ABCL-262: Lymphocyte Subpopulation Dynamics in a Model of Cytotoxic Stress Caused by R(G)-DHAP

Context Anti-tumor effects in patients with non-Hodgkin lymphomas (NHL) receiving chemotherapy are achieved as a result of the synergy between cytotoxic effects of chemotherapy and anti-tumor autoimmunity. However, chemotherapeutic depletion of lymphoid cells may impair the effectiveness of the anti-tumor immune response. The dynamics of lymphocyte subpopulations during R(G)-DHAP therapy has not been previously analyzed and are of interest. Objective To analyze changes in lymphocyte fractions and determination of the time period for the restoration of T-cell and NK-cell immunity. Design The study included 5 patients with NHL. Lymphocyte subpopulations were examined at 6–7 time points: before treatment, on the 1st, 5th, 8th, 11th, 16th days of the inter-course break and before the start of the next cycle. Setting Analysis of the subpopulations of lymphocytes was performed using flow cytometry with a panel of antibodies for lymphocytes (CD45+), T-helper cells (CD3+CD4+), cytotoxic T-cells (CD3+CD8+), NK cells (CD3-CD56+) and B-lymphocytes (CD19+). Patients Inclusion criterion: NHL patients receiving R(G)-DHAP chemotherapy. Main Outcomes Measures Estimation of time parameters of dynamics of lymphocyte subpopulations. Results The number of lymphocytes critically decreases on the 1st day of the break after (R/G)-DHAP and gradually increased. CD8+ cells are most sensitive to chemotherapy. The number of CD4+ lymphocytes is characterized by the formation of a second minimum on the 10th–12th day of the inter-course break, while the dynamics of effector cytotoxic lymphocytes and NK cells is more linear and gradually increases. By day 16, the absolute number of lymphocytes is restored or approaching the level before the start of chemotherapy. Conclusions The parameters of the dynamics of lymphocytes under cytotoxic stress can be taken into account in the case of combined use of chemotherapy and immunotherapy.