{"doi":"10.1002/hon.70094_382","title":"382 | GENE COPY NUMBER ALTERATIONS IDENTIFY SUBSET OF SEZARY SYNDROME PATIENTS WITH WORSE SURVIVAL OUTCOMES","abstract":"A. Kiwan, M. Girardi, M. Xu, and A. Siddon equally contributing author. Background: Sezary syndrome (SS) is an aggressive primary cutaneous T-cell lymphoma (CTCL) characterized by erythroderma and leukemic involvement of peripheral blood. In this study, we investigated the effect of specific GCNAs and clinical features on survival outcomes among pts with SS in attempt to obtain better insight on risk stratification and molecular-clinical correlation reflecting the underpinning pathophysiology. Methods: We identified 125 pts with SS, 85 of whom had a validated FISH panel at diagnosis. FISH probes designed to capture 97.5% of GCNAs in pts with CTCL and SS included probes for TP53, MYC, RB1, CDKN2A, ATM, STAT3, STAT5B, ARID1A, ZEB1, FAS, CARD11, and DNMT3A genes. Overall survival (OS) analysis was conducted using the Kaplan-Meier method to estimate survival probabilities and the log-rank test to compare survival distributions between different groups. Results: Of 85 pts who had FISH at diagnosis, 54% exhibited GCNAs. Deletions were identified in ATM (11q22.3) in 14%, DNMT3A (2p23) in 17%, TP53 (17p13.1) in 40%, ZEB1 (10p11.2) in 18%, RB1 (11q14.2) in 13%, ARID1A (1p35.3) in 13%, and CDKN2A (9p21.3) in 15% of all pts. Amplifications were observed in STAT3 (17q21.31) in 26%, MYC (8q24.21) in 37%, and CARD11 (7p22) in 11% of all pts. The median OS of all pts was 54 months (95% CI: 33–84). Univariate Cox regression analysis identified several significant prognostic factors for OS, including age, elevated ALC (hazard ratios [HR] = 1.1, p < 0.001), WBC (HR = 1.02, p < 0.001), LDH (HR = 1.001, p < 0.000) and ANC (HR = 1.2, p = 0.016. The presence of ARID1A deletion (HR = 3.3, p = 0.001) and ZEB1 deletion (HR = 2.05, p = 0.04) were strongly associated with poorer OS. None of amplifications of STAT3 (HR = 1.4, p = 0.3), MYC (HR = 1.2, p = 0.5), or CARD11 (HR = 1.3, p = 0.6), were significantly associated with poorer OS. A total number of 78 pts had full data and were included in the multivariate CPH model. Among GCNAs, ZEB1 deletion (HR = 5.8, p = 0.008), ARID1A deletion (HR = 5.7, p = 0.009), or ATM deletion (HR = 5.5, p = 0.01) were all significantly associated with poorer OS. Clinical variables including male gender (HR = 7.3, p < 0.001), higher ANC (HR = 1.3, p = 0.05) and lower Hgb (HR = 0.6, p < 0.000) were all significant predictors. GCNAs were documented in 50% of alive pts (vs 58% of deceased pts, p = 0.5). The median OS (months, 95%CI) for pts with ZEB1 deletion (34, 14-NA) was significantly lower compared to wild-type ZEB1 (86, 46-NA). Pts with ATM deletion (39, 20-NA) and AIRD1A deletion (21, 19-NA) had significantly lower OS compared to wild type cases (93 and 94, respectively). Summary: In summary, we identified novel molecular prognostic markers for pts with SS. In conjunction with clinical data, our results will help identify high risk pts with specific GCNAs alteration who will benefit from intensive treatment approaches. Research funding declaration: none Encore Abstract: Regional or national meetings with up to 1000 attendees Keywords: cutaneous non-Hodgkin lymphoma No potential sources of conflict of interest.","journal":"Hematological Oncology","year":2025,"id":568597,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":944943,"name":"Francine M. Foss","orcid":"0000-0001-7843-3162","position":1,"is_corresponding":false},{"id":725641,"name":"Michael Girardi","orcid":"0000-0003-1887-9343","position":2,"is_corresponding":false},{"id":1035750,"name":"Meiyu Xu","orcid":"0000-0002-6669-3028","position":3,"is_corresponding":false},{"id":513165,"name":"Alexa J. Siddon","orcid":"0000-0002-2372-3653","position":4,"is_corresponding":false},{"id":1473756,"name":"T Sethi","orcid":null,"position":5,"is_corresponding":false},{"id":1473755,"name":"Alisar Kiwan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:55.795846Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}