Background

Recently, a few data showed that Granulocyte-colony-stimulating factor (G-CSF) modified bone marrow (G-BM) grafts leaded a lower morbidity and mortality of graft-versus-host disease(GVHD), compared with G-CSF mobilized peripheral blood stem cells (G-PBSCs) and steady state bone marrow (SS-BM) grafts. However, the mechanism of this difference is not fully understood. In this study, we compared the immune components in the three grafts.

Methods

Twenty patients undergoing HLA-matched sibling donor stem cell transplantation(SCT) were enrolled in this study. Patients were randomized to receive G-BM (n=10) or G-PBSCs (n=10) transplantation. Immune components, including Human leucocyte antigen-G (HLA-G), Myeloid-derived suppressor cells (MDSCs) and T cell subsets, were detected in bone marrow (BM) and peripheral blood (PB) of donors before and at day 5 after G-CSF mobilization.

Results

Among 20 patients, 2 patients developed acute GVHD (aGVHD) and 5 developed chronic GVHD (cGVHD) in G-PBSCs group, and no patients developed aGVHD and only 1 developed limited cGVHD in G-BM group. For the grafts, the proportion of MDSCs in PB and BM was 1.47% ± 0.12% and 2.26% ± 0.35% (P=0.001), respectively, before mobilization. After 5 days of G-CSF mobilization, the proportion of MDSCs in PB and BM increased to be 2.73% ± 0.68% and 2.56% ± 0.12%, respectively. The increase is significant both in PB and BM (P=0.000,P=0.002, respectively), while no significant difference was found between the proportion of MDSCs in G-PB and G-BM graftes (P=0.115). The levels of HLA-G (both soluble and membrane bound) in PB and BM all increased significantly after G-CSF mobilization (all P<0.05). And the levels of HLA-G (both soluble and membrane bound) in BM were all higher than that in PB, including before and after G-CSF mobilization (all P<0.05). The total numbers of CD3+ cells were similar in BM before and after mobilization, both significantly lower than that in PB (both P<0.001). However, the lowered CD4+ cells and increased CD8+ cells in G-BM leaded to a significantly lower CD4:CD8 ratio than that in SS-BM and G-PB (both P<0.001).

Conclusions

The differences of immune components in the grafts might play a part in the different morbidity and mortality of GVHD. The higher expression of HLA-G in the grafts might be the main reason for the lower morbidity and mortality of GVHD in G-CSF-primed bone marrow transplantation.

Disclosures:

Liu:It was supported by 863 Program (No. 2011AA020105), National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; It was supported by National Natural Science Foundation of China (Grant No.81000231, No.81270647) and Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

Author notes

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Asterisk with author names denotes non-ASH members.

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