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 versus 27.8 cells/μL, P=0.0009) and CD34⁺ cell AUC over 24 hours was significantly increased (mean 553 versus 446 h cells/μL, P<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. (ClinicalTrials.gov, identifier: NCT00322127).

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