LUIS ALBERTO DE PADUA COVAS LAGE
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
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
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- 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.
- Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients(2020) GOUVEIA, Gisele R.; FERREIRA, Suzete C.; SIQUEIRA, Sheila A. C.; LAGE, Luis Alberto de Padua Covas; HALLACK NETO, Abrahao E.; COSTA, Renata de Oliveira; PEREIRA, JulianaBackgroundOCT-1 gene is a member of the POU-homeodomain family of transcriptional regulators of B-lymphocyte differentiation by controlling expression of B-cell specific genes. BCL-2 gene is a potent inhibitor of apoptosis and it is essential during B-cell differentiation into germinal center. These genes may be expressed in diffuse large B-cell lymphoma (DLBCL), but the role of BCL-2 in its prognosis has been contradictory, and OCT-1 has yet to be tested.MethodsIn this study, we aimed to investigate the prognostic impact of OCT-1 and BCL-2 expression in DLBCL treated in the real world with immunochemotherapy in a single center. BCL-2 and OCT-1 genes were available in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR was isolated from formalin-fixed paraffin-embedded samples. The values obtained for gene expression were transformed in categorical variable according to their median.ResultsCohort median age was 54.5years (15-84), 49 (50%) were male, 38/77 (49.4%) and 40/77 (51.9%) presented OCT-1 and BCL-2 expression >= median, respectively. The overall response rate (ORR) in all patients was 68.4% (67/98), 65,3% (64/98) of patients acquired complete response, and 3.1% (3/98) partial response, while 6.1% (6/98) were primary refractory. The median follow-up was 3.77years (95% CI: 3.2-4.1), with 5.43 (95% CI: 2.2-NR) of overall survival (OS) and 5.15years (95% CI: 2.9-NA) of progression free survival (PFS). OCT-1 >= median was associated with shorter OS at univariate analysis (p =0.013; [HR] 2.450, 95% CI: 1.21-4.96) and PFS (p =0.019; [HR] 2.270, 95%CI: 1.14-4.51) and BCL-2 gene overexpression presented worse PFS (p =0.043, [HR] 2.008, 95% CI: 1.02-3.95). At multivariate analysis, OCT-1 overexpression was associated with poor PFS (p =0.035, [HR] 2.22, 95% CI: 1.06-4.67).ConclusionIn this study, we showed that overexpression of OCT1 gene was an independent prognostic factor of adverse outcomes in DLBCL.