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Development and validation of a predictive model to guide the use of plerixafor in pediatric population

Plerixafor, a CXCR4 receptor antagonist, reduces the binding and chemotaxis of hematopoietic stem cells to the bone marrow stroma, resulting in predictable peak of cluster of differentiation 34(+) (CD34(+)) cells in the peripheral blood (PB) approximately 10 h after its administration. We developed...

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Detalles Bibliográficos
Autores principales: Sebastien, Bernard, Cheverton, Peter, Magnin, Catherine, Aouni, Jihane, Castan, Remi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715428/
https://www.ncbi.nlm.nih.gov/pubmed/36163427
http://dx.doi.org/10.1038/s41409-022-01831-2
Descripción
Sumario:Plerixafor, a CXCR4 receptor antagonist, reduces the binding and chemotaxis of hematopoietic stem cells to the bone marrow stroma, resulting in predictable peak of cluster of differentiation 34(+) (CD34(+)) cells in the peripheral blood (PB) approximately 10 h after its administration. We developed a model that could predict the CD34(+) harvest volume on the first day of apheresis (AP-CD34(+)) based on PB-CD34(+) counts immediately prior to commencing apheresis in pediatric population. In all, data from 45 pediatric patients from the MOZAIC study who received either granulocyte colony-stimulating factor (G-CSF) alone or G-CSF plus plerixafor were included. The modeling of the data exhibited a strong and highly predictive linear relationship between the counts of PB-CD34(+) cells on the first day of apheresis and AP-CD34(+) cells collected on the same day. It is predicted that there are approximately 13 new collected CD34(+) cells for 100 new circulating CD34(+) cells before apheresis. Our predictive algorithm can be used to quantify the minimal count of PB-CD34(+) cells that enables to collect at least 2 × 10(6) or 5 × 10(6) AP-CD34(+) cells/kg with sufficient assurance (probability = 0.90) and can guide the use of plerixafor in patients at higher perceived risk for mobilization failure. Trial registration of MOZAIC study: ClinicalTrials.gov, NCT01288573; EudraCT, 2010-019340-40.