IC-05. The role of CD8+ T naive and memory stem cells in acute GVHD development after allogeneic hematopoietic stem cell transplantation performed in patients with acute leukemia

Summary

Acute graft-versus-host disease (GVHD) is a life-threatening complication often seen in allogeneic stem cell transplantation (allo-HSCT) recipients. It occurs due to the damage to the recipient’s organs and tissues by donor T cells. Identification of risk factors and possible predictors of acute GVHD is extremely important as it may help modify immunosuppressive therapy. Our aim was to analyze an impact of different memory T cell subsets in patients receiving allo-HSCT for acute leukemia after acute GVHD onset.

Materials and methods

65 patients with acute leukemia were enrolled in the study. All patients underwent allo-HSCT in National Research Center for Hematology. The median age was 33 (17-61) years. Engraftment was registered in all patients and full donor chimerism was confirmed. The peripheral blood samples were used on day +30 to analyze the absolute count of T memory cell subsets. Flow cytometry (BD FACS Canto II, Becton Dickinson, USA) was performed to determine CD8+ T cells: naïve and T memory stem cells (Tnv+Tscm) – CD45R0^–CCR7⁺CD28⁺; T central memory cells (Tcm) – CD45R0⁺CCR7⁺CD28⁺; T transitional memory cells (Ttm) – CD45R0⁺CCR7^–CD28⁺; T effector memory (Tem) – CD45R0⁺CCR7^–CD28^–; and terminal effectors (Tte) – CD45R0^–CCR7^–CD28^–. All patients were subdivided in two groups to analyze the influence of every cell subset on acute GVHD development. The first included the patients who developed acute GVHD after day +30. The others were the patients without acute GVHD.

Results

The absolute count of CD8+ Tnv+Tscm on day + 30 was statistically different in two groups. We carried out ROC-analysis to determine cut off of CD8+ Tnv+scm on day +30. If the absolute count of CD8+ Tnv+scm in peripheral blood on day +30 was less 1.31 cells/µl the risk of acute GVHD was 12.9% versus 46.2%, р=0.008 (Fig. 1).

Discussion

Earlier we have already presented the data about the comparable impact of GVHD prophylaxis with post-transplant Cyclophosphamide and ex vivo ТCR αβ depletion on short-term T cell recovery after allo-HSCT. Together with the obtained data we can conclude that CD8+ Tnv+scm in peripheral blood is the important participant in the development of acute GVHD.

Conclusion

Quantitative measurement of CD8+ Tnv+scm in peripheral blood on day +30 after allo-HSCT seems to be useful for assessing the risks of acute GVHD and early modification of immunosuppressive therapy.

Keywords

T memory cells, immune reconstitution, allogeneic stem cell transplantation.