Intermittent Sargramostim Administration Expands Proliferating Naïve T Cells, Tregs, HLA-DR+ PD-L1+ Monocytes and Myeloid-Derived Suppressor Cells: Results from a Randomized Placebo-Controlled Clinical Trial of GM-CSF in Patients with Peripheral Artery Disease

Introduction: Sargramostim (rhuGM-CSF; Leukine ®) is an FDA-approved drug known for mobilizing hematopoietic progenitor cells and expediting hematopoietic reconstitution in patients with acute myeloid leukemia (AML) as well as after autologous and allogeneic bone marrow transplantation. While GM-CSF has been explored as an adjuvant for cancer vaccines due to its ability to promote dendritic cell differentiation and maturation, continuous daily administration of sargramostim has been associated with leukocytosis and adverse side effects. To validate and expand upon our previously published findings that thrice-weekly sargramostim administration in patients with severe peripheral artery disease (PAD) is both well-tolerated and beneficial for claudication symptoms, we conducted a placebo-controlled randomized clinical trial to assess the efficacy of an extended dosing regimen of sargramostim in PAD patients. Data regarding progenitor mobilization kinetics and claudication symptoms will be presented elsewhere. In this analysis, we investigated the impact of intermittent sargramostim dosing on immune cell subsets in the bloodstream, aiming to support the use of this dosing schedule for enhancing adaptive immunity.