Transfusion‐related Epstein‐Barr virus ( EBV ) infection: A multicenter prospective cohort study among pediatric recipients of hematopoietic stem cell transplants ( TREASuRE study)

Background Epstein-Barr virus (EBV) infection is a common complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), leading to fatal post-transplant lymphoproliferative disorders (PTLD) and other EBV-associated diseases. A few studies suggested that cytomegalovirus (CMV) might play a role in PTLD. In this study, the effect of CMV on EBV DNA-emia and EBV-associated diseases was evaluated in the recipients of allo-HSCT. Methods Three hundred and fifty-two patients undergoing allo-HSCT were enrolled in this prospective study between July 2008 and June 2013. The EBV-DNA and CMV-DNA levels in blood and secretion were monitored by quantitative real-time polymerase chain reaction (RQ-PCR) before and in different time points after transplantation. EBV and CMV DNA-emia were diagnosed when EBV-DNA or CMV-DNA in the blood was positive twice consecutively. Results During the follow-up period, 99 patients (28.1%) developed EBV DNA-emia and 41 (11.6%) developed EBV-associated diseases including 27 EBV-associated PTLD and 14 other EBV-associated diseases. One hundred and fifty-nine patients (45.2%) developed CMV DNA-emia and 10 (2.8%) developed CMV-associated diseases. Of the 99 patients who developed EBV DNA-emia, 56 had CMV DNA-emia before EBV DNA-emia, and the median time from occurrence of CMV DNA-emia to EBV DNA-emia and EBV-associated diseases were 15 (range, 0-269) days and 26 (range, 0-255) days, respectively. Six patients developed co-existing CMV DNA-emia at the time of EBV-associated diseases diagnosed. DNA-emia before EBV infection had positive correlation with EBV DNA-emia (r=0.14, p=0.007) and EBV-associated diseases (r=0.15, p=0.005), but both correlation coefficients were weak. There was a strong positive correlation between EBV DNA-emia and EBV-associated diseases (r=0.56, p<0.001). The patients with CMV DNA-emia had a higher risk for developing EBV infection than those without (OR 2.279, 95% conﬁdence interval [CI] 1.420-3.657, p=0.001). After EBV infection occurred, 15 patients developed CMV DNA-emia, including 4 developed CMV-associated diseases, at a median time of 33 days (range, 12-50 days). EBV infection was not related to CMV DNA-emia (p=0.87) or CMV associated diseases (p=0.27) occurring after EBV infection. Conclusion The results suggest that CMV may play a contributory role in the development of EBV DNA-emia and EBV-associated diseases. Disclosures: Liu: This work was supported by the National High Technology Research and Development Program of China (863 Program) (No. 2011AA020105), the National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; This work was also supported by National Natural Science Foundation of China (Grant No.81000231, No.30971300, No.81270647), the Science and Technology Project of Guangdong Province of China (Grant No.2009A030200007).: Research Funding; This work was also supported by the Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

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Rituximab in the Treatment of Epstein-Barr Virus Infection after hematopoietic stem cell Transplantation in Children

Blood ◽

10.1182/blood.v124.21.5892.5892 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5892-5892

Author(s):

Zhiyong Peng ◽

Chunfu Li ◽

Yuelin He

Keyword(s):

Stem Cell ◽

Epstein Barr Virus ◽

Epstein Barr Virus Infection ◽

Hematopoietic Stem ◽

Viral Loads ◽

Barr Virus ◽

Ebv Infection ◽

Infection Disease ◽

Epstein Barr ◽

Barr Virus Infection

Abstract OBJECTIVE: To investigate the efficacy and safety of Rituximab on Epstein-Barr virus infection disease after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in children. METHODS: A retrospective analysis was performed based on clinical data of 25 children with median age of 6 years, (3~14 years) diagnosed as EBV infection and received Rituximab from Jan. 2012 to Jun. 2014 in our center. Of them, 3 patients were diagnosed as post-transplant lymphoproliferative disorders (PTLD). All patients received Rituximab at dose of 375 mg/m2 once a week for 4 sequence weeks or discontinued therapy when EBV viral loads was <500 copies/mL two times consecutively. The complete remission (CR) was defined as EBV viral loads <500 copies/mL consecutively at least two time and without any related clinical symptoms. Side effects during infusion were evaluated by Common Terminology Criteria for Adverse Events. RESULTS: The median EBV-infection time was on day 70 (18~200) after HSCT. Each of patients received a median of 2 (1~4) infusions. There were no severe side effects during the infusion of Rituximab. The cumulative complete remission (CR) rate were 88% in total. The CR rate was 56.0±9.9 %, 80.0±8.0%, 84.0±7.3%, and 88.0±6.5%, respectively, in 1st, 2nd, 3rd, and 4th week. Two patients died, one due to infections and the other died of hepatitis while receiving therapy. The CR rate was 100% in patients with PTLD (3/3). CONCLUSIONS: These data suggest Rituximab is safe and effective when treating children with EBV infection disease after allo-HSCT. Disclosures No relevant conflicts of interest to declare.

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Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

Vaccines ◽

10.3390/vaccines9030288 ◽

2021 ◽

Vol 9 (3) ◽

pp. 288

Author(s):

Pascal Roland Enok Bonong ◽

Monica Zahreddine ◽

Chantal Buteau ◽

Michel Duval ◽

Louise Laporte ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Epstein Barr Virus ◽

Lymphoproliferative Disease ◽

Hematopoietic Stem ◽

Post Transplant ◽

Barr Virus ◽

Ebv Infection ◽

Relative Risks ◽

Epstein Barr

This systematic review was undertaken to identify risk factors associated with post-transplant Epstein–Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92–9.45) and 4.17 (95% CI: 2.61–6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing.

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HLA Polymorphisms and Epstein-Barr Virus Infection In The Recipient Of Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v122.21.3291.3291 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3291-3291

Author(s):

Ren Lin ◽

Qian Fan ◽

Sijian Yu ◽

Zhiping Fan ◽

Yu Zhang ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Research Funding ◽

Epstein Barr Virus ◽

Hematopoietic Stem ◽

Barr Virus ◽

Ebv Infection ◽

Associated Diseases ◽

Epstein Barr

Abstract Background Epstein-Barr virus (EBV) infection/reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cause fatal post-transplant lymphoproliferative disorders (PTLD) and other EBV-associated diseases. The development of EBV infection/reactivation and EBV-associated diseases are closely related to the immune function. Human leukocyte antigen (HLA) molecules are responsible for antigen processing and presentation to the immune system. Thus, it is supposed that HLA polymorphisms might be associated with EBV infection/reactivation and EBV-associated diseases. In this study, HLA polymorphisms and EBV infection/reactivation or EBV-associated diseases in the recipients of allo-HSCT were analyzed. Methods Three hundred and forty-nine recipients undergoing allo-HSCT were enrolled in this study between July 2008 to June 2013. For recipients and their donors, HLA-A, -B and HLA-DR were analyzed using PCR-sequence specific oligonueleotide probing (PCR-SSOP). The EBV-DNA levels of blood were monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR). Results With a median follow-up of 389 days post-transplantation (range, 7 to 1828 days), 96 cases developed EBV infection/reactivation and 40 developed EBV-associated diseases including 27 EBV-PTLD and 13 other EBV-associated diseases (i.e. 7 fever, 1 pneumonia, 2 encephalitis, 1 hepatitis, 1 encephalitis accompanying pneumonia and 1 enteritis accompanying hepatitis). The 3-year cumulative incidence of EBV infection/reactivation and EBV-associated diseases were 29.1%±2.6% and 13.1%±2.0%, respectively. 43.8% of the recipients with HLA-A11 developed EBV infection/reactivation, compared with 56.5% of those without HLA-A11 (p=0.039). Multivariate analysis showed that HLA-A11 was a protective factor for EBV infection/reactivation (OR 0.497, 95% conﬁdence interval [CI] 0.284-0.869, p=0.014). The recipients who had the donors with HLA-A31 had a higher incidence of EBV-associated diseases than those whose donors did not have HLA-A31 (10.3% vs. 2.9%, p=0.046); more patients carried HLA-B44 suffered EBV-associated diseases than those not carried HLA-B44 (7.7% vs. 1.3%, p=0.035). In multivariate analysis, recipient HLA-B44 were confirmed to be a risk factor for EBV-associated diseases (OR 17.749, 95% conﬁdence interval [CI] 1.946-161.917, p=0.011). The incidence of PTLD in the recipients with HLA-A74 was 7.4%, compared with 0.6% in those without HLA-A74 (p=0.031); the incidences of PTLD in recipients whose donors had and did not have HLA-DR04 were 37.0% and 20.2%, respectively (p=0.042). Multivariate analysis showed that recipient HLA-A74 (OR 11.350, 95%CI: 1.119-115.178, p=0.040) and donor HLA-DR04 (OR 3.227, 95%CI: 1.323-7.873, p=0.010) were risk factors for development of PTLD. Conclusion Our data suggest that HLA polymorphisms might affect EBV infection/reactivation and EBV-associated diseases. Disclosures: Liu: This work was supported by the National High Technology Research and Development Program of China (863 Program) (No. 2011AA020105), the National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; This work was also supported by National Natural Science Foundation of China (Grant No.81000231, No.30971300, No.81270647), the Science and Technology Project of Guangdong Province of China (Grant No.2009A030200007).: Research Funding; This work was also supported by the Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

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EBV Infection in XLP1 Manifested Solely by Behavioral Aggression and Effective Treatment Using Rituximab

Case Reports in Immunology ◽

10.1155/2018/3705376 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4

Author(s):

Michelle M. Korah-Sedgwick ◽

Luke A. Wall

Keyword(s):

Epstein Barr Virus ◽

Hematopoietic Stem Cell Transplant ◽

Lymphoproliferative Disease ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr ◽

Behavioral Aggression ◽

The Brain

Patients with X-linked lymphoproliferative disease 1 (XLP1) are exquisitely susceptible to Epstein-Barr virus (EBV), with the first EBV infection often resulting in rapid death. In a manner not previously described, a 5-year-old patient with XLP1 presented solely with behavioral aggression, with no laboratory evidence of organ dysfunction or inflammation. Although EBV-IgM was negative, PCR confirmed the presence of EBV in both the blood and cerebrospinal fluid. MRI of the brain showed frontal lobe foci. After failure to eradicate his viremia with ganciclovir, rituximab was administered. EBV was eradicated from the blood after the second rituximab infusion and remained absent for 5 months, at which time he underwent hematopoietic stem cell transplant. Although EBV classically produces fulminant infection in patients with XLP1, this case demonstrates that EBV infection may be initially subtle. Acute change in behavior should prompt evaluation. This case also demonstrates the possible effectiveness of rituximab in the treatment of acute EBV infection.

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