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Numerous studies have shown that high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT) led to a profound and long-lasting state of immunodeficiency characterized by persisting low levels of T cells in hemoblastosis patients. Well-timed T-cell reconstitution is crucial...

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Published in:European journal of cancer supplements 2015-11, Vol.13 (1), p.4-4
Main Authors: Batorov, E, Tikhonova, M, Kryuchkova, I, Sergeevicheva, V, Batorova, D, Sizikova, S, Ushakova, G, Gilevich, A, Ostanin, A, Chernykh, E
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Language:English
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Summary:Numerous studies have shown that high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT) led to a profound and long-lasting state of immunodeficiency characterized by persisting low levels of T cells in hemoblastosis patients. Well-timed T-cell reconstitution is crucial for early restoration of anti-infectious and anti- tumor immune response. Lymphocyte recovery is mediated through the two main mechanisms – a homeostatic proliferation of T cells and generation of new naive T cells via thymopoiesis. It is known, that homeostatic proliferation is important for the restoration of T cell count in immune competent host during the 1st year following AHSCT. Thymus begins to fill up T cell repertoire approximately from the 6th month following AHSCT. We have investigated dynamics of CD4+FOXP3+ Treg recovery following AHSCT and possible relationship between Tregs and clinical outcomes since the suppressive activity of Tregs under lymphopenic conditions may influence on peripheral expansion of T cells. Thymic activity following AHSCT has been evaluated by measuring amounts of CD4+ CD45RA+CD31+ naïve T cells, i.e. “recent thymic emigrants” (RTEs).109 patients with non-Hodgkin’s lymphomas, Hodgkin’s lymphoma and multiple myeloma underwent AHSCT in 2009–2014. The content of circulating CD4+FOXP3+ Tregs and CD4+CD45RA+CD31+ T cells was evaluated using flow cytometry before AHSCT, at the day of engraftment, and following 6 and 12 months. Pre-transplant count of CD4+FOXP3+ Tregs was significantly higher compared to healthy controls (5.4 ± 2.9 vs 3.8 ± 1.9%; pU = 0.011; here and below data presented as Mean ± SD). Percentage of Tregs restored rapidly and reached initially high level at the time of engraftment, and then subsequently decreased within a year until it lowered to healthy donors‘ values. CD4+FOXP3+ Tregs at the time of engraftment were increased in patients with relapse or progression of disease within 6 and 12 months following AHSCT compared to non-relapsed patients (11.0 ± 6.1 vs 6.2 ± 3.0%; pU = 0.016, and 10.1 ± 5.2 vs 6.1 ± 3.8%; pU = 0.008). Pre-transplant count of CD4+CD45RA+CD31+ T cells was significantly lower compared to healthy controls (17.1 ± 11.4 vs 30.3 ± 11.2%, pU = 0.0005) and did not reach donors‘ values following 12 month (23.1 ± 13.5%, pU = 0.032). Relapsed patients had the same quantity of RTEs as the patients with remission within the 1st year following AHSCT. There was no any significant association between RTE
ISSN:1359-6349
DOI:10.1016/j.ejcsup.2015.08.007