title: Graft monocytic myeloid-derived suppressor cell content predicts the risk of acute graft-versus-host disease after allogeneic transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.
abstract: Myeloid-derived suppressor cells (MDSCs) are powerful immunomodulatory cells that in mice play a role in infectious and inflammatory disorders, including acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Their relevance in clinical acute GVHD is poorly known. We analyzed whether granulocyte colony-stimulating factor (G-CSF) administration, used to mobilize hematopoietic stem cells, affected the frequency of MDSCs in the peripheral blood stem cell grafts of 60 unrelated donors. In addition, we evaluated whether the MDSC content in the peripheral blood stem cell grafts affected the occurrence of acute GVHD in patients undergoing unrelated donor allogeneic stem cell transplantation. Systemic treatment with G-CSF induces an expansion of myeloid cells displaying the phenotype of monocytic MDSCs (Lin(low/neg)HLA-DR(-)CD11b(+)CD33(+)CD14(+)) with the ability to suppress alloreactive T cells in vitro, therefore meeting the definition of MDSCs. Monocytic MDSC dose was the only graft parameter to predict acute GVHD. The cumulative incidence of acute GVHD at 180 days after transplantation for recipients receiving monocytic MDSC doses below and above the median was 63% and 22%, respectively (P = .02). The number of monocytic MDSCs infused did not impact the relapse rate or the transplant-related mortality rate (P > .05). Although further prospective studies involving larger sample size are needed to validate the exact monocytic MDSC graft dose that protects from acute GVHD, our results strongly suggest the modulation of G-CSF might be used to affect monocytic MDSCs graft cell doses for prevention of acute GVHD.
authors.affiliation: Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vendramin
authors.affiliation: Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gimondi
authors.affiliation: Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Anisa
authors.initials: A
authors.lastname: Bermema
authors.affiliation: Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Longoni
authors.affiliation: Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Rizzitano
authors.affiliation: Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hematology Department, Università degli Studi di Milano, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.affiliation: Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: cristiana.carniti@istitutotumori.mi.it.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Carniti
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D036102:Peripheral Blood Stem Cell Transplantation; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D019737:Transplants / Q000276:immunology* / Q000378:metabolism; D061349:Unrelated Donors
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: Allogeneic hematopoietic stem cell transplantation; Graft-versus-host disease; Granulocyte colony-stimulating factor mobilization; Myeloid-derived suppressor cells