Abstract LB-272: T-cell clonal dynamics determined by high resolution TCR-β sequencing in recipients of allogeneic hematopoietic cell transplantation

Abstract

Abstract Delayed reconstitution of the immune system after allogeneic hematopoietic cell transplantation (HCT) is a long-recognized complication. Specifically, loss of T-cell diversity has been implicated in infectious complications, graft-versus-host disease (GVHD), and disease relapse. We performed serial high-resolution next generation sequencing using the immunoSEQ® Assay (Adaptive Biotechnologies, Seattle, WA) to characterize the TCRβ locus in 99 HCT recipients in the first 3 months after transplant. Transplant donor type included unrelated (n=57) and related (n=42) donors. Conditioning regimen intensity included reduced intensity (n=55) and myeloablative (n=44). We measured T-cell fraction, clonality, and richness in the donor and at days +15, +30, +50 and +100 post-transplant in the recipient, and correlated metrics to clinical variables. In agreement with prior studies, we found that although absolute T-cell numbers recover relatively quickly after transplant, repertoire diversity remains diminished. Restricted diversity was associated with conditioning intensity, use of ATG, and donor type. Increased T-cell clonal expansion at Day +30 compared to the donor sample was associated with the incidence of acute GVHD (HR=1.11, p=5x10-5). Even after exclusion of the twelve patients who had experienced acute GVHD by day +30, the association between acute GVHD and clonal expansion persisted (HR=1.098, p=0.041), indicating that clonal expansion preceded the development of acute GVHD. Our results indicate the importance of early post-transplant sampling and highlight T-cell clonal expansion as a potential novel biomarker for GVHD which warrants further study. Citation Format: Rachel M. Gittelman, Mark Leick, Zachariah DeFilipp, Jerome Ritz, Erik Yusko, Catherine Sanders, Harlan Robins. T-cell clonal dynamics determined by high resolution TCR-β sequencing in recipients of allogeneic hematopoietic cell transplantation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-272.