Michael M B Green1, Nelson Chao1, Saurabh Chhabra2, Kelly Corbet1, Cristina Gasparetto1, Ari Horwitz1, Zhiguo Li3, Jagadish Kummetha Venkata2, Gwynn Long1, Alice Mims4, David Rizzieri1, Stefanie Sarantopoulos1, Robert Stuart2, Anthony D Sung1, Keith M Sullivan1, Luciano Costa2, Mitchell Horwitz1, Yubin Kang5,6. 1. Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA. 2. Division of Hematology/Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA. 3. Duke University Department of Biostatistics and Bioinformatics, Durham, NC, USA. 4. Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH, USA. 5. Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA. yubin.kang@duke.edu. 6. Division of Hematological Malignancies and Cellular Therapy, Duke University Medical Center, Box 3961, 2400 Pratt Street, Durham, NC, 27710, USA. yubin.kang@duke.edu.
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.
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.
Authors: John F DiPersio; Ivana N Micallef; Patrick J Stiff; Brian J Bolwell; Richard T Maziarz; Eric Jacobsen; Auayporn Nademanee; John McCarty; Gary Bridger; Gary Calandra Journal: J Clin Oncol Date: 2009-08-31 Impact factor: 44.544
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Authors: Darja Karpova; Julie K Ritchey; Matthew S Holt; Grazia Abou-Ezzi; Darlene Monlish; Lena Batoon; Susan Millard; Gabriele Spohn; Eliza Wiercinska; Ezhil Chendamarai; Wei Yang; Stephanie Christ; Leah Gehrs; Laura G Schuettpelz; Klaus Dembowsky; Allison R Pettit; Michael P Rettig; Halvard Bonig; John F DiPersio Journal: Blood Date: 2017-04-11 Impact factor: 22.113