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

Sagar Lonial, Mojtaba Akhtari, Jonathan Kaufman, Claire Torre, Mary J. Lechowicz, Christopher Flowers, Rajni Sinha, Hanna J. Khoury, Amelia A. Langston, Edmund K. Waller

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)460-467
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume19
Issue number3
DOIs
StatePublished - Mar 1 2013

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Granulocyte Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Dendritic Cells
Randomized Controlled Trials
Tissue Donors
T-Lymphocytes
Transplants
Transplantation
Peripheral Blood Stem Cell Transplantation
Blood Component Removal
Autologous Transplantation
Homologous Transplantation
Recovery of Function
Hematologic Neoplasms
HLA Antigens
Allografts
Siblings
Cell Differentiation
Arm
Stem Cells

Keywords

  • Dendritic cell content
  • Graft manipulation
  • Peripheral blood stem cell mobilization

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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. / Lonial, Sagar; Akhtari, Mojtaba; Kaufman, Jonathan; Torre, Claire; Lechowicz, Mary J.; Flowers, Christopher; Sinha, Rajni; Khoury, Hanna J.; Langston, Amelia A.; Waller, Edmund K.

In: Biology of Blood and Marrow Transplantation, Vol. 19, No. 3, 01.03.2013, p. 460-467.

Research output: Contribution to journalArticle

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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.",
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