Study of the Relationship between Granulocyte Colony-Stimulating Factor Together with Type 2 Dendritic Cells in Donor Grafts and the Allogeneic Hematopoietic Stem Cell Transplantation.

Objective

1. To evaluate the influence of granulocyte colony-stimulating factor (G-CSF)on the quantity, ratio of dendritic cell(DC)1 and DC2 in peripheral blood (PB)and bone marrow(BM);

2. To assess the influence of G-CSF on the cell composition of grafts (included the DC subsets) and the curative effect following Allogeneic hematopoietic stem cell transplantation (Allo-HSCT).

Methods

1. By FACS, the quantity, ratio of DC1 and DC2 were detected by 11 donors in granulocyte colony-stimulating factor mobilization peripheral blood hematopoietic stem cell(G-PBSC) graft, 20 donors in G-BM graft, 8 donors in primed PB, and 10 normal individuals in primed BM respectively.

Result

1. DC2 count in BM (from a mean of 14.37×10⁶/L to 29.68×10⁶/L P=0.013) was increased by G-CSF treatment with 10ug/kg per day for 5 days, whereas BM DC1 count did not change. The ratio of DC2 to DC1 was significantly higher in donor BM with G-CSF (1.83±0.81) than in resting unprimed BM (1.12±0.32)(P=0.013).

2. The number of PB DC2 (26.76×10⁶/L) and the ratio of DC2 to DC1 (2.02± 1.43) was selectively increased in normal donor treated with G-CSF, but a similar to number of DC1.

3. The absolute numbers of MNC, CD34⁺, CD3⁺, CD3⁺CD4⁺ or CD3⁺CD8⁺ cells contained in G-BM allograft were higher 1 to 2 times than those in BM allograft(P<0.05), but were comparable with those in G-PBSC allograft.

4. The median time of neutrophil engraftment in G-BMT group(13 days) was longer 1day than that in peripheral blood hematopoietic stem cell transplantation (PBSCT)group (12 days);The median time of platelet engraftment in G-BMT group was comparable with that in PBSCT group, but was earlier 4 days than that in BMT group (P=0.039).

5. PLT transfusion was significantly reduced in recipients of G-BM graft (50u) compared to BM (140u)(P=0.002); RBC transfusion did not differ between G-BMT and PBSCT or BMT;Median time to hospital discharge after transplantation was significantly reduced in patients receiving G-BM graft compared to BM (P=0.004).

6. The incidence of gradesII~IV and III~IV aGVHD was respectively higher and lower in the G-BMT (31.6%OE14.5%) group than in the PBSCT (25% OE 20%) group, was lower than in the BMT group (50.1% OE33 .4%).

7. The incidence rate of aGVHD in higher DC2 infusion group was 61.5% (lower DC2 infusion group:83.3%), the emergence time of aGVHD was 22days(18days).

Similarly, the incidence rate of gradesII~IVand III~IV aGVHD in higher infusion group was 23.08% and 15.38%(lower infusion group: 66.67% and 33.33%).

Conclusion

1. The number of PB and BM DC2 were selectively increased in normal donor treated with G-CSF but not PB or BM DC1.

2. G-PBSC graft used for allogeneic transplantation contained more DC2 counts than resting BM but a similar to number of DC1.

3. Compared to G-BMT, patients receiving G-BMT had prompt engraftment of platelet, lower platelet transfusion requirements, and shorted average length of stay.

4. There was a incidence of less skin, liver or gut aGVHD, and less grades II~IV or III~IVaGVHD in the G-BMT group than in the BMT group.

5. There was a tendency of rapid engraftment and decreased incidence or severity of aGVHD in the higher DC2 infusion group.