The Impact of Monitoring Epstein Barr Virus PCR in Paediatric Bone Marrow Transplant Patients: Can It Successfully Predict Outcome and Guide Intervention.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5064-5064
Author(s):  
Hayley M. Greenfield ◽  
Maged I. Gharib ◽  
Andrew J.L. Turner ◽  
Mary L. Coussons ◽  
Andrew M. Will ◽  
...  
Keyword(s):  
Quantitative Pcr ◽  
Immune Suppression ◽  
Epstein Barr Virus ◽  
Unrelated Donor ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr ◽  
High Level ◽  
The Impact ◽  
Donor Transplant

Abstract Epstein Barr Virus (EBV) associated Lymphoproliferative Disease (LPD) is a complication of allogeneic haemopoietic stem cell tranplantation (HSCT). In certain groups (congenital immunodeficiency, unrelated and mismatched donor transplants, T cell depletion) the risk may be as high as 25% with significant morbidity and mortality. Strategies to predict such illlness and allow early intervention have therefore assumed importance. We have routinely screened peripheral blood of paediatric, transplanted patients by quantitiative PCR. We report the results of such analysis of 28 successive patients and the EBV serial quantitation in 4 patients with EBV LPD. The median age at time of transplant was 6.5 years. 17 patients received an unrelated donor transplant and one patient received a haplo-identical transplant. The remainder (n=9) received a matched family donor transplant. 23 patients received either Alemtuzumab (n=19) or ATG (n=4). 13 patients had leukaemia, 5 had mucopolysaccharide syndrome, 4 for congential immune deficiency and 6 for non malignant haeamtological conditions. 9 (32%) patients showed no evidence of EBV reactivation using serial PCR monitoring. 10 patients had low level EBV reactivation as defined with a PCR log[copy number] <4.5 copies/ml. 9 patients had a higher level of EBV reactivation. 2 patients had clinical EBV LPD and 2 additional LPD patients with LPD and with archived serial blood samples were also analysed. All patients with clinical LPD fell in the high level reactivation group. All patients with high level reactivation had received either Alemtuzumab or ATG. Patients within this high level group with LPD had a higher PCR log value again than those without LPD (all patients with EBV LPD had levels > 6, whilst the highest level without disease was 5.2). All 4 patients responded to therapy for EBV LPD, with a combination of rituximab, withdrawal of immune suppression or administration of donor lymphocytes - DLI). At higher EBV levels the quantitative PCR had increasing positive predictive value for clinical LPD. We therefore conclude that EBV serial quantitative PCR is useful in discriminating those who will develop LPD from those that will not. Our data suggest that it is possible to use EBV PCR quantitation further to discriminate asymptomatic EBV reactivation that will resolve without therapy from EBV reactivation that will require intervention. This prevents over exposure of patients to treatments (rituximab, DLI, immune suppression withdrawal) with significant associated toxicity (prolonged B cell aplasia, graft versus host disease).

Rituximab Prophylaxis of EBV Reactivation after Unrelated Donor Transplants Using Anti-Thymocyte Globulin in the Conditioning Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3231-3231
Author(s):  
Andrea Bacigalupo ◽  
Alida Dominietto ◽  
Monica Soracco ◽  
Sarah Pozzi ◽  
Anna Maria Raiola ◽  
...  
Keyword(s):  
Clinical Data ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Lymphoproliferative Disease ◽  
Unrelated Donor ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Non Hodgkin Lymphoma ◽  
Epstein Barr ◽  
Donor Transplant

Abstract Background Epstein-Barr Virus (EBV) reactivation is a relatively common event in patients undergoing an unrelated donor transplant with anti-thymocyte globulin (ATG) in the conditioning regimen. In our first 71 patients monitored for EBV reactivartion, this occurred in 42 (59%) at a median interval of 48 days from transplant. Reactivation was higher (75%) in patients with acute lymphoblastic leukemia (ALL) non Hodgkin lymphoma (NHL) and Hodgkin’s disease (HD). When EBV reactivation exceeded 1000 copies /10^5 cells (n=12) the risk of developing a lymphoproliferative disease (LPD) was high (50%) and survival poor (30%). Aim of the study. To test whether rituximab 100 mg/m^2 given on day +5 after transplant would prevent EBV reactivation. Patients eligible for this trial were ALL, NHL and HD undergoing an unrelated donor transplant in 2004-2005, receiving ATG (Genzyme, 7.5 mg/kg) in the conditioning regimen: these patients received rituximab 100 mg/m^2 on day +5 after transplant. Controls were patients with ALL, NHL and HD allografted from similar donors between year 2000 and 2005, receiving the same dose of ATG in the conditioning. Clinical data of patients are outlined in Table 1. Clinical characteristics of controls and rituximab patients were comparable. All patients who reactivated with over 1000 copies received rituximab 375 mg/m^2 one dose, and if they did not clear EBV in 1 week, a second dose. Results. Patients receiving prophylactic rituximab on day+5 had similar neutrophil engraftment and acute GvHD as controls (Table 1). EBV reactivation occurred in 58% controls and 64% rituximab patients. There was a non significant delay of 20 days for time to reactivation (37 vs 57). The number of EBV copies at the time of reactivation was significantly higher in controls (334 vs 3, p=0.0001) and the maximum number of copies was also significantly higher in controls (1433 vs 11, p=0.001). Fourteen patients (34%) vs 1 (7%) (p=0.05) received rituximab for treatment of EBV reactivation. Transplant related mortality is 39% vs 21% (p=ns) and actuarial 1 year survival at 6 months 56% vs 63% (p=ns). Conclusions. Rituximab on day +5 significantly reduces the number of EBV copies at reactivation, without interfering with engraftment and reduces the need to treat patients for potential LPD. Table 1. Clinical data of patients Treatment group Controls Rituximab P Number 41 14 Patients age 31 27 ns ALL 27 7 NHL 7 5 HD 7 2 ns Advanced disease 75% 78% ns Day PMN 500/mmc 18 (15–31) 17 (14–21) ns GvHD grade II-IV 19% 29% 0.4 Number of EBV reactivation 24 (58%) 9 (64%) ns Day of EBV reactivation 37 (4–220) 57 (14–150) ns Copie EBV at reactivation 334 (2–5770) 3 (1–189) 0.0001 Man n. copies EBV 1433 (8–177000) 11 (3–2089) 0.001 N of patients >1000 copies 14 (34%) 1 (7%) 0.05 EBVLPD 6 (14%) 0 0.2 TRM 39% 21% 0.2 Survival at 180 days 56% 63% 0.4 Median follow up (dd) 274 131

Pre-Transplant Rituximab Is Associated with a Greatly Reduced Risk of Epstein-Barr Virus Reactivation Following Allogeneic Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 460-460
Author(s):  
David Burns ◽  
Shabeeha Rana ◽  
Andrew Howman ◽  
Sandeep Nagra ◽  
Janice Ward ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Epstein Barr Virus ◽  
Post Transplant ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr ◽  
High Level ◽  
Reduced Risk

Abstract Abstract 460 Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) remains an important complication of allogeneic stem cell transplantation (alloSCT). Monitoring of EBV genomes in blood using quantitative PCR (EBV qPCR) coupled with pre-emptive administration of Rituximab in response to high-level EBV reactivation has emerged as a strategy to reduce mortality from PTLD. However, the effect of pre-transplant Rituximab therapy on the risk of EBV reactivation and survival post-alloSCT is unknown. This retrospective study examined 193 consecutive adult patients undergoing T cell depleted or cord blood alloSCT at University Hospital Birmingham, UK (UHB) and Nottingham University Hospital, UK (NUH) between May 2009 and April 2011. Median age at transplant was 54 years (range 16–73 years). Conditioning was reduced intensity in 84% and myeloablative in 16%. Stem cell source was matched unrelated donor in 70%, sibling in 24% and cord blood in 6%. T cell depletion was with in vivo Alemtuzumab in 89% and ATG in 6%. Patients were monitored by EBV qPCR whole blood assay, performed every 1–2 weeks post-transplant. EBV reactivation was defined as a single positive EBV qPCR result, whilst high-level EBV reactivation was defined according to institutional thresholds; 30,000 and 10,000 EBV genomes/ml for UHB and NUH respectively. All patients with high-level reactivation were pre-emptively treated with Rituximab. Median follow-up was 23 months (interquartile range [IQR] 18–30 months), with EBV qPCR testing for a median of 8 months (IQR 4–13 months) post-transplant. The cumulative incidence of EBV reactivation, adjusting for the competing risk of death, was 41% at 2 years post-transplant. Amongst those reactivating, the median time to EBV qPCR positivity was 120 days (IQR 77–198 days). High-level EBV reactivation was observed in 34/193 (18%) patients, accompanied by PTLD in 10 patients (4 biopsy-proven and 6 probable cases). Of patients developing high-level EBV reactivation, in 30/34 (88%) the interval from first EBV qPCR positivity to high-level reactivation was less than 4 weeks, with 15/34 (44%) exhibiting high-level reactivation at first qPCR positivity. In univariate analysis, significant predictors for EBV reactivation were older age (hazard ratio [HR] 1.02 per year; p=0.04), male sex (HR 1.75; p=0.03) and T depletion with ATG (HR 4.8; p<0.0001). A primary diagnosis of non-Hodgkin lymphoma (NHL) carried a significantly reduced risk of EBV reactivation (HR 0.04; p=0.0018). Reduced intensity conditioning carried an increased risk of reactivation with borderline significance (HR 2.04; p=0.07). Donor type and HLA-mismatch were not significant risk factors. Acute graft-versus-host disease (GvHD) and cytomegalovirus (CMV) reactivation were also not significantly associated with EBV reactivation. Twenty-nine patients received Rituximab in the year preceding alloSCT, of whom 25 had NHL, 3 had chronic lymphocytic leukaemia (CLL) and 1 had acute lymphocytic leukaemia. Only one of these patients developed EBV reactivation by 12 months post-transplant - a patient with high-level reactivation associated with PTLD. Two other patients developed low-level EBV reactivation beyond 12 months. In univariate analysis, pre-transplant Rituximab was highly predictive for (lack of) EBV reactivation (HR 0.15, 95% confidence interval [CI] 0.05–0.48; p=0.0002; see figure). Applying a multivariate model including age, sex and ATG use, pre-transplant Rituximab remained highly predictive (HR 0.15, CI 0.05–0.47; p=0.0012). As expected, strong confounding between NHL and pre-transplant Rituximab made a model including both uninformative. There was no significant association between pre-transplant Rituximab and the risk of relapse, acute GvHD or CMV reactivation. Overall mortality was 50% at 2 years, with 4 deaths due to PTLD. There was no evidence of a link between EBV reactivation and survival (p=0.33). Pre-transplant Rituximab was associated with a significantly reduced risk of mortality (HR 0.49, CI 0.23–1.00; p=0.05) although the aforementioned confounding with NHL should be noted. We report the novel and clinically important finding that pre-transplant Rituximab is associated with a markedly reduced risk of EBV reactivation and a possible survival benefit after alloSCT. Our data make a strong case for prospectively evaluating the role of Rituximab in allograft conditioning. Disclosures: Off Label Use: Rituximab for prevention of Epstein-Barr virus reactivation after allogeneic stem cell transplantation. Fox:Roche: Honoraria.

scholarly journals Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase

2015 ◽  
Vol 90 (2) ◽  
pp. 1129-1138 ◽  
Author(s):  
XueQiao Liu ◽  
Jeffrey I. Cohen
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Epstein Barr Virus ◽  
Virus Production ◽  
Mitogen Activated Protein Kinase ◽  
Tegument Protein ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Mitogen Activated Protein ◽  
Epstein Barr

ABSTRACTEpstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus associated with both B cell and epithelial cell malignancies. EBV infection of B cells triggers activation of several signaling pathways that are critical for cell survival, virus latency, and growth transformation. To identify EBV proteins important for regulating cell signaling, we used a proteomic approach to screen viral proteins for AP-1 and NF-κB promoter activity in AP-1– and NF-κB–luciferase reporter assays. We found that EBV BGLF2 activated AP-1 but not NF-κB reporter activity. Expression of EBV BGLF2 in cells activated p38 and c-Jun N-terminal kinase (JNK), both of which are important for mitogen-activated protein kinase (MAPK) signaling. Deletion of the carboxyl-terminal 66 amino acids of BGLF2 reduced the ability of BGLF2 to activate JNK and p38. Expression of BGLF2 enhanced BZLF1 expression in latently EBV-infected lymphoblastoid cell lines, and knockdown of BGLF2 reduced EBV reactivation induced by IgG cross-linking. Expression of BGLF2 induced BZLF1 expression and virus production in EBV-infected gastric carcinoma cells. BGLF2 enhanced BZLF1 expression and EBV production by activating p38; chemical inhibition of p38 and MAPK/ERK kinases 1 and 2 (MEK1/2) reduced expression of BZLF1 and virus production induced by BGLF2. In summary, the EBV tegument protein BGLF2, which is delivered to the cell at the onset of virus infection, activates the AP-1 pathway and enhances EBV reactivation and virus production.IMPORTANCEEpstein-Barr virus (EBV) is associated with both B cell and epithelial cell malignancies, and the virus activates multiple signaling pathways important for its persistence in latently infected cells. We identified a viral tegument protein, BGLF2, which activates members of the mitogen-activated protein kinase signaling pathway. Expression of BGLF2 increased expression of EBV BZLF1, which activates a switch from latent to lytic virus infection, and increased production of EBV. Inhibition of BGFL2 expression or inhibition of p38/MAPK, which is activated by BGLF2, reduced virus reactivation from latency. These results indicate that a viral tegument protein which is delivered to cells upon infection activates signaling pathways to enhance virus production and facilitate virus reactivation from latency.

scholarly journals Cytolytic Epstein-Barr Virus Reactivation Therapy for EBV-Associated Gastric Carcinoma

2020 ◽  
pp. 1-10
Author(s):  
Jaap M. Middeldorp ◽  
Zlata Novalić ◽  
Sandra A.W.M. Verkuijlen ◽  
Astrid E. Greijer ◽  
Jaap M. Middeldorp
Keyword(s):  
Gastric Carcinoma ◽  
Mouse Model ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Drug Combinations ◽  
Model Systems ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr

Background: Epstein-Barr virus associated gastric carcinoma (EBVaGC) is considered a distinct GC disease entity, with the virus persisting in a latent phase. Treatment with Epirubicin, Capecitabine and Cisplatin (ECC combination) showed survival benefit in patients with GC in clinical trials (MAGIC study and CRITICS study) when compared to chemotherapy with Capecitabine and Cisplatin (GCb/Cis). Current treatment protocols for GC do not consider virus involvement. Methods: In this study, we tested a CytoLytic Virus Activation (CLVA) strategy consisting of the ECC combination or GCb/Cis together with the HDAC inhibitor Valproic acid (VPA) to define whether EBV reactivation and subsequent antiviral treatment with Ganciclovir (GCV) could be used as virus-targeted therapy for EBVaGC. Drug combinations with VPA and GCV were evaluated in multiple cell lines and in an EBVaGC mouse model based on human naturally EBV-infected SNU-719 cells. Results: EBV reactivation was demonstrated by lytic mRNA transcripts and proteins in treated cells, and the virus-reactivating capacity of different CLVA drug combinations was compared in C666.1, AGS-BX1 and SNU-719 cell lines. In an EBVaGC mouse model, GCb/Cis with VPA and GCV strongly reduced tumor volume and showed the highest potential for EBV-reactivation. Upon a single round of CLVA treatment, EBV DNA levels in circulation decreased, and loss of EBV-positive cells in treated tumors was observed. In vivo EBV-reactivation was revealed by the presence of lytic gene transcripts and proteins in tumor tissues 6 days after treatment. Conclusion: In EBVaGC model systems, CLVA treatment showed a more potent virus reactivation and killing of tumor cells when compared to standard chemotherapy alone, suggesting that addition of VPA plus GCV to the ECC or GCb/Cis combination should be considered in future clinical studies.

scholarly journals Clinical characteristics and outcomes of critically ill patients with acute COVID-19 with Epstein-Barr virus reactivation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yun Xie ◽  
Song Cao ◽  
Hui Dong ◽  
Hui Lv ◽  
Xiaolei Teng ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Mortality Rates ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Imaging Characteristics ◽  
Single Center Study ◽  
Significant Difference ◽  
Epstein Barr ◽  
Epstein Barr Virus Reactivation

Abstract Background Our goal is to further elucidate the clinical condition and prognosis of patients with severe acute COVID-19 with EBV reactivation. Method This is a retrospective single-center study of COVID-19 patients admitted to the intensive care unit of Wuhan No. 3 Hospital (January 31 to March 27, 2020). According to whether Epstein-Barr virus reactivation was detected, the patients were divided into an EBV group and a Non-EBV group. Baseline data were collected including epidemiological, larithmics, clinical and imaging characteristics, and laboratory examination data. Results Of the 128 patients with COVID-19, 17 (13.3%) were infected with Epstein-Barr virus reactivation. In the symptoms,the rate of tachypnoea in the EBV group was apparently higher than that in the Non-EBV group. In lab tests, the lymphocyte and albumin of EBV group decreased more significantly than Non-EBV group, and the D-dimer and serum calcium of EBV group was higher than Non-EBV group. Regarding the infection index, CRP of EBV group was apparently above the Non-EBV group, and no significant difference was found in procalcitonin of the two groups. The incidence of respiratory failure, ARDS, and hypoproteinaemia of EBV group had more incidence than Non-EBV group. The 28-day and 14-day mortality rates of EBV group was significantly higher than that of Non-EBV group. Conclusions In the COVID-19 patients, patients with EBV reactivation had higher 28-day and 14-day mortality rates and received more immuno-supportive treatment than patients of Non-EBV group.

scholarly journals Impact of tumor Epstein-Barr virus status on presenting features and outcome in age-defined subgroups of patients with classic Hodgkin lymphoma: a population-based study

Blood ◽  
2005 ◽  
Vol 106 (7) ◽  
pp. 2444-2451 ◽  
Author(s):  
Ruth F. Jarrett ◽  
Gail L. Stark ◽  
Jo White ◽  
Brian Angus ◽  
Freda E. Alexander ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Older Patients ◽  
Epstein Barr Virus ◽  
Statistical Significance ◽  
Survival Rates ◽  
Population Based ◽  
Population Based Study ◽  
Barr Virus ◽  
Epstein Barr ◽  
The Impact

AbstractThe association between tumor Epstein-Barr virus (EBV) status and clinical outcome in Hodgkin lymphoma (HL) is controversial. This population-based study assessed the impact of EBV status on survival in age-stratified cohorts of adults with classic HL (cHL). Data from 437 cases were analyzed with a median follow-up of 93 months. Overall survival (OS) was significantly better for EBV-negative compared with EBV-positive patients (P &lt; .001), with 5-year survival rates of 81% and 66%, respectively; disease-specific survival (DSS) was also greater for EBV-negative patients (P = .03). The impact of EBV status varied with age at diagnosis. In patients aged 16 to 34 years, EBV-associated cases had a survival advantage compared with EBV-negative cases, but differences were not statistically significant (P = .21). Among patients 50 years or older, EBV positivity was associated with a significantly poorer outcome (P = .003). Excess deaths occurred in EBV-positive patients with both early- and advanced-stage disease. In multivariate analysis of OS in the older patients, EBV status retained statistical significance after adjusting for the effects of sex, stage, and B symptoms (P = .01). Impaired immune status may contribute to the development of EBV-positive cHL in older patients, and strategies aimed at boosting the immune response should be investigated in the treatment of these patients. (Blood. 2005;106:2444-2451)

Pre-Emptive Use of Rituximab in Epstein-Barr Virus Reactivation: Incidence, Predictive Factors, Monitoring, and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-31
Author(s):  
Apostolia Papalexandri ◽  
Eleni Gavriilaki ◽  
Anna Vardi ◽  
Eirini Baldoumi ◽  
Christos Demosthenous ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Viral Load ◽  
Epstein Barr Virus ◽  
Chronic Gvhd ◽  
Molecular Monitoring ◽  
Post Transplantation ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Reactivation ◽  
Epstein Barr

Introduction: Reactivation of Epstein-Barr virus (EBV) is common in allogeneic hematopoietic cell transplantation (HCT). EBV infection leads to post-transplantation lymphoproliferative disease (PTLD), a life-threatening complication in this setting. Frequent molecular monitoring of viral load, especially in high risk patients and pre-emptive use of Rituximab has improved the outcome of EBV infection. However, the expansion of alternative transplants, leads to higher incidence and effective measures are warranted. Methods: We have retrospectively studied the clinical characteristics of EBV reactivation in consecutive patients that underwent HCT between 2007-2019, when pre-emptive administration of Rituximab was a standard of care in our Unit and possible correlations were sought. EBV reactivation was considered when viral load &gt;8500 viral genomic copies (VGC)/ml in whole blood was documented during regular molecular monitoring with RQ-PCR. Patients received treatment with Rituximab, at a scheme according to physician's decision. We considered undetectable levels as resolution of infection. Patients with PTLD proven by lymph node biopsy were treated as previously described by our group. Results: Among 546 HCT recipients, EBV reactivation was detected in 100 patients, that suffered from hematologic malignancy (98) or aplastic anemia (2) and received grafts from matched sibling (23), unrelated (70) or haploidentical donors (12). Haploidentical donors were significantly higher in patients with EBV reactivation compared to our transplant population (12% versus 6%, p&lt;0.001). Eighty-eight patients received myeloablative and 12/100 reduced intensity conditioning. Overall, EBV reactivation was detected at median 65 (20-2970) post-transplant days (median load: 26100, range 8690-2670000 VGC/ml). Rituximab was administered in 74 patients at median 4 (3-158) days post EBV reactivation. Most patients (63/74) received one cycle of Rituximab until undetectable EBV load. Rituximab cycles (median 1, range 0-3) were not associated with outcomes. Relapse of EBV reactivation was noted in 13/100 patients, with greater incidence among patients with later resolution of infection (27 vs 14 days in non relapsed, p&lt;0.01). Late onset neutropenia related to Rituximab was noted in 16/74 patients and significantly correlated with increased EBV loads. Significantly higher viral loads were also noticed among patients who received ATG (44550 vs 20000 VGC/ml) or had haploidentical donors (60800 vs 22750 VGC/ml). Multivariate analysis confirmed that all above factors were independently associated to increased viral load. CMV concurrent reactivation was noted in 47 patients. Patients that received preemptive anti-CMV treatment presented with significantly delayed resolution of EBV infection, probably corresponding to greater immunosuppression. Five patients (two with haploidentical and three with unrelated donors) presented PTLD at 41 days post transplantation. ROC curve analysis identified a cut off of 67150 VGC/ml that predicts PLTD with 80% sensitivity and specificity (green line in Figure). Relapse free survival (RFS), overall survival (OS) and treatment-related mortality (TRM) in the entire cohort were similar regardless the EBV viral load or PTLD [4-year RFS 32.2%, 4-year OS 48.1% in a median follow up 29 months (4-216)]. ATG and chronic GVHD were independently associated with OS in the multivariate analysis (p&lt;0.001, p&lt;0.05 respectively). Similarly, ATG, chronic GVHD and age at transplant were independently associated to higher TRM in multivariate analysis (HR: 0.1, 1.16, 1.03, 95%CI: 0.15-0.5, 0.008-1.16, 1.007-1.05, respectively p&lt;0.05). A trend for higher TRM was also noted among patients with EBV loads higher than 50000VGC/ml. Conclusion: Our study indicates that regular monitoring and use of preemptive therapy is an effective strategy for prevention of EBV related complications. RFS and OS were not associated to severity of EBV reactivation. A useful cut off of EBV load for PTLD prevention was identified (67150 VGC/ml, specificity and sensitivity: 80%). However, expanding use of alternative transplants warrants a more effective treatment strategy. In this setting, use of specific antiviral cytotoxic cell lines could enhance viral specific cell mediated immunity and provide a better outcome in immunocompromised HCT recipients. Disclosures Gavriilaki: Omeros Pharmaceuticals: Consultancy.

scholarly journals An Absence of Epstein–Barr Virus Reactivation and Associations with Disease Activity in People with Multiple Sclerosis Undergoing Therapeutic Hookworm Vaccination

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 487
Author(s):  
Peter A. C. Maple ◽  
Bruno Gran ◽  
Radu Tanasescu ◽  
David I. Pritchard ◽  
Cris S. Constantinescu
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Virus Reactivation ◽  
Serum Samples ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Reactivation ◽  
Epstein Barr

Background: Epstein–Barr virus (EBV) infection is strongly associated with multiple sclerosis (MS). Helminth infection can downregulate antiviral immune responses, potentially protecting against MS, but with a theoretical risk for reactivating latent EBV infection. Objective: To investigate parameters of EBV infection and their relationship with disease activity in people with MS (PwMS) therapeutically vaccinated with Necator americanus (hookworm). Methods: Sequential serum samples from 51 PwMS; 26 therapeutically infected (25 larvae) with N. americanus and 25 controls were tested for EBV virus capsid antigen (VCA) IgG and IgM, EBV nuclear antigen-1 (EBNA-1) IgG, and EBV early antigen (EA) IgG. Disease activity was assessed by periodic MRI. Significance was set at p < 0.05. Results: All PwMS were EBV VCA IgG and EBNA-1 IgG positive, and 35.2% were EBV EA IgG positive. EBV antibody levels were generally stable, and EBV reactivation in PwMS was not demonstrated by significant increases in IgG titre over 12 months. Disease activity was most frequent in PwMS possessing high levels of EBV VCA IgG (>600 units/mL) or EBNA-1 IgG (>150 units/mL); however, there was no association with hookworm treatment. Interpretation: Therapeutic hookworm vaccination was not associated with EBV reactivation. Multiple sclerosis disease activity was associated with high levels of EBV VCA IgG or EBNA-1 IgG.

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