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 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 + ≤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 )