Experiencia clínica de uso de Brentuximab-vedotin como terapia de linfoma de Hodgkin recaído o refractario en Hospital Guillermo Grant Benavente, Concepción, Chile / Clinical experience of using brentuximab-vedotin as therapy in relapsed/refractory Hodgkin's lymphoma at Hospital Guillermo Grant Benavente, Concepción, Chile

INTRODUCCIÓN: El linfoma de Hodgkin es una neoplasia de células B de buen pronóstico, pero con mala respuesta a quimioterapia en casos refractarios o recaídas. Brentuximab vedotin es un anticuerpo monoclonal antiCD30 aprobado para su uso en estos casos. El presente trabajo tiene como objetivo describir la experiencia clínica de los pacientes tratados con brentuximab vedotin bajo la modalidad de acceso expandido. MATERIAL Y MÉTODOS: Estudio retrospectivo sobre información clínica de pacientes diagnosticados de linfoma de Hodgkin refractario o en recaída y tratados con brentuximab-vedotin en el Hospital Regional de Concepción en el período 2015-2021. RESULTADOS: Se identificaron 7 pacientes, 5/7 de sexo masculino, con una mediana de edad de 35 años (21-50). Cinco casos fueron celularidad mixta y 2 esclerosis nodular. Cuatro estaban en etapa II, 1/7 en etapa III y 3/7 en etapa IV. La mediana de líneas de tratamiento previas fue 4 (3-5) y en 2 casos la recaída fue postrasplante. En 6/7 casos se empleó como inducción y en un caso se empleó como mantención postransplante autólogo de médula ósea. La administración fue ambulatoria por vía periférica con una mediana de dosis 150 mg y 10 ciclos. En un caso se necesitó ajuste de dosis por toxicidad. Tres de 6 pacientes lograron remisión completa y fueron a trasplante autólogo de médula ósea. CONCLUSIONES: brentuximab vedotin es un medicamento ambulatorio de baja toxicidad que puede optimizar el tratamiento de pacientes con linfoma de Hodgkin recaído-refractario.

INTRODUCTION: Hodgkin's lymphoma is a B-cell neoplasm with a good prognosis but a poor response to chemotherapy in refractory or relapsed cases. Brentuximab-vedotin is an anti-CD30 monoclonal antibody approved for use in these cases. This study aims to describe the clinical experience of patients treated with brentuximab-vedotin through expanded access modality. MATERIALS AND METHODS: A retrospective study on clinical information of patients diagnosed with refractory or relapsed Hodgkin's lymphoma treated with brentuximab-vedotin at the Regional Hospital of Concepción in the period 2015-2021. RESULTS: 7 patients were identified, 5/7 male, with a median age of 35 years (21-50). Five cases were mixed cellularity, and two were nodular sclerosis. Four were in stage II, 1/7 in stage III, and 3/7 in stage IV. The median number of previous treatment lines was 4 (3-5), and the relapse was post-transplantation in two cases. In 6/7 cases, brentuximab-vedotin was used as induction, and in one case, it was used as post-autologous bone marrow transplant maintenance. The administration was outpatient via a peripheral route with a median dose of 150 mg and ten cycles. In one case, dose adjustment was required due to toxicity. Three out of 6 patients achieved complete remission and underwent autologous stem cell transplantation. CONCLUSION: brentuximab-vedotin is an outpatient medication with low toxicity that can optimize the treatment of patients with relapsed-refractory Hodgkin's lymphoma.

Linfoma de Hodgkin: neuronopatía sensitiva y autonómica como manifestación paraneoplásica / Hodgkin's lymphoma: sensitive and autonomic neuropa thy as a paraneoplastic manifestation

Resumen El linfoma de Hodgkin (LH) comprende un grupo heterogéneo de neoplasias linfoides cuyo origen radica en linfocitos B. Las manifestaciones neurológicas de dicha enfermedad son infrecuentes, pudiendo tener su origen por invasión directa de las células neoplásicas en el sistema nervioso, o indirectamente, a través de síndromes paraneoplásicos o como complicación del tratamiento. Dentro de los síndromes neurológicos paraneoplásicos que afectan a pacientes con LH, la degeneración cerebelosa paraneoplásica es la más frecuente. Otros reportados con menor frecuencia en series de casos o casos aislados incluyen encefalitis límbica, neuronopatía sensitiva, motora y autonómica. Estos pueden ser la manifestación inicial de la enfer medad neoplásica, y la falta de conocimiento de dicha asociación puede retrasar el diagnóstico, con inicio tardío del tratamiento y peor pronóstico. Reportamos el caso de una mujer con LH que presentó al inicio de su enfermedad neuronopatía sensitiva y autonómica como manifestaciones neurológicas paraneoplásicas. Una vez iniciado el tratamiento específico para su lin foma, la neuronopatía autonómica tuvo resolución casi completa a diferencia de la neuronopatía sensitiva, la cual demostró escasa recuperación.

Abstract Hodgkin lymphoma (HL) comprises a heterogeneous group of lymphoid neoplasms whose origin lies in B lym phocytes. The neurological manifestations of this pathol ogy are infrequent, and may arise from direct invasion of neoplastic cells to the nervous system, or indirectly, through paraneoplastic syndromes or as a complication of treatment. Among the neurological paraneoplastic syndromes that affect patients with HL, paraneoplastic cerebellar degeneration is the most common. Other few cases include limbic encephalitis, sensory, motor, and autonomic neuronopathy. These syndromes can be the initial manifestation of neoplastic disease, and the lack of information regarding this association can lead to a delay in diagnosis and consequently in the initiation of therapy worsening the prognosis. We report the case of a woman with HL who presented sensory and autonomic neuronopathy at the onset of her disease as paraneo plastic neurological manifestations. After the initiation of the specific treatment for the lymphoma, the autonomic neuronopathy had almost complete resolution, unlike the sensory neuronopathy, which showed limited recovery.

Análisis del manejo del linfoma de Hodgkin clásico durante 10 años en el Hospital Clínico Red Salud UC-Christus con énfasis en el uso del PET CT / Decade of Hodgkin lymphoma: PET CT vs biopsy in single Academic Chilean Center

INTRODUCCIÓN: El Linfoma de Hodgkin (LH) es una causa prevalente de morbilidad por Cáncer Hematológico en el mundo y también en nuestro entorno. OBJETIVOS: Mostrar la experiencia de diez años tratando el LH en un centro docente chileno. Adicionalmente, exponer el rendimiento de diagnóstico del PET CT y la Biopsia de Médula Ósea. MATERIAL Y MÉTODOS: Se realiza un estudio de Cohorte retrospectivo para recopilar datos y resultados de los pacientes tratados en nuestro centro. RESULTADOS: Se analizaron 82 pacientes (edad promedio 35 años. Razón entre hombres y mujeres de 1,9:1). La sobrevida libre de progresión de 88,6% y 66,4% para estadios localizados y avanzados respectivamente. El PET como estrategia de etapificación tuvo mejor sensibilidad al comparar con la Biopsia de Médula. CONCLUSIONES: El resultado clínico de los pacientes tratados en este centro docente chileno fueron comparables a la literatura internacional. Adicionalmente, el PET CT evidenció ser una herramienta superior en el diagnóstico y etapificación superior a la biopsia en nuestros pacientes.

INTRODUCTION: Hodgkin Lymphoma (HL) is a prevalent hematological cancer in the world and Chile. OBJECTIVES: Show the experience of 10 years treating HL in a Chilean academic center. Additionally, it exposes the diagnostic performance of PET CT and Bone Marrow Biopsy. MATERIAL AND METHODS: We conducted a retrospective cohort study to collect data and outcomes of patients treated in our center. RESULTS: 82 patients were analyzed (Average age, 35 years old; the ratio between men and women was 1.9:1). Progression-free survival was 88.6% and 66.4% for localized and advanced stages, respectively. PET as a staging strategy had better sensitivity than Marrow Biopsy. CONCLUSIONS: The clinical results of the patients treated in this Chilean teaching center were comparable to the international literature. Additionally, PET CT proved to be a superior tool in diagnosis and staging compared to biopsy in our patients.

Vírus Epstein-Barr associado ao Linfoma de Hodgkin clássico: um estudo de casos / Epstein-Barr virus associated with classical Hodgkin lymphoma: a case study

Introdução: A expressão da positividade do vírus Epstein-Barr nas células de Reed-Sternberg/Hodgkin e o impacto dessa relação na sobrevida do Linfoma de Hodgkin clássico (LHc) permanecem controversos. Objetivo: Avaliar a presença de Epstein Baar Vírus (EBV) em pacientes com LHc, associando com características anatomopatológicas e clínicas. Materiais e Métodos: Para determinar a presença de EBV, a partir de um material de biópsia de tecidual foi realizada analise por hibridização para RNA codificado para EBV (EBER) e imuno-histoquímica para proteína de membrana latente viral (LMP-1) de uma amostra de demanda de pacientes com diagnóstico entre janeiro de 2009 e janeiro de 2015. As características clínicas avaliadas foram as que compõem o Escore Prognóstico Internacional para estadiamento avançado e os fatores de risco desfavoráveis instituídos pelo Grupo Alemão de Estudos em Hodgkin para estadiamento limitado. Posteriormente, tais características foram relacionadas com a situação do vírus nas células tumorais. Resultados: Foram avaliadas as lâminas de biópsia de 29 pacientes com diagnóstico de Linfoma de Hodgkin. Em relação as características histológicas, o subtipo histológico de celularidade mista apresentou associação estatística com EBV positivo (p= 0,02). Além disso, a presença de EBV foi mais comum em pacientes com 45 anos ou mais (p= 0,07). Embora sem significância estatística, houve uma tendência de melhor sobrevida livre de eventos (p= 0,07), para os pacientes EBV positivo. Conclusão: O subtipo histológico de celularidade mista, apresentou uma relação estatisticamente significativa com a presença de EBV nas células tumorais, em conformidade com a literatura. São necessários estudo com maior número de casos para que se possa entender melhor a relação entre a presença de EBV e o prognóstico do LHc em nosso meio.

Introduction: The expression of Epstein-Barr virus positivity in Reed-Sternberg/Hodgkin cells and the impact of this relationship on survival in classical Hodgkin Lymphoma (cHL) remain controversial. Objective: To evaluate the presence of Epstein Baar Virus (EBV) in patients with cHL, associating it with anatomopathological and clinical characteristics.Materials and Methods: To determine the presence of EBV, analysis was carried out using a tissue biopsy material by hybridization for EBV-encoded RNA (EBER) and immunohistochemistry for viral latent membrane protein (LMP-1) from a demand sample of patients diagnosed between January 2009 and January 2015. The clinical characteristics evaluated were those that make up the International Prognostic Score for advanced stage and the unfavorable risk factors established by the German Hodgkin Study Group for limited stage. Subsequently, these characteristics were related to the status of the virus in tumor cells. Results: Biopsy slides from 29 patients diagnosed with Hodgkin's Lymphoma were evaluated. Regarding histological characteristics, the histological subtype of mixed cellularity showed a statistical association with positive EBV (p= 0.02). Furthermore, the presence of EBV was more common in patients aged 45 years or older (p= 0.07). Although not statistically significant, there was a trend towards better event-free survival (p= 0.07) for EBV positive patients. Conclusion: The histological subtype of mixed cellularity showed a statistically significant relationship with the presence of EBV in tumor cells, in accordance with the literature. Studies with a larger number of cases are needed to better understand the relationship between the presence of EBV and the prognosis of cHL in our country.

Effects of macrophages under the influence of tuberculosis antigen Ag85 on the proliferation and apoptosis of Hodgkin lymphoma KM-H2 cells / 白血病·淋巴瘤

Objective:To explore the effects of macrophages after influenced by tuberculosis antigen Ag85 on the proliferation and apoptosis of Hodgkin lymphoma cells, and to discuss the possible role of tuberculosis infection in the progression of Hodgkin lymphoma.Methods:The indirect co-culture system between Hodgkin lymphoma cell line KM-H2 and human monocytic leukemia cell line THP-1 (simulated macrophage) was established by using Transwell nesting. KM-H2 cells were cultured as KM-H2 group alone, KM-H2 cells interfered with Ag85 were taken as KM-H2+Ag85 group, and KM-H2 cells co-cultured with THP-1 cells were taken as KM-H2+THP-1 group. The co-culture system of KM-H2 cells and THP-1 cells interfered by Ag85 was taken as KM-H2+THP-1+Ag85 group. The proliferation of KM-H2 cells in each group was detected by using CCK-8 assay, and the growth curve was drawn. The apoptosis of cells in each group was detected by using flow cytometry. The mRNA expression levels of p53, c-myc, bcl-2 and vascular endothelial growth factor receptor 3 (VEGFR3) in each group were detected by using quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). The expressions of bax and bcl-2 proteins were detected by using Western blotting.Results:The cell proliferation ability of KM-H2+Ag85 group was higher than that of KM-H2 group (all P = 0.001) after 24 and 48 h culture, but the cell proliferation ability of KM-H2+THP-1 group was lower than that of KM-H2 group after 24 h, 48 h and 72 h culture (all P < 0.05). The cell proliferation ability of KM-H2+THP-1+Ag85 group was lower than that of KM-H2 group after 48 h and 72 h culture (all P < 0.05), but the cell proliferation ability of KM-H2+THP-1+Ag85 group was enhanced after 24 h and 48 h culture compared with KM-H2+THP-1 group, and there was no statistically significant difference between the two groups after 72 h culture ( P > 0.05). The apoptosis rate of KM-H2+Ag85 group was lower than that of KM-H2 group [(0.92±0.80)% vs. (6.02±1.63)%, P < 0.001], and the apoptosis rate of KM-H2+THP-1 group [(8.57±0.57)%] was higher than that of KM-H2 group ( P < 0.05). The apoptosis rate [(0.60±0.13)%] in KM-H2+THP-1+Ag85 group was lower than that in KM-H2+THP-1 group ( P < 0.001). The relative expression of bcl-2 and VEGFR3 mRNA in KM-H2+Ag85 group was higher than that in KM-H2 group ( P = 0.018, P = 0.017), while the relative expression of c-myc mRNA in KM-H2+Ag85 group was lower than that in KM-H2 group ( P = 0.016), and there was no statistically significant difference of p53 mRNA relative expression level between the both groups ( P > 0.05).The relative expression of p53 mRNA in KM-H2+THP-1+Ag85 group was lower than that in KM-H2+THP-1 group ( P = 0.048), while the relative expressions of bcl-2 and VEGFR3 mRNA in KM-H2+THP-1+Ag85 group were higher than those in KM-H2+ THP-1 group ( P = 0.016; P = 0.021). The expression of bax protein in KM-H2+Ag85 group was lower than that in KM-H2 group ( P = 0.019), and bcl-2 protein was more than that in KM-H2 group ( P = 0.001). The expression of bax protein in KM-H2+THP-1+Ag85 group was lower than that in KM-H2+THP-1 group ( P = 0.011), but there was no statistically significant difference in the expression of bcl-2 protein between the two groups ( P > 0.05). Conclusions:Tuberculosis antigen Ag85 may inhibit the apoptosis of Hodgkin lymphoma KM-H2 cells and enhance the proliferative activity by affecting the function of macrophages.

Linfoma de Hodgkin pulmonar primario

Se presenta el caso de una mujer de 25 años con tos, fiebre, disnea y dolor pleurítico de tres meses de evolución, con una lesión cavitante en la tomografía de tórax. Ella recibió tratamiento antituberculoso en otra institución de salud sin respuesta favorable. Se le realizó biopsia por toracoscopía que reveló presencia de células de Reed Sternberg consistentes con el subtipo de esclerosis nodular del Linfoma de Hodgkin. La paciente cumplió los criterios de linfoma de Hodgkin pulmonar primario, entidad extremadamente infrecuente y muy poco reportada.

We present the case of a 25-year-old woman with a three-month history of cough, fever, dyspnea, pleuritic pain, and a cavitating lesion on chest tomography. She received antituberculous treatment in another health institution without a favorable response. A thoracoscopic biopsy revealed the presence of Reed Sternberg cells consistent with the nodular sclerosis subtype of Hodgkin's lymphoma. The patient met the criteria for primary pulmonary Hodgkin's lymphoma, an extremely infrequent and rarely reported entity. A brief review of the literature is carried out.

Overall survival in Chilean patients with lymphoma and human immunodeficiency virus: A retrospective cohort study

ABSTRACT Introduction: People living with human immunodeficiency virus (PLWH) still face high morbidity and mortality resulting from lymphoma. Aim: To describe a population of PLWH and lymphoma in a Chilean public hospital and compare the overall survival (OS) with a previously reported cohort from the same institution. Methods: Retrospective single-center cohort study. All the patients diagnosed between 2010 and 2017 were included. Demographic and clinical variables were obtained from medical records. The overall survival (OS) was estimated in treated patients from diagnosis until death or October 2020. The OS was then compared with a cohort of patients diagnosed between 1992 and 2008. Main Results: Eighty-four patients were included. The most common histological types were Burkitt's lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), Hodgkin's lymphoma (HL) and plasmablastic lymphoma (PBL) at 31%, 27%, 21% and 14%, respectively. The three-year OS for the whole cohort of BL, DLBCL, HL and PBL was 58.9%, 65.2%, 47.4%, 76.4% and 50%, respectively. Compared to the cohort of 1992 to 2008, a global increase in the OS was found after excluding HL and adjusting for age and clinical stage (HR 0.38, p = 0.002). However, when the main types were analyzed individually, the increase in the OS was statistically significant only in DLBCL (HR 0.29, p = 0.007). Most patients with DLBCL received CHOP chemotherapy, as in the previous cohort. Conclusion: The OS has improved in this population, despite no major changes in chemotherapy regimens, mainly due to the universal access to antiretroviral therapy.

Expresión del ligando de proteína de muerte programada 1 (PD-L1) en linfoma de Hodgkin en pacientes peruanos / Programmed death-ligand 1 (PD-L1) expression in Hodgkin's lymphoma among Peruvian patients

RESUMEN Objetivo: Diversos estudios realizados sobre el linfoma de Hodgkin (LH) han determinado la expresión de la proteína de muerte programada (PD-L1) en las células de Reed-Sternberg-Hodgkin (HRS), con resultados variables. Esta proteína ha adquirido relevancia por su papel en la respuesta inmunitaria en las neoplasias malignas. El objetivo de este trabajo fue determinar la expresión inmunohistoquímica de PD-L1 en las HRS y su relación con la edad, sexo, estadio clínico y supervivencia global en una cohorte de pacientes peruanos. Materiales y métodos: Se evaluaron 25 biopsias de pacientes con diagnóstico de LH, lo que permitió determinar la expresión inmunohistoquímica de PD-L1 en las HRS en asociación con la sobrevida global (SG) y los datos clínicos de los pacientes. Resultados: Todos los casos mostraron expresión de PD-L1 en más del 1 %. No hubo diferencia estadística significativa en la SG cuando se comparó dos grupos de acuerdo con la expresión de PD-L1 con punto de corte en 50 %, ni tampoco con el estadio clínico (EC), la edad y el sexo. Conclusiones: Se ha encontrado una alta expresión de PD-L1 en los tumores con LH previos al tratamiento. No se ha encontrado asociación entre la expresión de PD-L1, la SG, la edad, el sexo o el EC. Son necesarios otros estudios con mayor cantidad de pacientes para reevaluar el impacto pronóstico de la expresión de esta proteína en LH.

ABSTRACT Objective: Various studies on Hodgkin's lymphoma (HL) have determined programmed death-ligand 1 (PD-L1) expression in Hodgkin and Reed-Sternberg (HRS) cells, with variable results. This protein has gained relevance for its role in the immune response in malignant neoplasms. This work aimed to determine PD-L1 immunohistochemical expression in HRS cells and its relationship with age, sex, clinical stage and overall survival (OS) in a cohort of Peruvian patients. Materials and methods: Twenty-five (25) biopsies from patients diagnosed with HL were assessed, which allowed determining PD-L1 immunohistochemical expression in HRS cells in relation to OS and clinical data of the patients. Results: All cases showed PD-L1 expression in more than 1 % of tumor cells. There was no statistically significant difference in OS when two groups were compared in terms of PD-L1 expression with a cut-off point of 50 %, clinical stage (CS), age and sex. Conclusions: High PD-L1 expression was found in pre-treatment HL tumors. No association was found between PD-L1 expression, OS, age, sex or CS. Further studies with a larger number of patients are necessary to reassess the prognostic impact of the expression of this protein in HL.

Reactivación de brucelosis en paciente receptor de trasplante hematopoyético autólogo: reporte de caso / Reactivation of brucellosis in an autologous hematopoietic transplant recipient: a case report

Introducción: La brucelosis es la zoonosis más frecuente, producida por el género brucella, que afecta a varias especies de mamíferos y dentro de ellos a los humanos. Se transmite al hombre por contacto directo con los animales infectados, por sus excretas o por la ingestión de productos no pasteurizados. En los últimos años se ha descrito un incremento de la enfermedad en los pacientes inmunocomprometidos. Objetivo: Describir la reactivación de la brucelosis en paciente receptor de un trasplante hematopoyético, su curso y manejo. Presentación de caso: Se presenta una paciente con linfoma de Hodgkin y antecedentes de brucelosis que recibió un trasplante hematopoyético autólogo mieloablativo. Después de la recuperación hematológica, inició con cuadro de fiebre, diaforesis, dolores articulares y hepato-esplenomegalia. Se le diagnosticó brucelosis, por lo que se inició tratamiento con doxiciclina y rifampicina, con lo que se logró la eliminación de los síntomas y la negativización de las pruebas evolutivas. Conclusiones: La brucelosis puede mantenerse meses o años asintomática y reactivarse después de la inmunosupresión en los pacientes trasplantados. Su sospecha y rápido tratamiento puede lograr la curación y evitar complicaciones(AU)

Introduction: Brucellosis is the most frequent zoonosis, produced by the genus brucella, which affects several species of mammals, including human beings. It is transmitted to persons by direct contact with infected animals, by their excreta or by ingestion of unpasteurized products. In recent years, an increase has been described in immunocompromised patients. Objectives: To describe the reactivation of brucellosis in a hematopoietic transplant recipient patient, its course and management. Case presentation: A patient with Hodgkin's lymphoma and a history of brucellosis is presented; that she received a myeloablative autologous hematopoietic transplant. After haematological recovery, she started with symptoms of fever, diaphoresis, joint pain and hepato-splenomegaly. She was diagnosed with brucellosis, so treatment with doxycycline and rifampin was started, which eliminated the symptoms and made the evolutionary tests negative. Conclusions: Brucellosis can be asymptomatic for months or years and after immunosuppression it can be reactivated in transplanted patients. Suspicion and prompt treatment can bring about a cure and avoid complications(AU)

Prognostic value of pretreatment 18F-FDG PET/CT metabolic parameters in elderly classical Hodgkin′s lymphoma / 中华核医学与分子影像杂志

Objective:To investigate the prognostic value of pretreatment 18F-FDG PET/CT metabolic parameters in patients with elderly classical Hodgkin′s lymphoma (cHL). Methods:From April 2011 to April 2020, the pretreatment clinical and 18F-FDG PET/CT metabolic parameters of 42 elderly cHL patients (29 males and 13 females, median age 69 years) pathologically confirmed in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained with 41%SUV max as the threshold. ROC curve analysis was applied to obtain the best prognostic cut-off value of SUV max, MTV and TLG. Kaplan-Meier method and log-rank test were used for univariate survival analysis, and Cox proportional hazard regression model was used for multivariate survival analysis. Results:SUV max, MTV and TLG of 42 elderly cHL patients were 16.49(12.24, 23.59), 79.29(26.29, 184.51) ml and 729.02(206.03, 2 073.98) g, respectively. ROC curve showed that the AUCs of SUV max, MTV and TLG were 0.425, 0.882 and 0.832, respectively, and the best prognostic cut-off values were 16.49, 82.38 ml and 556.26 g, respectively. Univariate analysis showed that age, B symptoms, lactate dehydrogenase (LDH) level, Hb content, Ann Arbor stage, German Hodgkin Study Group (GHSG) score, MTV and TLG were relative factors affecting progression-free survival (PFS) rate ( χ2 values: 4.50-12.60, all P<0.05), and age, B symptoms, LDH level, Ann Arbor stage, GHSG score, MTV and TLG were relative factors affecting overall survival (OS) rate ( χ2 values: 5.20-11.17, all P<0.05). Multivariate analysis showed that MTV (relative risk ( RR)=5.370, 95% CI: 1.697-16.277) and TLG ( RR=4.854, 95% CI: 1.228-23.352) were independent prognostic predictors of PFS rate (both P<0.05), and GHSG score ( RR=3.761, 95% CI: 1.092-12.955; RR=3.668, 95% CI: 1.068-12.571), MTV ( RR=6.173, 95% CI: 1.431-16.322) and TLG ( RR=5.162, 95% CI: 1.200-22.199) were independent prognostic predictors of OS rate (all P<0.05). Conclusion:MTV and TLG in pretreatment 18F-FDG PET/CT are independent prognostic factors for predicting PFS and OS in patients with elderly cHL patients, which have certainly reference value for prognosis.

Uso de nivolumab en pacientes con recaída postrasplante alogénico de progenitores hematopoyéticos en enfermedad de Hodgkin: reporte de dos casos clínicos / Treatment of Hodgkin disease relapse after allogeneic transplantation with nivolumab. Report of two cases

Hodgkin's Lymphoma has a very good prognosis. In the unusually refractory patients allogeneic transplantation offers a chance of cure. The so-called checkpoint inhibitors, such as Nivolumab can play a relevant role in this type of patients. Their side effects and usefulness after allogeneic transplantation are under investigation. Relapse after allogeneic transplantation has an extremely poor prognosis. We report two patients with refractory Hodgkin's lymphoma who relapsed after an allogeneic transplant and who were successfully treated with Nivolumab.

Linfoma de Hodgkin em Pacientes HIV Positivo em Uso de Antirretrovirais de Alta Efetividade / Hodgkin Lymphoma in HIV Positive Patients in The Use of High-Effective Antiretroviral / Linfoma de Hodgkin en Pacientes VIH Positivos en el Uso de Antiretrovirales de Alta Efectividad

Introdução: A capacidade do vírus da imunodeficiência humana (HIV) de invadir células do sistema imunológico, principalmente células T CD4+, para se multiplicar e manter-se vivo, quando não revertido, possui, como desfecho inevitável, a síndrome da imunodeficiência adquirida (SIDA), evento no qual os pacientes começam a apresentar doenças secundárias como infecções oportunistas e câncer. Objetivo:Identificar casos de linfoma de Hodgkin em pacientes HIV+ em uso dos antirretrovirais de alta efetividade. Método: Estudo do tipo observacional transversal com delineamento exploratório e descritivo e abordagem quali-quantitativa, realizado durante o mês de outubro de 2018, a partir da análise de 57prontuários de pacientes HIV+ diagnosticados com câncer e internados em um hospital localizado em Fortaleza, CE. Resultados: Foi identificado um total de 21 cânceres não definidores de SIDA. Destes, os mais comuns foram o câncer de pele com 14,3% (3); seguido do câncer de mama com 9,5% (2); linfoma de Hodgkin com 9,5% (2); e o câncer de estômago com 9,5% (2) dos casos. Conclusão: Os dados obtidos no presente estudo colocam o linfoma de Hodgkin em segundo lugar entre os cânceres não definidores de SIDA encontrados. Contudo, ao considerar o baixo número de casos, resultante das limitações da pesquisa, essas informações não permitem concluir sobre a real quantidade de linfomas de Hodgkin entre os demais cânceres não definidores de SIDA ocorridos em pacientes HIV+ na localidade, tampouco estimar a participação do HIV, carga viral, condição imunológica e coinfecções como fatores de risco.

Introduction: The ability of the human immunodeficiency virus (HIV) of invading immune system cells, especially CD4+ to multiply and stay alive, when not reversed, has as inevitable outcome the acquired immunodeficiency syndrome (AIDS), an event in which patients start to develop secondary diseases such as opportunistic infections and cancer. Objective: To identify cases of Hodgkin's lymphoma in HIV+ patients using highly effective antiretrovirals. Method: Cross-sectional observational study with exploratory and descriptive design and qualitative and quantitative approach, carried out during the month of October 2018 based on the analysis of 57 HIV-infected patients' charts diagnosed with cancer and admitted to a hospital located in Fortaleza, CE. Results: A total of 21 non-AIDS-defining cancers were detected. Of these, skin cancer, with 14.3% (3) followed by breast cancer, with 9.5% (2), Hodgkin's lymphoma, 9.5% (2) and stomach cancer, with 9.5% (2) were the most common cases. Conclusion: The data obtained in the present study rank Hodgkin's lymphoma in second place among the non-AIDS-defining cancers encountered. However, while considering the small number of cases, due to the study limitations, these data are scanty to conclude the actual quantity of Hodgkin's lymphoma among the non-AIDS-defining cancers occurred in HIV-positive patients locally or to estimate the participation of HIV, viral load, immune condition and co-infection as risk factors.

Introducción: La capacidad del virus de inmunodeficiencia humana (VIH) para invadir las células del sistema inmunitario, especialmente las células T CD4 + para multiplicarse y mantenerse con vida, cuando no se revierte, tiene el resultado inevitable del síndrome de inmunodeficiencia adquirida (SIDA), evento en el que los pacientes comienzan a presentar enfermedades secundarias como infecciones oportunistas y cáncer. Objetivo: Identificar los casos de linfoma de Hodgkin en pacientes VIH+ utilizando los antirretrovirales de alta eficacia. Método: Este es un estudio observacional transversal con diseño exploratorio y descriptivo y enfoque cualitativo, realizado durante octubre de 2018 a partir del análisis de 57 registros médicos de pacientes VIH + diagnosticados con cáncer y hospitalizados en un hospital ubicado en Fortaleza, CE. Resultados: Se identificaron un total de 21 cánceres que no definen el SIDA. De estos, los más comunes fueron cáncer de piel con 14,3% (3), seguido de cáncer de seno con 9,5% (2), linfoma de Hodgkin 9,5% (2) y cáncer de estómago con 9,5% (2) de los casos. Conclusión: Los datos obtenidos en el presente estudio colocan al linfoma de Hodgkin en segundo lugar entre los cánceres no definitorios de SIDA encontrados. Sin embargo, considerando el bajo número de casos resultantes de las limitaciones de la investigación, esta información no nos permite concluir acerca de la cantidad real de linfoma de Hodgkin entre los otros cánceres no definitorios de SIDA en pacientes VIH + en la localidad, ni estimar la participación del VIH, la carga viral, la condición inmune y las coinfecciones como factores de riesgo.

Xist noncoding RNA could act as a tumor suppressor gene in patients with classical Hodgkin's disease

Background: Xist is a long noncoding RNA involved in the X chromosome inactivation in females. It may act as an onco-suppressor gene in hematologic malignancies, and its activity is strongly dependent from SATB1 gene expression. However, its potential role in Hodgkin's disease (HD) onset and progression is unknown. Materials and Methods: Three gene expression microarray datasets were analyzed for the expression of Xist and SATB1 in patients with classical HD, namely, GDS4222 (130 patients and 54,000 gene features), GSE39134 (29 patients and 54,000 features), and E-MEXP-507 (29 patients and 27,648 probes). The first two were oligonucleotide arrays (platform: Affymetrix gene chip HG-U133-Plus2), whereas the latter was a cDNA two-channel array (platform: OncoChip. v2). Summary and time-dependent receiver operating characteristic (ROC) analysis were applied to obtain a summary measure (summary area under the ROC curve [sAUC]) of association between gene expression and unfavorable patient outcome in each probe set. Results: Xist was overexpressed among females in each data set. A slight overexpression was associated with a good prognosis both in males (sAUC = 0.75, 95% confidence interval [CI]: 0.70–0.80) and at a lesser extent, in females (sAUC = 0.64, 95% CI: 0.59–0.69). However, this finding was limited to the analysis of the biggest database (GDS4222). No association was found between Xist and SATB1 expression. Conclusions: A reactivation of Xist might act as an onco-suppressor gene in male patients with HD, which seems independent from SATB1 expression. The possibility that Xist could contribute to the better survival of female patients should also be investigated

Enfoque del paciente con adenopatías generalizadas. Importancia de la estrategia didáctica del estudio de casos clínicos: a propósito de un paciente con linfoma de Hodgkin asociado a una infección por el virus de Epstein-Barr / Approach of the patient with generalized adenopathies. Importance of the didactic strategy of the study of clinical cases: a purpose of a patient with Hodgkin's lymphoma associated with an infection with the Epstein-Barr virus

Se muestra el caso de un paciente con 56 años de edad, con un síndrome adenomegálico generalizado que presentó un linfoma de Hodgkin de celularidad mixta, asociado al virus de Epstein-Barr. El paciente previo al inicio del linfoma presentó episodios prolongados de estrés emocional, lo que posiblemente contribuyó a la disminución de la vigilancia inmunológica. El caso fue abordado por los estudiantes de quinto semestre en la asignatura Acto médico, una estrategia didáctica interdisciplinaria. Este artículo presenta los aspectos a tener en cuenta en el enfoque clínico de los pacientes con adenopatías desde una perspectiva integradora de la inmunología, la clínica y los diagnósticos diferenciales. Se resalta el valor del estudio de los casos clínicos con varios métodos diagnósticos como estrategia didáctica. Finalmente, se realiza una revisión de la literatura sobre el linfoma Hodgkin orientada al papel en el que participa la infección por el virus de Epstein-Barr, relacionada con la inmunosupresión por estrés.

SUMMARY We present the case of a 56-year-old patient with a generalized adenomegalic syndrome who presented a mixed cellular Hodgkin's lymphoma associated with Epstein Barr Virus. The patient had had great emotional stress prior to the onset of lymphoma, which possibly contributed to the decrease in immunological surveillance. The case was addressed by the students of the fifth semester in the subject "Medical Act", an interdisciplinary didactic strategy. We present the aspects to be taken into account in the approach of the clinician of patients with adenopathies from an integrative perspective of immunology, clinical and differential diagnoses; and the value of the study of clinical cases with several diagnostic approaches as a didactic strategy is highlighted. Finally, we present a literature review about Hodgkin lymphoma and the role which plays stress related Epstein Barr Virus infection.

The poor insane Ophelia: reconsidering Ophelia syndrome / La pobre e insensata Ofelia: reconsiderando el síndrome de Ofelia

ABSTRACT The association between memory loss and Hodgkin's lymphoma has been given the eponym of Ophelia syndrome, in memory of Shakespeare's character in The Tragedy of Hamlet, Prince of Denmark. Nevertheless, there are differences between the disease and the character. Objective: To review the origins and uses of the eponym through an original article by pathologist Ian Carr, its relation to the character Ophelia, and the related autoantibodies. Methods: Historical narrative review. Results: Besides an eloquent description in the original article, Carr presaged the presence of autoantibodies, before they had been thoroughly researched. Since then, five different autoantibodies (mGluR5, Hu, NMDAR, SOX, PCA2) have been associated with Hodgkin's disease. It is interesting to note the divergent outcomes of Shakespeare's character and the patient in the original description by Carr, the latter recovering to lead a normal life, and the former deceased. Conclusions: Although there is little relationship between the fictional character and the syndrome, both imply the unintentional trigger of self-harm (suicide in one case, autoimmunity in the other), thus remaining associated.

RESUMO El síndrome de Ofelia describe la asociación entre pérdida de memoria y enfermedad de Hodgkin, en memoria del personaje de La Tragedia de Hamlet, Príncipe de Dinamarca, de William Shakespeare. Sin embargo, existen diferencias entre ambos. Objetivo: Revisar los orígenes y usos del epónimo a través del artículo original, su relación con el personaje y los autoanticuerpos relacionados. Métodos: Revisión narrativa histórica. Resultados: Además de una descripción elocuente, el artículo original prefigura los autoanticuerpos, cuando no se buscaban de rutina. Desde entonces, cinco distintos (mGluR5, Hu, NMDAR, SOX, PCA2) han sido asociados. Cabe destacar, que el desenlace del personaje y del paciente fueron diametralmente opuestos, el primero falleció y el segundo se recuperó, llevando una vida normal. Conclusiones: A pesar de la poca relación entre el personaje y el síndrome, ambos implican el desencadenamiento no intencional de daño auto-inflingido (suicidio en un caso, autoinmunidad en el otro), manteniendo así la adecuacía.

Cardiotoxicidad por irradiación en pediatría / Cardiotoxicity by irradiation in Pediatrics

Introducción: La cardiotoxicidad depende de varios factores y se manifiesta por las alteraciones cardiovasculares inducidas por los tratamientos oncoespecíficos en la función y morfología del corazón. Objetivo: Determinar las manifestaciones de cardiotoxicidad en pacientes pediátricos. Métodos: Estudio descriptivo transversal en el que se incluyeron 79 pacientes tratados en el Instituto de Oncología y Radiobiología de Cuba con irradiación tórax-mediastino, entre enero 2008 a diciembre 2014. La enfermedad de Hodgkin estaba presente en 54 pacientes y en 25, tumores del sistema nervioso central: meduloblastomas en 19 y tumores primarios neuroectodérmicos en 6 pacientes. A todos se les hizo historia clínica con examen físico, electrocardiograma de 12 derivaciones y ecocardiograma 2D pre- y postratamientos. Se analizaron las características demográficas y clínicas. Los enfermos con Hodgkin recibieron irradiación con intensidad de 2 400 centigray y de 2 340 los pacientes con tumores del sistema nervoso central; la poliquimioterapia se realizó con antraciclinas, vincristina, vinblastina y otros. Resultados: La edad promedio de todos los pacientes fue de 7 años con predominio del sexo masculino. No se registraron síntomas o signos de cardiotoxicidad. Conclusiones: En nuestra serie de pacientes la irradiación del área cardiaca aparentemente es bien tolerada, sin aparición temprana de cardiotoxicidad, ni en periodos de seguimiento de hasta 9 años. Aparecieron naúseas y leucopenias transitorias en algunos casos. No existió diferencias en las toxicidades en los grupos de tumores estudiados Es necesario mantener un seguimiento estrecho para descartar la aparición de cardiotoxicidad en años siguientes(AU)

Introduction: Cardiotoxicity depends on various factors and it is evident in cardiovascular alterations induced by oncologic treatments directed to the heart´s function and morphology. Objective: To determine the symptoms of cardiotoxicity in pediatric patients. Methods: Descriptive and cross-sectional study in which there were included 79 patients treated in the Cuban Institute of Oncology and Radiobiology with thorax-mediastine irradiation from January 2008 to December 2014. Hodgkin disease was present in 54 patients, tumors of the central nervous system in 25, medulloblastomas in 19, and neuroectodermic primary tumors in 6. All the patients underwent physical examination, 12 -lead electrocardiogram and pre- and post-treatment 2D echocardiograms to include in the clinical records. The demographic and clinic characteristics were analyzed. Hodgkin disease's patients received irradiation with 2 400 cGy intensity and the patients presenting tumors in the central nervous system with 2 340 cGy. Polychemotherapy was carried out with antracyclines, vincristine, vinblastine and others. Results: Average age of all patients was 7 years with predominance of male sex. Symptoms of cardiotoxicity were not recorded. Conclusions: In the serie of analyzed patients, irradiation in the heart area was apparently well beared by the patients, without early appearance of cardiotoxicity, not even in follow up periods of 9 years. Transitory nausea and leucopenia appeared in some cases. There are no differences in the toxicities of the different tumour's groups studied. It is necessary to keep the regular follow up to rule out the appearence of cardiotoxicity in the next years(AU)

Plan de cuidados de enfermería con enfoque educativo dirigido a paciente adulta con insomnio y linfoma de Hodgkin / Nursing care plan with an educational approach aimed at an adult female patient with insomnia and Hodgkin lymphoma

Introducción: el plan de cuidados de enfermería estandarizado (PLACE) es un protocolo específico de cuidados, apropiado para aquellos pacientes que padecen los problemas normales o previsibles relacionados con un diagnóstico concreto o una enfermedad. Objetivo: diseñar un PLACE de quimioterapia, como una propuesta para el profesional de enfermería en la programación de los cuidados. Desarrollo: se presenta el caso de una paciente adulta de 34 años, con diagnóstico médico de linfoma de Hodgkin y tratamiento de quimioterapia, hospitalizada en el servicio de Quimioterapia Ambulatoria. Para la evaluación del estado de la paciente se utilizó la Guía de valoración para el paciente adulto por dominios y clases de la NANDA (North American Nursing Diagnosis Association); con base en un proceso de razonamiento diagnóstico, se jerarquizaron y determinaron los diagnósticos de enfermería, los resultados esperados y las intervenciones de enfermería. Se diseñó un plan de cuidados basado en la interrelación de las taxonomías NANDA, NOC (Nursing Outcomes Classification) y NIC (Nursing Interventions Classification). Derivado del razonamiento diagnóstico, se priorizó el siguiente diagnóstico de enfermería: insomnio R/C factores del entorno M/P dificultad para conciliar el sueño. Conclusión: el plan de cuidados de enfermería con enfoque educativo puede ayudar a mejorar el patrón y la calidad del sueño al disminuir la dificultad para conciliar el sueño. Asimismo un adecuado manejo de la medicación, manejo de la energía y del ambiente en casa y en el hospital favorece un adecuado control de la enfermedad y la recuperación.

Introduction: The standardized nursing care plan (SNCP) is a specific care protocol, appropriate for those patients who suffer from normal or foreseeable problems related to a specific diagnosis or illness. Objective: To design an SNCP with an educational approach aimed at a female adult patient with insomnia, Hodgkin lymphoma and chemotherapy treatment, as a proposal for the nursing professional in the patient care program. Development: It is presented the case of a 34-year-dd female adult patient with a medical diagnosis of Hodgkin lymphoma and chemotherapy treatment, hospitalized in the Outpatient Chemotherapy Service. The NANDA (North American Nursing Diagnosis Association) Assessment Cuide for the Adult Patient by Domains and Classes was used to assess the patient's condition; based on a process of diagnostic reasoning, the nursing diagnoses, expected results and nursing interventions were hierarchized and determined. A care plan was designed based on the interrelation of the NANDA NOC (Nursing Outcomes Classification) and NIC (Nursing Interventions Classification) taxonomies. Derived from the diagnostic reasoning, the following nursing diagnosis was prioritized: Insomnia R/T environmental factors M/B difficulty falling asleep. Conclusión: The nursing care plan with an educational approach can help to improve the pattern and quality of sleep by decreasing the difficulty in falling asleep. Likewise, proper medication management, energy management and the environment at home and in the hospital favors adequate disease control and recovery.

Evaluación del tratamiento de linfoma de Hodgkin con esquema ABVD en Chile / Treatment of Hodgkin lymphoma: analysis of 915 patients

Background: Hodgkin lymphoma has a high rate of curability, even in advanced stages. Aim: To assess the results of Hodgkin lymphoma treatment using the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy regimen. Material and Methods: Analysis of a database held by the Chilean Ministry of Health, including all patients treated at accredited cancer treatment centers. Results: Data for 915 patients, median age 35 years (range 15-86 years) and followed for a median of 97 months (range 1-347 months) were analyzed. Forty-one percent had localized disease. Overall survival at five years for localized and advanced stages was 92% and 74%, respectively. The figures for progression free survival were 87% and 64%, respectively. Patients with relapse who received autologous stem cell transplantation (ASCT) had a five year overall survival of 92%, compared to 64% among those who did not undergo this procedure (p < 0.01). The Guarantees in Health Program set up by the Ministry of Health, was associated with earlier stage disease at diagnosis. Conclusions: The ABVD regimen achieves high rates of cure in localized stages of the disease but the results in advanced stages are not optimal. ASCT significantly improves survival in patients with relapse. The Guarantees in Health Program is associated with earlier diagnosis of the disease.

Aconselhamento telefônico: identificação de sintomas em pacientes com linfoma em quimioterapia antineoplásica / Consulta telefónica: identificación de síntomas en pacientes con linfoma en quimioterapia antineoplásica / Telephone counseling: identification of symptoms in patients with lymphoma undergoing antineoplastic chemotherapy

Resumo Objetivo Identificar os sinais e sintomas apresentados por pacientes com Linfoma de Hodgkin submetidos ao protocolo quimioterápico composto por Doxorrubicina, Bleomicina, Vimblastina e Dacarbazina (ABVD) por meio de aconselhamento telefônico e comparar os escores de gradação dos sinais e sintomas apresentados nos ciclos do protocolo. Métodos Descritivo, prospectivo, quantitativo. Sete pacientes receberam aconselhamento telefônico, em 24 tempos de chamadas programadas e não programadas, correspondentes a 6 ciclos de quimioterapia com protocolo ABVD. Utilizou-se o Inventário de Sintomas do M.D Anderson e o Critério Comum de Terminologia para Eventos Adversos, para a gradação dos sintomas e um protocolo de condutas. Realizou-se análise descritiva e analítica. Resultados Duzentas e oitenta e seis chamadas telefônicas geraram1.870 queixas sintomáticas. Nas chamadas programadas, as queixas com maior prevalência foram fadiga, preocupações, falta de apetite, vômitos e náuseas. Quanto a interferência nas atividades de vida diária, os itens relacionados a atividades em geral, no trabalho e dificuldade para caminhar, além de alterações no humor foram relatados em maior frequência. Nas chamadas não programadas, a falta de apetite e desregulação menstrual foram as queixas mais recorrentes. Na análise da progressão dos sintomas, observou-se aumento de náuseas e vômitos (p=0,02), diminuição da fadiga e falta de ar (p≤0,03), melhora do sono (p=0,02) e diminuição do estresse (p=0,02). Conclusão A fadiga, náusea, vômito e alteração nas atividades de trabalho foram relatados frequentemente. Houve progressão de náuseas e vômitos, mas regressão da fadiga e do estresse. O aconselhamento telefônico permitiu a comunicação e o manejo rápido de um número expressivo de sintomas.

Resumen Objetivo Identificar los signos y síntomas presentados por pacientes con linfoma de Hodgkin sometidos al protocolo quimioterápico compuesto por doxorrubicina, bleomicina, vinblastina y dacarbazina (ABVD) mediante consulta telefónica, y comparar los puntajes de graduación de los signos y síntomas presentados en los ciclos del protocolo. Métodos Descriptivo, prospectivo, cuantitativo. Siete pacientes recibieron asesoramiento telefónico en 24 momentos de llamadas programadas y no programadas, correspondientes a 6 ciclos de quimioterapia con protocolo ABVD. Se utilizó el Inventario de Síntomas de M. D. Anderson y el Criterio de Terminología Común para Efectos Adversos, para la puntuación de lis síntomas, y un protocolo de conductas. Se realizó análisis descriptivo y analítico. Resultados Doscientas ochenta y seis llamadas telefónicas determinaron 1.870 quejas sintomáticas. En las llamadas programadas, las quejas más prevalentes fueron: fatiga, preocupaciones, falta de apetito, vómitos y náuseas. Respecto a interferencia en actividades cotidianas, los ítems relacionados con actividad en general, laboral y dificultad para caminar, además de cambios del humor, fueron informados con mayor frecuencia. En llamadas no programadas, la falta de apetito y la irregularidad menstrual resultaron las quejas más habituales. En el análisis de progresión de los síntomas se observó aumento de náuseas y vómitos (p=0,02), disminución de fatiga y falta de aire (p≤0,03), mejora del sueño (p=0,02) y disminución del estrés (p=0,02). Conclusión Hubo informe frecuente de fatiga, náuseas, vómitos y cambios en actividades laborales. Existió progresión de náuseas y vómitos, y regresión de fatiga y estrés. La consulta telefónica permitió comunicación y rápido manejo de una expresiva cantidad de síntomas.

Abstract Objective To identify through telephone counselling the signs and symptoms presented by patients with Hodgkin's Lymphoma undergoing chemotherapy with the protocol composed by doxorubicin, bleomycin, vinblastine and dacarbazine and to compare severity scores of the signs and symptoms presented in the cycles of the protocol. Methods Descriptive, prospective, quantitative study. Seven patients received telephone counselling in 24 scheduled and unscheduled calls, corresponding to 6 ABVD chemotherapy cycle. The MD Anderson Symptom Inventory and the Common Terminology Criteria for Adverse Events were used for scoring the symptoms, along with a conduct protocol. A descriptive and analytical analysis was conducted. Results Two hundred and eighty-six telephone calls generated 1,870 symptomatic complaints. In scheduled calls, the most prevalent complaints were fatigue, distress, lack of appetite, vomiting and nausea. As for the interference in daily life activities, the items related to general activities, work, difficulty walking, and mood changes were reported more frequently. In unscheduled calls, lack of appetite and irregular menstruation were the most recurring complaints. The analysis of the progression of symptoms showed an increase in nausea and vomiting (p=0.02), decrease in fatigue and shortness of breath (p≤0.03), improvement in sleep (p=0.02) and decrease of stress (p=0.02). Conclusion Fatigue, nausea, vomiting and alterations in work activities were frequently reported. There was progression of nausea and vomiting but regression of fatigue and stress. Telephone consultation allowed a rapid communication and management of an expressive number of symptoms.