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
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- WHO-2016 Classification in ALL By Cytogenetics, FISH and Molecular Biology - Experience of Two Reference Centers in Brazil(2018) VELLOSO, Elvira D. R. P.; CORDEIRO, Maria Gabriella; LUCON, Danielle; KISHIMOTO, Renata; LEAL, Aline Medeiros; MAIA, Ana Carolina Arrais; BUCCHERI, Valeria; BENDIT, Israel; SILVA JR., Wellington Fernandes; MANGUEIRA, Cristovao; REGO, Eduardo Magalhaes; ROCHA, Vanderson
conferenceObject Familial myelodysplastic syndrome/acute leukemia in adult setting - Experience from a single Brazilian center(2013) SILVA, M.; LEAL, A.; FERREIRA, P.; NARDINELLY, L.; SILVA, M.; PELICARIO, L.; LOPES, T.; BENDIT, I.; VELLOSO, E.- 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.
- Real-life Outcomes on Acute Promyelocytic Leukemia in Brazil - Early Deaths Are Still a Problem(2019) JR, Wellington F. da Silva; ROSA, Lidiane Ines da; MARQUEZ, Gabriel Lacerda; BASSOLLI, Lucas; TUCUNDUVA, Luciana; SILVEIRA, Douglas Rafaele Almeida; BUCCHERI, Valeria; BENDIT, Israel; REGO, Eduardo Magalhaes; ROCHA, Vanderson; VELLOSO, Elvira D. R. P.Real-life outcomes in acute promyelocytic leukemia are apparently worse than those reported by prospective studies. Retrospective data on 61 adult patients were reviewed. An early death rate of 20% was found, with a 5-year overall survival estimated at 59%. The results of real-life studies differ from prospective trials. Early actions and supportive care are needed, aiming to decrease toxicity, especially in developing countries. Introduction: Although a considerable improvement in survival of patients with acute promyelocytic leukemia (APL) has been seen over the past decades, real-life outcomes seem to be worse than those reported by prospective studies. We aim to describe clinical characteristics and outcomes of adult patients diagnosed with APL in an academic hospital from the University of Sao Paulo. Patients and Methods: We retrospectively reviewed the medical charts of 61 patients with APL diagnosed between January 2007 and May 2017. Baseline clinical features and follow-up data were collected, focusing on early toxicity variables such as infection, bleeding, and thrombosis in the first 30 days from diagnosis. Results: Among the 61 patients with APL, 54 received any chemotherapy. All patients also received alltrans retinoic acid (ATRA). Bleeding events were the main cause of death before receiving chemotherapy. Most patients belonged to the intermediate (43%) and high-risk (41%) groups, according to Sanz score. The '7 + 3 + ATRA' regimen was the most used regimen (n = 38). An early death rate of 20% was found, predominantly owing to sepsis. After a median follow-up of 5 years, only 1 relapse was diagnosed. The overall survival at 5 years was 59%. Discussion: In comparison with prospective trials with ATRA-based regimens, we found an inferior overall survival, mostly on account of a high early-death rate. Our results are in line with other real-life retrospective reports published in the past decades. Conclusion: Results of real-life studies differ from those found by prospective trials. Accordingly, early actions and supportive care are still needed, aiming to decrease toxicity, especially in developing countries.
- Integrating clinical features with genetic factors enhances survival prediction for adults with acute myeloid leukemia(2020) SILVEIRA, Douglas R. A.; QUEK, Lynn; SANTOS, Itamar S.; CORBY, Anna; COELHO-SILVA, Juan L.; PEREIRA-MARTINS, Diego A.; VALLANCE, Grant; BROWN, Benjamin; NARDINELLI, Luciana; SILVA, Wellington F.; VELLOSO, Elvira D. R. P.; LUCENA-ARAUJO, Antonio R.; TRAINA, Fabiola; PENIKET, Andy; VYAS, Paresh; REGO, Eduardo M.; BENDIT, Israel; ROCHA, VandersonThe 2017 European LeukemiaNet 2017 acute myeloid leukemia (AML) risk stratification (ELN2017) is widely used for risk-stratifying patients with AML. However, its applicability in low- and middle-income countries is limited because of a lack of full cytogenetic and molecular information at diagnosis. Here, we propose an alternative for risk stratification (the Adapted Genetic Risk [AGR]), which permits cytogenetic or molecular missing data while retaining prognostic power. We first analyzed 167 intensively treated patients with nonacute promyelocytic leukemia AML enrolled in Sao Paulo, Brazil (Faculdade de Medicina da Universidade de Sao Paulo), as our training data set, using ELN2017 as the standard for comparison with our AGR. Next, we combined our AGR with clinical prognostic parameters found in a Cox proportional hazards model to create a novel scoring system (survival AML score, SAMLS) that stratifies patients with newly diagnosed AML. Finally, we have used 2 independent test cohorts, Faculdade de Medicina de Ribeirao Preto (FMRP; Brazil, n = 145) and Oxford University Hospitals (OUH; United Kingdom, n =157) for validating our findings. AGR was statistically significant for overall survival (OS) in both test cohorts (FMRP, P = .037; OUH, P = .012) and disease-free survival in FMRP (P = .04). The clinical prognostic features in SAMLS were age (>45 years), white blood cell count (<1.5 or >30.0 x 10(3)/mu L), and low albumin levels (<3.8 g/dL), which were associated with worse OS in all 3 cohorts. SAMLS showed a significant difference in OS in the training cohort (P < .001) and test cohorts (FMRP, P = .0018; OUH, P < .001). Therefore, SAMLS, which incorporates the novel AGR evaluation with clinical parameters, is an accurate tool for AML risk assessment.
- A multicenter comparative acute myeloid leukemia study: can we explain the differences in the outcomes in resource-constrained settings?(2021) SILVEIRA, Douglas R. A.; COELHO-SILVA, Juan L.; SILVA, Wellington F.; VALLANCE, Grant; PEREIRA-MARTINS, Diego A.; MADEIRA, Maria I. A.; FIGUEREDO-PONTES, Lorena L.; VELLOSO, Elvira D. R. P.; SIMOES, Belinda P.; PENIKET, Andy; DANBY, Robert; REGO, Eduardo M.; VYAS, Paresh; TRAINA, Fabiola; BENDIT, Israel; QUEK, Lynn; ROCHA, VandersonOutcomes in acute myeloid leukemia (AML) are dependent on patient- and disease-characteristics, treatment, and socioeconomic factors. AML outcomes between resource-constrained and developed countries have not been compared directly. We analyzed two cohorts: from Sao Paulo state, Brazil (USP,n = 312) and Oxford, United Kingdom (OUH,n = 158). USP cohort had inferior 5-year overall survival compared with OUH (29% vs. 49%, adjusted-p=.027). USP patients have higher early-mortality (23% vs. 6%p<.001) primarily due to multi-resistant Gram-negative bacterial and fungal infections. USP had higher 5-year cumulative incidence of relapse (60% vs. 50%,p=.0022), were less likely to undergo hematopoietic stem cell transplant (HSCT) (28% vs. 75%,p<.001) and waited longer for HSCT (median, 23.8 vs. 7.2 months,p<.001). Three-year survival in relapsed patients was worse in USP than OUH (10% vs. 39%,p<.001). Our study indicates that efforts to improve AML outcomes in Brazil should focus on infection prevention and control, and access to HSCT.
- Combining Clinical Features with Genetic Factors Improves Survival Prediction for Adults with Acute Myeloid Leukemia: Validation of a New Score System in 3 Cohorts(2019) SILVEIRA, Douglas R. A.; QUEK, Lynn; CORBY, Anna; COELHO-SILVA, Juan L.; PEREIRA-MARTINS, Diego A.; VALLANCE, Grant; BROWN, Benjamin; NARDINELLI, Luciana; SILVA, Wellington F.; VELLOSO, Elvira Drp; TRAINA, Fabiola; PENIKET, Andy; VYAS, Paresh; REGO, Eduardo M.; BENDIT, Israel; ROCHA, Vanderson
- Adult acute lymphoblastic leukemia in a resource-constrained setting: outcomes after expansion of genetic evaluation(2022) SILVA, Wellington F.; AMANO, Mariane T.; PERRUSO, Luiza L.; CORDEIRO, Maria Gabriella; KISHIMOTO, Renata Kiyomi; LEAL, Aline de Medeiros; NARDINELLI, Luciana; BENDIT, Israel; VELLOSO, Elvira D. R. P.; REGO, Eduardo M.; ROCHA, VandersonAcute lymphoblastic leukemia (ALL) is a challenging disease with a growing genetic landscape, even though there is substantial gap between developed and non-developed countries when it comes to availability of such new technologies. This manuscript reports a 5-year retrospective cohort of newly diagnosed ALL patients and their genetic findings and outcomes. An expanded genetic evaluation by using FISH and RT-PCR was implemented, aiming to identify Ph-like alterations. Patients were treated according to our local protocol, which allocated patients according to age and Philadelphia-chromosome status. A total of 104 patients was included, with median age of 37.5 years. Philadelphia chromosome was detected in 33 cases of B-lineage. Among 45 Ph-negative B-lineage, after excluding KMT2A or TCF3-PBX1 cases, we identified 9 cases with Ph-like fusion. Ph-positive and Ph-like patients had higher initial WBC (p = 0.06). Out of 104 cases, two cases did not start chemotherapy and an early death rate of 10.8% was found. Allogeneic transplantation was performed in 18 cases, being ten performed in first CR. Three-year overall survival (OS) and 3-year event-free survival were 42.8% and 30.8%, respectively. For patients treated with a pediatric regimen, 3-year OS was 52.5%. Extramedullary disease (HR 0.42) and platelet counts (HR 0.9) were independently associated with OS. We still face excessive non-relapse mortality that compromises our results. Alternative strategies implementing FISH and RT-PCR are feasible and able to identify Ph-like fusions. Delays in allogeneic transplantation, as well as the unavailability of new agents, impact long-term survival. Measures to decrease early infection are desirable.
- Simultaneous Occurrence of Biphenotypic T Cell/Myeloid Lesions Involving t(12;13)(p13;q14) in a Pediatric Patient(2012) BORBA, Claudio Carneiro; CHAUFFAILLE, Maria de Lourdes; SANABNAI, Sabri Saeed; FERNANDES, Juliana Folloni; KUMEDA, Cristina Aiko; VELLOSO, Elvira Deolinda Rodrigues Pereira; SANTOS, Katia Jarandilha dos; PUPIM, Marcia Puato Vieira; HAMERSCHLAK, Nelson; ODONE FILHO, Vicente; BENDIT, IsraelThis paper chronicles a 2-year-old girl who presented with acute leukemia/lymphoma syndrome of the T cell immuno-phenotype. At this time, the cytogenetic analysis of her bone marrow cells showed a reciprocal translocation between the short arm of chromosome 12 and the long arm of chromosome 13, t(12;13)(p13;q14). The immunophenotyping of bone marrow blast cells by flow cytometry revealed a population of cells positive for CD56, CD117, CD45, partial CD33, partial HLA-DR, CD13, CD7, CD2 and CD5. Therefore, a diagnosis of acute leukemia with a mixed T cell/myeloid phenotype was made. The patient had a poor response to classic T cell acute lymphocytic leukemia/lymphoma therapy; thus, her treatment was changed to a myeloid leukemia protocol, which produced a good response. She underwent a successful cord blood transplantation from an unrelated HLA partially matched donor. The coexistence of these two phenotypes prompts questions about the existence of clonal instability, which might influence the choice of therapy. The rarity of the t(12;13)(p13;q14) and the coexistence of T cell/myeloid markers suggest a nonrandom association. To the best of our knowledge, this is the first reported case in which a cell clone bearing a t(12;13)(p13;q14) translocation in a mixed T cell/myeloid lesion was detected.
conferenceObject INHERITED PREDISPOSITION TO MYELOID MALIGNANCIES: DESCRIPTION OF TWO NEW CASES(2015) SILVA, M. C. A.; KREPISCHI, A. C. V.; NARDINELLY, L.; LEAL, A. M.; FERREIRA, P. B.; MARINHO, T. T.; CORDEIRO, M. G.; SILVA, M. M.; LIMA, F. T.; BENDIT, I.; ROSEMBERG, C.; VELLOSO, E. D. R. P.