PS1261 CLINICAL CHARACTERISTICS AND PROGNOSTIC FACTORS OF 33 PATIENTS WITH SEZARY SYNDROME AT MOFFITT CANCER CENTER: A SINGLE‐INSTITUTION COHORT
Authors: Zhang Y. , Lu Y. , SeminarioVidal L. , Sokol L. 
Published: June 2019

Background:

Sezary syndrome (SS) is a rare aggressive leukemia variant of cutaneous T‐cell lymphoma (CTCL) characterized by erythroderma and Sezary cells in peripheral blood and lymphoadenopathy. It has a poor prognosis with reported median overall survival ranging from 2–4 years. Limited studies exist to describe the SS cohorts in modern era of biological therapy.

Aims:

To analyze clinical and laboratory characteristics such as age, lesion characteristics, hematological parameters to determine their impact on survival in patients with SS.

Methods:

A retrospective chart review was conducted to identify patients with SS seen at Moffitt Cancer Center, Tampa, FL from 2016 to 2018. Kaplan Meier estimates were calculated for overall survival. Log rank test and cox proportional hazard model were used to evaluate categorical and continuous factors associated with overall survival respectively.

Results:

In total, 33 patients were identified with a clinicopathologic diagnosis of SS. 76% were white, 21% African American and 3% Hispanic; 67% were male and 33% female (2:1 ratio). Mean age was 67.3 years (range: 43–89). 49% had primary SS and 51% had a previous diagnosis of mycosis fungoides (MF). The average time to progression to SS was 6.4 years. The majority presented with advanced stage (III/IV). Seven patients were known to be deceased with a median time to death of 2.4 years. Other 26 patients had a median follow up time of 3.8 years. OS was 68.5% and 42.8% at 1 and 5 years, respectively. Prior diagnosis of MF indicated a poor prognosis (p = 0.005). Age, race, the presence of erythroderma, absolute Sezary cell count, LDH level, CD4/CD8 ratio, ferritin level, and lymph node involvement at the time of diagnosis did not correlate with OS. There was a trend to favorable survival in the group of patients <60 years old at diagnosis and with the presence of large granular lymphocytes (LGL) proliferations.

Sezary cells of the immunophenotype of CD3+CD4+CD7‐CD26‐ were present in 78% patients. TCR gene was clonally rearranged in 30/31 tested patients. 28 (90.3%) was TCRβ+TCRγ+; 1 TCRβ+TCRγ‐; 1 TCRβ+TCRγ‐. Median Sezary cell count is 1.81x109 cells/L.

Foundation Medicine Hematology gene panel was done in selected patients, which tested 437 genes that are known to be somatically altered in human hematologic malignancies, sarcomas and pediatric cancers and that unambiguous driver of oncogenesis based on current knowledge. 21 mutations were detected in 4 patients: CCND3, MKI67, CDKN2A, EP300, MAPK1, BCOR, RHOA in cell cycle regulation and cell proliferation; TET2, ASXL1, DNMT in DNA methylation; STED2, ARID2 in DNA repair; CBL, DTX1, TNFAIP3 in protein Ubiquination; TP63 (P53 mediated apoptosis), TNFAIP3 (NFkB signaling apoptosis), MPAK1 in Cell Apoptosis; CD 58, BTK and CIITA in immune surveillance; STAT3 in JAK/STAT pathway; TP63 and DTX1 in Notch signaling pathway. GRIN2A, involved in NMDA receptor signaling, was detected with unclear role in oncogenesis. GRIN2A and CDKN2A were detected in 2/4 patients. TET2, DNMT3A, TNFAIP3 were previously reported in CTCL. CCND3, CDKN2A, MAP1, ASXL1, EP300, STAT3 were reported in other T‐cell malignancies.

Summary/Conclusion:

Our study confirmed overall poor prognosis of SS with OS of 68.5% and 42.8% at 1 and 5 years despite advances in therapy. The preexisting diagnosis of MF was a poor prognostic factor. Younger age at diagnosis and the presence of LGL proliferations are potentially favorable prognostic factors. However, due to limited sample sizes, the results need to be interpreted with caution and verified with a larger cohort.

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