AML-405: T-Cell Dynamics Associated with Outcomes in Acute Myeloid Leukemia Before and After Allogeneic Stem Cell Transplant

Abstract

Background Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many patients with adverse-risk acute myeloid leukemia (AML). This is principally mediated by donor T-cells through the graft-versus-leukemia (GVL) effect. Therefore, we sought to characterize the T cell repertoire in AML before and after HSCT and compare those who achieve durable remission to those with relapse. Methods We identified 77 bone marrow biopsy samples from 33 patients with AML who were paired pre- and post-HSCT (19 patients who relapsed and 14 in remission for > 2 years as of last follow-up). We performed immunosequencing of the TCRβ repertoire (Adaptive Biotechnologies). DNA was amplified in a bias-controlled multiplex PCR, resulting in amplification of rearranged VDJ segments, followed by high-throughput sequencing. Changes in the TCR repertoire were characterized with the following metrics: (1) clonality (range: 0–1; values closer to 1 indicate a more oligoclonal repertoire); (2) richness (higher numbers indicating a more diverse repertoire with more unique rearrangements); (3) T cell density (range: 0–1; values closer to 1 indicate a higher proportion of T cells in the sample). Results The median age of patients was 52 years (range: 19–70); 43% and 37% of patients had a matched, related donor in the remission and relapse cohorts, respectively. Richness was greater in the pre-HSCT samples for patients who relapsed (13750 vs 3982, P = 0.001) compared to post-HSCT samples (3319 vs 2920, P = 0.1). Patients who relapsed had a greater productive clonality compared to remission patients in post-HSCT (0.15 vs 0.05, P = 0.06) samples, but were similar in pre-HSCT (0.07 vs 0.02, P = 0.1) samples. Patients who relapsed had a higher T cell density than those who achieved remission in both pre- (0.36 vs 0.13, P = 0.01) and post-HSCT (0.14 vs 0.11, P = 0.01) samples. Conclusion A more diverse baseline host TCR response was associated with relapse after HSCT. This may reflect host-intrinsic immune factors that affect transplant outcomes. To adequately capture how the GVL effect influences outcomes, studies incorporating TCR sequencing of the HSCT donor samples are ongoing.