Risk Factors for Large Cell Transformation in Patients with Sezary Syndrome

Abstract Objectives Large cell transformation (LCT) of Sezary Syndrome (SS) is associated with an aggressive clinical course. To date, there are no rigorous studies identifying risk factors for the development of this phenomenon. We aim to characterize the clinicopathologic risk factors that may predispose patients with SS to develop LCT in the largest such study to date that the authors have identified. Materials/Methods We retrospectively evaluated all SS patient records available in the Michigan Medicine Cancer Registry from 2010–2019. The Mann-Whitney U test and Fisher exact test were used to compare age, sex, race, time to diagnosis, stage, total body surface area (TBSA) involvement, pathologic features, complete blood counts, flow cytometry data, and T cell receptor rearrangements. The Kaplan-Meier method and log-rank test were used to assess overall survival (OS). Univariate analyses were conducted for endpoints of LCT and OS and visualized with Forest plots using the “survival” and “forestplot” packages in R. Results Of the 28 SS patients included in the analysis, eight patients with LCT were identified, and 20 without nonlarge cell transformation (NLCT). Mean peak LDH before LCT (p = 0.0012), mean maximum TBSA involvement before diagnosis of LCT (p = 0.0114), absolute CD8 + cell count on flow cytometry or on biopsy at diagnosis of SS (p = 0.0455), presence of Langerhans cell hyperplasia (p = 0.0171), and presence of ulceration on biopsy (p = 0.0034) were clinicopathologic variables identified as differing significantly between the two groups. On univariate analysis, increased TBSA involvement (HR 1.043 per unit increase, 95% CI 1.001 – 1.081, p = 0.018) and increased peak LDH prior to LCT diagnosis (HR 1.002 per unit increase, 95% CI 1.001 – 1.003, p = 0.002) were identified as poorly prognostic, while unit increase in CD8 + absolute cell count at diagnosis of SS (HR 0.988, 95% CI 0.976 – 0.999, p = 0.041) was identified as protective for development of LCT. There was no survival difference identified between patients with “High” vs. “Low” CD8 + cell counts, or between LCT and NLCT groups. Conclusions Maximum TBSA involvement, peak LDH, presence of ulceration, Langerhans cell hyperplasia, and decreased levels of CD8 + cells in the peripheral blood may predict the development of LCT in patients with SS.