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Background <p>Myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells. Their role in modulating acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. This study aimed to investigate the impact of MDSC levels in granulocyte colony-stimulating factor (G-CSF)–mobilized peripheral blood stem cell (PBSC) grafts on the incidence of II–IV° aGVHD.</p> Results <p>We retrospectively analyzed 170 allo-HSCT recipients. Employing an exposure-based analytical framework, patients were stratified into high- and low-dose groups based on the infused dose of polymorphonuclear MDSCs (PMN-MDSCs). In Fine-Gray competing risk analyses, a high dose of PMN-MDSCs per kilogram (&gt; 17.5 × 10⁶/kg) was an independent protective factor against aGVHD (subdistribution hazard ratio [sHR] 0.25, 95% CI 0.07–0.88, <i>P</i> = 0.039). A clinically applicable optimal cut-off was identified at 11.3 × 10⁶/kg. Patients receiving a PMN-MDSC dose &gt; 11.3 × 10⁶/kg had significantly superior 300-day overall survival (92.4% vs. 74.9%, <i>P</i> = 0.005) and GVHD-free relapse-free survival (76.3% vs. 40.4%, <i>P</i> &lt; 0.001) compared to the low-dose group. In the malignant disease subset (<i>n</i> = 147), a high dose of the activated LOX-1⁺ PMN-MDSC subset was associated with a markedly lower cumulative incidence of relapse (1.37% vs. 11.42%, <i>P</i> = 0.015). Longitudinal monitoring revealed that the peak incidence of aGVHD (median day + 29) closely followed the peak and subsequent decline of circulating MDSC levels.</p> Conclusions <p>The absolute dose of PMN-MDSCs in G-CSF-mobilized grafts is an independent determinant of II–IV°aGVHD risk and survival outcomes, with a defined threshold of 11.3 × 10⁶/kg. These findings position PMN-MDSC dose as a promising biomarker for risk stratification and a potential lever for optimizing graft composition in allo-HSCT.</p>

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Infused PMN-MDSCs from G-CSF–mobilized PBSCs protect against II–IV° acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月22日

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  • Man Chen,
  • Xue-qiao Wang,
  • Jing Long,
  • Min-Jing Fu,
  • Hui Wang,
  • Yi Li,
  • Wei Zhao

摘要

Background

Myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells. Their role in modulating acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. This study aimed to investigate the impact of MDSC levels in granulocyte colony-stimulating factor (G-CSF)–mobilized peripheral blood stem cell (PBSC) grafts on the incidence of II–IV° aGVHD.

Results

We retrospectively analyzed 170 allo-HSCT recipients. Employing an exposure-based analytical framework, patients were stratified into high- and low-dose groups based on the infused dose of polymorphonuclear MDSCs (PMN-MDSCs). In Fine-Gray competing risk analyses, a high dose of PMN-MDSCs per kilogram (> 17.5 × 10⁶/kg) was an independent protective factor against aGVHD (subdistribution hazard ratio [sHR] 0.25, 95% CI 0.07–0.88, P = 0.039). A clinically applicable optimal cut-off was identified at 11.3 × 10⁶/kg. Patients receiving a PMN-MDSC dose > 11.3 × 10⁶/kg had significantly superior 300-day overall survival (92.4% vs. 74.9%, P = 0.005) and GVHD-free relapse-free survival (76.3% vs. 40.4%, P < 0.001) compared to the low-dose group. In the malignant disease subset (n = 147), a high dose of the activated LOX-1⁺ PMN-MDSC subset was associated with a markedly lower cumulative incidence of relapse (1.37% vs. 11.42%, P = 0.015). Longitudinal monitoring revealed that the peak incidence of aGVHD (median day + 29) closely followed the peak and subsequent decline of circulating MDSC levels.

Conclusions

The absolute dose of PMN-MDSCs in G-CSF-mobilized grafts is an independent determinant of II–IV°aGVHD risk and survival outcomes, with a defined threshold of 11.3 × 10⁶/kg. These findings position PMN-MDSC dose as a promising biomarker for risk stratification and a potential lever for optimizing graft composition in allo-HSCT.