title: Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft.
abstract: A single subcutaneous (SC) injection of plerixafor results in rapid mobilization of hematopoietic progenitors, but fails to mobilize 33% of normal allogeneic sibling donors in 1 apheresis. We hypothesized that changing the route of administration of plerixafor from SC to IV may overcome the low stem cell yields and allow collection in 1 day. A phase 1 trial followed by a phase 2 efficacy trial was conducted in allogeneic sibling donors. The optimal dose of IV plerixafor was determined to be 0.32 mg/kg. The primary outcome of reducing the failure to collect ≥2 × 106CD34+/kg recipient weight in 1 apheresis collection to ≤10% was not reached. The failure rate was 34%. Studies evaluating the stem cell phenotype and gene expression revealed a novel plasmacytoid dendritic cell precursor preferentially mobilized by plerixafor with high interferon-α producing ability. The observed cytomegalovirus (CMV) viremia rate for patients at risk was low (15%), as were the rates of acute grade 2-4 graft-versus-host disease (GVHD) (21%). Day 100 treatment related mortality was low (3%). In conclusion, plerixafor results in rapid stem cell mobilization regardless of route of administration and resulted in novel cellular composition of the graft and favorable recipient outcomes. These trials were registered at clinicaltrials.gov as #NCT00241358 and #NCT00914849.
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schroeder
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rettig
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lopez
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Christ
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Mark
authors.initials: M
authors.lastname: Fiala
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: William
authors.initials: W
authors.lastname: Eades
authors.affiliation: Division of Hematology and Medical Oncology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO; and.
authors.forename: Fazia A
authors.initials: FA
authors.lastname: Mir
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Jin
authors.initials: J
authors.lastname: Shao
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Kyle
authors.initials: K
authors.lastname: McFarland
authors.affiliation: Division of Biostatistics and.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Trinkaus
authors.affiliation: Division of Biostatistics and.
authors.forename: William
authors.initials: W
authors.lastname: Shannon
authors.affiliation: Division of Biostatistics and.
authors.forename: Elena
authors.initials: E
authors.lastname: Deych
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Yu
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Keith
authors.initials: K
authors.lastname: Stockerl-Goldstein
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Cashen
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Uy
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Camille N
authors.initials: CN
authors.lastname: Abboud
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Peter
authors.initials: P
authors.lastname: Westervelt
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D001596:Benzylamines; D001781:Blood Component Removal; D000080027:Cyclams; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072916:Peripheral Blood Stem Cells / Q000166:cytology / Q000187:drug effects*; D014019:Tissue Donors; D059467:Transcriptome / Q000187:drug effects; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods
chemical_list: D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor