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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.

SUBMITTER: Hoare RL 

PROVIDER: S-EPMC5579758 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Predicting CD4 T-Cell Reconstitution Following Pediatric Hematopoietic Stem Cell Transplantation.

Hoare R L RL   Veys P P   Klein N N   Callard R R   Standing J F JF  

Clinical pharmacology and therapeutics 20170526 2


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  ...[more]

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