Effect of high-dose plerixafor on CD34 cell mobilization in healthy stem cell donors: results of a randomized crossover trial.

Hematopoietic stem cells can be mobilized from healthy donors using single-agent plerixafor without granulocyte colony-stimulating factor and, following allogeneic transplantation, can result in sustained donor-derived hematopoiesis. However, when a single dose of plerixafor is administered at a conventional 240 μg/kg dose, approximately one-third of donors will fail to mobilize the minimally acceptable dose of CD34 cells needed for allogeneic transplantation. We conducted an open-label, randomized trial to assess the safety and activity of high-dose (480 μg/kg) plerixafor in CD34 cell mobilization in healthy donors. Subjects were randomly assigned to receive either a high dose or a conventional dose (240 μg/kg) of plerixafor, given as a single subcutaneous injection, in a two-sequence, two-period, crossover design. Each treatment period was separated by a 2-week minimum washout period. The primary endpoint was the peak CD34 count in the blood, with secondary endpoints of CD34 cell area under the curve (AUC), CD34 count at 24 hours, and time to peak CD34 following the administration of plerixafor. We randomized 23 subjects to the two treatment sequences and 20 subjects received both doses of plerixafor. Peak CD34 count in the blood was significantly increased (mean 32.2 27.8 cells/μL, =0.0009) and CD34 cell AUC over 24 hours was significantly increased (mean 553 446 h cells/μL, <0.0001) following the administration of the 480 μg/kg dose of plerixafor compared with the 240 μg/kg dose. Remarkably, of seven subjects who mobilized poorly (peak CD34 ≤20 cells/μL) after the 240 μg/kg dose of plerixafor, six achieved higher peak CD34 cell numbers and all achieved higher CD34 AUC over 24 hours after the 480 μg/kg dose. No grade 3 or worse drug-related adverse events were observed. This study establishes that high-dose plerixafor can be safely administered in healthy donors and mobilizes greater numbers of CD34 cells than conventional-dose plerixafor, which may improve CD34 graft yields and reduce the number of apheresis procedures needed to collect sufficient stem cells for allogeneic transplantation. ().