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

Abstract

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 × 10⁶ or 5 × 10⁶ 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.