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Introduction: Nodal peripheral T-cell lymphomas (nPTCLs) comprise a heterogeneous group of mature and aggressive T-cell lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphomas (ALCL) ALK1-positive and ALK1-negative. The differential diagnosis of nPTCL can be very challenging in clinical practice and it has a markedly heterogeneous prognosis. Accurate biomarkers to distinguish the different histological subtypes of nPTCL and to stratify its prognosis are essential to improve the therapeutic approach. The aim of this study was to assess the prognostic impact of GATA3 gene expression, as well as its ability to discriminate between different histopathological subtypes of nPTCLs. Methods: In this observational, retrospective and single-center study, we analyzed clinical-epidemiological data, outcomes and molecular characteristics of 80 nPTCL patients treated at the largest Brazilian cancer center from January 2000 to December 2017. Analysis of GATA3 gene expression was assessed by quantitative real-time polimerase chain reaction (qRT-PCR) of tumor tissue biopsies fixed in formalin and embedded in paraffin (FFPE) at the time of diagnosis. The association of relative expression of the GATA3 gene with pathological variants of nPTCL was determined by the Kruskal-Wallis test and the Dunn's post-hoc test. The cutoff value of GATA3 expression capable of differentiating nPTCLs variants was determined by constructing receiver-operator-characteristic (ROC) curves. Overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method. Results: The clinical and epidemiological characteristics of the 80 nPTCL patients are summarized in Table 1. Median age was 49 years (IqR 34-59), 43-80 (53.7%) of patients were male. Of these, 36.3% were classified as PTCL-NOS, 31.2% as ALK-negative ALCL, 21.2% as ALK-positive ALCL and 11.3% as AITL. Most of the cases had an advanced stage (III and IV Ann Arbor). With a median follow-up of 1.72 years, the estimated OS at 2 years and PFS were 52.2% and 39.5%, respectively. The median level of GATA3 gene expression was 0.49% (range 0 - 7.07%) in the global cohort, being 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL, NOS and 0.67% for AITL. The difference in expression of the GATA3 gene between different nPTCL variants was statistically significant (p <0.001) - Figure 1. The levels of expression of the GATA3 gene ≥ 0.71% discriminated PTCL, NOS from ALK-negative ALCL and AITL with a sensitivity of 62% and specificity of 80.3%, contributing to the differential diagnosis of these neoplasms, particularly in cases of ALK-negative ALCL versus PTCL, NOS CD30-positive. Overexpression of GATA3 ≥ median was associated with poor 2-year OS for PTCL, NOS (46.7% x 21.4%, p = 0.04) and for ALK-negative ALCL (85.7% x 54.5%, p = 0.04) - Figures 2 and 3. Conclusion: Despite the relatively small number of patients in our cohort, preliminary results suggest that overexpression of the GATA3 gene may be an important biomarker associated with poor prognosis in PTCL, NOS and ALK-negative ALCL. Our results corroborate the findings of Iqbal et al, 2014, reinforcing the adverse prognostic impact of GATA3 gene expression in PTCL/NOS, and we show that its overexpression may be a potential novel biomarker related to poor prognosis for ALK-negative ALCL. In addition, it has been demonstrated here that GATA3 can play an auxiliary role in discriminating different subtypes of nPTCLs, aiding the differential diagnosis of these neoplasms, which often have overlapping clinical and pathological aspects. Other studies with larger series of patients should confirm our findings. Disclosures No relevant conflicts of interest to declare.

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

Introduction: Nodal PTCL constitute a heterogeneous group of rare malignancies derived from CD4+ T-helper, CD8+ T-cytotoxic or follicular T-helper lymphocytes. It presents aggressive clinical-biological behavior and distinct outcomes [1]. These tumors have significant geographic variation, making important studies of clinical and epidemiological characteristics and outcomes of patients in specific areas of the word. Latin American data on nPTCL are scarce in the literature [2] and its first-line treatment is still controversial and ineffective, due to high rates of primary chemo-resistance. Therefore, this study aims to describe clinical, laboratory and epidemiological characteristics, identify prognostic factors and analyze the outcomes of patients with nPTCL treated with CHOP/CHOP-like regimens as first-line therapy in Brazil. Methods: This is a retrospective, observational and unicentric study involving 124-Brazilian patients with nPTCL treated at HC/FMUSP from January 2000 to December 2017. All cases were submitted to centralized histopathological review and classified according to WHO-2016 criteria on PTCL/NOS, AITL, ALK+/ALCL or ALK-/ALCL. Clinical-laboratory and outcomes data were obtained from digital medical records. Descriptive variables were arranged in absolute numbers and relative frequencies. OS and PFS curves were estimated by the Kaplan-Meier method. Univariate Cox analysis was used to determine factors with prognostic impact through the association between categorical variables and survival curves. Variables that were significant in the univariate analysis were tested in a multivariate analysis to establish independent variables. Statistical analysis was performed using SPSS V.22 software and p-values ≤ 0.05 were considered statistically significant. Results: The clinical-laboratory characteristics of 124 nPTCL patients were summarized in Table 1. With a median age of 48.5 years (18-87 years) and 57.3% of male, about 81.5% had B-symptoms, 88.7% with CS III/IV and 58.1% had IPI ≥ 3. ORR to first-line treatment was 58.9%, 37.9% (47/124) were treated with CHOP regimen and 35.5% (44/124) with CHOEP, 30.1% (37/124) were submitted to radiotherapy and 32.3% (40/124) were consolidated with ASCT. We observed a higher 2-year OS for patients treated with CHOP versus CHOEP (78.7% vs. 61.4%; p=0.05), as well as a better 2-year PFS for the same regimen (69.7% vs. 25.0%; p<0.0001) - Figure 1. CHOEP treatment was associated with higher rates of G3-4 neutropenia, febrile neutropenia and G3-4 thrombocytopenia (57% x 88% p=0.001, 38% x 70% p=0.003 and 27% x 63% p=0.0007, respectively). Overall mortality was 55.6% (69/124) during all follow-up, with disease progression being the major cause of death (29/69 - 42.0%). With a median follow-up of 23.7 months (0.10-278.6 months), medians of OS and PFS were 48.0 months (95% CI: 9.0-86.9) and 8.8 months (95% CI: 3.9-13.7), respectively. Estimative of 2-year OS and PFS for the global cohort were 61.3% and 41.5%, respectively. In the univariate analysis, factors with a favorable prognostic impact on OS were: IPI < 3 (HR: 0.30; 95% CI: 0.15-0.58; p<0.0001), absence of bone marrow infiltration (HR: 0.39; 95% CI: 0.20-0.75; p=0.005), LDH < 480 U/L (HR: 0.36; 95% CI: 0.19-0.68; p=0.002), radiotherapy (HR: 0.23; 95% CI: 0.10-0.55; p=0.001) and ASCT (HR: 0.28; 95% CI: 0.004-0.30; p<0.0001). Factors associated with better 2-year PFS were: IPI < 3 (HR: 0.36; 95% CI: 0.18-0.71, p=0.004), absence of bone marrow infiltration (HR: 0.30; 95% CI: 0.26-0.55; p=0.03 ), LDH < 480 U/L (HR: 0.36; 95% CI: 0.19-0.67; p=0.001), radiotherapy (HR: 0.17; 95% CI: 0.06-0.44; p<0.0001) and ASCT (HR: 0.03 ; 95% CI: 0.004-0.23); p=0.001). In the multivariate analysis, factors associated with better 2-year OS were: LDH < 480 U/L (HR: 0.40; 95% CI: 0.21-0.76); p=0.005) and ASCT (HR: 0.47; 95% CI: 0.006-0.34; p=0.003). LDH < 480 U/L (HR: 0.45; 95% CI: 0.23-0.87; p=0.01) and ASCT (HR: 0.07; 95% CI: 0.01-0.54; p=0.01) were also associated with higher 2-year PFS. Conclusion: This is the largest real-life Latin American nPTCL cohort published to date. Patients with nPTCL have poor survival and high rate of chemo-resistance. In our cohort, adding etoposide to the CHOP regimen showed no survival benefit and was associated with high toxicity. Normal values of LDH and consolidation with ASCT were independent factors associated with better outcomes in Brazilian patients with nPTCL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.