Human Leukocyte Antigen-Haploidentical Transplantation for Relapsed/Refractory Hodgkin Lymphoma: A Multicenter Analysis.

Reduced-intensity-conditioned allogeneic stem cell transplantation (SCT) remains a potentially curative approach for patients with relapsed/refractory Hodgkin lymphoma (HL) after an autologous stem cell transplantation. In the absence of an HLA-identical donor, haploidentical SCT (haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy) has been evaluated with favorable preliminary results. We evaluated 24 patients who underwent haplo-SCT for relapsed/refractory HL. The conditioning regimen consisted of cyclophosphamide, fludarabine, and total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of a calcineurin inhibitor, mycophenolate mofetil, and PT-Cy (50 mg/kg/day for 2 days) for all patients. After a median follow-up of 2 years, the cumulative incidence (CI) of nonrelapse mortality was 26% and the CI of grades II to IV acute GVHD and chronic GVHD were 17% and 24%, respectively. Estimation of progression-free and overall survival at 2 years were 54% and 66%%, respectively. Haplo-SCT is a valuable option for relapsed/refractory HL patients after a failed autologous SCT, with favorable survival and relatively low risk of GVHD.

Incidence of cardioembolic stroke related to atrial fibrillation in Joinville, Brazil.

BACKGROUND: Atrial fibrillation (AF) is an important cause of cardioembolic stroke, and population aging has increased its prevalence. OBJECTIVE: To evaluate the incidence of cardioembolic stroke caused by AF in the city of Joinville, Brazil, as well as previous diagnoses and use of medication. METHODS: Between 2017 and 2020 we extracted data from the population-based Joinville Stroke Registry. Demographic characteristics, diagnosis of AF, and patterns of medication use were collected, and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) system was used to classify the etiology. RESULTS: There were 3,303 cases of ischemic stroke, 593 of which were cardioembolic, and 360 had AF. Of the patients with AF, 258 (71.6%) had a previous diagnosis of the disease, and 102 (28.3%) were newly diagnosed after the stroke. Among patients with a previously-diagnosed AF, 170 (47.2%) were using anticoagulants, and 88 (24.4%) were using other medications. CONCLUSION: During the analyzed period, ischemic stroke caused by AF was a significant burden on the population of Joinville, and a considerable number of patients had undiagnosed or untreated AF.

ANTECEDENTES: A fibrilação atrial (FA) é uma importante causa de acidente vascular cebebral (AVC) cardioembólico, e o envelhecimento populacional aumentou a sua prevalência. OBJETIVO: Avaliar a incidência de AVC cardioembólico causado por FA em Joinville, além dos diagnósticos prévios e do uso de medicamentos. MéTODOS: Entre 2017 e 2020, foram extraídos dados do registro de base populacional de AVC de Joinville. Características demográficas, diagnóstico de FA e padrões de uso de medicamentos foram coletados, e o sistema Trial of ORG 10172 in Acute Stroke Treatment (TOAST) foi utilizado para classificar a etiologia. RESULTADOS: Houve 3.303 casos de AVC isquêmico, sendo 593 cardioembólicos e 360 com FA. Dos pacientes com FA, 258 (71,6%) tinham diagnóstico prévio da doença, e 102 (28,3%) foram recém-diagnosticados após o AVC. Entre os pacientes com FA previamente diagnosticada, 170 (47,2%) estavam em uso de anticoagulante, e 88 (24,4%), em uso de outra medicação. CONCLUSãO: Durante o período analisado, o AVC isquêmico causado por FA foi um ônus significativo para a população de Joinville, e um número considerável de pacientes apresentava FA não diagnosticada ou não tratada.

Deregulation of Ikaros expression in B-1 cells: New insights in the malignant transformation to chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a chronic form of leukemia that originates from an abnormal expansion of CD5+ B-1 cells. Deregulation in the BCR signaling is associated with B-cell transformation. Contrariwise to B-2 cells, BCR engagement in B-1 cells results in low proliferation rate and increased apoptosis population, whereas overactivation may be associated with lymphoproliferative disorders. It has been demonstrated that several transcription factors that are involved in the B cell development play a role in the regulation of BCR function. Among them, Ikaros is considered an essential regulator of lymphoid differentiation and activation. Several reports suggest that Ikaros expression is deregulated in different forms of leukemia. Herein, we demonstrated that CLL cells show decreased Ikaros expression and abnormal cytoplasmic cell localization. These alterations were also observed in radioresistant B-1 cells, which present high proliferative activity, suggesting that abnormal localization of Ikaros could determine its loss of function. Furthermore, Ikaros knockdown increased the expression of BCR pathway components in murine B-1 cells, such as Lyn, Blnk, and CD19. Additionally, in the absence of Ikaros, B-1 cells become responsive to BCR stimulus, increasing cell proliferation even in the absence of antigen stimulation. These results suggested that Ikaros is an important controller of B-1 cell proliferation by interfering with the BCR activity. Therefore, altered Ikaros expression in CLL or radioresistant B-1 cells could determine a responsive status of BCR to self-antigens, which would culminate in the clonal expansion of B-1 cells.

Incidence of cardioembolic stroke related to atrial fibrillation in Joinville, Brazil / Incidência de acidente vascular encefálico relacionado à fibrilaçao atrial em Joinville, Brasil

Abstract Background Atrial fibrillation (AF) is an important cause of cardioembolic stroke, and population aging has increased its prevalence. Objective To evaluate the incidence of cardioembolic stroke caused by AF in the city of Joinville, Brazil, as well as previous diagnoses and use of medication. Methods Between 2017 and 2020 we extracted data from the population-based Joinville Stroke Registry. Demographic characteristics, diagnosis of AF, and patterns of medication use were collected, and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) system was used to classify the etiology. Results There were 3,303 cases of ischemic stroke, 593 of which were cardioembolic, and 360 had AF. Of the patients with AF, 258 (71.6%) had a previous diagnosis of the disease, and 102 (28.3%) were newly diagnosed after the stroke. Among patients with a previously-diagnosed AF, 170 (47.2%) were using anticoagulants, and 88 (24.4%) were using other medications. Conclusion During the analyzed period, ischemic stroke caused by AF was a significant burden on the population of Joinville, and a considerable number of patients had undiagnosed or untreated AF.

Resumo Antecedentes A fibrilação atrial (FA) é uma importante causa de acidente vascular cebebral (AVC) cardioembólico, e o envelhecimento populacional aumentou a sua prevalência. Objetivo Avaliar a incidência de AVC cardioembólico causado por FA em Joinville, além dos diagnósticos prévios e do uso de medicamentos. Métodos Entre 2017 e 2020, foram extraídos dados do registro de base populacional de AVC de Joinville. Características demográficas, diagnóstico de FA e padrões de uso de medicamentos foram coletados, e o sistema Trial of ORG 10172 in Acute Stroke Treatment (TOAST) foi utilizado para classificar a etiologia. Resultados Houve 3.303 casos de AVC isquêmico, sendo 593 cardioembólicos e 360 com FA. Dos pacientes com FA, 258 (71,6%) tinham diagnóstico prévio da doença, e 102 (28,3%) foram recém-diagnosticados após o AVC. Entre os pacientes com FA previamente diagnosticada, 170 (47,2%) estavam em uso de anticoagulante, e 88 (24,4%), em uso de outra medicação. Conclusão Durante o período analisado, o AVC isquêmico causado por FA foi um ônus significativo para a população de Joinville, e um número considerável de pacientes apresentava FA não diagnosticada ou não tratada.