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Predicting CD4 T-cell reconstitution following paediatric haematopoietic stem cell transplantation.

Hoare, RL; Veys, P; Klein, N; Callard, R; Standing, JF; (2017) Predicting CD4 T-cell reconstitution following paediatric haematopoietic stem cell transplantation. Clin Pharmacol Ther 10.1002/cpt.621. (In press). Green open access

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Abstract

Haematopoietic stem cell transplantation is an increasingly common treatment for children with a range of haematological disorders. Conditioning with cytotoxic chemotherapy and total body irradiation leaves patients severely immunocompromised. T-cell reconstitution can take several years due to delayed restoration of thymic output. Understanding T-cell reconstitution in children is complicated by normal immune system maturation, heterogeneous diagnoses, and sparse uneven sampling due to the long time spans involved. We describe here a mechanistic mathematical model for CD4 T-cell immune reconstitution following pediatric transplantation. Including relevant biology and using mixed-effects modelling allowed the factors affecting reconstitution to be identified. Bayesian predictions for the long-term reconstitution trajectories of individual children were then obtained using early post-transplant data. The model was developed using data from 288 children; its predictive ability validated on data from a further 75 children, with long-term reconstitution predicted accurately in 81% of patients. This article is protected by copyright. All rights reserved.

Type: Article
Title: Predicting CD4 T-cell reconstitution following paediatric haematopoietic stem cell transplantation.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cpt.621
Publisher version: http://dx.doi.org/10.1002/cpt.621
Language: English
Additional information: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/cpt.621
Keywords: NONMEM, pediatrics, pharmacodynamics, transplantation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
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 > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1535878
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