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1.
Cancer Sci ; 111(1): 279-287, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31743514

RESUMO

Epstein-Barr virus (EBV) is a well-established tumor virus that has been implicated in a wide range of immunodeficiency-associated lymphoproliferative disorders (LPDs). Although rituximab, a CD20 mAb, has proven effective against EBV-associated LPDs, prolonged use of this drug could lead to resistance due to the selective expansion of CD20- cells. We have previously shown that cyclin-dependent kinase (CDK) inhibitors are able to specifically suppress the expression of viral late genes, particularly those encoding structural proteins; however, the therapeutic effect of CDK inhibitors against EBV-associated LPDs is not clear. In this study, we examined whether CDK inhibitors confer a therapeutic effect against LPDs in vivo. Treatment with alsterpaullone, an inhibitor of the CDK2 complex, resulted in a survival benefit and suppressed tumor invasion in a mouse model of LPDs. Inhibition of CDK efficiently induced G1 cell cycle arrest and apoptosis in EBV-positive B cells. These results suggest that alsterpaullone suppresses cell cycle progression, resulting in the antitumor effect observed in vivo.


Assuntos
Antineoplásicos/farmacologia , Benzazepinas/farmacologia , Herpesvirus Humano 4/patogenicidade , Indóis/farmacologia , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/virologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Fase G1/efeitos dos fármacos , Células HEK293 , Humanos , Transtornos Linfoproliferativos/genética , Camundongos , Camundongos Endogâmicos NOD
4.
Zhonghua Bing Li Xue Za Zhi ; 48(10): 762-766, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31594039

RESUMO

Objective: To investigate the clinicopathological features of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Methods: Five cases of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract from the Affiliated Hospital of Qingdao University from 2016 to 2019 were retrospectively reviewed. The clinical and pathological parameters were analyzed by combining clinical data and reviewing the available literature of 35 cases (34 cases abroad and 1 case in China). Results: There were 4 males and 1 female with a median age of 47 years (18-66 years). All patients had abdominal pain and constitutional symptoms including diarrhea, emaciation, intermittent mucous stool or oral and epiglottic ulcers. Endoscopic manifestations included multiple punctate congestion, erosion and ulcer at the terminal ileum and colorectum. Two cases had congestion and erosion of antrum and angle of stomach, and the lesions did not fuse and form tumors. Histologically, the lamina propria was expanded by a dense, medium to small lymphocyte infiltration, which was monomorphic, with slightly irregular nuclei without prominent nucleolus or lymphoepithelial lesions. There were admixed small amount of plasma cells and eosinophils. In 4 cases, immunohistochemistry showed the lesional cells were positive for CD3, CD8, TIA1, and negative for CD4, CD56, granzyme B and Ki-67 index was ≤10%. In situ hybridization showed that EBER was negative and clonal TCR gene rearrangement was detected. One consultation case was CD3(+), CD5(-) and Ki-67 index of 10%, although other indicators were not done. All five patients were treated with symptomatic support. In follow-up observation for 2 to 25 months, all patients were alive with the disease. Conclusions: Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract is a newly classified monoclonal T-cell proliferative disease, with low incidence, clinical inertia and long-term survival. It has unique clinicopathological features but pathologically it is easily misdiagnosed as inflammatory bowel disease or T-cell lymphoma. Correct diagnosis is of great important clinical significance.


Assuntos
Trato Gastrointestinal/patologia , Transtornos Linfoproliferativos/fisiopatologia , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Membrana Mucosa/patologia , Estudos Retrospectivos , Linfócitos T/patologia , Adulto Jovem
5.
Transplant Proc ; 51(9): 3163-3166, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619339

RESUMO

Posttransplant lymphoproliferative disorder (PTLD) is caused by uncontrolled proliferation of lymphoid cells after a hematopoietic stem cell or solid organ transplant procedure related to the Epstein-Barr virus (EBV) infection. A primary central nervous system (CNS) PTLD (CNS-PTLD) is rare and important to distinguish from an intracranial lesion after transplantation. A 66-year-old man with pulmonary arterial hypertension who underwent living-donor lung transplantation 9 years prior noticed disorientation regarding route and dates. Brain magnetic resonance imaging revealed multiple white matter lesions and fluorodeoxyglucose (FDG) positron emission tomography showed FDG uptake in the brain and skin. CNS-PTLD was diagnosed by craniotomy biopsy and EBV-encoded RNA was positive in in situ hybridization findings and elevated in brain tissue. The treatment was started with immunosuppressant reduction and whole brain radiotherapy. But the condition progressed rapidly over 2 months after the first symptom and the patient was passed away 25 days after hospitalization. CNS-PTLD can occur several years after transplantation and it is necessary to keep in mind to distinguish brain disease because early diagnosis and treatment are important.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Pulmão , Transtornos Linfoproliferativos/imunologia , Complicações Pós-Operatórias/imunologia , Idoso , Encéfalo/patologia , Infecções por Vírus Epstein-Barr/imunologia , Humanos , Masculino
6.
Rinsho Ketsueki ; 60(9): 1331-1336, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597860

RESUMO

Chronic active EBV infection (CAEBV) is one of the EBV-associated T/NK lymphoproliferative diseases. The prognosis of CAEBV is very poor, and without curative therapy, almost half of patients will die within five years of onset. The results of a 3-step treatment regimen consisting of step 1 (immunochemotherapy), step 2 (multi-drug chemotherapy), and step 3 (hematopoietic cell transplantation, HCT) are excellent. HCT is the only cure for CAEBV, and reduced-intensity conditioning (RIC) is superior to myeloablative conditioning (MAC). The overall survival rate is typically more than 90% following bone marrow transplantation and cord blood transplantation.


Assuntos
Infecções por Vírus Epstein-Barr/terapia , Transplante de Células-Tronco Hematopoéticas , Transtornos Linfoproliferativos/terapia , Tratamento Farmacológico , Humanos , Transtornos Linfoproliferativos/virologia , Prognóstico , Taxa de Sobrevida , Condicionamento Pré-Transplante
7.
Isr Med Assoc J ; 21(7): 480-486, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507125

RESUMO

BACKGROUND: Serum rheumatoid factors are autoantibodies of different isotypes directed against the Fc fraction of immunoglobulin G (IgG) and represent paradigmatic autoantibodies that have been largely used in clinical practice for decades. Traditionally IgG has been associated with rheumatoid arthritis and more recently included also in the classification criteria for SjÓ§gren's syndrome. Researchers have established that rheumatoid factors are positive in a variety of infectious, autoimmune, and neoplastic disorders, thus requiring a comprehensive evaluation of seropositive patients. Of note, hepatitis B and C viruses represent a crossroad that includes the high rheumatoid factor seroprevalence and chronic inflammatory disease, as well as progression to non-Hodgkin's lymphomas. Chronic antigen stimulation is the likely common ground of these processes and rheumatoid factors may represent mere bystanders or drivers of pathology. Mixed cryoglobulinemia and lymphoproliferative disease are prime examples of the deleterious effects of rheumatoid factor-B cell activity, possibly associated with hepatitis B and C. More importantly, they show a clear association in a physiological host response to infection, chronic inflammation, and the slide toward autoimmunity and malignancy. The association between hepatitis B and C infections and the appearance of serum rheumatoid factors is further supported by prevalence data, which support a coexistence of these markers in a significant proportion of cases, with viral infections being frequent causes of rheumatoid factors in patients without a rheumatic condition. We provide a comprehensive overview of the known connections between hepatitis B and C infections and rheumatoid factors.


Assuntos
Hepatite B/imunologia , Hepatite C/imunologia , Fator Reumatoide/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Crioglobulinemia/imunologia , Humanos , Transtornos Linfoproliferativos/imunologia , Neoplasias/imunologia , Fator Reumatoide/sangue
10.
Rinsho Ketsueki ; 60(8): 932-943, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484893

RESUMO

Methotrexate-associated lymphoproliferative disorders (MTX-LPD) is categorized into other iatrogenic immunodeficiency-associated lymphoproliferative disorders, developing LPD in patients with autoimmune diseases (AIDs) under low dose MTX administration. Two-thirds of MTX-LPDs regresses after MTX withdrawal with the higher incidence in Japanese patients, MTX-LPDs consist of various subtypes of LPDs, the feature of each LPD such as the regressive rate, relapse/regrowth rate, and prognosis, widely varies. The absolute lymphocyte count (ALC) in peripheral blood is suggested to influence LPD development, regression, and relapse/regrowth events. Because various factors might effect the pathogenesis and clinical features of MTX-LPD, careful attention should be paid to assess MTX-LPD.


Assuntos
Artrite Reumatoide , Transtornos Linfoproliferativos , Metotrexato/efeitos adversos , Antirreumáticos , Humanos , Incidência , Transtornos Linfoproliferativos/induzido quimicamente , Prognóstico
11.
Rinsho Ketsueki ; 60(8): 944-952, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484894

RESUMO

Chronic active Epstein-Barr virus infection (CAEBV) presents with mononucleosis-like symptoms such as chronic persistent or recurrent pyrexia, lymphadenopathy, and hepatosplenomegaly because of the reactivation of Epstein-Barr virus (EBV) as demonstrated by the recurrence of EBV-infected cells. The mechanism of CAEBV remains obscure, and CAEBV can lead to fatal conditions such as hemophagocytic syndrome and malignant lymphoma by clonal expansion of EBV-infected T- or NK-cells. Without hematopoietic stem cell transplantation, CAEBV has a poor prognosis. CAEBV is listed in the revised 2016 World Health Organization classification as a chronic active EBV infection of T- and NK-cell types, systemic form, among EBV-positive T- and NK-cell lymphoproliferative diseases of childhood. However, similar clinical conditions have been reported in adult patients. Therefore, we investigated the clinical features of adult patients with CAEBV-like features (adult-onset CAEBV) in a relatively small number of cases. Additionally, genetic alterations related to CAEBV development have also been reported. Along with these results, we reviewed the clinical characteristics of adult-onset CAEBV.


Assuntos
Infecções por Vírus Epstein-Barr , Mononucleose Infecciosa , Linfo-Histiocitose Hemofagocítica , Transtornos Linfoproliferativos , Adulto , Criança , Doença Crônica , Humanos
13.
Int J Infect Dis ; 88: 31-33, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31398454

RESUMO

A 69-year-old man who underwent cord blood transplantation seven years ago was admitted because of fever, elevated liver enzymes and thrombocytopenia. Bone marrow aspirate revealed hemophagocytic lymphohistiocytosis. Viral capsid antigen (VCA)-immunoglobulin (Ig) G, VCA-IgM, VCA-IgA, Epstein-Barr virus nuclear antigen-IgG, early antigen-diffuse-type and restricted-type (EA-DR) IgG, and EA-DR IgA titers were 2560, <10, 10, 40, 40, and <10, respectively. Real-time polymerase chain reaction assay of peripheral whole blood for Epstein-Barr virus-deoxyribonucleic acid (EBV-DNA) revealed 240,000 copies/µg DNA. Flow cytometric in situ hybridization assay confirmed that EBV-infected cells were NK-cells. Clonality evaluation by Southern blot assay of EBV-DNA terminal repeats proved to be bi-clonal. Accordingly, we made a diagnosis of NK-cell post-transplant lymphoproliferative disease with chronic active EBV infection-like clinical findings (CAEBV-like NK-cell PTLD). Although CAEBV-like PTLD is extremely rare, its prognosis seems to be very poor. The disease should be considered in such patients who present persistent or recurrent infectious mononucleosis-like symptoms after transplantation.


Assuntos
Anticorpos Antivirais/imunologia , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/imunologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Idoso , Doença Crônica , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Humanos , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/virologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/virologia , Masculino , Prognóstico
14.
Presse Med ; 48(7-8 Pt 1): 792-806, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447335

RESUMO

Chronic lymphoproliferative disorders should be classified according to the revised 2016 WHO classification. Biopsies are not mandatory for all chronic lymphoproliferative disorders as blood or bone marrow cytologroachical approach can be sufficient for some lymphoma entities. Diagnostic is based on a multidiscplinary approach taking into account clinical presentation, histopathological, cytological, immunophenotypical features (immunohistochemistry and Flow cytometry) and molecular pattern (translocation by FISH, Mutations landscape by NGS, and genomic abnormalities by CGH array). An important heterogeneity of clinical presentation and prognosis arises within the same lymphoma subtype. Clinical evolution is characterized by relapses, cytological progression and transformation into diffuse large B cell lymphoma, aggressive lymphoma or high-grade lymphomas.


Assuntos
Linfócitos B/patologia , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/patologia , Transtornos Linfoproliferativos/classificação , Transtornos Linfoproliferativos/patologia , Doença Crônica , Diagnóstico Diferencial , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Síndrome
15.
J Korean Med Sci ; 34(30): e203, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31373185

RESUMO

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV. METHODS: Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed. RESULTS: Diagnosis of PTLD was made in seven patients (PTLD group), and 39 patients had EV only (EV only group). The median time from KT to EV and PTLD diagnosis was 6.7 (range 0.4-47.8) months and 8.2 (range, 2.8-98.9) months, respectively. There were no significant differences between the groups in terms of sex, age at transplantation, donor type, EBV viral load, or EV-free duration after KT. Higher tacrolimus level before EV (hazard ratio, 44.5; P = 0.003) was an independent risk factor for PTLD in multivariate Cox regression analysis. Six patients with a high EBV load (median 171,639 copies/mL) were treated with preemptive rituximab (RTX) therapy, resulting in transient reduction of EBV load. None of these patients developed PTLD (median follow-up 51.5 months); however, two had neutropenia and two developed infection requiring hospital admission. CONCLUSION: In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD.


Assuntos
Herpesvirus Humano 4/isolamento & purificação , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/terapia , Viremia/etiologia , Antineoplásicos Imunológicos/uso terapêutico , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neutropenia/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Rituximab/uso terapêutico , Transplante Homólogo , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia
17.
Eur J Oncol Nurs ; 42: 21-27, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446260

RESUMO

PURPOSE: Hematopoietic stem cell transplant (HSCT) is an intensive treatment associated with distressing treatment and disease-related symptoms that affect patient outcomes such as functional status and quality of life. Self-efficacy for symptom management (SESM) is a person's belief in their ability to perform behaviors to prevent and relieve symptoms. Presence of SESM can impact symptom distress and functional status. This study describes the changes over time and relationships among SESM, symptom distress, and physical functional status in adults during the acute phase of HSCT. METHODS: Patients (n = 40) completed measures of symptom distress, SESM, and physical function at time points prior to and at days 7, 15 and 30 post-transplant. Clinical outcomes were length of stay and number of readmissions. RESULTS: Symptom distress, physical function, and SESM changed significantly over time. There was a significant negative relationship between symptom distress and physical function and between symptom distress and SESM at all points. The lowest levels of SESM and physical function were at day 7 when symptom distress was highest. Symptom distress was a moderator for the relationship between physical function and SESM at day 15. CONCLUSION: This was the first study to examine SESM in the acute phase of HSCT. Higher SESM was associated with fewer symptoms and increased physical function. Less symptom distress was associated with higher physical function and confidence to manage symptoms. These findings provide the basis for development of patient-centered interventions to enhance SESM when symptoms are at their highest immediately after HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/psicologia , Transtornos Linfoproliferativos/psicologia , Síndromes Mielodisplásicas/psicologia , Cuidados Paliativos , Autoeficácia , Adulto , Idoso , Feminino , Hospitalização , Humanos , Leucemia/terapia , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Projetos Piloto , Qualidade de Vida , Autocuidado , Avaliação de Sintomas
19.
Surg Pathol Clin ; 12(3): 719-731, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352984

RESUMO

Technical advances in diagnostic modalities have led to the characterization of indolent lymphoid disorders similar to the in situ lesions described in epithelial malignancies. These early and indolent lymphoid lesions share clinicopathologic characteristics with well-characterized lymphoid malignancies such as chronic lymphocytic leukemia and follicular lymphoma. The in situ lesions have an indolent clinical course with only a minor subset shown to progress to frank malignancies. In addition to the in situ lesions, new indolent lymphoproliferative disorders have been recently characterized. Diagnosis and characterization of these indolent lesions is necessary to prevent overtreatment with aggressive therapeutic regimens.


Assuntos
Linfoma Folicular/patologia , Transtornos Linfoproliferativos/patologia , Linfócitos B/patologia , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Leucemia Linfocítica Crônica de Células B/patologia , Linfocitose/patologia , Linfoma de Célula do Manto/patologia , Prognóstico
20.
Surg Pathol Clin ; 12(3): 733-743, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352985

RESUMO

The gastrointestinal tract is a common extranodal site of involvement by lymphomas. These may be diagnostically challenging because they can mimic a variety of benign conditions and may be difficult to subclassify when malignant. The classification of gastrointestinal lymphomas is an evolving area with some recent changes. Although some of these entities are rare, they are important to recognize because of the variable clinical presentations, comorbidities, and treatment implications. This article explores new and revised entities in gastrointestinal lymphoproliferative disorders.


Assuntos
Neoplasias Gastrointestinais/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Doença Celíaca/complicações , Doença Crônica , Diagnóstico Diferencial , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/terapia , Humanos , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/terapia , Prognóstico
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