Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery.
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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.
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Green, Michael MB, Nelson Chao, Saurabh Chhabra, Kelly Corbet, Cristina Gasparetto, Ari Horwitz, Zhiguo Li, Jagadish Kummetha Venkata, et al. (2018). Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery. J Hematol Oncol, 9(1). p. 71. 10.1186/s13045-016-0301-2 Retrieved from https://hdl.handle.net/10161/16168.
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Nelson Jen An Chao
My research interests are in two broad areas, clinical hematopoietic stem cell and cord blood transplantation and in the laboratory studies related to graft vs. host disease and immune reconstitution. On the clinical side we are currently conducting approximately 50 different clinical protocols ranging from preparatory regimens, supportive care studies and disease specific protocols. Most of these clinical studies are centered around studies of the sources of stem cells and the methods to improve the long term outcome. There are exploratory protocols for novel therapies such as dendritic cell therapy for several malignancies, antiangiogenesis therapy, graft engineering to prevent graft-versus-host disease and antigen specific T cells or non specific NK cells to prevent relapse. Moreover a strong focus of the program is to develop cord-blood transplantation for adult patients with hematologic malignancies. The laboratory studies center on understanding the immunological events that occur with graft-vs-host disease and methods to prevent this disease. The current efforts focus on understanding murine reconstitution following transplantation, use of a peptide polymer to block MHC class II recognition of minor histocompatibility antigens, use of T cell engineering to prevent graft-versus-host disease at the same time preserving a graft-versus-malignancy effect.
For more information see http://ed-media.mc.duke.edu/BMT.nsf
Cristina Gasparetto
Dr. Gasparetto performs both laboratory and clinical research in the field of multiple myeloma. Her primary research interests are in developing immunotherapy approaches to treating multiple myeloma particularly in conjunction with hematopoietic stem cell transplantation. Ongoing laboratory research projects include the development of dendritic cell vaccines and antibody therapies. Clinical studies include a recently approved trial involving vaccination with autologous dendritic cells pulsed with idiotypic protein following high dose chemotherapy and autologous peripheral blood stem cells transplant. Upcoming trials include novel antibody therapies for multiple myeloma. Dr. Gasparetto is also an investigator on several other clinical trials for myeloma including non-myeloablative allogeneic transplantation, high dose sequential chemotherapy and autologous peripheral blood stem cell transplantation and transplantation of partially HLA matched unrelated cord blood.
Zhiguo Li
survival analysis, dynamic treatment regimes, clinical trials
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