title: 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 32.2versus27.8 cells/μL,P=0.0009) and CD34+cell AUC over 24 hours was significantly increased (mean 553versus446 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).
authors.affiliation: Hematology and Oncology, Department of Medicine, Augusta University, GA, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Pantin
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Enkhtsetseg
authors.initials: E
authors.lastname: Purev
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Cook
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Donohue-Jerussi
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Cho
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Reger
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hsieh
authors.affiliation: Department of Transfusion Medicine, Clinical Research Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hanh
authors.initials: H
authors.lastname: Khuu
authors.affiliation: Sanofi Oncology, Cambridge, MA, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Calandra
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Geller
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA childsr@nih.gov.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism*; D001596:Benzylamines; D003114:Colony-Forming Units Assay; D018592:Cross-Over Studies; D000080027:Cyclams; D005260:Female; D064368:Healthy Volunteers; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; C088327:plerixafor