Allogeneic Hematopoietic Stem Cell Transplantation Mobilized With Pegylated Granulocyte Colony-Stimulating Factor Ameliorates Severe Acute Graft-Versus-Host Disease Through Enrichment of Monocytic Myeloid-Derived Suppressor Cells in the Graft: A Real World Experience.

Lin Li,Yang Cao,Yicheng Zhang,Li Lin,Yun Li,Na Wang,Jia Wei,Jinhuan Xu,Jin Yin,Chunyan Wang,Xia Mao

doi:10.3389/fimmu.2021.621935

Abstract

We compared the effectiveness and safety of pegylated granulocyte colony-stimulating factor (peg-G-CSF) vs. non-peg-G-CSF for hematopoietic stem cell mobilization in allogeneic hematopoietic stem cell transplantation in a real-world setting. We included 136 consecutive healthy donors treated with non–peg-G-CSF (n = 53) or peg-G-CSF (n = 83), and 125 consecutive recipients (n = 42 and 83, respectively) in this study. All harvesting was completed successfully. No significant difference in leukapheresis number and adverse events frequency was observed, nor were there severe adverse events leading to discontinuation of mobilization. The leukapheresis products mobilized by peg-G-CSF had higher total nucleated cells (p < 0.001), monocytic myeloid-derived suppressor cells (p < 0.001), granulocytic myeloid-derived suppressor cells (p = 0.004) and B cells (p = 0.019). CD34+ cells and other lymphocyte subsets (T cells, regulatory T cells, natural killer [NK] cells, etc.) were similar in both apheresis products. Patients who received grafts mobilized by peg-G-CSF exhibited a lower incidence of grade III-IV acute graft-versus-host disease (p = 0.001). The 1-year cumulative incidence of chronic graft-versus-host disease and relapse, 1-year probability of graft-versus-host disease-free relapse-free survival, and overall survival did not differ significantly between subgroups. Our results suggest that collecting allogeneic stem cells after the administration of peg-G-CSF is feasible and safe. Peg-G-CSF mobilized grafts may reduce severe acute graft-versus-host disease compared with non-peg-G-CSF mobilized grafts after allogeneic stem cell transplantation. The beneficial effects of a peg-G-CSF graft might be mediated by increased numbers of monocytic myeloid-derived suppressor cells.

Highlights

Mobilization with recombinant human granulocyte colonystimulating factor (G-CSF) followed by leukapheresis has become the standard procedure for obtaining CD34+ peripheral blood stem cells (PBSCs) for hematopoietic stem cell transplantation (HSCT)
We designed this study to evaluate the safety and feasibility of stem cell mobilization with peg-G-CSF administered to allogeneic donors
Peg-G-CSF has been shown to be comparable to conventional non-peg-G-CSF in chemotherapy-induced neutropenia and in mobilizing autologous PBSCs [5, 10, 11]

Summary

Introduction

Mobilization with recombinant human granulocyte colonystimulating factor (G-CSF) followed by leukapheresis has become the standard procedure for obtaining CD34+ peripheral blood stem cells (PBSCs) for hematopoietic stem cell transplantation (HSCT). Some studies optimizing the dosage and schedule of G-CSF have reported an association between G-CSF trough blood levels and mobilization efficacy [1,2,3]. Peg-G-CSF induced the mobilization of CD34 + progenitor cells in animal models [7] and in preliminary human studies involving patients with hematological malignancies as well as healthy donors [8,9,10,11,12]. Peg-G-CSF showed a modulating impact on both graft-versus-leukemia (GVL) effects [13] and graft-versus-host disease (GVHD) [14] by regulating T cells. Further studies are required to evaluate the mobilization of peg-G-CSF and G-CSF, and to elucidate the mechanisms affecting the recipient’s outcome

Methods

Results

Conclusion