AML-260: Influence of Chimerism in T-Regulatory Cells on Relapse Rate in Acute Leukemia Patients after Allo-HSCT

Abstract

<h3>Introduction:</h3> T-regulatory cells (Treg) prevent the development of graft-versus-host disease (GVHD) after allo-HSCT (Beres & Drobyski, 2013). At the same time, this cell population can limit the anti-tumor response (graft-versus-leukemia, GVL), which can cause relapses. We report data of chimerism in a Treg population and the frequency of relapses in acute leukemia patients (ALL and AML) after allo-HSCT. <h3>Objective:</h3> To evaluate a possible relationship between mixed chimerism in Treg cells and the rate of relapses in acute leukemia patients after allo-HSCT. <h3>Methods:</h3> The study included 31 patients after allo-HSCT (ALL n=6, AML n=25). The median age was 38 years (19–66). Peripheral blood samples for analysis were taken on day +30 after transplantation. Immunomagnetic separation (Miltenyi Biotec, Germany) was used to isolate cell population with CD4+CD25+ phenotype, which is predominantly associated with Treg cells. Extraction of DNA was performed from the obtained cells. Chimerism in DNA samples was determined using the STR-PCR method. The percentage of donor chimerism was calculated using standard procedures (Nollet <i>et al.,</i> 2001). Statistical analysis of the data was carried out using SPSS ver 23 (IBM, Chicago, IL, USA). Fisher's exact test was used to analyze the 2 × 2 contingency tables. <h3>Results:</h3> In the group of patients with less than 11% of cells with host genotype (more than 89% of cells of donor origin), the relapse rate was significantly higher: 52.6% (10 of 19) than in the other group of patients with 11% and more cells with host genotype: 8.3% (1 of 12; p=0.02). At the same time, donor chimerism in the unselected bone marrow did not differ significantly from the groups (p = 0.36) and reached 100% (75–100%) and 97.5% (90–100%). The study groups were balanced for all other factors that could affect the relapse rate: disease status, graft source, and GVHD. <h3>Conclusions:</h3> According to our data, we proposed that host Treg cells are not capable to suppress GVL, which explains significant differences in relapse frequencies in patients with acute leukemia after allo-HSCT. Predominance of host Treg cells may be a favorable prognostic sign, but this hypothesis needs to be confirmed on the larger cohort of patients.