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

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/negHLA-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.     

Impact of Single-Dose Plerixafor as an Adjunct to Granulocyte Colony-Stimulating Factor–Based Peripheral Blood Stem Cell Mobilization on the Graft Composition and Outcome for T Cell–Replete Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: A Comparative Study

We conducted a prospective study on T and natural killer (NK) cell subset composition of graft and transplant outcomes in T cell–replete haploidentical transplantation with a single dose of subcutaneous plerixafor (Px) added to granulocyte colony-stimulating factor (G-CSF)-based mobilization in allogeneic donors to collect 10?×?10⁶/kg CD34⁺ hematopoietic stem cells (HSCs) at single apheresis. Twnety-six donors received G-CSF?+?Px and 25 G-CSF alone for mobilization. Despite significantly lower peripheral blood (PB) CD34⁺ HSCs on day 4 in the G-CSF?+?Px group (33 [range, 6-47] cells/µL versus 81 [range, 50-168] cells/µL in the G-CSF group; P?=?.0001), PB CD34⁺ HSC count (median 136 versus 139 cells/µL) on day 5 as well as that in the graft (2.7 versus 2.3?×?10⁶/mL, P?=?.1) were comparable between the 2 groups. The total nucleated cell count was higher (3.4 versus 3.1?×?10⁸/mL, P?=?.05), but CD4⁺ T cells (2.3 versus 2.7?×?10⁷/mL, P?=?.09) were lower in the G-CSF group with mobilization of regulatory T cells being similar. NK cells were skewed toward the CD56⁺/16^? subset in both groups, varying significantly from the steady-state NK subset ratio in PB. The time to engraftment, incidences of acute and chronic graft-versus-host disease, nonrelapse mortality, and overall survival were also similar. Addition of single-dose Px to G-CSF mobilization improves CD34 recovery and does not significantly alter the T and NK cell composition of the graft, including regulatory T cells, with no adverse impact on transplant outcomes.