Introduction:
Mycosis Fungoides/Sézary Syndrome (MF/SS) are primary cutaneous T-cell lymphomas (CTCLs) characterized by cutaneous involvement by clonal CD4+ mature T cells. Many patients with advanced disease develop circulating tumor cells, and even low levels of blood involvement (<250 clonal tumor cells/μL) are associated with poor prognosis. While many molecular aberrations have been identified, prognostication based on gene copy number alterations (GCNAs) by fluorescence in situ hybridization (FISH) has not been well established.
Objectives:
We investigated the impact of GCNAs in circulating tumor cells and clinical features on survival outcomes.
Methods:
We reviewed 125 MF/SS patients diagnosed from 2012 to 2024 with blood involvement who had molecular studies. A validated FISH panel using 11 probes designed to capture 97.5% of GCNAs in CTCL and SS was used. OS was estimated using the Kaplan-Meier method, and Cox regression identified predictors of survival.
Results:
The median age was 74 years (IQR: 67–81) (68% male, 32% female). Among 85 patients with FISH, 54% had GCNAs. The most common deletions were TP53 (40%), DNMT3A (17%), ATM (14%), ZEB1 (18%), and CDKN2A (15%). Multivariate analysis (n=78) identified ZEB1 (HR=5.8, p=0.008), ARID1A (HR=5.7, p=0.009), and ATM (HR=5.5, p=0.01) deletions as significantly associated with poorer OS. Male gender (HR=7.3, p<0.001), elevated ANC (HR=1.3, p=0.05), and lower Hgb (HR=0.6, p<0.001) were also significant. Patients with ZEB1, ATM, and ARID1A deletions had significantly shorter OS.
Conclusion:
We identified novel molecular prognostic markers in circulating tumor cells. Our results help identify high-risk patients with specific GCNAs who may benefit from more intensive or novel treatment approaches.
