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Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery.

dc.contributor.author Green, Michael MB
dc.contributor.author Chao, Nelson
dc.contributor.author Chhabra, Saurabh
dc.contributor.author Corbet, Kelly
dc.contributor.author Gasparetto, Cristina
dc.contributor.author Horwitz, Ari
dc.contributor.author Li, Zhiguo
dc.contributor.author Venkata, Jagadish Kummetha
dc.contributor.author Long, Gwynn
dc.contributor.author Mims, Alice
dc.contributor.author Rizzieri, David
dc.contributor.author Sarantopoulos, Stefanie
dc.contributor.author Stuart, Robert
dc.contributor.author Sung, Anthony D
dc.contributor.author Sullivan, Keith M
dc.contributor.author Costa, Luciano
dc.contributor.author Horwitz, Mitchell
dc.contributor.author Kang, Yubin
dc.coverage.spatial England
dc.date.accessioned 2018-03-05T01:26:31Z
dc.date.available 2018-03-05T01:26:31Z
dc.date.issued 2018-03-04
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/27535663
dc.identifier 10.1186/s13045-016-0301-2
dc.identifier.uri https://hdl.handle.net/10161/16168
dc.description.abstract BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT01280955.
dc.language eng
dc.publisher Springer Science and Business Media LLC
dc.relation.ispartof J Hematol Oncol
dc.relation.isversionof 10.1186/s13045-016-0301-2
dc.subject Antagonist
dc.subject CXCR4
dc.subject Hematopoietic stem cell transplantation
dc.subject Hematopoietic stem cells
dc.subject Neutrophil engraftment
dc.subject Outcomes
dc.subject Platelet engraftment
dc.subject Stromal-derived factor-1
dc.subject Adult
dc.subject Aged
dc.subject Case-Control Studies
dc.subject Chemokine CXCL12
dc.subject Female
dc.subject Graft Survival
dc.subject Hematologic Neoplasms
dc.subject Hematopoiesis
dc.subject Hematopoietic Stem Cell Transplantation
dc.subject Heterocyclic Compounds
dc.subject Humans
dc.subject Male
dc.subject Middle Aged
dc.subject Myeloablative Agonists
dc.subject Neutrophils
dc.subject Platelet Count
dc.subject Receptors, CXCR4
dc.subject Recovery of Function
dc.subject Transplantation Conditioning
dc.subject Young Adult
dc.title Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery.
dc.type Journal article
duke.contributor.id Chao, Nelson|0137379
duke.contributor.id Gasparetto, Cristina|0098068
duke.contributor.id Li, Zhiguo|0543616
duke.contributor.id Long, Gwynn|0199503
duke.contributor.id Rizzieri, David|0098101
duke.contributor.id Sarantopoulos, Stefanie|0630373
duke.contributor.id Sung, Anthony D|0562808
duke.contributor.id Sullivan, Keith M|0219732
duke.contributor.id Horwitz, Mitchell|0310008
duke.contributor.id Kang, Yubin|0436150
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/27535663
pubs.begin-page 71
pubs.issue 1
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Global Health Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published online
pubs.volume 9
dc.identifier.eissn 1756-8722
duke.contributor.orcid Sullivan, Keith M|0000-0002-1379-9216
duke.contributor.orcid Horwitz, Mitchell|0000-0001-9863-8464


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