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.