Kania, Soumya P;
Silva, Juliana MF;
Charles, Oscar J;
Booth, John;
Cheung, SY Amy;
Yates, James WT;
Worth, Austen;
... Standing, Joseph F; + view all
(2022)
Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model.
Frontiers in Immunology
, 13
, Article 903063. 10.3389/fimmu.2022.903063.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2022.903063 |
| Publisher version: | https://doi.org/10.3389/fimmu.2022.903063 |
| Language: | English |
| Additional information: | © 2022 Kania, Silva, Charles, Booth, Cheung, Yates, Worth, Breuer, Klein, Amrolia, Veys and Standing. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Epstein-Barr virus, haematopoietic stem cell transplant, immune reconstitution, mathematical modelling, paediatrics, viral kinetics, viral reactivation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10153166 |
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