High Proliferating Regulatory T Cells Post-Transplantation Are Associated with Poor Survival in Lymphoma Patients Treated with Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic cell transplantation (AHCT) in lymphoma is well established and yields improved survival for patients with chemotherapy-sensitive disease. The patterns of immune cell reconstitution after AHCT have emerged as independent predictors of clinical outcomes. We sought to analyze the patterns of regulatory T cell (Treg) reconstitution after AHCT in non-Hodgkin lymphoma (NHL) and their correlations with clinical outcomes. In our prospective cohort study, we analyzed patterns of lymphocyte reconstitution and focused on T reg subsets for 41 patients who underwent AHCT for NHL between 2010 and 2016. Flow cytometry analysis was performed on blood samples collected prospectively at days +28, +60, and +100 post-AHCT. Patients' overall survival (OS) and progression-free survival (PFS) were correlated with Treg immune cell reconstitution. At day +28, Tregs comprised a median of 2.7% (range, 0.4% to 16.8%) of the total lymphocyte population. The proportion of proliferating Tregs (Ki67⁺ Tregs) varied widely from 6.3% to 59.2% (median, 16.1%) of total Tregs and has a significant effect on post-transplantation outcomes. AHCT recipients with low levels of proliferating Tregs (ie, <16.1%, Ki67⁺ Tregs) at 28 days had better 5-year OS compared to patients with high Ki67⁺ Treg levels (75% versus 42%; P = .01). Higher levels of proliferating Tregs at day +28 post-AHCT were associated with higher mortality, with the most frequent cause of death due to lymphoma progression. This association suggests that immunosuppressive cellular reconstitution adversely impacts survival in AHCT recipients with NHL.