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,

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Successful Stem Cell Remobilization Using Plerixafor (Mozobil) Plus Granulocyte Colony-Stimulating Factor in Patients with Non-Hodgkin Lymphoma: Results from the Plerixafor NHL Phase 3 Study Rescue Protocol

In a phase 3 multicenter, randomized, double-blinded, placebo-controlled study of 298 patients with non-Hodgkin lymphoma (NHL), granulocyte colony-stimulating factor (G-CSF) plus plerixafor increased the proportion of patients who mobilized ≥5 × 106 CD34+ hematopoietic stem cells (HSCs)/kg compared with placebo plus G-CSF (P < .001). Patients in either study arm who failed mobilization (< 0.8 × 106 CD34+ cells/kg in 2 collections or <2 × 106 CD34+ cells/kg in 4 collections) were eligible to enter the opened-label rescue protocol. Following a 7-day minimum rest period, these patients received G-CSF (10 μg/kg/day) for 4 days, followed by daily plerixafor (0.24 mg/kg) plus G-CSF and apheresis for up to 4 days. Of the 68 patients failing initial mobilization (plerixafor, n = 11; placebo, n = 57), 62 patients (91%) entered the rescue procedure (plerixafor, n = 10; placebo, n = 52). Four of 10 patients (40%) from the plerixafor group and 33 of 52 (63%) from the placebo group mobilized sufficient CD34+ cells (≥ 2 × 106 cells/kg) for transplantation from the rescue mobilization alone (P = .11). Engraftment of neutrophils (11 days) and platelets (20 days) was similar to that in patients who did not fail initial mobilization, and all patients had durable grafts at the 12-month follow-up. Common plerixafor-related adverse events (AEs) included mild gastrointestinal (GI) effects and injection site reactions. There were no drug-related serious AEs. These data support that plerixafor plus G-CSF can safely and effectively remobilize patients with NHL who have failed previous mobilization

Plerixafor Plus Granulocyte Colony-Stimulating Factor Improves the Mobilization of Hematopoietic Stem Cells in Patients with Non-Hodgkin Lymphoma and Low Circulating Peripheral Blood CD34+ Cells

AbstractMany institutions have adopted algorithms based on preapheresis circulating CD34+ cell counts to optimize the use of plerixafor. However, a circulating peripheral blood CD34+ cell threshold that predicts mobilization failure has not been defined. The superiority of plerixafor + granulocyte colony-stimulating factor (G-CSF) over placebo + G-CSF for hematopoietic stem cell mobilization and collection was shown for patients with non-Hodgkin lymphoma in a phase III, prospective, randomized, controlled study. The question remains as to which patients may benefit most from the use of plerixafor. In this post hoc retrospective analysis, mobilization outcomes were compared between the 2 treatment arms in patients stratified by peripheral blood CD34+ cell count (<5, 5 to 9, 10 to 14, 15 to 19, or ≥20 cells/μL) obtained before study treatment and apheresis. Compared with placebo plus G-CSF, plerixafor plus G-CSF significantly increased the peripheral blood CD34+ cells/μL over prior day levels in all 5 stratified groups. The probability of subsequent transplantation without a rescue mobilization was far greater in the plerixafor-treated patients for the lowest initial (day 4) peripheral blood CD34+ cells/μL groups (<5, 5 to 9, or 10 to 14). Engraftment and durability were the same for the 2 treatment groups for all strata, but the effect in the lower strata could be altered by the addition of cells from rescue mobilizations. These findings may provide insight into the optimal use of plerixafor in all patients undergoing stem cell mobilization