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
Natalia N. Popova, Mikhail Yu. Drokov, Julia O. Davydova, Nikolay М. Kapranov, Feruza A. Omarova, Ulyana V. Maslikova, Ekaterina D. Mikhaltsova, Olga M. Koroleva, Zoya V. Konova, Anna A. Dmitrova, Mariya V. Dovydenko, Olga S. Starikova, Darya S. Dubnyak, Elmira I. Kolgaeva, Natalia M. Nikiforova, Vera A. Vasilyeva, Irina V. Galtseva, Larisa A. Kuzmina, Elena N. Parovichnikova
National Medical Research Center of Hematology, Moscow, Russia
Dr. Mikhail Yu. Drokov, phone: +7 (495) 614-90-42, e-mail: firstname.lastname@example.org
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.
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).
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.
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.
T memory cells, immune reconstitution, allogeneic stem cell transplantation.
Figure 1. Development of acute GVHD in terms of the absolute count of CD8+ Tnv+scm in peripheral blood on day +30