HEBERT FABRICIO CULLER
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Risk adapted approach: How to treat splenic marginal zone lymphoma in resource-poor settings? - The real-life experience of a Brazilian cancer treatment center(2020) LAGE, Luis Alberto de Padua Covas; SANTOS, Felipe Faganelli Caboclo dos; LEVY, Debora; MOREIRA, Frederico Rafael; COUTO, Samuel Campanelli Freitas; CULLER, Hebert Fabricio; COSTA, Renata de Oliveira; ROCHA, Vanderson; PEREIRA, JulianaBackgroundSplenic marginal zone lymphoma (SMZL) is a rare lymphoid B-cell malignant neoplasm with primary involvement of the spleen. It is a chronic disease, of indolent behavior and prolonged survival. However, 25% of cases have higher biological aggressiveness, propensity for histological transformation to high grade B-cell non-Hodgkin lymphoma and shortened survival. Recognition of these cases of reserved outcome is important for selecting a risk-adapted therapeutic approach in a resource-poor settings.MethodsWe described clinical and epidemiological characteristics, survival analysis and prognostic factors in a retrospective cohort of 39 SMZL patients, treated in Latin America.ResultsWe observed a predominance of female (71.8%), median age of 63 years and higher incidence of B symptoms (56.4%) and extra-splenic involvement (87.1%) than in European and North-American series. With a median follow-up of 8.7 years (0.6-20.2 years), estimated 5-year overall survival (OS) and progression-free survival (PFS) were 76.9% and 63.7%, respectively. Factors with adverse prognostic impact on OS and PFS were Hb < 100 g/L, platelet count < 100 x 10(9)/L, albumin < 3.5 g/dL, LDH > 480 U/L and high-risk Arcaini and SMZL/WG scores. Despite a relative low number of patients, no superiority was observed among the therapeutic regimens used including rituximab monotherapy, splenectomy and cytotoxic chemotherapy.ConclusionTherefore, in resource-poor settings, where access to immunotherapy is not universal for all SMZL patients, we suggest that first-line should consist on rituximab therapy for elderly patients or with high surgical risk or with at least 1 risk factor identified in our study. Remainders can be safely managed with splenectomy.
- Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen–Results of a Real-Life Study From a Middle-Income Country(2022) LAGE, L. A. D. P. C.; BRITO, C. V.; BARRETO, G. C.; CULLER, H. F.; REICHERT, C. O.; LEVY, D.; COSTA, R. D. O.; ZERBINI, M. C. N.; ROCHA, V.; PEREIRA, J.Background: Nodal peripheral T-cell lymphoma (nPTCL) constitute a heterogeneous group of neoplasms with aggressive behavior and poor-survival. They are more prevalent in Latin America and Asia, although data from Brazil are scarce. Its primary therapy is still controversial and ineffective. Therefore, we aim to describe clinical-epidemiological characteristics, outcomes, predictors factors for survival and compare the results of patients treated with CHOP and CHOEP regimens. Methods: Retrospective, observational and single-center study involving 124 nPTCL patients from Brazil treated from 2000 to 2019. Results: With a median follow-up of 23.7 months, the estimated 2-year overall survival (OS) and progression-free survival (PFS) were 59.2% and 37.3%, respectively. The median age was 48.5 years and 57.3% (71/124) were male, 81.5% (101/124) had B-symptoms, 88.7% (110/124) had advanced disease (stage III/IV) and 58.1% (72/124) presented International Prognostic Index (IPI) score ≥3, reflecting a real-life cohort. ORR to first-line therapy was 58.9%, 37.9% (N = 47) received CHOP-21 and 35.5% (N = 44) were treated with CHOEP-21; 30.1% (37/124) underwent to consolidation with involved field radiotherapy (IF-RT) and 32.3% (40/124) were consolidated with autologous hematopoietic stem cell transplantation (ASCT). The overall response rate (ORR) was similar for CHOP-21 (76.6%) and CHOEP-21 (65.9%), P =.259. Refractory disease was less frequent in the CHOEP-21 group (4.5% vs. 21.2%, P =.018). However, few patients were able to complete 6-cycles of CHOEP-21 (31.8%) than to CHOP-21 (61.7%), P =.003. Delays ≥2 weeks among the cycles of chemotherapy were more frequent for patients receiving CHOEP-21 (43.1% vs. 10.6%), P =.0004, as well as the toxicities, including G3-4 neutropenia (88% vs. 57%, P =.001), febrile neutropenia (70% vs. 38%, P =.003) and G3-4 thrombocytopenia (63% vs. 27%, P =.0007). The 2-year OS was higher for CHOP (78.7%) than CHOEP group (61.4%), P =.05, as well as 2-year PFS (69.7% vs. 25.0%, P <.0001). In multivariate analysis, high LDH (HR 3.38, P =.007) was associated with decreased OS. CR at first line (HR: 0.09, P <.001) and consolidation with ASCT (HR: 0.08, P =.015) were predictors of increased OS. Conclusion: In the largest cohort of nPTCL from Latin America, patients had poor survival and high rate of chemo-resistance. In our cohort, the addition of etoposide to the CHOP-21 backbone showed no survival benefit and was associated with high-toxicity and frequent treatment interruptions. Normal LDH values, obtaintion of CR and consolidation with ASCT were independent factors associated with better outcomes. © 2022 Elsevier Inc.
- Up-Front ASCT Overcomes the Survival Benefit Provided by HDAC-Based Induction Regimens in Mantle Cell Lymphoma: Data from a Real-Life and Long-Term Cohort(2023) LAGE, Luis Alberto de Padua Covas; ELIAS, Marcela do Vale; REICHERT, Cadiele Oliana; CULLER, Hebert Fabricio; FREITAS, Fabio Alessandro de; COSTA, Renata de Oliveira; ROCHA, Vanderson; SIQUEIRA, Sheila Aparecida Coelho da; PEREIRA, JulianaSimple Summary This study aimed to assess clinical outcomes, determine survival predictors, and compare responses between different primary therapeutic modalities in a large real-world cohort of patients with mantle cell lymphoma (MCL), with a focus on assessing the impact of intensified immunochemotherapy regimens based on high doses of cytarabine (HDAC) on outcomes in ASCT-eligible patients. A total of 165 Brazilian patients with biopsy-proven MCL were included from 2010 to 2022. After a long follow-up, our results demonstrated that patients treated with (R)-HDAC-based regimens had higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those treated with (R)-CHOP, as well as lower rates of early relapses (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, enhanced induction regimens employing (R)-HDAC were not associated with a real overall survival benefit in MCL patients undergoing ASCT (2-year OS: 88.7% for (R)-HDAC plus ASCT vs. 78.8% for (R)-CHOP plus ASCT, p = 0.289). Additionally, up-front ASCT was independently associated with improvement in OS (p < 0.001), EFS (p = 0.005), and POD-24 (p < 0.001) in MCL. In conclusion, in the largest real-world Latin American study involving MCL patients, we were able to ratify the benefit of up-front ASCT in young and physically fit patients regardless of the intensity of the induction immunochemotherapy regimen used. Although HDAC-based induction regimens were not associated with improved survival in ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses in the whole cohort. These findings can decisively impact the therapeutic management of MCL patients in different clinical settings.Abstract Background: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, the role of more intensive induction regimens, such as those based on high doses of cytarabine (HDAC), remains controversial in the management of ASCT-eligible patients. Methods: This retrospective, observational, and single-center study involved 165 MCL patients treated at the largest oncology center in Latin America from 2010 to 2022. We aimed to assess outcomes, determine survival predictors, and compare responses between different primary therapeutic strategies, with a focus on assessing the impact of HDAC-based regimens on outcomes in ASCT-eligible patients. Results: The median age at diagnosis was 65 years (38-89 years), and 73.9% were male. More than 90% of the cases had a classic nodal form (cnMCL), 76.4% had BM infiltration, and 56.4% presented splenomegaly. Bulky >= 7 cm, B-symptoms, ECOG >= 2, and advanced-stage III/IV were observed in 32.7%, 64.8%, 32.1%, and 95.8%, respectively. Sixty-four percent of patients were categorized as having high-risk MIPI. With a median follow-up of 71.1 months, the estimated 2-year OS and EFS were 64.1% and 31.8%, respectively. Patients treated with (R)-HDAC-based regimens had a higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those receiving (R)-CHOP, as well as lower POD-24 rates (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, intensified induction regimens with (R)-HDAC were not associated with a real OS benefit in MCL patients undergoing up-front consolidation with ASCT (2-year OS: 88.7% vs. 78.8%, p = 0.289). Up-front ASCT was independently associated with increased OS (p < 0.001), EFS (p = 0.005), and lower POD-24 rates (p < 0.001) in MCL. Additionally, CNS infiltration, TLS, hypoalbuminemia, and the absence of remission after induction were predictors of poor OS. Conclusions: In the largest Latin American cohort of MCL patients, we confirmed the OS benefit promoted by up-front consolidation with ASCT in young and fit patients, regardless of the intensity of the immunochemotherapy regimen used in the pre-ASCT induction. Although HDAC-based regimens were not associated with an unequivocal increase in OS for ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses for the whole cohort.
- Tumor mutation burden involving epigenetic regulatory genes and the RhoA GTPase predicts overall survival in nodal mature T-cell lymphomas(2022) LAGE, Luis Alberto de Padua Covas; CULLER, Hebert Fabricio; BARRETO, Guilherme Carneiro; REICHERT, Cadiele Oliana; LEVY, Debora; COSTA, Renata de Oliveira; ROCHA, Vanderson; PEREIRA, JulianaNodal mature T-cell lymphomas (nMTCL) comprises a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena, including mutations in genes that control DNA methylation and histone deacetylation, in addition to inactivating mutations in the RhoA GTPase, play a central role in its pathogenesis and constitute potential new targets for therapeutic intervention. Tumor mutational burden (TMB) reflects the process of clonal evolution, predicts response to anti-cancer therapies and has emerged as a prognostic biomarker in several solid neoplasms; however, its potential prognostic impact remains unknown in nMTCL. In this study, we conducted Sanger sequencing of formalin-fixed paraffin-embedded (FFPE) diagnostic tumor samples using a target-panel to search for recurrent mutations involving the IDH-1/IDH-2, TET-2, DNMT3A and RhoA genes in 59 cases of nMTCL. For the first time, we demonstrated that high-TMB, defined by the presence of >= two mutations involving the aforementioned genes, was associated with decreased overall survival in nMTCL patients treated with CHOP-like regimens. Additionally, high-TMB was correlated with bulky disease, lower overall response rate, and higher mortality. Future studies using larger cohorts may validate our preliminary results that indicate TMB as a potential molecular biomarker associated with adverse prognosis in nMTCL.
- The role of whole-brain radiotherapy (WBRT) in primary central nervous system lymphoma: is it an alternative to ASCT for consolidation following HD-methotrexate based induction in low-income settings?(2022) LAGE, Luis Alberto de Padua Covas; SOARES, Vinicius Araujo; MENEGUIN, Thales Dalessandro; CULLER, Hebert Fabricio; REICHERT, Cadiele Oliana; JACOMASSI, Mayara D'Auria; REIS, Diego Gomes Candido; ZERBINI, Maria Claudia Nogueira; COSTA, Renata de Oliveira; ROCHA, Vanderson; PEREIRA, JulianaBackground Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy. Although potentially curable, its prognosis remains dismal. Its treatment is based on high-doses of methotrexate (HD-MTX) and rituximab, followed by consolidation therapy with whole-brain radiotherapy (WBRT) or autologous stem cell transplantation (ASCT). Currently, there is no consensus about the best consolidation strategy, but better outcomes with ASCT are obtained with conditioning regimens based on thiotepa, a high-cost drug with restricted use in resource-constrained settings. Latin American data on clinical outcomes, prognostic factors, and therapeutic management in PCNSL are virtually unknown. Methods This is a retrospective, observational, and single-center study involving 47-Brazilian patients with PCNSL. We aim to assess outcomes, determine predictors of survival, and compare responses, as well as toxicities in patients consolidated with chemotherapy alone versus chemotherapy plus WBRT. Results The median age at diagnosis was 59 years (24-88 years), and 53.1% were male. LDH >= UVN occurred in 44.7%, ECOG >= 2 in 67.6%, and 34.1% had multifocal disease. Hemiparesis was the main clinical presentation, observed in 55.3%, 51.0% had intermediate-/high-risk IELSG prognostic score, and 57.6% had an ABC-like phenotype by IHC. With a median follow-up of 24.4 months, estimated 5-year OS and PFS were 45.5% and 36.4%, respectively. Among 40 patients treated with HD-MTX-based induction, estimated 2-year OS was 85.8% for those consolidated with WBRT plus HIDAC versus only 41.5% for those consolidated with HIDAC alone (p < 0.001). Hematologic and non-hematologic toxicities were not significant, and severe cognitive impairment occurred in only 6.3% (3/47) of cases, all of them treated with WBRT. Age < 60 years, Hb >= 120 g/L and WBRT consolidation were associated with increased OS, however, LDH >= UVN, hypoalbuminemia, ECOG >= 2, Karnofsky PS < 70 and intermediate-/high-risk Barcelona score were associated with decreased OS. Conclusion Combined consolidation therapy (CCT) based on WBRT plus HIDAC was associated with increased OS in PCNSL compared to isolated consolidation therapy (ICT) based on HIDAC alone. Here, severe late neurotoxicity was uncommon with this approach. These data suggest that WBRT may be an effective and safe alternative to ASCT for consolidation therapy in PCNSL, particularly in resource-constrained settings, where access to thiotepa for pre-ASCT conditioning is not universal.
- Cell Cycle Changes, DNA Ploidy, and PTTG1 Gene Expression in HTLV-1 Patients(2020) LEVY, Debora; FERREIRA, Mari Cleia M. R.; REICHERT, Cadiele O.; ALMEIDA, Lis Vilela de; BROCARDO, Graciela; LAGE, Luis Alberto P. C.; CULLER, Hebert F.; NUKUI, Youko; BYDLOWSKI, Sergio P.; PEREIRA, JulianaHuman T-cell lymphotropic virus type-1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). Genetic instability is the hallmark of ATL. Cell cycle progression is needed for virus particle reproduction. HTLV-1 encoded Tax protein ultimately disrupts the mitotic spindle checkpoint, leading to incorrect chromosome segregation, resulting in aneuploidy. Cell cycle abnormalities have been described in T cells transfected with HTLV-1 virusin vitro, but not in HTLV-1 asymptomatic carriers. PTTG1 and HTLV-1 viral protein Tax exhibit a cooperative transforming activity. Overexpressed PTTG1 results in chromosome instability and aneuploidy, which has been suggested as a mechanism underlying PTTG1 transforming activity. Here we aimed to investigate cell cycle, DNA ploidy and PTTG1 mRNA expression in CD4(+)and CD8(+)T cells in healthy subjects (HS), HTLV-1 asymptomatic carriers and ATL patients. We have identified that HTLV-1 asymptomatic carriers have shown DNA aneuploidy and cell cycle arrest at cell cycle phase G(0)/G(1)in CD4(+)T cells. CD8(+)T cells of HTLV-1 asymptomatic carriers also demonstrated DNA aneuploidy but without alteration in cell cycle. In ATL, CD4(+)and CD8(+)T cells present a higher number of cells in cell cycle S-phase and PTTG1 overexpression. These studies provide insight into malignant transformation of HTLV-1 asymptomatic carriers to ATL patients.
- New genetic prognostic biomarkers in primary central nervous system lymphoma (PCNSL)(2021) REIS, Diego Gomes Candido; LEVY, Debora; LAGE, Luis Alberto de Padua Covas; CULLER, Hebert Fabricio; ROCHA, Vanderson; BYDLOWSKI, Sergio Paulo; ZERBINI, Maria Claudia Nogueira; PEREIRA, JulianaBackground PCNSL is a rare extranodal NHL with poor prognosis. Tumorigenesis has been associated with hyperactivation of BCR downstream and NFkB pathways. We studied the prognosis of the relative expression profile of target genes of NFkB pathway (MYC, BCL2), the essential transcriptional regulator in hematopoiesis LMO2, the checkpoint regulation pathway MGMT, the transcription factor POU2F1, the immune checkpoint gene PDCD1, and the proto-oncogene and transcriptional repressor gene BCL6 and its proteins in PCNSL. Methods This study is a retrospective cohort study; 35 immunocompetent PCNSL-DLBCL patients had their gene expression (RT-qPCR) normalized to internal control gene GUSB. Results Median patient age was 62 years, median OS was 42.6 months (95% CI: 26.6-58.6), PFS was 41 months (95% CI: 19.7-62.4), and DFS was 59.2 months (95% CI 31.9-86.6). A moderate correlation was found between the gene/protein expressions of MYC (kappa = 0.596, p = .022) and of BCL2 (kappa = 0.426, p = .042). Relative gene expression of MYC >= 0.201 (HR 6.117; p = .003) was associated with worse 5-year OS. Relative gene expression of MYC >= 0.201 (HR 3.96; p = .016) and MGMT >= 0.335 (HR 3.749; p = .056) was associated with worse PFS. Age > 60 years and IELSG score moderate/high were also associated with worse prognosis. Conclusions Overexpression of MYC and overexpression of MGMT were prognostic markers associated with unfavorable clinical outcomes in PCNSL.
- High-dose extended-field radiotherapy plus chemotherapy improved survival in extranodal NK/T-cell lymphoma in a real-life setting: results from the multicenter T-Cell Brazil Project(2022) LAGE, Luis Alberto de Padua Covas; MACHADO, Pedro Paulo Faust; REICHERT, Cadiele Oliana; MIRANDA, Eliana; CULLER, Hebert Fabricio; SIQUEIRA, Sheila Aparecida Coelho da; COSTA, Renata de Oliveira; MIYASHIRO, Denis Ricardo; SANCHES, Jose Antonio; ROCHA, Vanderson; CHIATTONE, Carlos Sergio; PEREIRA, JulianaExtranodal natural-killer/T-cell lymphoma (ENKTL) is a rare and aggressive Epstein-Barr virus related mature T-cell and natural-killer malignancy. Although highly prevalent in South America, few studies covering data from this geographic location have been published. Therefore, this study aims to report clinical characteristics, prognostic factors, and outcomes in a multicenter cohort of ENKTL patients from Brazil. This retrospective, observational and multicenter study included 98 ENKTL patients treated during two decades in Brazil. Data were extracted from the T-Cell Brazil Project database. In our cohort, 59/98 patients (60.2%) were male, with a median age of 50 years. Sixty-two patients (63.3%) had B-symptoms, 26/98 (26.5%) had Eastern Cooperative Oncology Group scale >= 2; 16/98 (16.3%) presented extranasal disease and 34.7% (34/98) were advanced-stage (Ann Arbor/Cotswolds III/IV). The median follow-up for the whole cohort was 49 months, with an estimated 2-year overall survival (OS) and progression-free survival (PFS) of 51.1% and 17.7%, respectively. In early-stage disease (IE/IIE), the median OS was 21.8 months for patients treated with concurrent radiotherapy plus chemotherapy (CCRT-VIPD [etoposide/vp-16, ifosfamide, cisplatin and dexamethasone), 16.2 months for sequential chemoradiotherapy (SCRT) followed by asparaginase-based regimens, and 56.7 months for SCRT followed by CHOP-like (cyclophosphamide, doxorrubicin, vincristine and prednisone) treatments, p = 0.211. CCRT was associated with higher rates of early-mortality, hematological toxicity, and mucositis. Median OS was 8.2 months for patients with advanced-stage disease receiving regimens containing asparaginase compared to 3.2 months for anthracycline-based therapy, p = 0.851. Chemo-radiotherapy (CRT) regimens demonstrated better OS (p = 0.001) and PFS (p = 0.007) than chemotherapy alone. Multivariate analysis revealed anemia, relapsed/refractory (R/R) disease and radiotherapy omission as poor outcome predictors for OS. Lymphopenia and radiotherapy omission adversely affected PFS. Concerning progression of disease within 24-months (POD-24), clinical stage III/IV was a poor outcome predictor. In this real-life Brazilian cohort, ENKTL presented dismal outcomes. Radiation therapy was an independent factor for increased OS and PFS, but CCRT regimens were associated with higher toxicities. Polychemotherapy based on anti-multi drug resistant agents was not associated with survival benefit in either early or advanced-stage disease in our patient cohort.
- GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms(2022) GENG, Xiangrong; WANG, Chenguang; GAO, Xin; CHOWDHURY, Pinki; WEISS, Jonathan; VILLEGAS, Jose A.; SAED, Badeia; PERERA, Thilini; HU, Ying; RENEAU, John; SVERDLOV, Maria; WOLFE, Ashley; BROWN, Noah; HARMS, Paul; BAILEY, Nathanael G.; INAMDAR, Kedar; HRISTOV, Alexandra C.; TEJASVI, Trilokraj; MONTES, Jaime; BARRIONUEVO, Carlos; TAXA, Luis; CASAVILCA, Sandro; LAGE, J. Luis Alberto de Padua Covas; CULLER, Hebert Fabricio; PEREIRA, Juliana; RUNGE, John S.; QIN, Tingting; TSOI, Lam C.; HONG, Hanna S.; ZHANG, Li; LYSSIOTIS, Costas A.; OHE, Rintaro; TOUBAI, Tomomi; ZEVALLOS-MORALES, Alejandro; MURGA-ZAMALLOA, Carlos; WILCOX, Ryan A.Neoplasms originating from thymic T-cell progenitors and post-thymic mature T-cell subsets account for a minority of lymphoproliferative neoplasms. These T-cell derived neoplasms, while molecularly and genetically heterogeneous, exploit transcription factors and signaling pathways that are critically important in normal T-cell biology, including those implicated in antigen-, costimulatory-, and cytokine-receptor signaling. The transcription factor GATA-3 regulates the growth and proliferation of both immature and mature T cells and has recently been implicated in T-cell neoplasms, including the most common mature T-cell lymphoma observed in much of the Western world. Here we show that GATA-3 is a proto-oncogene across the spectrum of T-cell neoplasms, including those derived from T-cell progenitors and their mature progeny, and further define the transcriptional programs that are GATA-3 dependent, which include therapeutically targetable gene products. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients.
- TET-2 mutations predict poor outcomes and are associated with unfavorable clinical-biological features in PTCL, not otherwise specified and angioimmunoblastic T-cell lymphoma in Brazilian patients(2022) LAGE, Luis Alberto de Padua Covas; BARRETO, Guilherme Carneiro; CULLER, Hebert Fabricio; CAVALCANTE, Jessica Billar; ALVES, Lucas Bassolli de Oliveira; NARDINELLI, Luciana; BENDIT, Israel; ZERBINI, Maria Claudia Nogueira; ROCHA, Vanderson; PEREIRA, JulianaINTRODUCTION: Nodal peripheral T-cell lymphomas [nPTCL] constitute a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena involving genes that control DNA-methylation and histone deacetylation play a central role in their pathogenesis. However, the mutational landscape involving epigenetic regulators has never been reported in Latin American patients and their prognostic impact remains controversial. PATIENTS AND METHODS: From 2000 to 2019, 59-Brazilian patients with nPTCL were eligible for screening mutations in the IDH-1, IDH-2, RHOA, TET-2 and DNMT3A genes by Sanger sequencing at Formalin-Fixed Paraffin-Embedded samples [FFPE] of diagnosis. We reported the frequency, distribution and potential prognosis of these mutations. RESULTS: With a median follow-up of 3.70 years, estimate 2-year OS and PFS were 57.1% and 49.2%, respectively. Mutations in the IDH-1 gene were not found, mutations in the IDH-2 occurred in 3.4% (2/59), RHOA in 23.7% (14/59), TET-2 in 50.8% (30/59) and DNMT3A in 62.7% (37/59). RHOA gene mutations were more frequent in PTCL, NOS and AITL (p = 0.06). Almost half of the patients had more than one mutation in concomitance, particularly RHOA-mut and TET-2-mut. Mutations in RHOA (p = 0.030) and TET-2 (p = 0.046) were associated with high-tumor burden. In the non-ALCL subgroup (PTCL, NOS and AITL) TET-2 mutations were associated with decreased 2-year PFS [HR: 2.22, p = 0.048]. Likewise with lower overall response rate [ORR] (p = 0.048) and unfavorable clinical features, as bulky disease (p = 0.012), ECOG >= 2 (p = 0.032), B-symptoms (p = 0.012), >= 2 extranodal sites compromised (p = 0.022) and high-risk Prognostic Index for T-cell lymphoma (p = 0.005). CONCLUSION: Mutations in RHOA, TET-2 and DNMT3A were frequent in Brazilian patients with nPTCL. TET-2 mutations were associated with lower ORR for CHOP-like chemotherapy, decreased PFS and unfavorable clinical-biological characteristics in non-ALCL (PTCL, NOS and AITL). Further studies using a larger cohort may validate our findings.