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

Abstract

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)

The efficacy and prescription of neuromuscular electrical stimulation (NMES) in adult cancer survivors: a systematic review and meta-analysis

“…Eight full text articles and one abstract were included for final analysis; four RCTs [22][23][24][25], one case control study [26], three interventional cohort studies [27][28][29], and one case report [30]. Authors were contacted for further information for four additional studies identified [31][32][33][34]. Following three contact attempts with the corresponding authors, studies were excluded where no response was received.…”

The feasibility and efficacy of subcutaneous plerixafor for mobilization of peripheral blood stem cells in allogeneic HLA–identical sibling donors: results of the HOVON‐107 study

“…The kinetics data suggest that mobilization of CD34+ cells starts within 2 hours after administration of SC PXF and continues during the apheresis procedure, that is, until 14 hours after administration of PXF. A recent study showed a similar pattern with 0.240 mg/kg and 0.480 mg/kg of PXF SC . Considering this long period with CD34+ cells present in the peripheral blood, a large‐volume apheresis might be useful in donors who are mobilized with PXF.…”

“…The failure rate of 48% after the first injection is somewhat higher compared to other studies: Most describe failure rates around 30% to mobilize at least 2 × 10 6 CD34+ cells with a single SC or IV injection PXF (Table ). As peak CD34+ cells in the blood appeared higher with a single dose of 0.480 mg/kg PXF IV, it was suggested that this dose might improve the failure rates . However, in this study, no subsequent stem cell collection was performed.…”

Repopulating hematopoietic stem cells from steady-state blood before and after ex vivo culture are enriched in the CD34+CD133+CXCR4low fraction

“…This is not surprising since CXCR4 and its ligand SDF-1 have been demonstrated to have a major role in homing/mobilization of HPCs and HSCs. 33 , 34 …”