scholarly journals Double-Stranded DNA (dsDNA) Viral Infections Among Allogeneic Hematopoietic Cell Transplant (HCT) Recipients in the First Year after Transplant

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3296-3296 ◽  
Author(s):  
Vernon F Schabert ◽  
Essy Mozaffari ◽  
Yi-Chien Lee ◽  
Roman Casciano
Keyword(s):  
Viral Infection ◽  
Viral Infections ◽  
Bk Virus ◽  
First Year ◽  
Cell Transplant ◽  
Post Transplant ◽  
Allogeneic Hct ◽  
Barr Virus ◽  
Epstein Barr ◽  
One Year

Abstract Introduction: Double-stranded DNA (dsDNA) viral infections (including cytomegalovirus, adenoviruses, BK virus, and Epstein-Barr virus) can lead to significant morbidity and mortality among immunocompromised patients following allogeneic hematopoietic stem cell transplant (HCT). The lack of a broad-spectrum antiviral with the safety and tolerability to prevent viral infections poses management challenges for patients at risk of multiple dsDNA viral infections. Using a large US insurance claims database, this study describes the incidence of dsDNA viral infections and co-infections among allogeneic HCT recipients. Methods: The MarketScan Research Databases were used to identify commercial and Medicare enrollees with an ICD-9 or CPT procedure code for an allogeneic HCT between 7/1/2009 and 6/30/2014. Eligible patients were required to have 365 days of health plan enrollment prior to HCT, but no minimum enrollment was required post-HCT. Incidence of cytomegalovirus (CMV), adenovirus (AdV), BK virus, Epstein-Barr virus, herpes simplex, varicella zoster, and other dsDNA virus infection was measured from the date of the transplant until one year post-transplant. The rates of infection with two dsDNA viral infections or three or more dsDNA viral infections were assessed, and in-hospital mortality or transfer to hospice services within one year of transplant was reported by the number of observed dsDNA viral infection. Results: We identified 3,035 allogeneic HCT patients (mean age 47.3 years, 56.9% male), including 30.4% (n=924) with at least one dsDNA viral infection within the first year post-transplant. Of these, 69.2% had CMV infection (n=639), 5.4% had AdV infection (n=50), and 10.3% had BK virus infection (n=95). Among patients with a reported dsDNA viral infection, 17.6% (n=163) had more than one dsDNA viral infection, including 14.6% (n=135) with two dsDNA viral infections and 3.0% (n=28) with three or more viral infections. A statistically significant increase in the rate of in-hospital death or transfer to hospice within the first year post-transplant was observed for patients with reported dsDNA viral infection vs those without. Specifically, the rate of in-hospital mortality/transfer to hospice increased from 14.9% (315/2111) for patients without a reported dsDNA viral infection to 19.2% (146/761, p=0.0060) with one dsDNA viral infection, 23.0% (31/135, p=0.0121) for patients with two dsDNA viral infections, and 35.7% (10/28, p=0.0023) for patients with three or more dsDNA viral infections. Conclusions: A substantial proportion of allogeneic HCT recipients with a dsDNA viral infection have two or more dsDNA viral infections. Diagnoses on insurance claims may underestimate true incidence of dsDNA viral infection and co-infection. Mortality risk increases significantly with the number of dsDNA viral infections. Availability of a safe and well-tolerated broad spectrum antiviral for prevention of primary or reactivation infections could potentially reduce the morbidity and mortality associated with dsDNA viral infections and their significant sequelae. Disclosures Schabert: LASER Analytica: Employment. Mozaffari:Chimerix Inc.: Employment, Equity Ownership. Lee:LASER Analytica: Employment. Casciano:LASER Analytica: Employment.

scholarly journals Gammaherpesvirus infection licenses age-associated B cells for pathogenicity in MS and EAE

2021 ◽  
Author(s):  
Isobel C. Mouat ◽  
Jessica R. Allanach ◽  
Vina Fan ◽  
Anna M. Girard ◽  
Iryna Shanina ◽  
...  
Keyword(s):  
B Cells ◽  
Viral Infection ◽  
Viral Infections ◽  
Autoimmune Encephalomyelitis ◽  
Barr Virus ◽  
Ebv Infection ◽  
Latent Viral Infection ◽  
Epstein Barr ◽  
Gammaherpesvirus 68 ◽  
Experimental Autoimmune

While age-associated B cells (ABCs) are known to expand and persist following viral infection and during autoimmunity, their interactions are yet to be studied together in these contexts. Epstein-Barr virus (EBV) infection has long been implicated in multiple sclerosis (MS), and it is not known whether ABCs could play a role in mediating viral contribution to autoimmunity. Here, we show that the circulating ABC population is expanded in people with MS and that EBV infection and MS status differentially impact the circulating ABC phenotype. We then directly compared ABCs during viral infection and autoimmunity using mouse models of EBV, gammaherpesvirus 68 (γHV68), and MS, experimental autoimmune encephalomyelitis (EAE). We observed that splenic ABCs are expanded in a sex-biased manner during both latent virus infection and EAE, and each event drives the ABC population to opposing phenotypes. We have previously shown that latent γHV68 infection exacerbates EAE and here we show that mice lacking ABCs fail to display γHV68-enhanced disease. Collectively, these findings indicate that latent viral infection and central nervous system autoimmunity differentially impact the ABC population and suggests that viral infections such as EBV prime ABCs to contribute pathogenically in MS.

scholarly journals In vitrotoxicity and efficacy of verdinexor, an exportin 1 inhibitor, on opportunistic viruses affecting immunocompromised individuals

2018 ◽  
Author(s):  
Douglas G. Widman ◽  
Savanna Gornisiewicz ◽  
Sharon Shacham ◽  
Sharon Tamir
Keyword(s):  
Small Molecules ◽  
Nuclear Export ◽  
Viral Infections ◽  
Phase 1 ◽  
Dose Range ◽  
Adaptive Immune Response ◽  
Bk Virus ◽  
Healthy Human ◽  
Barr Virus ◽  
Epstein Barr

AbstractInfection of immunocompromised individuals with normally benign opportunistic viruses is a major health burden globally. Infections with viruses such as Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), Kaposi’s sarcoma virus (KSHV), adenoviruses (AdV), BK virus (BKPyV), John Cunningham virus (JCPyV), and human papillomavirus (HPV) are significant concerns for the immunocompromised, including when these viruses exist as a co-infection with human immunodeficiency virus (HIV). These viral infections are more complicated in patients with a weakened immune system, and often manifest as malignancies resulting in significant morbidity and mortality. Vaccination is not an attractive option for these immune compromised individuals due to defects in their adaptive immune response. Verdinexor is part of a novel class of small molecules known as SINE (Selective Inhibitor of Nuclear Export) compounds. These small molecules demonstrate specificity for the nuclear export protein XPO1, to which they bind and block function, resulting in sequestration of XPO1-dependent proteins in the nucleus of the cell. In antiviral screening, verdinexor demonstrated varying levels of efficacy against all of the aforementioned viruses including previously with HIV. Studies by other labs have discussed likely mechanisms of action for verdinexor (ie. XPO-1-dependence) against each virus. GLP toxicology studies suggest that anti-viral activity can be achieved at a tolerable dose range, based on the safety profile of a previous phase 1 clinical trial of verdinexor in healthy human volunteers. Taken together, these results indicate verdinexor has the potential to be a broad spectrum antiviral for immunocompromised subjects for which vaccination is a poor option.

scholarly journals Post-transplant lymphoproliferative disorder in childhood

2014 ◽  
Vol 155 (8) ◽  
pp. 313-318
Author(s):  
Anita Stréhn ◽  
László Szőnyi ◽  
Gergely Kriván ◽  
Lajos Kovács ◽  
György Reusz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lung Transplant ◽  
Epstein Barr Virus ◽  
Stem Cell Transplant ◽  
Lymphoproliferative Disease ◽  
Solid Organ ◽  
Cell Transplant ◽  
Post Transplant ◽  
Barr Virus ◽  
Epstein Barr

Introduction: Among possible complications of transplantation the post-transplant lymphoproliferative disease due to immunosuppressive therapy is of paramount importance. In most cases the direct modulating effect of Epstein–Barr virus on immune cells can be documented. Aim: The aim of the authors was to evaluate the incidence os post-transplant lymphoproliferative diseases in pediatric transplant patients in Hungary. Method: The study group included kidney, liver and lung transplant children followed up at the 1st Department of Pediatrics, Semmelweis University, Budapest and stem cell transplant children at Szent László Hospital, Budapest. Data were collected from 78 kidney, 109 liver and 17 lung transplant children as well as from 243 children who underwent allogenic stem cell transplantation. Results: Between 1998 and 2012, 13 children developed post-transplant lymphoproliferative disorder (8 solid organ transplanted and 5 stem cell transplanted children). The diagnosis was based on histological findings in all cases. Mortality was 3 out of the 8 solid organ transplant children and 4 out of the 5 stem cell transplant children. The highest incidence was observed among lung transplant children (17.6%). Conclusions: These data indicate that post-transplant lymphoproliferative disease is a rare but devastating complication of transplantation in children. The most important therapeutic approaches are reduction of immunosuppressive therapy, chemotherapy and rituximab. Early diagnosis may improve clinical outcome and, therefore, routine polymerase chain reaction screening for Epstein–Barr virus of high risk patients is recommended. Orv. Hetil., 2014, 155(8), 313–318.

EBV Associated Post-Transplant Lymphoproliferative Disorder Complicated with Haemophagocytic Lymphohistiocytosis After Allogeneic Stem Cell Transplant: A Rare Complication with Fatal Outcome

2020 ◽  
Vol 4 (02) ◽  
pp. 49-51
Author(s):  
Tangia Muquith
Keyword(s):  
Stem Cell ◽  
Lymphoproliferative Disorder ◽  
Epstein Barr Virus ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Post Transplant ◽  
Barr Virus ◽  
Epstein Barr

Epstein –Barr virus related post-transplant lymphoproliferative disorder is a fatal and life-threatening complication because of immunocompromised state.1 Haemophagocytic lymphohistiocytosis is a sign of poor outcome in EBV associated PTLD after allogeneic stem cell transplantation. It is particularly common when in vivo T cell depletion strategies have been applied.2 In both situations, post-transplant lymphoproliferative disorder and Haemophagocytic lymphohistiocytosis, infection with EBV is the key mechanism. Here I present a case of 29 years old female with acute myeloid leukaemia after second allogeneic stem cell transplant, who developed PTLD complicated with Haemophagocytic lymphohistiocytosis secondary to Epstein – Barr virus (EBV) infection. Patient was treated with chemo immunotherapy and responded but ultimately died after 100 days of transplant. The association of HLH and EBV related PTLD is rare and data on outcome of these patients are limited with very high mortality.

scholarly journals Presumed Virus-Induced Punctal Occlusion

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Michael Yulish ◽  
Joseph Pikkel
Keyword(s):  
Viral Infection ◽  
Nested Pcr ◽  
Influenza A ◽  
Medical Center ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Epstein Barr ◽  
One Year ◽  
Excised Tissue ◽  
Punctal Occlusion

Purpose.To investigate viral infection as a cause of punctal stenosis in individuals without any ocular or systemic risk factors.Methods.The study group comprised patients with no known cause for punctal occlusion who underwent surgery at one medical center during a one-year period. Excised tissue was subjected to histological examination, PCR, and nested PCR testing for common viruses (adenovirus, influenza A and B, enterovirus, varicella-zoster, CMV, herpes simplex types 1 and 2, Epstein-Barr virus, and parainfluenza type 1).Results.All nine patients identified were female, 20–38 years of age. The three-snip-procedure resolved tearing in eight of them. All excised samples showed chronic mononuclear inflammation compatible with viral infection or with viral infection immune inflammatory reaction. PCR testing was negative for all the viruses examined; however, nested PCR was positive in three patients.Conclusion.This study supports the proposition that punctal occlusion in young healthy females may be due to viral infection.

scholarly journals Risk of Patients Developing Post-Transplant Lymphoproliferative Disorder within the First Year after an Allogeneic Hemopoietic Stem Cell Transplant, 2011 to 2016: A US Claims Database Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5840-5840
Author(s):  
Arie Barlev ◽  
Hairong Xu ◽  
Nicole Fulcher ◽  
Crystal Watson ◽  
Ila Sruti ◽  
...  
Keyword(s):  
Large Scale ◽  
Hemopoietic Stem Cell ◽  
First Year ◽  
Cell Transplant ◽  
Employment Equity ◽  
Claims Database ◽  
Post Transplant ◽  
Allogeneic Hct ◽  
Equity Ownership ◽  
The Mean

Abstract Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a heterogenous disease that can develop after solid organ or allogeneic hemopoietic stem cell transplant (HCT). PTLD after HCT is primarily of the monomorphic subtype and driven by the Epstein-Barr Virus. It is an ultra-rare disease that follows an aggressive clinical course with poor outcomes and for which there is no approved standard treatment. The risk of PTLD after HCT in the current clinical setting is insufficiently quantified, and large-scale data from the US are lacking. The objective of this study was to estimate the incidence of PTLD after allogeneic HCT using a large US claims database. Methods: A retrospective cohort study using the MarketScan Commercial and Medicare Supplemental database was conducted. Patients who received an allogeneic HCT between January 1, 2011 and December 31, 2016 with at least 6 months of continuous enrollment prior to allogeneic HCT were included in the analysis. PTLD cases were identified as having a diagnosis of PTLD (ICD-9 code 238.77 or ICD-10 code D47Z1) or one inpatient or two outpatient claims for preselected, clinically relevant lymphoma codes within 1-year post-transplant. Patients with a clinically relevant lymphoma diagnosis in the 6 months prior to HCT were excluded. The percentage of patients who developed PTLD during the first year after allogeneic HCT was calculated, the average time to PTLD diagnosis was estimated, and patient characteristics at PTLD diagnosis were described. Results: A total of 2,735 eligible patients were included in the analysis; the mean (range) post-transplant follow-up time was 576 (1-2555) days. Overall, 103 patients (3.8%; 95% CI: 3.1%-4.6%) developed PTLD during the first year after allogeneic HCT, and the median (range) time from allogeneic HCT to PTLD diagnosis was 90 (0-364) days. The mean (SD) age at time of first PTLD diagnosis was 46.8 (17.2) years, with 84.5% of patients 18 to < 65 years old, 8.7% of patients < 18 years old, and 6.8% of patients ≥ 65 years old. There was a higher percentage of male versus female PTLD patients: 55.3% versus 44.7%. Conclusions: This analysis of a large-scale US claims database showed that 3.8% (95%CI: 3.1%-4.6%) of post-allogeneic HCT patients had PTLD within the first year after transplant. Most patients impacted by PTLD were younger than 65 (93.2%), and a substantial proportion were pediatric patients (8.7%). Future studies are needed to better understand the disease state and burden of PTLD as well as the unmet medical need for this patient population. Disclosures Barlev: Atara Biotherapeutics, Inc: Employment, Equity Ownership. Xu:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Fulcher:IBM Watson Health: Employment. Watson:Atara Biotherapeutics, Inc: Employment, Equity Ownership. Sruti:IBM Watson Health: Employment. Sudhindra:Atara Biotherapeutics, Inc: Employment, Equity Ownership.

Sign in / Sign up

Export Citation Format

Share Document