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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- Treatment outcomes of adult Burkitt lymphoma: results with a modified LMB protocol in Brazil and feasibility of outpatient administration(2018) SILVA JUNIOR, Wellington Fernandes da; ROSA, Lidiane Ines da; BELESSO, Marcelo; LAGE, Luis Alberto P. C.; ROCHA, Vanderson; PEREIRA, JulianaWhile Burkitt lymphoma (BL) is an aggressive subtype of non-Hodgkin lymphoma more prevalent in tropical areas, few studies on BL have been conducted in Latin America. Here, we evaluate the clinical presentation and outcomes of an adapted LMB regimen for adults with sporadic BL. We retrospectively evaluated hospital records from University of Sao Paulo (USP) between 1999 and 2017. Thirty-six patients were included, the median age was 33.5 years and 69% (25) were male. Most patients presented advanced stage disease (81%), 8% had CNS disease, and the majority belonged to LMB group B (75% (27)). Three patients died during the induction phase, and the remaining patients (33) achieved complete response. There was one relapse over a median follow-up of 6 years. Overall survival estimated at 5 years was 89%. We conclude that an adapted LMB protocol is safe and feasible in Brazil.
conferenceObject Diffuse Large B-Cell Lymphoma, NOS: Prognostic Significance of Immunohistochemical Algorithms and Biomarkers in Newly Diagnosed Patients Treated With Rituximab Plus a CHOP-Like Regimen(2015) PAULA, Henrique de; SIQUEIRA, Sheila; PEREIRA, Juliana; LAGE, Luis Alberto; XAVIER, Flavia; COSTA, Renata; ZERBINI, Maria Claudia- Bone marrow necrosis: literature review(2016) CABRAL, Tamara C. S.; FERNANDES, Carolina M.; LAGE, Luis Alberto C.; ZERBINI, Maria Claudia; PEREIRA, JulianaABSTRACT Introduction: Bone marrow necrosis (BMN) is a rare pathologic entity that is commonly undiagnosed, and often associated with hematologic diseases. Methodology: We conducted a literature review at PubMed using ""bone marrow necrosis"" as key words. Our search retrieved 25 articles written in English, and a further 65 case reports. Results and discussion: BMN pathophysiology is not well understood, but appears to be associated with vascular injuries that lead to oxygen and nutrient deprivation. Destructive tumor necrosis factor alpha (TNF-α) activity is also likely involved in the development of endothelial and bone marrow sinusoidal lesions. Diagnoses of BMN are commonly indicated by anemia, thrombocytopenia, high levels of lactic dehydrogenase and alkaline phosphatase, and the identification of leukoerythroblastic reactions. Bone marrow (BM) aspirate and biopsy, and magnetic nuclear resonance imaging are the main diagnostic options. The only available treatments are those directed against the primary cause, with associated supportive care for what is ordinarily a rapidly lethal state. Conclusion: The search for an underlying associated malignancy is important for the management of BMN.
- Comparison of two immunohistochemical staining protocols for ALK demonstrates non-inferiority of a 5A4 clone-based protocol versus an ALK01 clone-based protocol for the diagnosis of ALK plus anaplastic large cell lymphoma(2023) FERNANDEZ-POL, Sebastian; FERREIRA, Cristiane R.; MANOHAR, Vidhya; SANCHES, Jose Antonio; LAGE, Luis A. P. C.; PEREIRA, Juliana; ZERBINI, Maria C. N.; GRATZINGER, Dita; NATKUNAM, YasodhaDetection of ALK rearrangement and/or expression of the ALK protein is an essential component in the evaluation of many neoplasms. Variability has been reported in the ability of different antibody clones to detect ALK expression. The ALK01 clone is commonly used to detect ALK expression in ALK-positive anaplastic large cell lymphoma (ALK + ALCL). However, this clone has been shown to lack sensitivity when used for solid tumors. The aim of this study was to determine if our high-sensitivity 5A4-based immunohistochemistry protocol is non-inferior to our ALK01-based protocol for the detection of ALK expression in ALK + ALCL. To compare the two protocols, we stained tissue microarrays of 126 hematolymphoid neoplasms and an additional 21 primary cutaneous ALK-negative anaplastic large cell lymphomas with both protocols. All 28 ALK + ALCL samples that were positive for the ALK01 antibody were also positive for the 5A4 clone. Three cases on the tissue microarray that were negative with the ALK01 antibody were clearly positive with the 5A4 antibody. We subsequently stained whole tissue sections of these three cases with the ALK01 antibody and found that these three cases were indeed positive with the ALK01 protocol, suggesting that the absence of staining on the tissue microarray samples was due to a combination of sampling error as well as a dimmer signal with the ALK01 protocol. Our study demonstrates that our 5A4-based protocol is non-inferior to the ALK01 antibody for the diagnosis of ALK-positive anaplastic large cell lymphoma, thus allowing our laboratory to discontinue the use of the ALK01-based protocol.
- FOXP3-positive T-cell lymphomas in non-HTLV1 carriers include ALK-negative anaplastic large cell lymphoma: expanding the spectrum of T-cell lymphomas with regulatory phenotype(2018) FERREIRA, Cristiane R.; ZHAO, Shuchun; SAHOO, Malaya K.; PINSKY, Benjamin; WEBER, Jenna; LAGE, Luis A. P. C.; PEREIRA, Juliana; ZERBINI, Maria C. N.; NATKUNAM, YasodhaForkhead box P3 (FOXP3) is a specific marker for regulatory T-cells (Tregs). We report 6 cases of T-cell lymphomas with Treg phenotype based on diffuse positivity for FOXP3 in tumor cells. The patients showed a median age of 56 years with a male predominance. Sites of disease included lymph nodes (4), skin (2), subcutaneous tissue (1) and bone marrow (1). All cases showed monomorphic large cells, some with Hodgkin-like or anaplastic cells. All cases expressed pan T-cell markers and lacked cytotoxic markers; one case showed diffuse PD1 staining. Only one case harbored human T-lymphotrophic virus (HTLV)-1 DNA within tumor cells and was classified as adult T-cell leukemia/lymphoma (ATLL). Among 5 HTLV1-negative cases, 3 were classified as peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and 2 fulfilled criteria for ALK-negative anaplastic large cell lymphoma (ALCL) with diffuse and strong CD30 positivity. We concluded that Treg phenotype may be rarely seen in HTLV1-negative cases, such as PTCL, NOS and ALK-negative ALCL. Our findings expand the spectrum of T-cell lymphomas with regulatory phenotype and suggest that consideration should be given to HTLV1 DNA testing in the appropriate clinical setting to rule out ATLL.
conferenceObject Diffuse Large B-Cell Lymphoma, NOS: Prognostic Significance of Immunohistochemical Algorithms and Biomarkers in Newly Diagnosed Patients Treated With Rituximab Plus a CHOP-Like Regimen(2015) PAULA, Henrique de; SIQUEIRA, Sheila; PEREIRA, Juliana; LAGE, Luis Alberto; XAVIER, Flavia; COSTA, Renata; ZERBINI, Maria Claudia- Genetic Subtypes of Systemic Anaplastic Large Cell Lymphoma Show Distinct Differences in PD-L1 Expression and Regulatory and Cytotoxic T Cells in the Tumor Microenvironment(2020) FERREIRA, Cristiane R.; MANOHAR, Vidhya; ZHAO, Shuchun; BANGS, Charles D.; CHERRY, Athena; AZEVEDO, Raymundo Soares; LAGE, Luis A. P. C.; PEREIRA, Juliana; ZERBINI, Maria C. N.; GRATZINGER, Dita; NATKUNAM, YasodhaAnaplastic large cell lymphomas (ALCL) encompass several subgroups that differ in their clinical presentation, genetic features, and prognosis. We characterized the genetic subgroups of 74 patients with ALCL and correlated programmed death ligand 1 (PD-L1) protein expression and compared the densities and ratios of FOXP3+ T regulatory cells and CD8+ tumor-infiltrating lymphocytes (TILs) in tumor cells and the immune microenvironment. The subgroups included anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and ALK-negative (ALK-) ALCL and DUSP22-rearranged and nonrearranged ALK- ALCL. None of our cases represented the TP63-rearrangement ALK- ALCL subgroup. Our results showed that ALK+ ALCL had a higher expression of PD-L1 in the tumor cells, in contrast to ALK- ALCL, which expressed high PD-L1 in tumor-associated macrophages (TAMs). DUSP22-rearranged ALK- ALCL lacked PD-L1 expression in the tumor cells and instead expressed PD-L1 only in TAMs. There was a significant positive correlation of PD-L1 expression between tumor and TAMs in ALK+ ALCL with a negative correlation in ALK- ALCL. Systemic ALCL subgroups had similar densities of CD8+ tumor-infiltrating lymphocytes and FOXP3 T regulatory cells, but differences were observed in the ratio of CD8/FOXP3. Our results suggest that alterations in tumor microenvironment and immune responses exist among systemic ALCL subgroups and these features may account for different clinical behavior and prognosis.