ELVIRA DEOLINDA RODRIGUES PEREIRA VELLOSO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
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
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
- The PIP4K2 inhibitor THZ-P1-2 exhibits antileukemia activity by disruption of mitochondrial homeostasis and autophagy(2022) LIMA, Keli; PEREIRA-MARTINS, Diego Antonio; MIRANDA, Livia Bassani Lins de; COELHO-SILVA, Juan Luiz; LEANDRO, Giovana da Silva; WEINHAUSER, Isabel; CAVAGLIERI, Rita de Cassia; LEAL, Aline de Medeiros; SILVA, Wellington Fernandes da; LANGE, Ana Paula Alencar de Lima; VELLOSO, Elvira Deolinda Rodrigues Pereira; GRIESSINGER, Emmanuel; HILBERINK, Jacobien R.; AMMATUNA, Emanuele; HULS, Gerwin; SCHURINGA, Jan Jacob; REGO, Eduardo Magalhaes; MACHADO-NETO, Joao AgostinhoThe treatment of acute leukemia is challenging because of the genetic heterogeneity between and within patients. Leukemic stem cells (LSCs) are relatively drug-resistant and frequently relapse. Their plasticity and capacity to adapt to extracellular stress, in which mitochondrial metabolism and autophagy play important roles, further complicates treatment. Genetic models of phosphatidylinositol-5-phosphate 4-kinase type 2 protein (PIP4K2s) inhibition have demonstrated the relevance of these enzymes in mitochondrial homeostasis and autophagic flux. Here, we uncovered the cellular and molecular effects of THZ-P1-2, a pan-inhibitor of PIP4K2s, in acute leukemia cells. THZ-P1-2 reduced cell viability and induced DNA damage, apoptosis, loss of mitochondrial membrane potential, and the accumulation of acidic vesicular organelles. Protein expression analysis revealed that THZ-P1-2 impaired autophagic flux. In addition, THZ-P1-2 induced cell differentiation and showed synergistic effects with venetoclax. In primary leukemia cells, LC-MS/MS-based proteome analysis revealed that sensitivity to THZ-P1-2 is associated with mitochondrial metabolism, cell cycle, cell-of-origin (hematopoietic stem cell and myeloid progenitor), and the TP53 pathway. The minimal effects of THZ-P1-2 observed in healthy CD34(+) cells suggest a favorable therapeutic window. Our study provides insights into the pharmacological inhibition of PIP4K2s targeting mitochondrial homeostasis and autophagy, shedding light on a new class of drugs for acute leukemia.
- Patterns and Prognostic Impact of CNS Infiltration in Adults with Newly Diagnosed Acute Lymphoblastic Leukemia(2022) PERRUSO, Luiza Lapolla; VELLOSO, Elvira; ROCHA, Vanderson; REGO, Eduardo M.; SILVA, Wellington F.
- Toxicity Profile of PEG-Asparaginase in Adult Patients With Acute Lymphoblastic Leukemia in Brazil: A Multicenter Cross-Sectional Study(2020) SILVA, Wellington F. da; MASSAUT, Ires H. B.; BENDLIN, Rodrigo M.; ROSA, Lidiane I.; VELLOSO, Elvira D. R. P.; REGO, Eduardo M.; ROCHA, VandersonPegylated asparaginase was recently approved for use in Brazil. We reviewed its toxicity in adults with acute lymphoblastic leukemia. Fifty-seven patients were included, with remarkable thromboembolic (17%) and hepatic (77%) event rates. No fatal event was registered. Our incidence is similar to those reported in other trials. These effects should not preclude further use because most events are manageable. Background: Currently, pediatric-inspired regimens are commonly applied to adults with acute lymphoblastic leukemia (ALL) after the recent recognition that these protocols improve survival. While asparaginase in whatever available formulation is a key component of modern treatment of ALL, many adult oncologists and hematologists struggle to deal with its particular toxicities in clinical practice. We reviewed toxicity outcomes of pegylated asparaginase (PEG-ASP) in adults with ALL treated in 3 reference centers in Brazil. Patients and Methods: This was a cross-sectional retrospective chart-review study encompassing patients aged 15 years and older diagnosed with ALL or ambiguous-lineage leukemia who received at least one dose of PEG-ASP, regardless of the adopted regimen. Results: A total of 57 patients were included (age range, 15-57 years). Most patients (70%) received 2000 IU/m(2) as the initial dose, by intravenous route (72%). The incidence of thromboembolic events was 17.5%, and the main site was cerebral venous sinus (4/10). Thrombosis was more frequent in patients receiving second-line treatment. In obese patients, grade 3 hepatotoxicity and hyperbilirubinemia were more common. Clinical pancreatitis (grade 3 or higher) was found in 2 of 57 cases. PEG-ASP had to be discontinued in 19.3% of exposed patients (11/57). Conclusion: By reviewing the medical charts of adult patients with ALL from 3 reference centers, we found that our incidence of thrombotic and hepatic adverse events is similar to those reported in other trials involving PEG-ASP. Usually these effects should not preclude further use of the drug because most events are manageable in routine clinical practice.
- Paper Assessing the impact of prophylactic anidulafungin during remission induction of acute myeloid leukemia - A propensity-score matching analysis(2023) SILVA, Wellington Fernandes da; MENDES, Fernanda Rodrigues; MELO, Raphael da Costa Bandeira de; VELLOSO, Elvira Deolinda Rodrigues Pereira; ROCHA, Vanderson; REGO, Eduardo MagalhaesIntroduction: Invasive fungal infection (IFI) accounts for substantial morbidity during the treatment of acute myeloid leukemia (AML) in adults. Antifungal prophylaxis (AP) is needed during intensive chemotherapy, and posaconazole is not widely available. In this study, we aimed to examine the impact of prophylactic anidulafungin during intensive AML remission induction. Methods: This is a retrospective cohort encompassing newly diagnosed AML adult patients. All subjects received intensive chemotherapy and were divided into three groups: patients who did not receive any AP and patients who received fluconazole (150-400 mg/day) or anidulafungin (100 mg/day). Results: During AML induction, 82 patients did not receive AP, 108 and 14 patients received anidulafungin and fluconazole, respectively. IFI incidence was 27%, classified as possible, probable, and proven in 65, 2 and 33%, respectively. Multivariable analysis showed that lower neutrophil counts are associated with IFI (OR = 2.8), whereas age, genetic classification, and lymphocyte counts were not. To examine the impact of anidulafungin in comparison with 'no AP', a propensity score matching analysis was performed. Use of anidulafungin was not related to less IFI during induction, while neutrophil counts remained significant. Patients under prophylactic anidulafungin received less amphotericin B (p < 0.001) but not voriconazole (p = 0.49). Discussion: To our knowledge, this is the first study addressing the role of anidulafungin during AML induction. Here, the incidence of mold infections did not decrease with AP, suggesting that in a setting with a high incidence of IFI, broad spectrum AP might be more suitable.
- Long Term Outcomes of Adult Lymphoblastic Lymphoma Patients Treated with Pediatric Regimen in Brazil(2021) MAIA, Ana Carolina Arrais; SILVA, Wellington F.; VELLOSO, Elvira; REGO, Eduardo M.; PEREIRA, Juliana; ROCHA, Vanderson
- Assessing Early Mortality in Intensively-Treated Acute Myeloid Leukemia in a Developing Country: Genetic, Laboratory Findings, and Comorbidities Add Prognostic Information(2020) MENDES, Fernanda Rodrigues; SILVA, Wellington F.; MELO, Raphael Bandeira; SILVEIRA, Douglas R. A.; VELLOSO, Elvira; ROCHA, Vanderson; REGO, Eduardo M.
- Predictive factors associated with induction-related death in acute myeloid leukemia in a resource-constrained setting(2022) MENDES, Fernanda Rodrigues; SILVA, Wellington Fernandes da; MELO, Raphael da Costa Bandeira de; SILVEIRA, Douglas Rafaele Almeida; VELLOSO, Elvira Deolinda Rodrigues Pereira; ROCHA, Vanderson; REGO, Eduardo MagalhaesDespite advances in supportive measures, acute myeloid leukemia (AML) remission induction still has a high mortality rate in real-world studies as compared to prospective reports. We analyzed data from 206 AML adult patients treated with conventional chemotherapy. The primary endpoint was the 60-day mortality rate, aiming to find risk factors and to examine the role of anti-infection prophylaxis. The 60-day mortality rate was 26%, raising to 41% among those older than 60 years. Complete response was documented at the end of induction in 49%. The final survival model showed that age > 60 years (HR 3.2), Gram-negative colonization (HR 3), monocytic AML (HR 1.8), C-reactive protein (CRP) > 15 mg/dL (HR 10), and an adverse risk in the genetic stratification (HR 3) were associated with induction death. Multidrug-resistant bacteria colonization, thrombosis, and AKI were documented in 71%, 12%, and 66% of the cohort, respectively. Antibacterial and antifungal prophylaxis did not improve outcomes in this study. Our report corroborated the higher mortality during AML induction compared to real-world data from the USA and Europe. In line with other publications, age and cytogenetic stratification influenced early death in this cohort. Noticeably, Gram-negative colonization, monocytic AML, and CRP were also significant to early mortality.
- Retrospective Comparison between MEC and FLAG-Ida Regimens for Refractory or Relapsed Acute Myeloid Leukemia in Adults(2019) SILVA, Wellington F.; ROSA, Lidiane Ines Da; SEGURO, Fernanda S.; SILVEIRA, Douglas R. A.; NARDINELLI, Luciana; BUCCHERI, Valeria; VELLOSO, Elvira D. R. P.; ROCHA, Vanderson; REGO, Eduardo M.
- Salvage treatment for refractory or relapsed acute myeloid leukemia: a 10-year single-center experience(2020) SILVA, Wellington Fernandes da; ROSA, Lidiane Ines da; SEGURO, Fernanda Salles; SILVEIRA, Douglas Rafaele Almeida; BENDIT, Israel; BUCCHERI, Valeria; VELLOSO, Elvira Deolinda Rodrigues Pereira; ROCHA, Vanderson; REGO, Eduardo M.OBJECTIVES: The outcomes of refractory and relapsed acute myeloid leukemia (AML) patients in developing countries are underreported, even though the similar classic regimens are widely used. METHODS: We conducted a retrospective comparison of ""MEC"" (mitoxantrone, etoposide, and cytarabine) and ""FLAG-IDA"" (fludarabine, cytarabine, idarubicin, and filgrastim) in adults with first relapse or refractory AML. RESULTS: In total, 60 patients were included, of which 28 patients received MEC and 32 received FLAG-IDA. A complete response (CR) rate of 48.3% was observed. Of the included patients, 16 (27%) died before undergoing bone marrow assessment. No statiscally significant difference in CR rate was found between the two protocols (p=0.447). The median survival in the total cohort was 4 months, with a 3-year overall survival (OS) rate of 9.7%. In a multivariable model including age, fms-like tyrosine kinase 3 (FLT3) status, and stem-cell transplantation (SCT), only the last two indicators remained significant: FLT3-ITD mutation (hazard ratio [HR] =4.6, p< 0.001) and SCT (HR=0.43, p=0.01). CONCLUSION: In our analysis, there were no significant differences between the chosen regimens. High rates of early toxicity were found, emphasizing the role of supportive care and judicious selection of patients who are eligible for intensive salvage therapy in this setting. The FLT3-ITD mutation and SCT remained significant factors for survival in our study, in line with the results of previous studies.
- Assessing the Impact of Prophylactic Anidulafungin during Remission Induction of Acute Myeloid Leukemia - a Propensity-Score Matching Analysis(2021) SILVA, Wellington F.; MENDES, Fernanda Rodrigues; MELO, Raphael Bandeira; VELLOSO, Elvira; ROCHA, Vanderson; REGO, Eduardo M.