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

• Published in: Journal of hematology and oncology Vol. 9; no. 1; p. 71
• Main Authors: Green, Michael M. B., Chao, Nelson, Chhabra, Saurabh, Corbet, Kelly, Gasparetto, Cristina, Horwitz, Ari, Li, Zhiguo, Venkata, Jagadish Kummetha, Long, Gwynn, Mims, Alice, Rizzieri, David, Sarantopoulos, Stefanie, Stuart, Robert, Sung, Anthony D., Sullivan, Keith M., Costa, Luciano, Horwitz, Mitchell, Kang, Yubin
• Format: Journal Article
• Language: English
• Published: London BioMed Central 17.08.2016; BioMed Central Ltd; BMC
• Subjects: Adult; Aged; Antagonist; Blood diseases; Bone marrow; Cancer Research; Case-Control Studies; Chemokine CXCL12 - antagonists & inhibitors; Chemokine CXCL12 - metabolism; Chemokines; Clinical trials; CXCR4; Cytokine storm; Disease prevention; Extracellular matrix; Female; Graft Survival; Graft versus host disease; Hematologic Neoplasms - therapy; Hematology; Hematopoiesis; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Heterocyclic Compounds - administration & dosage; Heterocyclic Compounds - therapeutic use; Humans; Leukemia; Lymphoma; Male; Medicine; Medicine & Public Health; Middle Aged; Mortality; Myeloablative Agonists - therapeutic use; Neutrophils - cytology; Oncology; Outcomes; Patients; Platelet Count; Receptors, CXCR4 - antagonists & inhibitors; Receptors, CXCR4 - metabolism; Recovery of Function; Stem cell transplantation; Stromal-derived factor-1; Transplantation; Transplantation Conditioning - methods; Young Adult; Stromal-derived factor-1; Platelet engraftment; Neutrophil engraftment; CXCR4; Antagonist; Hematopoietic stem cell transplantation; Hematopoietic stem cells; Outcomes
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-016-0301-2

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