HEBERT FABRICIO CULLER

(Fonte: Lattes)
Índice h a partir de 2011
4
Lattes
ResearcherID
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

Filtros

Limpar filtros

Configurações

Autor e Coautores FMUSP-HC Normalizados: LUIS ALBERTO DE PADUA COVAS LAGE ×

Resultados de Busca

Agora exibindo 1 - 10 de 26
  • article 2 Citação(ões) na Scopus
    Angioimmunoblastic T-cell lymphoma and correlated neoplasms with T-cell follicular helper phenotype: from molecular mechanisms to therapeutic advances
    (2023) LAGE, Luis Alberto de Padua Covas; CULLER, Hebert Fabricio; REICHERT, Cadiele Oliana; SIQUEIRA, Sheila Aparecida Coelho da; PEREIRA, Juliana
    Angioimmunoblastic T-cell lymphoma (AITL) is the second most frequent subtype of mature T-cell lymphoma (MTCL) in the Western world. It derives from the monoclonal proliferation of T-follicular helper (TFH) cells and is characterized by an exacerbated inflammatory response and immune dysregulation, with predisposition to autoimmunity phenomena and recurrent infections. Its genesis is based on a multistep integrative model, where age-related and initiator mutations involve epigenetic regulatory genes, such as TET-2 and DNMT3A. Subsequently, driver-mutations, such as RhoA G17V and IDH-2 R172K/S promote the expansion of clonal TFH-cells (""second-hit""), that finally begin to secrete cytokines and chemokines, such as IL-6, IL-21, CXCL-13 and VEGF, modulating a network of complex relationships between TFH-cells and a defective tumor microenvironment (TME), characterized by expansion of follicular dendritic cells (FDC), vessels and EBV-positive immunoblasts. This unique pathogenesis leads to peculiar clinical manifestations, generating the so-called ""immunodysplastic syndrome"", typical of AITL. Its differential diagnosis is broad, involving viral infections, collagenosis and adverse drug reactions, which led many authors to use the term ""many-faced lymphoma"" when referring to AITL. Although great advances in its biological knowledge have been obtained in the last two decades, its treatment is still an unmet medical need, with highly reserved clinical outcomes. Outside the setting of clinical trials, AITL patients are still treated with multidrug therapy based on anthracyclines (CHOP-like), followed by up-front consolidation with autologous stem cell transplantation (ASCT). In this setting, the estimated 5-year overall survival (OS) is around 30-40%. New drugs, such as hypomethylating agents (HMAs) and histone deacetylase inhibitors (HDAi), have been used for relapsed/refractory (R/R) disease with promising results. Such agents have their use based on a biological rationale, have significant potential to improve the outcomes of patients with AITL and may represent a paradigm shift in the therapeutic approach to this lymphoma in the near future.
  • conferenceObject
    Immune Senescence-Related Gene Expression Profile in CD4+T-Lymphocytes of HTLV-1 Asymptomatic Carriers and Patients with Adult T-Cell Leukemia/Lymphoma (ATLL): A Brazilian Preliminary Study
    (2021) ASSIS FILHO, Jose Roberto; CULLER, Hebert Fabricio; LEVY, Debora; OLIVEIRA, Karolliny Silva de; NOGUEIRA, Daniel Silva; ALMEIDA, Lis Vilela de; ROCHA, Vanderson; NUKUI, Youko; LAGE, Luis Alberto de Padua Covas; PEREIRA, Juliana
  • conferenceObject
    Circulating Cell-Free DNA (ccfDNA) Isolation from Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Comparative Analysis of Commercial Kits
    (2021) OLIVEIRA, Karolliny Silva de; CULLER, Hebert Fabricio; LEVY, Debora; ASSIS FILHO, Jose Roberto; NOGUEIRA, Daniel Silva; ALMEIDA, Lis Vilela de; SILVA, Luiz Henrique da; FONSECA, Fernando Luiz Affonso; ALVES, Sarah Isabel Pinto Monteiro do Nascimento; LAGE, Luis Alberto de Padua Covas; PEREIRA, Juliana
  • conferenceObject
    High Tumor Mutation Burden in Epigenetic Regulatory Genes Predicts Decreased Overall Survival in Nodal Peripheral T-Cell Lymphomas
    (2022) LAGE, Luis Alberto de Padua Covas; BARRETO, Guilherme Carneiro; CULLER, Hebert Fabricio; CAVALCANTI, Jessica Billar; REICHERT, Cadiele Oliana; COSTA, Renata Oliveira; LEVY, Debora; ZERBINI, Maria Claudia Nogueira; ROCHA, Vanderson; PEREIRA, Juliana
  • conferenceObject
    Splenic Marginal Zone Lymphoma (SMZL) - Outcomes, Prognostic Factors and Risk-Adapted Therapy in Resource-Poor Settings: Data from a Latin American Retrospective Cohort
    (2020) LAGE, Luis Alberto de Padua Covas; SANTOS, Felipe Faganelli Caboclo dos; GERVATAUSKAS, Kasys Meira; LEVY, Debora; MOREIRA, Frederico Rafael; COUTO, Samuel Campanelli Freitas; CULLER, Hebert Fabricio; COSTA, Renata Oliveira; ROCHA, Vanderson; PEREIRA, Juliana
  • article 0 Citação(ões) na Scopus
    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, Juliana
    BackgroundSplenic 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.
  • article 2 Citação(ões) na Scopus
    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.
  • article 1 Citação(ões) na Scopus
    Follicular Lymphoma: Refining Prognostic Models and Impact of Pod-24 in Clinical Outcomes
    (2022) NOGUEIRA, Daniel Silva; LAGE, Luis Alberto de Padua Covas; CULLER, Hebert Fabricio; PEREIRA, Juliana
    Follicular lymphoma (FL) is the most common indolent lymphoma, accounting for 20%-25% of all non-Hodgkin's lymphomas (NHLs). It is a malignancy with variable biologic presentation and heterogeneous clinical outcomes. Several models incorporating clinical laboratory variables and molecular biomarkers are able to predict its prognosis, allowing to stratify patients into different risk groups. However, these prognostic scores should not be used to indicate first-line treatment or risk-adapted therapeutic recommendations. Over the past 5 years, progression of disease within 24 months (POD-24) of first-line chemo-immunotherapy has emerged as a robust adverse prognostic factor, capable of assessing overall survival and identifying high-risk patients with indication for more aggressive therapeutic approaches, such as consolidation based in autologous stem cell transplantation. It should be reinforced that POD-24 is not a baseline measurement, it is based on a post-treatment strategy, and is usually applied to patients with a high tumor burden. The identification of newly diagnosed patients at high risk for disease progression, particularly those with low tumor volume is still a challenge in the context of FL. Therefore, the primary purpose of this review is to provide an overview of the main prognostic models validated to date for FL. Moreover, using these scores, which incorporate clinical and genetic variables, we aim to identify individuals with newly diagnosed FL, advanced disease, and low tumor burden with a high probability of progression or relapse within 24 months of first treatment. Thus, a decision regarding risk-adapted induction therapy could be better stablished for these subset of patients.
  • conferenceObject
    High Toxicity and Poor Survival with Association CHOP Plus Etoposide Compared to CHOP Regimen in 124 Brazilian Patients with Nodal PTCL Lymphomas (nPTCL): A Real-Life Experience
    (2021) LAGE, Luis Alberto de Padua Covas; BRITO, Claudio Vinicius; BARRETO, Guilherme Carneiro; REICHERT, Cadiele Oliana; LEVY, Debora; CULLER, Hebert Fabricio; ZERBINI, Maria Claudia Nogueira; ROCHA, Vanderson; PEREIRA, Juliana
  • article 0 Citação(ões) na Scopus
    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, Juliana
    Simple 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.