title: FLT3L and plerixafor combination increases hematopoietic stem cell mobilization and leads to improved transplantation outcome.
abstract: Hematopoietic stem cell (HSC) transplantation has curative potential for patients with hematological malignancies. Clinically, HSCs derived from mobilized peripheral blood are used more frequently than bone marrow. However, current standard mobilizing agents yield grafts that may not contain sufficient HSCs. Here, using murine models, we discovered that FLT3L synergized with plerixafor to mobilize phenotypically defined HSCs and their combination (FP) was superior to granulocyte colony-stimulating factor (G-CSF) alone or in combination with plerixafor (GP). Additionally, FP mobilized more regulatory T cells, natural killer cells, and plasmacytoid dendritic cells compared with G-CSF alone or GP. Both syngeneic and allogeneic grafts mobilized by FP led to long-term survival in transplanted mice. Collectively, FP represents a promising novel and potent mobilization regimen with potential clinical application in both the autologous and allogeneic transplantation settings.
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, Ohio; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Shun
authors.initials: S
authors.lastname: He
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Chu
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, Ohio; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio; Blood and Marrow Transplantation Program, The James Cancer Hospital, Ohio State University, Columbus, Ohio.
authors.forename: Sumithira
authors.initials: S
authors.lastname: Vasu
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Youcai
authors.initials: Y
authors.lastname: Deng
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio; Department of Lymphoma, PLA 307 Hospital, Beijing, China.
authors.forename: Shunzong
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Center for Biostatistics, Department of Biomedical Informatics, Ohio State University, Columbus, Ohio.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, Ohio; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Hofmeister
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio; Department of Biomedical Engineering, Ohio State University, Columbus, Ohio.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: He
authors.affiliation: Celldex Therapeutics, Inc., Needham, Massachusetts.
authors.forename: Henry C
authors.initials: HC
authors.lastname: Marsh
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, Ohio; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio; Blood and Marrow Transplantation Program, The James Cancer Hospital, Ohio State University, Columbus, Ohio.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, Ohio; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio; Blood and Marrow Transplantation Program, The James Cancer Hospital, Ohio State University, Columbus, Ohio. Electronic address: Jianhua.yu@osumc.edu.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D001596:Benzylamines; D000080027:Cyclams; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D004338:Drug Combinations; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D004338:Drug Combinations; D006571:Heterocyclic Compounds; D008565:Membrane Proteins; D011994:Recombinant Proteins; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor
keywords: Cell mobilization; FLT3L; Plerixafor; Transplantation