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
12 resultados
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- Analysis of clonal immunoglobulin chain gene rearrangement by the technique of polymerase chain reaction (PCR) to aid in the diagnosis of B-cell cutaneous lymphoproliferative processes(2023) GUIMARAES, Adriana Borba; SANCHES JUNIOR, Jose Antonio; ZERBINI, Maria Claudia; MIYASHIRO, Denis Ricardo; CURY-MARTINS, Jade; PEREIRA, Juliana; CULLER, Hebert Fabricio; CASTRO, Bruno
- Image-guided lymph node core needle biopsy in mycosis fungoides/Sezary syndrome: Direct comparison to surgical excision(2022) CURY-MARTINS, Jade; COUTO NETTO, Sergio Dias do; CASTRO, Stephanie Catarine Carqueijo de; SIQUEIRA, Sheila Aparecida Coelho; GIANNOTTI, Marcelo Abrantes; ZERBINI, Maria Claudia Nogueira; PEREIRA, Juliana; CULLER, Hebert; TEIXEIRA JR., Frederico Jose Ribeiro; MENEZES, Marcos Roberto de; SANCHES, Jose Antonio
- 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
- 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.
- 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
- Whole Brain Radiotherapy Is an Effective and Safe Strategy to Consolidate Primary Central Nervous System Lymphoma Patients in Middle-Income Countries: A Real-Life Experience from Brazil(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 Oliveira; ROCHA, Vanderson; PEREIRA, Juliana
- 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.
- 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.
conferenceObject Clinical Outcome and Characteristics of Patients with Primary Central Nervous System Lymphomas (PCNSL) in a Brazilian Population(2017) REIS, Diego; ISHIDA, Tatiane; LAGE, Luis A. P. C.; CULLER, Hebert F.; COSTA, Renata O.; ZERBINI, Maria C.; LEVY, Debora; ROCHA, Vanderson; PEREIRA, Juliana- 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.