W232 - T Cell Receptor Sequencing Used to Monitor Changes Associated with Two Immunosuppressive Regimens in Pediatric and Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplant

Stephanie Bien, PhD – Sr Manager, Computational Biology, Adaptive Biotechnologies; Danielle Scheffey, PhD – Director, Business Development, Adaptive Biotechnologies; Steven Siegel, MD PhD – Boston Children’s Hospital; Alexandre Albanese, PhD – Boston Children’s Hospital; Paula Keskula – Boston Children’s Hospital; Leslie Kean, MD PhD – Boston Children’s Hospital; Catherine Sanders, MT PhD – VP, Business Development, Adaptive Biotechnologies; Harlan Robins, PhD – CSO, Innovation, Adaptive Biotechnologies

Abstract Text: Assessment of immune dysregulation after allogeneic hematopoietic stem cell transplantation (allo-HCT) is essential to efforts in reducing morbidity and mortality associated with complications from disease relapse, infectious disease, and graft versus host disease. Immunosuppressive regimens are routinely administered to allo-HCT patients in an effort to suppress alloreactive T-cells. To better understand differences in the effectiveness of new immunosuppressive regimens, it is helpful to evaluate restoration of immune competence, and to longitudinally monitor expansions of donor T cells and the dynamics of T-cell receptor (TCR) repertoire reconstitution in transplant recipients. We investigated these dynamics with the immunoSEQ® Assay (Adaptive Biotechnologies, Seattle, WA) in both the donor stem cell product and peripheral TCRß repertoires of pediatric and adult patients enrolled on the ABA2 multicenter randomized trial of abatacept for GVHD prophylaxis (NCT# NCT01743131, PMID: 33449816). All patients received a standard immunosuppressive regimen of a calcineurin inhibitor (tacrolimus or cyclosporine) and methotrexate (MTX). The CNI/MTX group (n=288 samples analyzed) was compared to a subset of patients that additionally received abatacept (ABA, n=526 samples analyzed). In both groups, there wasn’t a significant difference in the peripheral repertoire skewness at day 180 and 365. Furthermore, we found that clones from the donor transplant were present at a moderate frequency as far out as one-year post-infusion. These findings shed light on post–allo-HCT adaptive immune reconstitution and demonstrate that immunoSEQ can be used to quantifiably assess immune responses, track clonal specificities, and may help in evaluating alloreactive responses following allo-HCT.