Evaluation of Pre-Transplantation T-Cell Receptor Excision Circles (TREC) in Reduced-Intensity Stem Cell Transplantation (RIST) Recipients.

〈Background and Methods〉: Previous studies have shown that the recipient’s thymic function before hematopoietic stem cell transplantation (HSCT) is critical for subsequent immune reconstitution and that the value of pre-transplantation T-cell receptor excision circles (TREC) is related to the incidence of graft-versus-host disease (GVHD), infection and survival. However, these observations have been mainly based on younger patients, who were eligible for myeloablative HSCT. In contrast, little is known about thymic function in elderly patients and its influence on the outcome of reduced-intensity stem cell transplantation (RIST). In this study, TREC values were measured in a total of 180 HSCT recipients who received myeloablative HSCT (n=60: mean age, 34 y) or RIST (n=120, 51 y). Quantification of thymic signal joint TREC was performed by real-time quantitative PCR and TREC values were calculated as TREC copies per 10 ng DNA obtained from peripheral blood mononuclear cells.

〈Results〉: The mean and median pre-transplantation TREC values were 3.9 and 1.3, respectively, and these showed a significant inverse correlation with patient age (p=0.0002). The mean TREC value was 3.0 in males and 5.1 in females (p=0.22), and was significantly lower in 19 patients who had received previous radiation therapy involving the mediastinum (0.96, p=0.003). The TREC value was 3.7 in 99 patients who had a disease duration of longer than 365 days, and 4.2 in 81 patients with a shorter duration (p=0.61). The TREC value was 5.5 for solid tumor (n=10), 5.0 for CML (n=10), 4.8 for AML (n=52), 3.7 for MDS (n=23), 4.0 for ALL (n=23), 2.8 for lymphoma (n=60) and 0.4 for myelofibrosis (n=2), with no difference between those in complete remission and others (both 3.9). The clinical outcome in relation to the TREC value was analyzed in 98 patients who received RIST from an HLA-identical donor. A comparison of 51 patients with lower pre-transplant TREC values (<1.3) and 47 patients with higher values (>1.3) disclosed that the incidence of acute GVHD was 64% vs 57% (p=0.52), that of chronic GVHD was 69% vs 77% (p=0.56), CMV reactivation was 72% vs 60% (p=0.20) and progression-free survival at day 100 was 72% vs 100% (p=0.0001).

〈Conclusion〉: Pre-transplant TREC values showed an inverse correlation with age, and were significantly lower among patients who received radiotherapy involving the thymus. Although these differences were not statistically significant, patients with lymphoid malignancy, patients with longer disease duration and male patients tended to have lower TREC values, while the disease status did not influence the TREC value. This study provides the baseline reference data regarding the thymic function in patients undergoing RIST, although further study is required to evaluate the significance of TREC on the clinical outcome of RIST.