scholarly journals High risk of relapsed disease in patients with NK/T cell chronic active Epstein-Barr virus disease outside of Asia

2021 ◽  
Author(s):  
Blachy J Dávila Saldaña ◽  
Tami D John ◽  
Challice L Bonifant ◽  
David Buchbinder ◽  
Sharat Chandra ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Virus Disease ◽  
Control Strategies ◽  
The United States ◽  
High Rate ◽  
Hematopoietic Stem ◽  
Curative Therapy ◽  
Barr Virus ◽  
Epstein Barr ◽  
Relapsed Disease

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or NK cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis (HLH) and/or lymphoma. The disease is more common in Asia than in the United States and Europe. While allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown. Here, we retrospectively assessed an international cohort of 57 patients outside of Asia. Treatment for the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% v 25%, p<0.01), there was still a high rate of death in both groups. Mortality was largely not affected by age, ethnicity, cell type involvement, or disease complications, but development of lymphoma showed a trend with increased mortality (56% v 35%, p=0.1). The overwhelming majority (75%) of patients who died after HSCT succumbed to relapsed disease. CAEBV remains challenging to treat when advanced disease is present. Outcomes would likely improve with better disease control strategies, earlier referral for HSCT, and close follow-up after HSCT including aggressive management of rising EBV DNA levels in the blood.

scholarly journals How I treat T-cell chronic active Epstein-Barr virus disease

Blood ◽  
2018 ◽  
Vol 131 (26) ◽  
pp. 2899-2905 ◽  
Author(s):  
Catherine M. Bollard ◽  
Jeffrey I. Cohen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Histone Deacetylase Inhibitors ◽  
Virus Disease ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Curative Therapy ◽  
Barr Virus ◽  
Epstein Barr

Abstract T-cell chronic active Epstein-Barr virus (CAEBV) is a rare disease in which EBV is present predominantly in T cells that infiltrate the tissues; patients have high levels of EBV in the blood. If untreated, patients often develop liver failure, hemophagocytic lymphohistiocytosis, coronary artery aneurysms, EBV infiltrating T cells impairing organ function, or T-cell lymphomas refractory to treatment. At present, hematopoietic stem-cell transplantation is the only curative therapy, and it is critical to make a proper diagnosis and initiate transplantation before the disease progresses to an irreversible stage. Specific medications such as high-dose systemic corticosteroids or ganciclovir combined with either histone deacetylase inhibitors or bortezomib may temporarily reduce systemic toxicity associated with T-cell CAEBV and allow the patient time to receive a transplant. Relapses of the disease after transplantation have also occurred, and the use of donor-derived virus-specific T cells may help to treat these relapses.

scholarly journals Clinical analysis of chronic active EBV infection with coronary artery dilatation and a matched case–control study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ang Wei ◽  
Honghao Ma ◽  
Liping Zhang ◽  
Zhigang Li ◽  
Yitong Guan ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Serum Ferritin ◽  
Epstein Barr Virus ◽  
Epstein Barr Virus Infection ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Coronary Artery Dilatation ◽  
Tnf Α ◽  
Epstein Barr

Abstract Objective To investigate the clinical characteristics, treatment, prognosis and risk factors for chronic active Epstein–Barr Virus infection (CAEBV) associated with coronary artery dilatation (CAD) in children. Methods Children with CAEBV associated with CAD hospitalized at Beijing Children’s Hospital, Capital Medical University from March 2016 to December 2019 were analyzed. Children with CAEBV without CAD were selected as the control group and matched by sex, age, treatment and admission time. The clinical manifestations, laboratory and ultrasound examinations, treatment and prognosis of the children were collected in both groups. Results There were 10 children with CAEBV combined with CAD, including 6 males and 4 females, accounting for 8.9% (10/112) of CAEBV patients in the same period, with an onset age of 6.05 (2.8–14.3) years. The median follow-up time was 20 (6–48) months. All the patients had high copies of EBV-DNA in whole blood [1.18 × 107 (1.90 × 105–3.96 × 107) copies/mL] and plasma [1.81 × 104 (1.54 × 103–1.76 × 106) copies/mL], and all biopsy samples (bone marrow, lymph nodes or liver) were all positive for Epstein–Barr virus-encoded small RNA. Among the 10 children, 8 had bilateral CAD, and 2 patients had unilateral CAD. After diagnosis, 7 children were treated with L-DEP chemotherapy in our hospital. After chemotherapy, four patients underwent allogeneic hematopoietic stem cell transplantation (HSCT). The others were waiting for HSCT. At the time of the last patients follow up record, the CAD had returned to normal in 3 patients, and the time from the diagnosis of CAD to recovery was 21 (18–68) days. LDH, serum ferritin, TNF-α and IL-10 levels were statistically significantly different between the two groups (P = 0.009, 0.008, 0.026 and 0.030). There were no significant differences in survival rate between the two groups (P = 0.416). Conclusion The incidence of CAEBV with CAD was low. CAEBV with CAD did not influence the prognosis. Patients who had high LDH, serum ferritin, TNF-α, and IL-10 levels early in their illness were more likely to develop CAD.

Epstein-Barr Virus Infection

1994 ◽  
Vol 15 (2) ◽  
pp. 63-68
Author(s):  
William A. Durbin ◽  
John L. Sullivan
Keyword(s):  
Epstein Barr Virus ◽  
Western Europe ◽  
Age Groups ◽  
The United States ◽  
The Philippines ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
The Usa ◽  
Epstein Barr ◽  
Barr Virus Infection

Introduction Virtually all humans become infected with Epstein-Barr virus (EBV). The vast majority of these infections are inapparent, occur early in life, and are associated with lifelong latent infection and persistent shedding of virus. Epidemiology The prevalence of antibody to EBV has been determined in many age groups throughout the world. In developing and tropical areas, infection takes place early in life and is inapparent, with most children demonstrating antibody by age 6 years. Infection is believed to be related to hygiene and crowding as well as to cultural patterns that lead to exposure to saliva (eg, prechewing of food). In contrast, infection in Western Europe and the United States in childhood is less common, with only 35% to 50% of 5-year-olds demonstrating antibody. Infectious mononucleosis (IM) emerges as a significant clinical entity only in populations where a sizable percentage of young adults lack immunity to EBV. Thus, IM is unknown among college freshman in Thailand or the Philippines, virtually all of whom have antibody to EBV at the time of admission. On the other hand, in schools in the USA and England, where the susceptibility percentage is in the range of 35% to 50%, infection is seen commonly. In such university settings, approximately 12% of susceptible students become infected with EBV during the freshman year.

scholarly journals Nivolumab treatment of relapsed/refractory Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis in adults

Blood ◽  
2020 ◽  
Vol 135 (11) ◽  
pp. 826-833 ◽  
Author(s):  
Pengpeng Liu ◽  
Xiangyu Pan ◽  
Chong Chen ◽  
Ting Niu ◽  
Xiao Shuai ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Epstein Barr Virus ◽  
Sequencing Analysis ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Life Threatening ◽  
Programmed Death Protein 1 ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening hyperinflammatory syndrome triggered by EBV infection. It often becomes relapsed or refractory (r/r), given that etoposide-based regimens cannot effectively clear the virus. r/r EBV-HLH is invariably lethal in adults without allogeneic hematopoietic stem cell transplantation. Here, we performed a retrospective analysis of 7 r/r EBV-HLH patients who were treated with nivolumab on a compassionate-use basis at West China Hospital. All 7 patients tolerated the treatment and 6 responded to it. Five of them achieved and remained in clinical complete remission with a median follow-up of 16 months (range, 11.4-18.9 months). Importantly, both plasma and cellular EBV-DNAs were completely eradicated in 4 patients. Single-cell RNA-sequencing analysis showed that HLH syndrome was associated with hyperactive monocytes/macrophages and ineffective CD8 T cells with a defective activation program. Nivolumab treatment expanded programmed death protein-1–positive T cells and restored the expression of HLH-associated degranulation and costimulatory genes in CD8 T cells. Our data suggest that nivolumab, as a monotherapy, provides a potential cure for r/r EBV-HLH, most likely by restoring a defective anti-EBV response.

scholarly journals Epstein-Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes for the Treatment of Patients With EBV-Positive Relapsed Hodgkin's Disease

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2925-2934 ◽  
Author(s):  
Marie A. Roskrow ◽  
Nobuhiro Suzuki ◽  
Yan-jun Gan ◽  
John W. Sixbey ◽  
Catherine Y.C. Ng ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Barr Virus ◽  
Specific Ctls ◽  
Epstein Barr ◽  
Relapsed Disease

Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) is effective prophylaxis and treatment of EBV-positive immunoblastic lymphoma in immunocompromised patients. In 50% of patients with Hodgkin's disease, the tumor cells are EBV antigen-positive and may therefore also be suitable targets for treatment with virus-specific CTLs. However, Hodgkin's disease may produce several inhibitory effects on immune induction and effector function in vivo, which may preclude the generation or effector function of CTLs reactive against EBV viral proteins, including those expressed by the tumor cells. We have investigated whether EBV-specific CTLs could be generated ex vivo from 13 patients with Hodgkin's disease: nine with active relapsed disease and four who were in clinical remission after a first or subsequent relapse. CTL lines were successfully generated from nine of 13 patients (five active disease, four remission). Although these lines had an abnormal pattern of expansion comparable to EBV-specific CTLs generated from normal donors, their phenotype was normal except for reduced expression of the zeta chain of the T-cell receptor (TCR). Their cytotoxicity was also compared to EBV-specific lines generated from normal donors and included activity against LMP2a, one of the three weakly immunogenic viral antigens expressed by Hodgkin's tumor cells. To assess the activity of the CTLs in vivo, they were gene-marked and infused into three patients with multiply relapsed disease. The CTLs persisted for more than 13 weeks postinfusion and retained their potent antiviral effects in vivo, thereby enhancing the patient immune response to EBV. This approach may therefore have value in the treatment of EBV-positive Hodgkin's disease.

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