title: Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery.
abstract: The binding of CXCR4 with its ligand (stromal-derived factor-1) maintains hematopoietic stem/progenitor cells (HSPCs) in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT) promotes hematopoiesis by inducing HSC proliferation.
  
  
  
  We conducted a phase I/II trial of plerixafor on hematopoietic cell recovery following myeloablative allogeneic HSCT. Patients with hematologic malignancies receiving myeloablative conditioning were enrolled. Plerixafor 240 μg/kg was administered subcutaneously every other day beginning day +2 until day +21 or until neutrophil recovery. The primary efficacy endpoints of the study were time to absolute neutrophil count >500/μl and platelet count >20,000/μl. The cumulative incidence of neutrophil and platelet engraftment of the study cohort was compared to that of a cohort of 95 allogeneic peripheral blood stem cell transplant recipients treated during the same period of time and who received similar conditioning and graft-versus-host disease prophylaxis.
  
  
  
  Thirty patients received plerixafor following peripheral blood stem cell (n = 28) (PBSC) or bone marrow (n = 2) transplantation. Adverse events attributable to plerixafor were mild and indistinguishable from effects of conditioning. The kinetics of neutrophil and platelet engraftment, as demonstrated by cumulative incidence, from the 28 study subjects receiving PBSC showed faster neutrophil (p = 0.04) and platelet recovery >20 K (p = 0.04) compared to the controls.
  
  
  
  Our study demonstrated that plerixafor can be given safely following myeloablative HSCT. It provides proof of principle that blocking CXCR4 after HSCT enhances hematopoietic recovery. Larger, confirmatory studies in other settings are warranted.
  
  
  
  ClinicalTrials.gov NCT01280955.
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Michael M B
authors.initials: MM
authors.lastname: Green
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Nelson
authors.initials: N
authors.lastname: Chao
authors.affiliation: Division of Hematology/Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Chhabra
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Corbet
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: Horwitz
authors.affiliation: Duke University Department of Biostatistics and Bioinformatics, Durham, NC, USA.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Hematology/Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Jagadish Kummetha
authors.initials: JK
authors.lastname: Venkata
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Gwynn
authors.initials: G
authors.lastname: Long
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Mims
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sarantopoulos
authors.affiliation: Division of Hematology/Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Stuart
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Sung
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Sullivan
authors.affiliation: Division of Hematology/Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Luciano
authors.initials: L
authors.lastname: Costa
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Horwitz
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA. yubin.kang@duke.edu.|Division of Hematological Malignancies and Cellular Therapy, Duke University Medical Center, Box 3961, 2400 Pratt Street, Durham, NC, 27710, USA. yubin.kang@duke.edu.
authors.forename: Yubin
authors.identifier: 0000-0001-6678-8732
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D001596:Benzylamines; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000080027:Cyclams; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000628:therapy; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009504:Neutrophils / Q000166:cytology; D010976:Platelet Count; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020127:Recovery of Function; D019172:Transplantation Conditioning / Q000379:methods; D055815:Young Adult
chemical_list: D001596:Benzylamines; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019653:Myeloablative Agonists; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: Antagonist; CXCR4; Hematopoietic stem cell transplantation; Hematopoietic stem cells; Neutrophil engraftment; Outcomes; Platelet engraftment; Stromal-derived factor-1