos ± 23,4, e a distribuição por gênero mostrou uma marcada predominância da população masculina de 147 (73%) em comparação com a feminina de 55 (27%). Pacientes na faixa etária (2-10 anos) tiveram a maior frequência, 48 (24%), de neoplasias hematológicas, seguida da idade (11-20 anos) com 40 (20%). Cariótipos normais (46, XX / 46, XY) foram encontrados em 51% (n = 103) dos pacientes. Além disso, a frequência de cariótipo complexo foi de 30 (15%), enquanto normal foi observada em 171 (85%) pacientes. Leucemia linfoblástica aguda pré-B (LLA Pré-B) foi a doença maligna mais prevalente de 66 (33%), seguida por leucemia mieloide crônica (LMC) de 41 (20%) e leucemia linfocítica aguda de 29 (14%). A translocação foi o 50 mais prevalente (25%), seguido por hipotriploidia 14 (7%) e monossomia 8 (4%) na análise de aberração cromossômica. Além disso, a translocação t (9:22) encontrada foi de 20 (10%) na LMC, com a maioria na faixa etária (31-40 anos). Este estudo recomenda que o cariótipo deve ser testado com frequência em condições hematológicas porque pode fornecer informações sobre as alterações cromossômicas relativas associadas a doenças malignas específicas.

Cytogenetic abnormalities in patients with hematological malignancies in Lahore city, Pakistan / Anormalidades citogenéticas em pacientes com neoplasias hematológicas na cidade de Lahore, Paquistão

Abstract Hematological and hematopoietic cells malignancies of the genes and hematopoietic cells are associated with the genetic mutation, often at the chromosomal level. The standard cytogenetic study is widely accepted as one of the main diagnostics and prognostic determinants in patients. Therefore, the current descriptive and cross-sectional study sought to determine the cytogenetic analysis of frequent hematological malignancies in Pakistan. A total of 202 peripheral bone marrow or blood samples from patients with benign and malignant hematological malignancy were taken using a conventional G-banding technique. Among enrolled patients, the mean age was 21.5 years ± 23.4, and gender-wise distribution showed a marked predominance of the male 147 (73%) population compared to the female 55 (27%). Patients in the age group (2-10 years) had the highest frequency, 48 (24%), of hematological neoplasms, followed by age (11-20 years) with 40 (20%). Normal karyotypes (46, XX/46, XY) was found in 51% (n=103) patients. Furthermore, the frequency of complex karyotype was 30 (15%), while normal was seen in 171 (85%) patients. Pre-B Acute Lymphoblastic Leukemia (Pre-B ALL) was the most prevalent malignancy of 66 (33%), followed by Chronic Myelogenous Leukemia (CML) of 41 (20%) and Acute Lymphocytic Leukemia of 29 (14%). Translocation was the most prevalent 50 (25%), followed by hypotriploidy 14 (7%) and monosomy 8 (4%) on chromosome aberration analysis. In addition, t(9:22) translocation was found to be 20 (10%) in CML, with the majority in the age group (31-40 years). This study recommends that karyotyping should be tested frequently in hematological conditions because it may provide insight into the relative chromosomal changes associated with particular malignancies.

Resumo As neoplasias hematológicas e de células hematopoiéticas dos genes e as células hematopoiéticas estão associadas à mutação genética, geralmente em nível cromossômico. O estudo citogenético padrão é amplamente aceito como um dos principais determinantes diagnósticos e prognósticos em pacientes. Portanto, o presente estudo descritivo e transversal buscou determinar a análise citogenética de neoplasias hematológicas frequentes no Paquistão. Um total de 202 amostras de medula óssea periférica ou sangue de pacientes com malignidade hematológica benigna e maligna foi coletado usando uma técnica convencional de banda G. Entre os pacientes inscritos, a média de idade foi de 21,5 anos ± 23,4, e a distribuição por gênero mostrou uma marcada predominância da população masculina de 147 (73%) em comparação com a feminina de 55 (27%). Pacientes na faixa etária (2-10 anos) tiveram a maior frequência, 48 (24%), de neoplasias hematológicas, seguida da idade (11-20 anos) com 40 (20%). Cariótipos normais (46, XX / 46, XY) foram encontrados em 51% (n = 103) dos pacientes. Além disso, a frequência de cariótipo complexo foi de 30 (15%), enquanto normal foi observada em 171 (85%) pacientes. Leucemia linfoblástica aguda pré-B (LLA Pré-B) foi a doença maligna mais prevalente de 66 (33%), seguida por leucemia mieloide crônica (LMC) de 41 (20%) e leucemia linfocítica aguda de 29 (14%). A translocação foi o 50 mais prevalente (25%), seguido por hipotriploidia 14 (7%) e monossomia 8 (4%) na análise de aberração cromossômica. Além disso, a translocação t (9:22) encontrada foi de 20 (10%) na LMC, com a maioria na faixa etária (31-40 anos). Este estudo recomenda que o cariótipo deve ser testado com frequência em condições hematológicas porque pode fornecer informações sobre as alterações cromossômicas relativas associadas a doenças malignas específicas.

Early integration of palliative care in hematology: an urgency for patients, a challenge for physicians

ABSTRACT Introduction: Early integration between palliative care and other medical specialties in the care of patients with serious illnesses is consolidating itself as good medical practice, based on scientific and ethical evidence. Despite this, palliative care is still not part of the routine care of patients with hematological diseases, even in specialized centers. Objective and method: In this article, we review the benefits and the main barriers described in the literature for early integration of hematology and palliative care. We also point out the challenges encountered in clinical practice, such as end-of-life prognosis assessment in patients with hematological diseases and management of the most common symptoms in hematology. Finally, we review models of integration between palliative care and oncology centers in outpatient and inpatient settings. Results and conclusion: Patients with hematological diseases can greatly benefit from early integration with palliative care, with improvement in symptom control, quality of life, reduction of emotional distress and the development of advanced care directives. It is necessary to make hematologists aware of the benefits of palliative care, provide adequate training for multidisciplinary teams and encourage specific studies of palliative care in patients with hematological diseases.

Expansion of cord blood stem cells in fibronectin-coated microfluidic bioreactor

ABSTRACT Background: Hematopoietic stem/progenitor cell transplantation is the main treatment option for hematological malignancies and disorders. One strategy to solve the problem of low stem cell doses used in transplantation is pre-transplant expansion. We hypothesized that using fibronectin-coated microfluidic channels would expand HSPCs and keep self-renewal potential in a three-dimensional environment, compared to the conventional method. We also compared stem cell homing factors expression in microfluidic to conventional cultures. Materials and methods: A microfluidic device was created and characterized by scanning electron microscopy. The CD133+ cells were collected from cord blood and purified. They were subsequently cultured in 24-well plates and microfluidic bioreactor systems using the StemSpan serum-free medium. Eventually, we analyzed cell surface expression levels of the CXCR4 molecule and CXCR4 mRNA expression in CD133+ cells cultured in different systems. Results: The expansion results showed significant improvement in CD133+ cell expansion in the microfluidic system than the conventional method. The median expression of the CXCR4 in the expanded cell was lower in the conventional system than in the microfluidic system. The CXCR4 gene expression up-regulated in the microfluidic system. Conclusion: Utilizing microfluidic systems to expand desired cells effectively is the next step in cell culture. Comparative gene expression profiling provides a glimpse of the effects of culture microenvironments on the genetic program of HSCs grown in different systems.

Aspectos clínicos do câncer durante o período gestacional: desafios diagnósticos e terapêuticos / Clinical aspects of cancer during the gestational period: diagnostic and therapeutic challenges

O câncer é uma das maiores causas de morte em mulheres na idade reprodutiva e ocorre em aproximadamente 0,05% a 0,1% das gestações. Os cânceres ginecológicos, de mama, tireoide e hematológicos são os mais comuns na gravidez. O obstetra é o principal médico para investigar sintomas que podem estar relacionados à malignidade. O diagnóstico pode ser dificultado devido à sobreposição de sintomas da gravidez, como náusea, vômitos, aumento do útero e das mamas, dor abdominal, além da limitação para uso de exames de imagem e alterações comuns em exames laboratoriais. O risco e o benefício do diagnóstico e o tratamento para o bem-estar materno e fetal devem ser avaliados com cuidado pelos profissionais envolvidos. Este artigo tem como objetivo realizar uma revisão sobre quando suspeitar e como investigar os principais cânceres na gestação.(AU)

Cancer is the major cause of death in women on reproductive age and occurs in approximately 0.05% to 0.1% of pregnancies. Gynecological, breast, thyroid and hema- tological cancers are the most common in pregnancy. The obstetrician is the primary physician to investigate symptoms that may be related to malignancy. The diagnosis can be difficult due to the overlap of pregnancy symptoms, such as nausea, vomiting, enlargement of the uterus and breasts, abdominal pain, in addition to the limitation for the use of imaging tests and common changes in laboratory tests. The risk and be- nefit of diagnosis and treatment for maternal and fetal well-being should be carefully assessed by the professionals involved. This article aims to conduct a review on when to suspect and how to investigate the main cancers in pregnancy.(AU)

Aplicación del índice de mortalidad pediátrica 3 y evaluación de falla orgánica secuencial pediátrica en una unidad de cuidados intensivos en México / Implementation of the Pediatric Index of Mortality 3 and the pediatric Sequential Organ Failure Assessment in an intensive care unit in Mexico

Introducción. El objetivo del estudio fue analizar el índice de mortalidad pediátrica 3 (PIM 3) y la evaluación de falla orgánica secuencial pediátrica (pSOFA) para predicción de muerte. Métodos. Estudio observacional prospectivo; se incluyeron pacientes de 1 mes a 17,9 años. La precisión se evaluó con el área bajo la curva (AUC) y se estimó la tasa de mortalidad estandarizada. Resultados. Se estudiaron 244 ingresos; la mediana de edad fue 60 meses. Los diagnósticos principales fueron neoplasias sólidas o hematológicas (26,5 %). La mortalidad por ingresos fue del 18 % (44/244). Para PIM 3 el AUC fue de 0,77 y para pSOFA, de 0,81; ambas escalas mostraron adecuada calibración (p > 0,05). La tasa de mortalidad estandarizada fue de 1,91. Conclusiones. Identificamos que las escalas de evaluación de mortalidad PIM 3 y pSOFA muestran capacidad de discriminación aceptable. En pacientes con neoplasias sólidas o hematológicas, PIM 3 no mostró adecuada calibración.

Introduction. The study objective was to analyze the Pediatric Index of Mortality 3 (PIM 3) and the pediatric Sequential Organ Failure Assessment (pSOFA) for the prediction of mortality. Methods. Observational, prospective study; patients aged 1 month to 17.9 years were included. Assessment of area under the curve (AUC) accuracy and estimation of standardized mortality rate. Results. A total of 244 admissions were studied: median age was 60 months. The main diagnoses were solid or hematologic neoplasms (26.5%). The mortality by admission was 18% (44/244). The AUC was 0.77 for PIM 3 and 0.81 for pSOFA; both scales showed an adequate calibration (p > 0.05). The standardized mortality rate was 1.91. Conclusions. We identified that the PIM 3 and pSOFA have an acceptable discrimination power. The calibration of the PIM 3 was not adequate in patients with solid or hematologic neoplasms.

Resignificación de la vida por parte de jóvenes sobrevivientes al cáncer hematológico / Resignification of Life by Young People Survivors of Hematologic Cancer

Introducción: Los jóvenes con enfermedades oncológicas enfrentan dificultades durante los períodos de diagnóstico, tratamiento y recuperación. Estos procesos complejos cargados de experiencias vitales inusitadas producen la transformación de su conciencia y los lleva a construir nuevos significados en la manera de comprender, relacionarse y actuar en el mundo que los rodea. Objetivo: Comprender el (re)significado de la vida a partir de la experiencia de los jóvenes que sobrevivieron al cáncer hematológico. Métodos: Estudio cualitativo, que utilizó la Teoría Fundamentada en Datos como metodología y el referencial de la Teoría de la Complejidad de Morin. Se realizaron entrevistas en profundidad a 12 adolescentes sobrevivientes de cáncer hematológico. El tamaño de muestra fue determinado al alcanzar nivel de saturación. El análisis fue simultáneo durante la recolección de los datos, mediante codificación abierta, axial y selectiva según lo señalan Strauss y Corbin. Resultados: Emergieron dos categorías: Reorganizando su vida por medio de cambios y aprendizajes para vencer al cáncer y, Asumiendo una mejor comprensión y compromiso con los demás y consigo mismo. Conclusiones: Las experiencias vividas por jóvenes sobrevivientes que padecen de cáncer modifican su forma de vivir y se tornan más comprensivos con el sufrimiento que ocasiona la enfermedad. Esta situación los hace más solidarios y comprometidos con su contexto social sobre todo con su familia y con pacientes oncológicos(AU)

Introduction: Young people with oncological diseases face difficulties during the periods of diagnosis, treatment and recovery. These complex processes loaded with unusual life experiences produce the transformation of their consciousness and lead them to construct new meanings in the way that they understand, relate and act in the world around them. Objective: To understand the (re)signification of life from the experience of young survivors of hematological cancer. Methods: A qualitative study was carried out, using the data driven theory as the methodology and Morin's complexity theory as the referent. In-depth interviews were conducted with twelve adolescent hematologic cancer survivors. The sample size was determined by reaching the saturation level. The analysis was simultaneous during data collection, using open, axial and selective coding according to Strauss and Corbin. Results: Two categories emerged: 1. reorganizing their life through changes and learning to overcome cancer and 2. assuming a better understanding and commitment to others and to themselves. Conclusions: The experiences lived by young cancer survivors modify their way of living as they become more understanding of the suffering caused by the disease. This situation makes them more supportive and committed to their social context, especially with their family and with cancer patients(AU)

Técnicas de citogenética para el estudio de las leucemias / Cytogenetic techniques for the study of leukemias

Introducción: La leucemia se define como un proceso clonal de células hematopoyéticas, que se origina cuando las células sanguíneas que se producen en la médula ósea, cambian y se multiplican sin control. Esta se caracteriza por su heterogeneidad genética y se explica a través de mecanismos causados por alteraciones cromosómicas utilizados en la práctica clínica diaria como biomarcadores útiles para el diagnóstico, el pronóstico o la predicción de respuesta al tratamiento. Objetivo: Describir las técnicas de citogenética convencional y molecular para el diagnóstico y seguimiento de las leucemias. Métodos: Se realizó una revisión de la literatura en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google Académico, de artículos publicados en los últimos cinco años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: En el transcurso de los años la citogenética ha proporcionado información crucial para el diagnóstico y el pronóstico de las neoplasias hematológicas. Tanto las técnicas de citogenética convencional y molecular, como la hibridación in situ fluorescente, la hibridación in situ fluorescente multicolor, el cariotipo espectral, la hibridación genómica comparada y los microarreglos, participan en el reconocimiento de alteraciones cromosómicas y de genes, así como de interacciones involucradas en el proceso de oncogénesis. Conclusiones: Las técnicas de citogenética contribuyen al diagnóstico, a la estratificación pronóstica y a la aplicación del tratamiento según el tipo o subtipo de leucemia(AU)

Introduction: Leukemia is defined as a clonal process of hematopoietic cells, which occurs when blood cells that are produced in the bone marrow change and multiply uncontrollably. This is characterized by its genetic heterogeneity and is explained through mechanisms caused by chromosomal alterations that are used in daily clinical practice as useful biomarkers for diagnosis, prognosis or prediction of response to treatment. Objective: To describe the conventional and molecular cytogenetic techniques used for the diagnosis and monitoring of leukemias. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine Google, for articles published in the last five years. We performed analysis and summary of the reviewed bibliography. Analysis and synthesis of information: Cytogenetics over the years has provided crucial information for the diagnosis and prognosis of hematologic malignancies. Both conventional and molecular cytogenetic techniques such as fluorescent in situ hybridization, multicolor fluorescent in situ hybridization, spectral karyotype, comparative genomic hybridization and microarrays, participate in the recognition of chromosomal and gene alterations, as well as interactions involved in the oncogenesis process. Conclusions: These cytogenetic techniques contribute to the diagnosis, prognostic stratification and application of treatment according to the type or subtype of leukemia(AU)

Enfermedad tromboembólica venosa en hemopatías malignas: un enfoque desde la prevención / Venous thromboembolic disease in hematologic malignancies: a preventive approach

Introducción: La enfermedad tromboembólica venosa es una complicación frecuente en las hemopatías malignas, con incidencia similar a la observada en tumores sólidos de alto riesgo trombótico. Objetivo: Describir la influencia de factores de riesgo y biomarcadores de la enfermedad tromboembólica venosa asociada a hemopatías malignas y su aplicación en el diseño de modelos de evaluación de riesgo para la prevención de esta enfermedad. Métodos: Se realizó una revisión exhaustiva en la literatura especializada de artículos publicados sobre la temática a través de las bases de datos: PubMed, SciELO, ScienceDirect, Medline y el motor de búsqueda Google académico. Análisis y síntesis de la información: En pacientes con hemopatías malignas han sido descritos múltiples factores de riesgo para la ocurrencia de eventos tromboembólicos venosos: moleculares, relacionados con el paciente, la enfermedad y el tratamiento, así como biomarcadores de riesgo. Basados en ellos, varias investigaciones han sido desarrolladas para elaborar y validar modelos predictivos de enfermedad tromboembólica venosa que guíen la estratificación del riesgo y el tratamiento profiláctico de esta enfermedad en hemopatías malignas, aunque aún son insuficientes. Enfermedades como los linfomas y el mieloma múltiple tienen más investigaciones en esta área que el resto de las hemopatías malignas. Conclusión: Se necesita diseñar nuevos modelos de riesgo y validar los existentes en un mayor número de casos; así como desarrollar estudios prospectivos en pacientes con riesgo de eventos tromboembólicos y hemopatías malignas, para realizar una estrategia de prevención primaria personalizada con estratificación de la tromboprofilaxis(AU)

Introduction: Venous thromboembolic disease is a frequent complication in hematologic malignancies with incidence similar to that observed in solid tumors with high thrombotic risk. Objective: To describe the influence of risk factors and biomarkers of venous thromboembolic disease associated with hematologic malignancies and their application in the design of risk assessment models for the prevention of this disease. Methods: An exhaustive review was carried out in the specialized literature of articles published on the subject using the following databases: PubMed, SciELO, ScienceDirect, Medline and the academic Google search engine. Analysis and synthesis of the information: Multiple risk factors for the occurrence of venous thromboembolism have been described in patients with hematologic malignancies: patient-related, disease-related, treatment-related and molecular, as well as biomarkers of risk. Based on these, several investigations have been developed to elaborate and validate predictive venous thromboembolism models to guide risk stratification and prophylactic treatment of venous thromboembolic disease in hematologic malignancies, although they are still insufficient. Lymphomas and multiple myeloma have more research in this area than other hematologic malignancies. Conclusion: There is a need to design new risk models and validate existing ones in a larger number of cases, as well as to develop prospective studies in patients at risk of thromboembolic events and hematologic malignancies, to carry out a personalized primary prevention strategy with thromboprophylaxis stratification(AU)

Linfoma del tejido linfoide asociado a las mucosas en paciente con tiroiditis de Hashimoto / Mucosa-associated lymphoid tissue lymphoma in a patient with Hashimoto's thyroiditis

RESUMEN El linfoma del tejido linfoide asociado a las mucosas es una variedad poco común y recientemente descubierta del linfoma no Hodgkin. Suele presentarse en la sexta década de la vida, con un predominio del sexo femenino y en sitios como el tracto digestivo, pulmón, riñón, hígado, piel, y solo en el 2 % de los casos, en la glándula tiroides, donde en muchas ocasiones se asocia a la tiroiditis autoinmune de Hashimoto. Su evolución es favorable cuando se diagnostica en estadios iniciales de la enfermedad. Se presenta una paciente de 22 años, con una historia de trastornos endocrinos, perceptibles desde la adolescencia, a quien se le diagnosticó una tiroiditis de Hashimoto, sobre la que subyacía un linfoma del tejido linfoide asociado a las mucosas, y que evolucionó satisfactoriamente luego del tratamiento quirúrgico.

ABSTRACT Mucosa-associated lymphoid tissue lymphoma is a rare and recently discovered variant of non-Hodgkin's lymphoma. It usually occurs in the sixth decade of life, with a predominance of females and may be observed in sites such as the digestive tract, lung, kidney, liver, skin, and only in 2% of cases, in the thyroid gland, where in many occasions it is associated with Hashimoto's autoimmune thyroiditis. Its evolution is favorable when it is diagnosed in the initial stages of the disease. We present a 22-year-old female patient with a history of perceptible endocrine disorders since adolescence, who was diagnosed with Hashimoto's thyroiditis, underlying mucosa-associated lymphoid tissue lymphoma, and who evolved satisfactorily after surgical treatment.

Proportion of hematological cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic: A systematic review and meta-analysis

Introduction The coronavirus disease-2019 (COVID-19) has emerged as a novel infection which has spread rapidly across the globe and currently presents a grave threat to the health of the cancer patient. Objective The aim of this meta-analysis was to evaluate the proportion of hematological cancer patients with the SARS-CoV-2 infection during the COVID-19 pandemic. Method A comprehensive literature review was performed on PubMed, Web of Science, Scopus, EKB SciELO, SID, CNKI and Wanfang databases to retrieve all relevant publications up to January 31, 2021. Observational studies, consecutive case-series and case-control studies were included. The proportion for hematological cancer patients with COVID-19 was estimated using the odds ratios (ORs) and 95% confidence interval (95% CIs). Results Fourteen studies with a total of 3,770 infected cancer patients and 685 hematological cancer cases with COVID-19 were selected. Combined data revealed that the overall proportion of hematological cancer patients with COVID-19 was 16.5% (95% CI 0.130 - 0.208, p ≤ 0.001). The stratified analysis by ethnicity showed that the proportion was 18.8% and 12.4% in Caucasian and Asian hematological cancer patients with COVID-19, respectively. Moreover, subgroup analysis by country of origin showed that its proportion was the highest in the United Kingdom (22.5%), followed by France (17.1%) and China (8.2%). Conclusion This meta-analysis result indicated that the proportion of hematological cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic was 16.5%. Further larger sample sizes and multicenter studies among different ethnic groups are necessary to get a better assessment of the proportion.

Can SARS-CoV-2 induce hematologic malignancies in predisposed individuals? A case series and review of the literature

Abstract Introduction Coronavirus disease 2019 (COVID-19) may present with extrapulmonary manifestations, including hematologic changes. Previous studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) can interact with the renin-angiotensin system, ultimately causing increased production of angiotensin II. By reporting the cases of previously healthy young adults diagnosed with a hematologic malignancy after experiencing COVID-19, we raise the hypothesis that the SARS-Cov-2 infection could act as a trigger for leukemogenesis in predisposed individuals. Methods This was a case series performed through extraction of relevant clinical information from the medical records of three patients admitted to our Hematology unit between August 2020 and September 2020. Main Results Considering the relatively rapid development of cytopenias following recovery from COVID-19, it cannot be ruled out that SARS-Cov-2 played a role in leukemogenesis in those patients. Based on previous in vitro studies, the renin-angiotensin system imbalance induced by SARS-CoV-2 could potentially promote in vivo leukemogenesis through several mechanisms. Conclusion Despite the advances in pathophysiological and clinical characterization of COVID-19, the consequences of the pandemic to the incidence of hematologic diseases are still to be elucidated. In this context, future dissection of the status of the local bone marrow renin-angiotensin system in leukemogenesis is a clinically relevant basic research area.

Gestão do cuidado ao paciente com doença hemato-oncológica sob a perspectiva do SUS: análise de hospitalizações e avaliação econômica do daratumumabe no tratamento do mieloma múltiplo / Health care manegement for patients with hematologic malignances from the perspective of the Brazilian Public Health System: analysis of hospitalizations and economic evaluation of daratumumab in the treatment of multiple myeloma

Com o objetivo de contribuir para a gestão do Sistema único de Saúde (SUS) no que se refere às neoplasias hematológicas (NH), este trabalho apresenta a elaboração de dois estudos: (a) analise de custos por hospitalização por NH, e (b) avaliação de custo-efetividade da adição de daratumumabe ao esquema de tratamento do Mieloma Múltiplo (MM) em pacientes não elegíveis para transplante autológico de células tronco hematopoiéticas (TCTH). Por meio da extração de dados do sistema de internações hospitalares do SUS, desenvolveu-se uma análise retrospectiva descritiva de frequências e custos das internações por NH de acordo com sua distribuição temporal, espacial (por estados e regiões), e por patologia, na década compreendida entre os anos de 2010 e 2019. Foram também calculados custo médio pro procedimento e taxa de acesso. Foi observado que houve uma tendência de crescimento estável das frequências e dos custos ao longo do período analisado. Além disso, contatou-se uma significativa discrepância na frequência dos procedimentos entre as regiões Norte e Sudeste, que registraram o menor e o maior número de procedimentos, respectivamente. Observou-se também eu a frequência das internações por patologia não refletiu a incidência estimada pela literatura no país para cada uma das patologias avaliadas. Para o estudo de custo-efetividade, foi desenvolvido um modelo de simulação de sobrevida particionado para a adição do daratumumabe ao esquema de tratamento composto por bortezomibe, melfalano e prednisona (VMP). O horizonte temporal de 30 anos e a perspectiva de análise do SUS, foram usados. Com base nos dados da literatura foi possível observar que a adição deste medicamento ao VMP no tratamento desses pacientes pode aumentar a sobrevida global e a sobrevida livre de progressão. Considerados os custos relacionados a esta tecnologia e ao manejo do paciente no cenário brasileiro, no entanto, a inclusão do daratumumabe está aparentemente acima do limiar de aceitabilidade adotado pelo SUS. Para que esta estratégia seja custo-efetiva no cenário observado, a tecnologia precisaria sofrer uma redução de quase 50% no custo. O estudo, portanto, não recomenda a adição do daratumumabe ao VMP no tratamento do MM em pacientes não elegíveis para TCTH.

Aiming to contribute to the management of the Brazilian Public Health System (SUS) regarding hematologic malignances (NH), this work presents the development of two studies: (a) cost analysis per hospitalization for NH, and (b) cost-effectiveness evaluation of adding daratumumab to the treatment scheme for Multiple Myeloma (MM) in patients not eligible for autologous hematopoietic stem cell transplantation (TCTH). By extracting data from the SUS hospital admissions system, we developed a retrospective descriptive analysis of frequencies and costs of NH admissions according to their temporal, spatial distribution (by states and regions), and by pathology, in the decade between the years 2010 and 2019. Average cost per procedure and access rate were also estimated. It was observed that there was a stable growth trend in frequencies and costs over the analyzed period. Furthermore, a significant discrepancy in the procedure frequency was found between the North and Southeast regions, which recorded the lowest and highest number of procedures, respectively. It was also observed that the frequency of hospitalizations per pathology did not reflect the incidence estimated by the literature in the country for each of the pathologies evaluated. For the cost-effectiveness study, a partitioned survival simulation model was developed for the inclusion of daratumumab in the treatment scheme consisting of bortezomib, melphalan, and prednisone (VMP). A 30-year time horizon and the perspective of the SUS were used for the analysis. Based on literature data, it was possible to observe that the inclusion of this drug to VMP in the treatment of these patients can increase overall survival and progression-free survival. Considering the costs related to this technology and patient management in the Brazilian scenario, however, the inclusion of daratumumab is seemingly above the threshold of acceptability adopted by SUS. For this strategy to be cost-effective in the observed scenario, the technology would require a cost reduction of almost 50%. The study, therefore, does not recommend the inclusion of daratumumab to VMP in the treatment of MM in patients not eligible for TCTH.

Terapia com células CAR-T: reprogramação celular para o combate de neoplasias malignas / CAR-T cell therapy: cell reprogramming to combat malignant neoplasms

As células CAR-T são linfócitos geneticamente modificados para reconhecerem um espectro amplo de antígenos de superfície celulares. Além disso, atacam células tumorais malignas, que expressam esses antígenos, por meio da ativação da coestimulação citoplasmática, secreção de citocinas, citólise de células tumorais e proliferação de células T. O objetivo desse estudo é abordar a imunoterapia com células CAR-T, a fim de explicar seu conceito, processo de fabricação e papel no tratamento de neoplasias hematológicas e tumores sólidos. Foi realizada uma revisão através do portal PubMed, utilizando como descritores: "car-t cell therapy" e "neoplasms", determinados com base nos "Descritores em Ciências da Saúde". Foram obtidos, inicialmente, 10 artigos, os quais foram lidos integralmente para a confecção dessa revisão. Além disso, foram adicionados 3 ensaios clínicos atualizados sobre o tema. Na terapia com células CAR-T, as células T são coletadas do paciente, geneticamente modificadas para incluir receptores de antígeno específicos e, posteriormente, expandidas em laboratórios e transfundidas de volta para o paciente. Assim, esses receptores podem reconhecer células tumorais que expressam um antígeno associado a um tumor. A terapia com células CAR-T é mais conhecida por seu papel no tratamento de malignidades hematológicas de células B, sendo a proteína CD19 o alvo antigênico mais bem estudado até o momento. Entretanto, estudos estão sendo feitos para verificar a eficácia desse tratamento, também, em tumores sólidos. Portanto, apesar de inicialmente ser indicada apenas para um grupo seleto de pessoas, essa terapia tem demonstrado grande potencial para atuar em um espectro maior de pacientes.

The CAR-T cells are lymphocytes genetically modified to recognize a broader spectrum of cell surface antigens. In addition, they attack malignant tumor cells, which express these antigens, by activating cytoplasmic co-stimulation, cytokine secretion, tumor cell cytolysis and T cell proliferation. The aim of this study is to address immunotherapy with CAR-T cells, in order to explain its concept, manufacturing process and role in the treatment of hematological neoplasms and solid tumors. This is a literature review conducted through the PubMed portal, that uses the terms "car-t cell therapy" and "neoplasms" as descriptors, determined based on the DeCS (Descritores em Ciências da Saúde). To prepare this review, initially 10 articles were found and read in full. In addition, 3 updated clinical trials on the subject were added. For CAR-T cell therapy, T cells are collected from the patient, genetically modified to include specific antigen receptors, and later expanded in laboratories and transfused back to the patient. Thus, these receptors can recognize tumor cells that express a tumor-associated antigen. CAR-T cell therapy is best known for its role in the treatment of B cell hematological malignancies, with the CD19 protein being the most studied antigenic target to date. However, studies are being conducted to verify the effectiveness of this treatment, also, in solid tumors. Therefore, despite being formulated only for a selected group of patients, this therapy has great potential to act on a broader spectrum of patients.

Fatores ocupacionais associados a neoplasias hematológicas em um polo fruticultor: estudo de caso-controle / Occupational factors associated with hematological neoplasms in a fruit production pole: a case-control study

Resumo Objetivos: identificar fatores de risco ocupacionais para neoplasias hematológicas, leucemia, linfomas e mieloma múltiplo. Métodos: estudo caso-controle conduzido com casos de neoplasias hematológicas e controles recrutados do mesmo serviço, com outros diagnósticos, pareados por frequência, sexo e idade. Entrevistas individuais foram realizadas por pesquisadores treinados, utilizando um questionário estruturado. Informações sobre a história ocupacional, uso e características de exposições a substâncias químicas, em geral, e a agrotóxicos foram registradas. Foram estimadas odds ratios (OR), por meio de modelos de regressão logística não-condicional multivariável para análise exploratória. Resultados: foram incluídos 61 casos e 146 controles. Trabalho na agropecuária (OR: 2,18; intervalo de confiança de 95% (IC95%): 1,10;4,30), exposição ocupacional a agrotóxicos (OR: 2,37; IC95%: 1,18;4,77), e tempo total de exposição ocupacional a agrotóxicos na vida laboral em horas - curto (OR: 3,52; IC95%: 1,25;9,87) e longo (OR: 3,95; IC95%: 1,54;10,14) - foram fatores de risco para neoplasias hematológicas, em comparação aos não expostos. Essas medidas foram ajustadas por consumo de álcool e tabagismo, prática de atividade física, renda, escolaridade e história de exposição ocupacional a produtos químicos. Conclusão: a exposição ocupacional a agrotóxicos se associa a neoplasias hematológicas, independentemente de características do estilo de vida e nível socioeconômico.

Abstract Objectives: to identify the occupational risk factors for hematological neoplasms, specifically leukemia, lymphomas, and multiple myeloma. Methods: this is a case-control study. Cases were individuals with hematological neoplasms and controls were individuals with other diagnoses; frequency-matched by sex and age. Individual interviews were conducted by trained researchers using a structured questionnaire. We collected information on participants' occupational history and chemicals use and exposure, in general, and pesticides, in particular. Odds ratios (OR) were used as association measurements, estimated by multivariate non-conditional logistic regression models for exploratory analysis. Results: 61 cases and 146 controls were included. We found that agricultural work (OR: 2.18; 95% confidence interval (95%CI): 1.10;4.30), occupational exposure to pesticides (OR: 2.37; 95%CI: 1.18;4.77), and total occupational exposure to pesticides throughout their working life (in hours) - both short (OR: 3.52; 95%CI: 1.25;9.87) and long (OR: 3.95; 95%CI: 1.54;10.14) - constituted risk factors for hematological neoplasms, when compared to those unexposed. We adjusted these measures for alcohol consumption and smoking, physical activity, income, education, and history of occupational exposure to chemicals. Conclusion: occupational exposure to pesticides is associated with hematological neoplasms regardless of lifestyle and socioeconomic status.