title: Predicting CD4 T-Cell Reconstitution Following Pediatric Hematopoietic Stem Cell Transplantation.
abstract: Hematopoietic stem cell transplantation (HSCT) is an increasingly common treatment for children with a range of hematological 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 modeling 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 the patients.
authors.affiliation: Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, London, United Kingdom.|Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
authors.forename: R L
authors.initials: RL
authors.lastname: Hoare
authors.affiliation: Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.|Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Veys
authors.affiliation: Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.|Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Klein
authors.affiliation: Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, London, United Kingdom.|Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Callard
authors.affiliation: Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, London, United Kingdom.|Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.|Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
authors.forename: J F
authors.initials: JF
authors.lastname: Standing
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000639:trends*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008954:Models, Biological; D011237:Predictive Value of Tests; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000639:trends