The Graft Monocytic Myeloid Derived Suppressor Cells Content Predicts the Risk of Acute Graft versus Host Disease after Allogeneic Transplantation of Granulocyte Colony-Stimulating Factor mobilized Peripheral Blood Stem Cells

Myeloid-derived suppressor cells are powerful immunomodulatory cells that in mice, play a role in infectious and inflammatory disorders including acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Their relevance in clinical acute graft-versus-host-disease is poorly known. We analyzed whether granulocyte-colony-stimulating-factor administration, used to mobilize hematopoietic stem cells, affects the frequency of myeloid-derived suppressor cells in the peripheral blood stem cell grafts of 60 unrelated donors. In addition we evaluated whether the myeloid-derived suppressor cell content in the peripheral blood stem cell grafts affects the occurrence of acute graft-versus-host disease in patients undergoing unrelated donor allogeneic stem cell transplantation. Systemic treatment with granulocyte-colony-stimulating-factor induces an expansion of myeloid cells displaying the phenotype of monocytic-myeloid-derived suppressor cells (Lin(low/neg)HLA-DR(-)CD11b(+)CD33(+)CD14(+)) with the ability to suppress alloreactive T-cells in-vitro, therefore meeting the definition of myeloid-derived suppressor cells. Monocytic-myeloid-derived suppressor cells dose was the only graft parameter to predict acute graft-versus-host disease. The cumulative incidence of acute graft-versus-host disease at 180 days after transplantation for recipients receiving monocytic-myeloid-derived suppressor cells doses below and above the median was 63% and 22% respectively (p=0.02). The number of monocytic-myeloid-derived suppressor cells infused did not impact the relapse rate nor the transplant-related mortality rate (p>0.05). Although further prospective studies involving larger sample size are needed to validate the exact monocytic-myeloid-derived suppressor cells graft dose protecting from acute graft-versus-host-disease, our results strongly suggest that the modulation of granulocyte-colony-stimulating factor might be used to affect monocytic-myeloid-derived suppressor cells graft cell doses for prevention of acute graft-versus-host disease.