Sézary Syndrome: Clinicopathological and Immunophenotypical Characteristics and Outcomes

Background

Sézary syndrome (SS) is a rare malignant T-cell lymphoproliferative disorder derived from mature CD4+ T-helper/inducer cells. Patients (pts) with SS usually manifest with generalized erythroderma, peripheral blood and lymph node involvement and severe pruritus. Current therapy usually consists of extracorporeal photopheresis, interferon alpha, alemtuzumab, histone deactylase inhibitors (HDACi) and monochemotherapy. SS is considered incurable with conventional skin directed or conventional systemic therapy. Reports in literature suggest overall survival (OS) between 2-5 years.

Methods

Between 2002 and 2015, 50 pts with SS were evaluated and treated at Moffitt Cancer Center (MCC). Patient demographics, disease/treatment characteristics, responses, and outcomes were collected from our CTCL database. We characterized four groups based on immunophenotype, aberrant loss of CD26 and CD7, or both. Responses to treatment were assessed using standard criteria: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Descriptive statistics were used to report baseline characteristics. Chi square and t-test were used for comparison of categorical and continuous variables respectively. Kaplan-Meier graphs were used for estimation of OS from time of diagnosis.

Results

We identified 50 patients with SS with median follow-up of 52 months.  Median age was 70 years. Male to female ratio was 1.6:1.  Most pts were Caucasians (88%),). A majority of patients (76%) had advanced stage disease (IVA+IVB). Measurable adenopathy was identified in 35 pts (70%). Median number of Sezary cell count in peripheral blood was 1,747/ul. Extracorporeal Photopheresis (ECP) was used in 43 pts (86%). Overall response rate (ORR) after 6 months of therapy was the following: CR 3(6%), PR 9 (18%), SD 7 (14%), PD 24 (48%). The only agents with activity achieving were interferon (ORR 6%, CR 2%), alemtuzumab (ORR 8%, CR6%), MTX (ORR 6%, CR 2%), and bexarotene (ORR10%, CR 2%), Responses to HDAC inhibitors were: romidepsin (ORR 6%, all PR) and vorinostat (ORR 4%, CR 2%). Median OS was 96 months (95% CI 70-121). Based on aberrant immunophenotype patterns, pts  were stratified into 4 groups: 1) CD4+CD7+CD26- 26% (13), 2) CD4 + CD 7- CD26+ in 12% (6), 3) CD4+ CD7- CD26- in 34% (17) and 4) CD4+ CD7+ CD26+ in 24% (12). The median OS for CD4+ CD 7- CD26- was 84 months versus not reached (NR) for other groups. This difference was statistically significant when groups 3 and 2 (p <0.05), and groups 3 and 4 (p< 0.02) were compared. However, there was only a trend observed when groups 3 and 2 were compared (p=0.3). The median OS was 86 month if absolute Sezary cell count was >1700/ul compared to 96 mo if < 1700/ul  (P< 0.4).

Conclusions

Pts with SS in this study showed an improved survival compared to historical studies. Advent of ECP, novel targeted agents such as HDACi inhibitors and monoclonal antibodies, earlier diagnosis, and better supportive care have most probably contributed to this phenomenon; except ECP, CR rates were very rare. A majority of the pts require multimodality induction therapy followed by maintenance therapy. Pts with Sezary cell immunophenotype characterized by aberrant loss of both CD26 and CD7 antigens had worse outcome. There was also a tendency for worse OS in pts with higher circulating absolute Sezary cell count.