Impact of CMV and EBV on Immune Recovery After Allogeneic Hematopoietic Cell Transplantation in Children

Pukownik, Ewelina; Kubicka, Małgorzata; Kuryło-Rafińska, Beata; Dębski, Robert; Gałązka, Przemysław; Czyżewski, K; Krenska, Anna; Bartoszewicz, Natalia; Demidowicz, Ewa; Marjańska, Agata; Dziedzic, Magdalena; Pogorzała, Monika; Wysocki, Mariusz; Styczyński, Jan

doi:10.21873/anticanres.12950

Cited by 6 publications

(3 citation statements)

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“…The small sample size of 56 patients is characteristic of the study being retrospective and based at a single centre as well as the outcome of interest, EBV reactivation in children post-HSCT, being uncommon. Nevertheless, other authors have also conducted multivariable analysis on data from a comparable number or fewer patients in the context of EBV reactivation ( 19 , 31 , 32 ). Another limitation is the lack of observed immune cell counts for the early post-HSCT period studied, which we were partly able to circumvent by leveraging previously developed mathematical models by our group.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model

et al. 2022

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Epstein-Barr virus (EBV) establishes a lifelong latent infection in healthy humans, kept under immune control by cytotoxic T cells (CTLs). Following paediatric haematopoetic stem cell transplantation (HSCT), a loss of immune surveillance leads to opportunistic outgrowth of EBV-infected cells, resulting in EBV reactivation, which can ultimately progress to post-transplant lymphoproliferative disorder (PTLD). The aims of this study were to identify risk factors for EBV reactivation in children in the first 100 days post-HSCT and to assess the suitability of a previously reported mathematical model to mechanistically model EBV reactivation kinetics in this cohort. Retrospective electronic data were collected from 56 children who underwent HSCT at Great Ormond Street Hospital (GOSH) between 2005 and 2016. Using EBV viral load (VL) measurements from weekly quantitative PCR (qPCR) monitoring post-HSCT, a multivariable Cox proportional hazards (Cox-PH) model was developed to assess time to first EBV reactivation event in the first 100 days post-HSCT. Sensitivity analysis of a previously reported mathematical model was performed to identify key parameters affecting EBV VL. Cox-PH modelling revealed EBV seropositivity of the HSCT recipient and administration of anti-thymocyte globulin (ATG) pre-HSCT to be significantly associated with an increased risk of EBV reactivation in the first 100 days post-HSCT (adjusted hazard ratio (AHR) = 2.32, P = 0.02; AHR = 2.55, P = 0.04). Five parameters were found to affect EBV VL in sensitivity analysis of the previously reported mathematical model. In conclusion, we have assessed the effect of multiple covariates on EBV reactivation in the first 100 days post-HSCT in children and have identified key parameters in a previously reported mechanistic mathematical model that affect EBV VL. Future work will aim to fit this model to patient EBV VLs, develop the model to account for interindividual variability and model the effect of clinically relevant covariates such as rituximab therapy and ATG on EBV VL.

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Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model

et al. 2022

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“…In spite of the outmost interest raised by PTLD and adoptive immunotherapy, the data about EBV reactivation and post-HSCT immune recovery are rather scant. Viral load has been reported to impair generically both B- and T-cell recovery ( 194 , 195 ). The expansion of CD8+ effector memory cells, characteristically related to CMV, has not been observed after EBV and ADV reactivation ( 196 ).…”

Section: Effects Of Viruses On Immunologic Recovery and Hsct Outcomementioning

confidence: 99%

Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications

et al. 2021

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In spite of an increasing array of investigations, the relationships between viral infections and allogeneic hematopoietic stem cell transplantation (HSCT) are still controversial, and almost exclusively regard DNA viruses. Viral infections per se account for a considerable risk of morbidity and mortality among HSCT recipients, and available antiviral agents have proven to be of limited effectiveness. Therefore, an optimal management of viral infection represents a key point in HSCT strategies. On the other hand, viruses bear the potential of shaping immunologic recovery after HSCT, possibly interfering with control of the underlying disease and graft-versus-host disease (GvHD), and eventually with HSCT outcome. Moreover, preliminary data are available about the possible role of some virome components as markers of immunologic recovery after HSCT. Lastly, HSCT may exert an immunotherapeutic effect against some viral infections, notably HIV and HTLV-1, and has been considered as an eradicating approach in these indications.

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“…The Epstein–Barr virus is a human lymphotropic herpes virus that causes a lifelong infection in approximately 95% of the global population ( 1 ). The primary EBV infection is more common in children and adolescents, and most cases are asymptomatic and atypical infections ( 2 , 3 ), which are easily missed and misdiagnosed.…”

Section: Introductionmentioning

confidence: 99%

A combined antibody and DNA assay for EBV infection in children

Yang

Zhu

2022

Front. Pediatr.

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ObjectiveThis paper studied the Epstein–Barr virus (EBV) infection status and influencing factors among children using a combined detection of specific antibodies and DNA.MethodsWe retrospectively analyzed children who visited the Affiliated Hospital of Hangzhou Normal University from January 2019 to December 2020, and correlations between the social environment and clinical data were analyzed.ResultsThe cumulative positive rates of specific antibody, DNA, and combined detection of EBV were 52.4%, 39.5%, and 54.0% (P = 0.001), respectively. The current infection rate was 15.7%, and the peak of infection occurred in the preschool group (P = 0.021). After adjusting for confounding factors, the number of siblings (OR = 1.550) and family members who smoke (OR = 1.524) were independent risk factors for EBV infection, whereas parents with a higher education level (OR = 0.493, OR = 0.316), longer breastfeeding time (OR = 0.578) and dedicated tableware (OR = 0.573) were independent protective factors.ConclusionA combination of antibody and DNA tests may be beneficial for the diagnosis of EBV infection. The EBV infection rate in children at our hospital was lower than the national average. Furthermore, the infection rate is closely related to the number of siblings, regardless of whether family members smoke, the status of parents' education, breastfeeding duration, and meal patterns. Overall, prevention measures should focus on the preschoolers.

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Impact of CMV and EBV on Immune Recovery After Allogeneic Hematopoietic Cell Transplantation in Children

Cited by 6 publications

References 0 publications

Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model

Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model

Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications

A combined antibody and DNA assay for EBV infection in children

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