Sequential quantification of T-cell receptor excision circles (TRECs) and K-deleting recombination excision circles (KRECs) and overall survival after allogeneic HSCT

The use of TRECs/KRECs in allogeneic HSCT (alloHSCT) has been limited by a lack of standard technical platforms to allow comparison and validation of results between centers. We quantified absolute TRECs/KRECs on sequential samples collected prospectively (pre-transplant, 1, 3, 6 and 12 months post-transplant) in 374 alloHSCT for hematological malignancies using LightCycler 480/TREC-KREC- ACTB (Roche Diagnostics). Following prompt decrease after transplant, KRECs recover as soon as 3 months posttransplant, while TRECs recovery takes up to 1 year (p < 0.001). KRECs do not associate with outcomes. However, higher pre-transplant TRECs strongly associate with reduced non-relapse mortality (NRM) and increased overall survival (OS), and remain independent in multivariate analysis (HR 0.37, p = 0.001, and HR 0.51, p < 0.001, respectively). In addition, faster TRECs recovery measured sequentially at 1, 3, 6 and 12 months after alloHSCT associates with better OS. Furthermore, landmark analyses showed that early survivors with higher TRECs levels at 6 and 12 months after alloHSCT had significantly better subsequent long-term survival, independent from graft-versus-host disease (GVHD) and other clinical factors in multivariate analysis (HR 0.33, p = 0.016 and HR 0.13, p < 0.001, respectively). TRECs levels pre-transplant and at 6 and 12 months post-transplant provide novel biomarker measurable data that associate with alloHSCT long-term outcomes.