Evidence map›Paper›PMID 35903096›Full record

ArticleFrontiers in immunology2022

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

Soumya P Kania, Juliana M F Silva, Oscar J Charles, John Booth, S Y Amy Cheung, James W T Yates, Austen Worth, Judith Breuer, Nigel Klein, Persis J Amrolia and 2 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Soumya P KaniaInfection, Immunity and Inflammation Research & Teaching Department, University College London (UCL) Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Juliana M F SilvaDepartment of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
Oscar J CharlesInfection, Immunity and Inflammation Research & Teaching Department, University College London (UCL) Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
John BoothDigital Research, Informatics and Virtual Environment Unit, National Institute for Health and Care Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre, London, United Kingdom.
S Y Amy CheungIntegrated Drug Development, Certara, Princeton, NJ, United States.
James W T YatesDrug Metabolism and Pharmacokinetics (DMPK) Modelling, In-Vitro In-Vivo Translation, GlaxoSmithKline, Stevenage, United Kingdom.
Austen WorthDepartment of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
Judith BreuerInfection, Immunity and Inflammation Research & Teaching Department, University College London (UCL) Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Nigel KleinInfection, Immunity and Inflammation Research & Teaching Department, University College London (UCL) Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Persis J AmroliaInfection, Immunity and Inflammation Research & Teaching Department, University College London (UCL) Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Paul VeysDepartment of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
Joseph F StandingInfection, Immunity and Inflammation Research & Teaching Department, University College London (UCL) Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
University College London · GBGreat Ormond Street Hospital · GBCertara (United States) · USGlaxoSmithKline (United Kingdom) · GB

Funding

Medical Research Council MR/M008665/1
6 · The paper itself

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.

Indexed as

Epstein-Barr Virus InfectionsHematopoietic Stem Cell TransplantationAntilymphocyte SerumChildHerpesvirus 4, HumanHumansModels, TheoreticalRetrospective StudiesRisk FactorsAntilymphocyte SerumEpstein-Barr virushaematopoietic stem cell transplantimmune reconstitutionmathematical modellingpaediatricsviral kineticsviral reactivation

Identifiers

PMID35903096
PMCPMC9314642
OpenAlexW4285024421

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.