Kinetics of Recovery of Naïve and Memory T Cells in Acute Leukemia Patients after Allogeneic Stem Cell Transplantation Depending on Different GVHD Prophylaxis Regimens

Natalia Popova; Mikhail Drokov; Yulia Davydova; Nikolay Kapranov; Vera Vasilieva; Irina Galtseva; Larisa Kuzmina; Elena Parovichnikova

doi:10.18502/ijhoscr.v18i1.14742

Natalia Popova Department of BMT, Immunotherapy and Post-BMT Complications Department, National Research Center for Hematology, Moscow, Russian Federation
Mikhail Drokov Department of BMT, Immunotherapy and Post-BMT Complications Department, National Research Center for Hematology, Moscow, Russian Federation
Yulia Davydova The Laboratory of Immunophenotyping of Blood and Bone Marrow Cells, National Research Center for Hematology, Moscow, Russian Federation
Nikolay Kapranov The Laboratory of Immunophenotyping of Blood and Bone Marrow Cells, National Research Center for Hematology, Moscow, Russian Federation
Vera Vasilieva Department of BMT, Immunotherapy and Post-BMT Complications Department, National Research Center for Hematology, Moscow, Russian Federation
Irina Galtseva The Laboratory of Immunophenotyping of Blood and Bone Marrow Cells, National Research Center for Hematology, Moscow, Russian Federation
Larisa Kuzmina Department of BMT, Immunotherapy and Post-BMT Complications Department, National Research Center for Hematology, Moscow, Russian Federation
Elena Parovichnikova Department of BMT, Immunotherapy and Post-BMT Complications Department, National Research Center for Hematology, Moscow, Russian Federation

DOI: https://doi.org/10.18502/ijhoscr.v18i1.14742

Keywords: GVHD prophylaxis; Immune reconstitution; T memory cells; Post-transplant cyclophosphamide; T cell depletion; Horse ATG

Abstract

Background: Memory T cells are a heterogeneous population of immune cells that provide adaptive immunity. Its full recovery seems essential for graft-versus-tumor reactions that provide an opportunity for biological cure in patients with acute leukemia. The use of mismatched or haploidentical donors has increased, which has become possible because of modifications in graft versus host disease (GVHD) prophylaxis.

Materials and Methods: Sixty-five leukemia patients (acute myeloid leukemia – 40, acute lymphoblastic leukemia – 25), median age 33 (17–61) years, underwent allo-HSCT from 2016 to 2019 in the National Research Centre for Hematology. Patients were divided into three groups based on the impact of GVHD prophylaxis on T cell recovery: horse antithymocyte globulin (ATG)-based regimen (n=32), horse ATG combined with posttransplant cyclophosphamide (PT-Cy) (n=18), and ex vivo T cell depletion (n=15).

Results: The early period after transplantation (before day +100) was characterized by significantly lower absolute numbers of T naïve, memory stem and T central memory cells in peripheral blood in patients after ATG+PT-Cy-regimen or ex vivo T cell depletion than after ATG-based prophylaxis (p<0.05). Moreover, strong depletion of naïve T and memory stem cells prevents the development of GVHD, and determining the absolute number of CD8⁺ naïve T and memory stem cells with a cutoff of 1.31 cells per microliter seems to be a perspective in assessing the risks of developing acute GVHD (p=0.008). The dynamics of T cell recovery showed the involvement of either circulating or bone marrow resident T effector cells shortly after allogeneic transplantation in all patients, but the use of manipulated grafts with ex vivo T cell depletion requires the involvement of naïve and memory stem cells. There was no significant effect of T cell recovery on leukemia relapse after allogeneic transplantation.

Conclusion: These experimental outcomes contribute to providing the best understanding of immunological events that occur early after transplantation and help in the rational choice of GVHD prophylaxis in patients who will undergo allogeneic transplantation. Our study demonstrated the comparable immunological effects of posttransplant cyclophosphamide and ex vivo T cell depletion and immunological inefficiency of horse ATG for GVHD prevention.