title: Mobilization of hematopoietic progenitors from normal donors using the combination of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor results in fewer plasmacytoid dendritic cells in the graft and enhanced donor T cell engraftment with Th1 polarization: results from a randomized clinical trial.
abstract: Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) both mobilize CD34(+) stem cells into the blood when administered before apheresis but have distinct effects on dendritic cell (DC) differentiation. We previously demonstrated that the combination of GM+G-CSF results in fewer plasmacytoid DCs (pDCs) when used to mobilize peripheral blood stem cells for autologous transplantation. To test the hypothesis that the content of pDCs in an allograft can be modulated with the cytokines used for mobilization, we randomized the human leukocyte antigen-matched sibling donors of 50 patients with hematological malignancies to a mobilization regimen of either GM+G-CSF (n = 25) or G-CSF alone (n = 25). Primary and secondary endpoints included the cellular constituents of the mobilized grafts, the kinetics of posttransplantation immune reconstitution, and clinical outcomes of the transplantation recipients. Grafts from donors receiving GM+G-CSF contained equivalent numbers of CD34(+) cells with fewer pDCs and T cells, with a higher fraction of Th1-polarized donor T cells than G-CSF mobilized grafts. Immune recovery was enhanced among recipients of GM+G-CSF. Survival was not significantly different between transplantation recipients in the two arms. The use of GM+G-CSF modulates immune function and recovery after allogeneic transplantation and should be explored in larger studies powered to evaluate clinical outcomes.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA. sloni01@emory.edu
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Akhtari
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kaufman
authors.forename: Claire
authors.initials: C
authors.lastname: Torre
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Lechowicz
authors.forename: Christopher
authors.initials: C
authors.lastname: Flowers
authors.forename: Rajni
authors.initials: R
authors.lastname: Sinha
authors.forename: Hanna J
authors.initials: HJ
authors.lastname: Khoury
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Langston
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000235:genetics / Q000276:immunology; D001781:Blood Component Removal; D001853:Bone Marrow / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008223:Lymphoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D014019:Tissue Donors; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor