Frequency, cell lineage, and clinical correlates of lymphopenia in untreated T-cell lymphomas (TCL).

Abstract

e19023 Background: Pre-treatment lymphopenia (Lp) independently predicts survival in TCL. However, lack of knowledge about the lineage of the decreased lymphocyte subset(s) prevents hypothesis formulation on pathophysiology of Lp and its effect on survival. Methods: We retrospectively identified 331 adult patients (pts) with biopsy-proven, newly diagnosed TCL between 2001-2016 at OSU. Pts had no prior chemotherapy or immunosuppressive treatment (tx). Clinical data including flow cytometry (FC) at diagnosis were abstracted from the EMR. Lp was defined as absolute lymphocyte count (ALC) <1,000/µL. Cutaneous TCL (CTCL) stage was defined according to modified EORTC/ISLC criteria. Lymphocyte subsets were defined by FC and reported as proportions of ALC. We examined group differences with Fisher’s Exact or the Wilcoxon Rank Sum tests. Survival was analyzed using Cox regression models. Results: Of 331 pts with TCL, 102 were excluded due to prior tx or incomplete data. Of the 229 pts included, 67 had peripheral TCL (PTCL) and 162 had CTCL; 112 mycosis fungoides/sezary syndrome; 99 (61%) early stage (Stage IA-B), 22 (13%) advanced stage (Stage IIB-IVB), and 41 (26%) cutaneous CD30+ lymphoproliferative disorder (CD30+ LPD). Lp was present in 10% of CTCL, 8% in early stage, 22% in late stage, 12% of CD30+LPD, and 34% of PTCL, with overall frequency of 17%. After median follow up of 1,105 days, Lp was associated with worse progression-free survival (PFS) in CTCL pts with an unadjusted hazard ratio of 3.19 (p=0.19). Adjusting for stage and albumin level on multivariate analysis, Lp retained statistical significance for PFS (HR 3.46, p=.04). For the entire cohort, lymphopenia was associated with inferior OS (p=.0027). Analysis of lymphocyte subsets in late stage CTCL compared to early stage showed a significant decrease in B (CD19+) p=.014, NK (CD56+) p=.012, and CD8+ (p=.0045) cell populations. Conclusions: Lp was prevalent (10-34%) in our cohort of newly diagnosed TCL pts and was associated with worse OS. Lp was more prevalent and lymphocyte subsets were significant altered in pts with advanced stage CTCL. These findings will inform further investigations into mechanisms of Lp in TCL, and its potential as predictive biomarker.