RESUMEN
BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. OBJECTIVES: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively. CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.
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Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Linfoma de Células B Grandes Difuso/virología , Linfoma de Células B Grandes Difuso/terapia , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/terapia , Rituximab/uso terapéutico , Trasplante Homólogo/efectos adversosAsunto(s)
Antineoplásicos Inmunológicos , Inmunoterapia Adoptiva , Linfoma de Células B , Linfoma de Células T , Neoplasias Primarias Secundarias , Humanos , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Productos Biológicos/administración & dosificación , Productos Biológicos/efectos adversos , Síndrome de Liberación de Citoquinas/inmunología , Herpesvirus Humano 4/aislamiento & purificación , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Linfoma de Células B/inmunología , Linfoma de Células B/terapia , Linfoma de Células B/virología , Linfoma de Células T/diagnóstico , Linfoma de Células T/inmunología , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/inmunología , Receptores Quiméricos de Antígenos/inmunología , RiesgoAsunto(s)
Antineoplásicos Inmunológicos , Hematopoyesis Clonal , Inmunoterapia Adoptiva , Linfoma de Células B , Linfoma de Células T , Neoplasias Primarias Secundarias , Humanos , Inmunoterapia Adoptiva/efectos adversos , Linfoma de Células T/diagnóstico , Linfoma de Células T/genética , Linfoma de Células T/inmunología , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/inmunología , Receptores Quiméricos de Antígenos/inmunología , Riesgo , Hematopoyesis Clonal/genética , Hematopoyesis Clonal/inmunología , Linfoma de Células B/genética , Linfoma de Células B/inmunología , Linfoma de Células B/terapia , Linfoma de Células B/virología , Herpesvirus Humano 4/aislamiento & purificación , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Productos Biológicos/administración & dosificación , Productos Biológicos/efectos adversos , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/inmunologíaRESUMEN
INTRODUCTION: This study investigated variables associated with mortality in kidney transplant recipients (KTRs) diagnosed with post-transplant lymphoproliferative disease (PTLD) and a simultaneous Epstein-Barr virus (EBV) viremia. METHODS: This was a retrospective cohort study enrolling KTRs diagnosed with PTLD between 2018 and 2020. Outcome: death within two years after diagnosis. RESULTS: Among 1,625 KTRs who collected EBV viremia (by PCR, 2018-2020) for any reason, 238 (14.6%) had a positive viral load and 41 (17.2%) simultaneous PTLD. These 41 patients were 40.1 years old at diagnosis and 8.6 years after transplantation; 26.8% were induced with rATG and 92.7% were maintained on tacrolimus and azathioprine (TAC/AZA) as immunosuppressive regimen. Lymph nodes (75.6%) was the most common site of PTLD, followed by the gastrointestinal tract (48.8%), with 61.0% at Lugano stage IV and 80.5% monomorphic PTLD. The mean EBV viral load was 12,198 IU/mL. One- and two-year patient survival post-diagnosis was 60.4% and 46.8%, respectively. In the Cox regression analysis, age at PTLD diagnosis (HR for each year = 1.039; p < 0.001) and EBV viral load (HR for each log = 1.695; p = 0.026) were associated with risk of death. CONCLUSION: This study suggests that in patients predominantly on TAC/AZA, PTLD with simultaneous EBV positive viral load is a late event, and worse survival is associated with older age and EBV viral load at diagnosis.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Trasplante de Riñón , Trastornos Linfoproliferativos , Complicaciones Posoperatorias , Carga Viral , Humanos , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/virología , Trastornos Linfoproliferativos/etiología , Estudios Retrospectivos , Masculino , Femenino , Adulto , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Persona de Mediana Edad , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Factores de Edad , Complicaciones Posoperatorias/virología , Complicaciones Posoperatorias/diagnóstico , Viremia/diagnóstico , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéuticoRESUMEN
Human papillomaviruses (HPVs) and herpesviruses are detected in patients with epithelial ovarian cancer (EOC). We sought to analyze the prevalence of HPV's 16 and 18, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA in peripheral blood, ovarian, and fallopian tube (FT) tissue samples collected from 97 EOC patients, including 71 cases of high-grade serous ovarian carcinoma (HGSOC), and from 60 women with other tumors or non-neoplastic gynecological diseases. DNA isolates were analyzed by PCR methods, including droplet digital PCR. The results demonstrate that (1) HPV16 DNA has been detected in one-third of the FT and tumor samples from EOCs; (2) the prevalence and quantity of HPV16 DNA were significantly higher in FT samples from HGSOCs, non-HGSOCs, and ovarian metastases than in those from non-neoplastic diseases; (3) CMV and EBV have been detected in approximately one-seventh of EOC samples. The results suggest that HPV16 might be a potential risk factor for EOC development.
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Carcinoma Epitelial de Ovario , Trompas Uterinas , Papillomavirus Humano 16 , Neoplasias Ováricas , Infecciones por Papillomavirus , Humanos , Femenino , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Factores de Riesgo , Carcinoma Epitelial de Ovario/virología , Carcinoma Epitelial de Ovario/patología , Persona de Mediana Edad , Trompas Uterinas/virología , Trompas Uterinas/patología , Adulto , Anciano , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Neoplasias Ováricas/virología , Neoplasias Ováricas/patología , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Citomegalovirus/aislamiento & purificación , Citomegalovirus/genética , ADN Viral/genéticaRESUMEN
A 62-year-old man presented with fever and anorexia since July X. Initial treatments were rendered ineffective, and due to altered consciousness and vomiting, he was referred to our hospital. On admission, he manifested delirium, drowsiness, and disorientation. While blood tests were normal, gastroscopy identified a type 3 tumor in his lower gastric body, later diagnosed as a poorly differentiated adenocarcinoma. Immunohistochemistry demonstrated negative human epidermal growth factor receptor 2 and positive programmed death-ligand 1 expression with a combined positive score ≥5. Furthermore, a positive Epstein-Barr virus-encoded small RNA in situ hybridization result was noted. Abdominal contrast-enhanced CT and PET-CT scans demonstrated multiple lymph node metastases around the stomach and liver, establishing the diagnosis of stage IVB gastric cancer (T4aN2M1). Brain magnetic resonance imaging (MRI) demonstrated enhanced lesions in the brainstem, cerebellar sulci, and right occipital lobe. Although cerebrospinal fluid cytology was negative for malignancy, the clinical symptoms and MRI findings confirmed leptomeningeal carcinomatosis (LMC). The patient underwent radiotherapy for LMC (total of 30Gy in 10 fractions), followed by combination therapy with a nivolumab and SOX regimen. Posttreatment, the LMC symptoms resolved;however, he experienced grade 3 immune-related adverse events related to liver dysfunction. Nivolumab was discontinued, and with steroid administration, the adverse events improved. Imaging evaluations posttreatment showed gastric tumor reduction and the absence of LMC. After 7 cycles, nivolumab was reintroduced, with no liver dysfunction recurrence noted through 15 cycles. Endoscopic examination 1 year postonset demonstrated that the gastric tumor had scarred, and MRI showed no signs of LMC recurrence. In 5-8% of solid tumors, LMC complications are present, resulting in limited treatment options and poor prognosis. Recent reports suggest the potential of immune checkpoint inhibitors in treating intracranial metastasis from solid tumors. In Japan, nivolumab was approved for gastric cancer treatment in 2017 and for first-line therapy in combination with chemotherapy since 2021. We report a case in which radiotherapy and chemotherapy combined with nivolumab provided durable control of LMC originating from gastric cancer for more than 1 year.
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Infecciones por Virus de Epstein-Barr , Carcinomatosis Meníngea , Nivolumab , Neoplasias Gástricas , Humanos , Masculino , Persona de Mediana Edad , Nivolumab/uso terapéutico , Nivolumab/administración & dosificación , Carcinomatosis Meníngea/secundario , Infecciones por Virus de Epstein-Barr/complicaciones , Resultado del Tratamiento , Herpesvirus Humano 4/aislamiento & purificaciónRESUMEN
AIMS: This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients. METHODS: In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus. FINDINGS: HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs. CONCLUSION: Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies.
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Virus BK , Infecciones por Citomegalovirus , Citomegalovirus , Infecciones por Virus de Epstein-Barr , Rechazo de Injerto , Herpesvirus Humano 4 , Trasplante de Riñón , Infecciones por Polyomavirus , Carga Viral , Viremia , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Virus BK/aislamiento & purificación , Virus BK/genética , Adulto , Estudios Transversales , Infecciones por Polyomavirus/virología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Citomegalovirus/virología , Citomegalovirus/aislamiento & purificación , Citomegalovirus/genética , Rechazo de Injerto/virología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Irán/epidemiología , Factores de Riesgo , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/sangre , Anciano , Adulto Joven , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
BACKGROUND: Epstein-Barr virus-positive mucocutaneous ulcer is one of the mature B-cell lymphoproliferative diseases occurring in patients with immune dysfunction including those with immunosuppressive treatment such as methotrexate. CASE PRESENTATION: A Japanese elderly man in his 80s with rheumatoid arthritis on methotrexate was admitted to our hospital complaining persistent pharyngeal pain. Laboratory tests revealed severe pancytopenia, elevated C-reactive protein, and increased creatinine levels. An otolaryngological examination showed ulceration of the right tonsil, from which diagnostic biopsy was performed. The diagnosis of Epstein-Barr virus-positive mucocutaneous ulcer was made and bone marrow aspiration revealed hypocellularity and megaloblastic changes. Pancytopenia was improved after discontinuing methotrexate, and repeated bone marrow aspiration test revealed recovery of normal cellularity and disappearance of dysplasia, confirming the diagnosis of methotrexate intoxication. Tonsil ulcer was improved only with discontinuation of methotrexate, which strongly supported the diagnosis of EBV-MCU. CONCLUSION: Our case suggested that even this best prognosis form of lymphoproliferative disease could lead to fatal complications if not appropriately managed.
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Artritis Reumatoide , Infecciones por Virus de Epstein-Barr , Metotrexato , Humanos , Metotrexato/efectos adversos , Masculino , Infecciones por Virus de Epstein-Barr/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Anciano de 80 o más Años , Úlcera/inducido químicamente , Inmunosupresores , Trastornos Linfoproliferativos/inducido químicamente , Herpesvirus Humano 4/aislamiento & purificación , Pancitopenia/inducido químicamente , Tonsila Palatina/patologíaRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients. METHODS: In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups. We compared the demographic characteristics, clinical manifestations and signs, laboratory tests and prognosis, and explored the risk factors of EBV infection by receiver operating characteristic (ROC) curve and logistic regression. RESULTS: A total of 120 hospitalized SFTS patients with EBV-DNA testing were enrolled in this study. Patients with EBV infection had statistically significant higher mortality rate (32.0% vs. 11.43%, P = 0.005). Compared with the non-infected group, the EBV-infected group had higher levels of C-reactive protein (CRP), creatine-kinase (CK), fasting blood glucose (FBG), blood urea nitrogen (BUN), D-dimer, and CD56+ cell counts, lower levels of immunoglobulin G (IgG), IgM, complement 3 (C3), and C4. The proportion of patients with age ≥ 60 years and ferritin > 1500.0 ng/ml in the EBV-infected group was significantly higher than that in the non-infected group. The results of ROC analysis showed that the cut-off values of CRP, IgG, C3, C4, and CD56+ cell counts to predict EBV infection were 13.2 mg/l, 12.5 g/l, 1.1 g/l, 0.6 g/l, 0.3 g/l, and 94.0 cells/µl. Multivariable logistic analysis showed that age ≥ 60 years old, CRP > 13.2 mg/l, BUN > 5.4 mmol/l, ferritin > 1500.0 ng/ml, IgG < 12.5 g/l, IgM < 1.1 g/l, C4 < 0.3 g/l, and CD56+ cell counts > 94.0 cells/µl were the independent risk factors of EBV infection in SFTS patients. CONCLUSIONS: SFTS combined with EBV infection is associated with high morbidity and mortality. It is necessary to strengthen screening for EBV infection and its early predictive markers after admission in SFTS patients.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Síndrome de Trombocitopenia Febril Grave , Humanos , Masculino , Femenino , Persona de Mediana Edad , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Estudios Retrospectivos , Síndrome de Trombocitopenia Febril Grave/virología , Síndrome de Trombocitopenia Febril Grave/sangre , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Anciano , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Factores de Riesgo , Pronóstico , Adulto , Curva ROC , China/epidemiología , Anticuerpos Antivirales/sangre , ADN Viral/sangreAsunto(s)
Herpesvirus Humano 4 , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/genética , Carcinoma/virología , Carcinoma/genéticaRESUMEN
PURPOSE: To find an association between oral mucosal human papilloma- and/or Epstein-Barr (HPV, EBV) virus infection in patients with dry mouth and/or Sjögren's syndrome (SS) compared to healthy controls and to find connections with salivary gland histopathological alterations. MATERIALS AND METHODS: Ninety-two participants were divided into four groups: 1. healthy controls (n = 32); 2. xerostomia (n = 28); 3. hyposalivation (n = 22); and 4. SS groups (n = 10). To detect virus infection brush biopsy was outlined in all groups. Detections of virus-specific sequences were achieved with polymerase chain reaction (PCR). Lip biopsy and histopathological assessment was performed in groups 2, 3 and 4. RESULTS: HPV positivity of oral mucosal cells was shown in group 1: 1 (3.12%); group 2: 3 (10.7%); group 3: 2 (8.26%); and in group 4: 0 of the samples. EBV was present in group 1: 14 (43.7%); group 2: 17 (60.7%); group 3: 6 (27.3%); and in group 4: 5 (50%) of the cases. There was no statistically significant difference between the attributes. Intact salivary gland in 28.2%, chronic sialadenitis in 28.2%, stromal fibrosis in 6.5%, lipomatous atrophy in 8.6%, fibrous atrophy in 6.5% and positive focus score (SS) in 26.1% were found in the subjects. Neither HPV nor EBV infection caused statistically significantly more histological abnormalities. CONCLUSION: Orofacial mucosal HPV and/or EBV DNA rates did not differ statistically significantly in patients with xerostomia or hyposalivation or SS compared to healthy controls, therefore, it cannot prove the provocative role of these viruses in dry mouth and/or SS. Neither dry mouth nor SS were accompanied by statistically significantly more salivary gland alterations in HPV- and/or EBV-positive subjects; these alterations are frequent in the virus-negative cases too.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Mucosa Bucal , Síndrome de Sjögren , Xerostomía , Humanos , Síndrome de Sjögren/virología , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Femenino , Mucosa Bucal/virología , Mucosa Bucal/patología , Persona de Mediana Edad , Masculino , Adulto , Infecciones por Virus de Epstein-Barr/complicaciones , Hungría , Infecciones por Papillomavirus/virología , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Glándulas Salivales/patología , Glándulas Salivales/virología , ADN Viral/análisis , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , Virus del Papiloma HumanoRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV-driven malignancies. The most frequent EBV-induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV-associated smooth muscle tumors (EBV-SMT). EBV-SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV-SMT (PT-SMT) are scarce in kidney transplant recipients. METHODS: We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT-SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT-SMT, evolution of graft function, and patient survival. RESULTS: Eight patients were included. The median age at PT-SMT diagnosis was 31 years (range 6.5-40). PT-SMT occurred after a median delay of 37.8 months after transplantation (range 6-175). PT-SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow-up after PT-SMT diagnosis (median 33 months (range 17-132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow-up. CONCLUSION: PT-SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT-SMT is low in kidney transplant recipients (0.07% in our cohort), PT-SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Trasplante de Riñón , Complicaciones Posoperatorias , Tumor de Músculo Liso , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Tumor de Músculo Liso/virología , Tumor de Músculo Liso/etiología , Tumor de Músculo Liso/patología , Tumor de Músculo Liso/diagnóstico , Adulto , Estudios de Seguimiento , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/aislamiento & purificación , Pronóstico , Francia/epidemiología , Adolescente , Adulto Joven , Niño , Complicaciones Posoperatorias/diagnóstico , Rechazo de Injerto/etiología , Fallo Renal Crónico/cirugía , Supervivencia de Injerto , Factores de Riesgo , Pruebas de Función Renal , Tasa de Filtración Glomerular , Tasa de SupervivenciaRESUMEN
BACKGROUND: The hyperinflammatory condition and lymphoproliferation due to Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) affect the detection of lymphomas by 18F-FDG PET/CT. We aimed to improve the diagnostic capabilities of 18F-FDG PET/CT by combining laboratory parameters. METHODS: This retrospective study involved 46 patients diagnosed with EBV-positive HLH, who underwent 18F-FDG PET/CT before beginning chemotherapy within a 4-year timeframe. These patients were categorized into two groups: EBV-associated HLH (EBV-HLH) (n = 31) and EBV-positive lymphoma-associated HLH (EBV + LA-HLH) (n = 15). We employed multivariable logistic regression and regression tree analysis to develop diagnostic models and assessed their efficacy in diagnosis and prognosis. RESULTS: A nomogram combining the SUVmax ratio, copies of plasma EBV-DNA, and IFN-γ reached 100% sensitivity and 81.8% specificity, with an AUC of 0.926 (95%CI, 0.779-0.988). Importantly, this nomogram also demonstrated predictive power for mortality in EBV-HLH patients, with a hazard ratio of 4.2 (95%CI, 1.1-16.5). The high-risk EBV-HLH patients identified by the nomogram had a similarly unfavorable prognosis as patients with lymphoma. CONCLUSIONS: The study found that while 18F-FDG PET/CT alone has limitations in differentiating between lymphoma and EBV-HLH in patients with active EBV infection, the integration of a nomogram significantly improves the diagnostic accuracy and also exhibits a strong association with prognostic outcomes.
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Infecciones por Virus de Epstein-Barr , Fluorodesoxiglucosa F18 , Linfohistiocitosis Hemofagocítica , Nomogramas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Femenino , Masculino , Linfohistiocitosis Hemofagocítica/diagnóstico por imagen , Linfohistiocitosis Hemofagocítica/virología , Persona de Mediana Edad , Estudios Retrospectivos , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico por imagen , Adulto , Anciano , Radiofármacos , Herpesvirus Humano 4/aislamiento & purificación , Pronóstico , Linfoma/diagnóstico por imagen , Linfoma/virologíaRESUMEN
Emerging biologic subsets and new prognostic markers are significantly important for aggressive diffuse large B-cell lymphoma (DLBCL). Nevertheless, the high cost of testing limits the availability of these tests in most hospitals, thus making prognostic judgment based on basic immunohistochemical testing, whole blood Epstein-Barr virus DNA (WBEBV) surveillance and clinical features advantageous for hospitals and patients with poor medical conditions. We included 647 DLBCL patients treated in our hospital from January 2009 to March 2023. Non-germinal center B-cell like, Ki-67, and International Prognostic Index (IPI) scores were related to cMYC/B-cell lymphoma 2 (Bcl-2)-double expression. Age, Epstein-Barr virus-encoded small RNA (EBER) positivity, and IPI scores were associated with mortality. The cutoffs for differential overall survival (OS) of age, WBEBV, Bcl-2, and cMYC were 57 years, 1514 copies/mL (baseline), 5.89 × 104 copies/mL (treatment), 40%, and 55%, respectively. EBER positivity was significantly associated with a worse OS. Patients with newly defined DE (Bcl-2 ≥ 40 and cMYC > 55) had a worse prognosis than controls (p = 0.04). We found that cMYC with an optimal cutoff of 47.5 could effectively predict high-grade DLBCL with an area under the curve of 0.912, and the specificity and sensitivity were 70.7% and 100%, respectively. Our study provides valuable insights into the prognostic factors and biomarker cutoffs that influence OS in DLBCL patients, which may guide clinicians in tailoring treatment strategies and improving patient outcomes.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/virología , Masculino , Femenino , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Persona de Mediana Edad , Pronóstico , Anciano , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Adulto , Anciano de 80 o más Años , Inmunohistoquímica/métodos , Adulto Joven , ADN Viral , Biomarcadores de Tumor , Adolescente , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Estudios RetrospectivosRESUMEN
Epstein-Barr virus (EBV) is a ubiquitous and oncogenic virus that is associated with various malignancies and non-malignant diseases and EBV DNA detection is widely used for the diagnosis and prognosis prediction for these diseases. The dried blood spots (DBS) sampling method holds great potential as an alternative to venous blood samples in geographically remote areas, for individuals with disabilities, or for newborn blood collection. Therefore, the objective of this study was to assess the viability of detecting EBV DNA load from DBS. Matched whole blood and DBS samples were collected for EBV DNA extraction and quantification detection. EBV DNA detection in DBS presented a specificity of 100 %. At different EBV DNA viral load in whole blood, the sensitivity of EBV DNA detection in DBS was 38.78 % (≥1 copies/mL), 43.18 % (≥500 copies/mL), 58.63 % (≥1000 copies/mL), 71.43 % (≥2000 copies/mL), 82.35 % (≥4000 copies/mL), and 92.86 % (≥5000 copies/mL), respectively. These results indicated that the sensitivity of EBV DNA detection in DBS increased with elevating viral load. Moreover, there was good correlation between EBV DNA levels measured in whole blood and DBS, and on average, the viral load measured in whole blood was about 6-fold higher than in DBS. Our research firstly demonstrated the feasibility of using DBS for qualitative and semi-quantitative detection of EBV DNA for diagnosis and surveillance of EBV-related diseases.
Asunto(s)
ADN Viral , Pruebas con Sangre Seca , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Sensibilidad y Especificidad , Carga Viral , Humanos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Carga Viral/métodos , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/sangre , ADN Viral/sangre , Pruebas con Sangre Seca/métodos , Manejo de Especímenes/métodos , Sangre/virologíaRESUMEN
BACKGROUND: Epstein-Barr Virus (EBV) is associated with lung disease in immunocompromised patients, particularly transplant recipients. EBV DNA testing of lower respiratory tract specimens may have diagnostic utility. METHODS: This was a retrospective, observational study of all patients with bronchoalveolar lavage (BAL) fluids submitted for EBV qPCR testing from February 2016 to June 2022 at the Stanford Clinical Virology Laboratory. RESULTS: There were 140 patients that underwent 251 EBV qPCR BAL tests (median 1; range 1 - 10). These patients had a mean age of 15.9 years (standard deviation, 15.1 years) and 50 % were female. Transplant recipients accounted for 67.1 % (94/140) of patients, including 67.0 % (63/94) solid organ transplant (SOT) and 33.0 % (31/94) hematopoietic cell transplant. Diagnostic testing was performed more commonly than surveillance testing [57.0 % (143/251) v. 43.0 % (108/251)]; 96.2 % (104/108) of surveillance samples were from lung transplant recipients. Excluding internal control failures, 34.7 % (83/239) of BAL had detectable EBV DNA, encompassing a wide range of viral loads (median=3.03 log10 IU/mL, range 1.44 to 6.06). Overall agreement of EBV DNA in BAL compared to plasma was 74.1 % [117/158; 95 % confidence interval (CI): 66.5 % to 80.7 %], with a kappa coefficient of 0.44 (95 % CI: 0.30 to 0.57). Only 20.1 % (48/239) of results were discussed in a subsequent clinical note, and one result (0.4 %; 1/239) changed clinical management. CONCLUSIONS: EBV qPCR testing on BAL offers limited clinical impact. Additional biomarkers are required to improve the diagnosis of EBV-associated lung diseases.
Asunto(s)
Líquido del Lavado Bronquioalveolar , ADN Viral , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Huésped Inmunocomprometido , Reacción en Cadena en Tiempo Real de la Polimerasa , Humanos , Líquido del Lavado Bronquioalveolar/virología , Femenino , Masculino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Estudios Retrospectivos , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Adolescente , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adulto Joven , Niño , ADN Viral/análisis , ADN Viral/genética , Adulto , Preescolar , Lactante , Persona de Mediana Edad , Carga Viral , Receptores de TrasplantesRESUMEN
Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.
Asunto(s)
Biomarcadores de Tumor , ADN Tumoral Circulante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Humanos , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Masculino , Femenino , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/sangre , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/diagnóstico , Adulto , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/diagnóstico , Estudios Longitudinales , ADN Viral/sangre , Estudios Prospectivos , Anciano , Pronóstico , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Biopsia Líquida/métodos , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicacionesRESUMEN
Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr Virus infection (EBV). Despite ubiquitous EBV infection worldwide, NPC displays a unique geographical distribution in Southern China and Southeast Asia. This observed phenomenon can be attributed to the interplay of different strains of EBV infection with host genetics and environmental factors. Polymorphisms on the EBV BALF2 gene have been shown to influence risk of nasopharyngeal carcinoma (NPC). Notably, two non-synonymous EBV polymorphisms (162476T>C, 163364C>T) account for majority of NPC risk in endemic regions. These polymorphisms confer amino acid changes (I1613V, V317M) within the BALF2 protein. However, their impact on NPC tumor biology is unknown. We evaluated the distribution of BALF2 risk polymorphisms in five independent genomic datasets comprising 351 NPC clinical samples, confirming the high prevalence of high-risk EBV strains in NPC. Importantly, we observed two biologically distinct groups of tumors based on their gene expression profiles when grouped by their EBV risk strains. NPC tumors with the V317M substitution demonstrated increased proliferation processes including cell cycle (NES = 1.71, p = 5.64x10-24) and keratinization (NES = 2.42, p = 6.95x10-17). In contrast, NPC tumors without the V317M substitution demonstrated increased immune-related processes, including cell activation (NES = 1.85, p = 8.29x10-31), myeloid leukocyte activation (NES = 2.16, p = 6.51x10-24) and leukocyte mediated immunity (NES = 1.99, p = 1.05x10-23). These findings provide further insight on the influence of BALF2 variants on NPC tumor biology. EBV risk strains may have the potential to define biologically important groups in NPC.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Proteínas Virales/genética , Proteínas Virales/metabolismo , Masculino , Polimorfismo de Nucleótido Simple , Femenino , Regulación Neoplásica de la Expresión GénicaRESUMEN
PURPOSE: Classic Hodgkin lymphoma (cHL) is a B-cell lymphoma that occurs primarily in young adults and, less frequently, in elderly individuals. A hallmark of cHL is the exceptional scarcity (1%-5%) of the malignant Hodgkin Reed-Sternberg (HRS) cells within a network of nonmalignant immune cells. Molecular determinants governing the relationship between HRS cells and their proximal microenvironment remain largely unknown. EXPERIMENTAL DESIGN: We performed spatially resolved multiplexed protein imaging and transcriptomic sequencing to characterize HRS cell states, cellular neighborhoods, and gene expression signatures of 23.6 million cells from 36 newly diagnosed Epstein-Barr virus (EBV)-positive and EBV-negative cHL tumors. RESULTS: We show that MHC-I expression on HRS cells is associated with immune-inflamed neighborhoods containing CD8+ T cells, MHC-II+ macrophages, and immune checkpoint expression (i.e., PD1 and VISTA). We identified spatial clustering of HRS cells, consistent with the syncytial variant of cHL, and its association with T-cell-excluded neighborhoods in a subset of EBV-negative tumors. Finally, a subset of both EBV-positive and EBV-negative tumors contained regulatory T-cell-high neighborhoods harboring HRS cells with augmented proliferative capacity. CONCLUSIONS: Our study links HRS cell properties with distinct immunophenotypes and potential immune escape mechanisms in cHL.