24 results on '"Clé DV"'
Search Results
2. AN UPDATED OF PERIPHERAL T-CELL LYMPHOMA PATIENTS REGISTRY OF T-CELL BRAZIL PROJECT: A PROSPECTIVE COHORT ANALYSIS
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Chiattone, CS, Miranda, E, Medina, SS, Baptista, RLR, Pereira, J, Brasil, SAB, Tavares, JV, Cecyn, KZ, Nogueira, FL, Bellosso, M, Farias, DFC, Borducchi, D, Castro, NS, Nabhan, S, Rakde, PPG, Macedo, CCG, Vilarim, CC, Dias, M, Negreiros, E, Figueiredo, VLP, Clé, DV, Schaffel, R, Gaiolla, RD, Schusterschitz, S, Fischer, T, Silva, GF, Gonzaga, Y, Zing, N, Cunha-Jr, AD, Souto-Filho, JTD, Mo, S, Ribeiro, EFO, Duarte, FB, Sousa, RR, Matedi, MAL, Pont, MD, Hamerschlak, N, Perini, G, Rabelo, YS, Bueno, ND, Cury, P, Hallack-Neto, A, Delamain, MT, Federico, M, and Souza, CA
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- 2023
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3. AVALIAÇÃO DE VIABILIDADE DE DETECÇÃO DE DRM EM LLA-B POR CITOMETRIA DE FLUXO MULTIPARAMÉTRICA INDEPENDENTE DE CD19
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Pacca, R, Marani, LO, Catto, LFB, Gonçalves, TE, Schiavinato, JL, Scheucher, PS, Garcia, CAB, Madeira, MIA, Clé, DV, and Figueired-Pontes, LL
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- 2023
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4. CLONAL SIGNATURES OF TELOMERE BIOLOGY DISORDERS AS SPECIFIC MARKERS FOR DISEASE DIAGNOSIS AND SURVEILLANCE
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Catto, LFB, Groarke, EM, Clé, DV, Santana, BA, Azambuja, AP, Oliveira, MM, Shalhoub, R, Bomfim, C, Young, NS, Gutierrez-Rodrigues, F, and Calado, R
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- 2023
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5. PROJETO T-CELL BRASIL: ATUALIZAÇÃO DO PROJETO PIONEIRO DE COLETA DE DADOS DE PACIENTES COM LNH DE CÉLULAS T NAS CINCO REGIÕES BRASILEIRAS
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Chiattone, CS, Miranda, E, Pereira, J, Cecyn, KZ, Castro, NS, Brasil, SAB, Farias, DFC, Bellesso, M, Duffles, G, Borducchi, D, Gonzaga, Y, Baptista, RLR, Vilarim, CC, Macedo, CCG, Dias, M, Salvino, MA, Tavares, JV, Nabhan, S, Cunha-Junior, AD, Zing, N, Silva, GF, Ribeiro, GN, Negreiros, E, Schaffel, R, Figueiredo, VLP, Souto-Filho, JTD, Radtke, PPG, Pont, MD, Nogueira, FL, Hamerschlak, N, Cle, DV, Gaiolla, R, Duarte, FB, Souza, RR, Mo, S, Hallack-Neto, A, Rabelo, YS, Ribeiro, EFO, Cordeiro, A, Perini, G, Bueno, ND, Matedi, MAL, Cury, P, Delamain, MT, Federico, M, and Souza, CA
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- 2022
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6. CARACTERIZAÇÃO IMUNOFENOTÍPICA DO COMPARTIMENTO DE CÉLULAS-TRONCO E PROGENITORAS HEMATOPOÉTICAS EM PACIENTES COM TELOMEROPATIAS
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Bicalho, FAT, Santana, BAA, Clé, DV, Ramos, FSD, Catto, LFB, Tellechea, MF, Carvalho, VS, and Calado, RT
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- 2022
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7. Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria.
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Scheinberg P, Clé DV, Kim JS, Nur E, Yenerel MN, Barcellini W, Bonito D, Giai V, Hus M, Lee Y, Lekue CB, Panse J, Ueda Y, Buatois S, Gentile B, Kiialainen A, Patel H, Sreckovic S, Uguen M, Edwards J, Nagy Z, and Kulasekararaj AG
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- Humans, Female, Male, Middle Aged, Adult, Aged, Complement C5 antagonists & inhibitors, Treatment Outcome, Hemoglobinuria, Paroxysmal drug therapy, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized administration & dosage, Complement Inactivating Agents therapeutic use, Complement Inactivating Agents adverse effects, Complement Inactivating Agents administration & dosage
- Abstract
Crovalimab, a novel C5 inhibitor, allows for low-volume, every-4- week, subcutaneous self-administration. COMMODORE 1 (NCT04432584) is a phase 3, global, randomized trial evaluating crovalimab versus eculizumab in C5 inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Adults with lactate dehydrogenase ≤1.5 × upper limit of normal and receiving approved eculizumab doses for ≥24 weeks were randomized 1:1 to receive crovalimab (weight-based tiered dosing) or continue eculizumab. The original primary study objective was efficacy; however, given the evolving treatment landscape, target recruitment was not met, and all efficacy endpoints became exploratory, with safety as the new primary objective. Exploratory efficacy endpoints included transfusion avoidance, hemolysis control, breakthrough hemolysis, hemoglobin stabilization, FACIT-Fatigue score, and patient preference (crovalimab vs. eculizumab). Eighty-nine patients were randomized (45 to crovalimab; 44 to eculizumab). During the 24-week primary treatment period, adverse events (AEs) occurred in 77% of patients receiving crovalimab and 67% receiving eculizumab. No AEs led to treatment withdrawal or death, and no meningococcal infections occurred. 16% of crovalimab-treated patients had transient immune complex reactions (also known as Type III hypersensitivity events), an expected risk when switching between C5 inhibitors that bind to different C5 epitopes; most were mild/moderate and all resolved without treatment modification. Crovalimab-treated patients had sustained terminal complement activity inhibition, maintained disease control, and 85% preferred crovalimab over eculizumab. Together with phase 3 COMMODORE 2 results in complement inhibitor-naive patients, these data support crovalimab's favorable benefit-risk profile. Crovalimab is a new C5 inhibitor for PNH that is potentially less burdensome than existing therapies for this lifelong disease., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)
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- 2024
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8. Safety and efficacy of a new academic CD19-directed CAR-T cell for refractory/relapsed non-Hodgkin lymphoma and acute lymphoblastic leukemia in Brazil.
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Donadel CD, De Santis GC, Gonçalves TE, Pires BG, Palma LC, Gava F, Guerino-Cunha RL, Faria JTB, Silva GVA, Darrigo-Junior LG, Fatobene G, Rocha V, Covas DT, Calado RT, and Clé DV
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- Humans, Brazil, Male, Female, Adult, Middle Aged, Receptors, Chimeric Antigen therapeutic use, Adolescent, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Lymphoma, Non-Hodgkin therapy, Antigens, CD19 immunology, Antigens, CD19 therapeutic use, Immunotherapy, Adoptive methods
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- 2024
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9. Effects of nandrolone decanoate on telomere length and clinical outcome in patients with telomeropathies: a prospective trial.
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Clé DV, Catto LFB, Gutierrez-Rodrigues F, Donaires FS, Pinto AL, Santana BA, Darrigo LG, Valera ET, Koenigkam-Santos M, Baddini-Martinez J, Young NS, Martinez EZ, and Calado RT
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- Humans, In Situ Hybridization, Fluorescence, Nandrolone Decanoate, Prospective Studies, Retrospective Studies, Telomere, Lung Diseases, Interstitial
- Abstract
Androgens have been reported to elongate telomeres in retrospective and prospective trials with patients with telomeropathies, mainly with bone marrow failure. In our single-arm prospective clinical trial (clinicaltrials gov. Identifier: NCT02055456), 17 patients with short telomeres and/or germline pathogenic variants in telomere biology genes associated with at least one cytopenia and/or radiologic diagnosis of interstitial lung disease were treated with 5 mg/kg of intramuscular nandrolone decanoate every 15 days for 2 years. Ten of 13 evaluable patients (77%) showed telomere elongation at 12 months by flow-fluorescence in situ hybridization (average increase, 0.87 kb; 95% confidence interval: 0.20-1.55 kb; P=0.01). At 24 months, all ten evaluable patients showed telomere elongation (average increase, 0.49 kb; 95% confidence interval: 0.24-1.23 kb; P=0.18). Hematologic response was achieved in eight of 16 patients (50%) with marrow failure at 12 months, and in ten of 16 patients (63%) at 24 months. Seven patients had interstitial lung disease at baseline, and two and three had pulmonary response at 12 and 24 months, respectively. Two patients died due to pulmonary failure during treatment. In the remaining evaluable patients, the pulmonary function remained stable or improved, but showed consistent decline after cessation of treatment. Somatic mutations in myeloid neoplasm-related genes were present in a minority of patients and were mostly stable during drug treatment. The most common adverse events were elevations in liver function test levels in 88%, acne in 59%, and virilization in 59%. No adverse events grade ≥4 was observed. Our findings indicate that nandrolone decanoate elongates telomeres in patients with telomeropathies, which correlated with clinical improvement in some cases and tolerable adverse events.
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- 2023
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10. Differential diagnosis of bone marrow failure syndromes guided by machine learning.
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Gutierrez-Rodrigues F, Munger E, Ma X, Groarke EM, Tang Y, Patel BA, Catto LFB, Clé DV, Niewisch MR, Alves-Paiva RM, Donaires FS, Pinto AL, Borges G, Santana BA, McReynolds LJ, Giri N, Altintas B, Fan X, Shalhoub R, Siwy CM, Diamond C, Raffo DQ, Craft K, Kajigaya S, Summers RM, Liu P, Cunningham L, Hickstein DD, Dunbar CE, Pasquini R, De Oliveira MM, Velloso EDRP, Alter BP, Savage SA, Bonfim C, Wu CO, Calado RT, and Young NS
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- Humans, Diagnosis, Differential, Bone Marrow Failure Disorders diagnosis, Bone Marrow Diseases diagnosis, Bone Marrow Diseases genetics, Bone Marrow Diseases therapy, Anemia, Aplastic diagnosis, Anemia, Aplastic genetics, Anemia, Aplastic therapy, Pancytopenia diagnosis
- Abstract
The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely, the misdiagnosis of inherited bone marrow failure (BMF) can expose patients to ineffectual and expensive therapies, toxic transplant conditioning regimens, and inappropriate use of an affected family member as a stem cell donor. To predict the likelihood of patients having acquired or inherited BMF, we developed a 2-step data-driven machine-learning model using 25 clinical and laboratory variables typically recorded at the initial clinical encounter. For model development, patients were labeled as having acquired or inherited BMF depending on their genomic data. Data sets were unbiasedly clustered, and an ensemble model was trained with cases from the largest cluster of a training cohort (n = 359) and validated with an independent cohort (n = 127). Cluster A, the largest group, was mostly immune or inherited aplastic anemia, whereas cluster B comprised underrepresented BMF phenotypes and was not included in the next step of data modeling because of a small sample size. The ensemble cluster A-specific model was accurate (89%) to predict BMF etiology, correctly predicting inherited and likely immune BMF in 79% and 92% of cases, respectively. Our model represents a practical guide for BMF diagnosis and highlights the importance of clinical and laboratory variables in the initial evaluation, particularly telomere length. Our tool can be potentially used by general hematologists and health care providers not specialized in BMF, and in under-resourced centers, to prioritize patients for genetic testing or for expeditious treatment.
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- 2023
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11. Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. III: anti-CD19 CAR-T cell therapy for patients with non-Hodgkin lymphoma.
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Alencar AJ, Hirayama AV, Clé DV, Salvino MA, Perini G, Arrais C, Baiocchi O, Palma LC, Colturato I, Vaz J, Chiattone R, de Lima M, Filho JS, Nabhan S, Rocha V, Guerino-Cunha RL, and Chiattone CS
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The treatment and evolution of B-cell non-Hodgkin lymphoma (B-NHL) has undergone important changes in the last years with the emergence of targeted therapies, such as monoclonal antibodies, small molecules, antibody-drug conjugates, and bispecific antibodies. Nevertheless, a significant portion of patients remains refractory or relapsed (R/R) to the new therapeutic modalities, representing thus an unmet medical need. The use of CAR-T cells for the treatment of B-NHL patients has shown to be a promising therapy with impressive results in patients with R/R disease. The expectations are as high as the imminent approval of CAR-T cell therapy in Brazil, which it is expected to impact the prognosis of R/R B-NHL. The aim of this manuscript is to offer a consensus of specialists in the field of onco-hematology and cellular therapy, working in Brazil and United States, in order to discuss and offer recommendations in the present setting of the use of CAR-T cells for patients with B-NHL., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021. Published by Elsevier España, S.L.U.)
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- 2021
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12. Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. I: Structuring centers for the multidisciplinary clinical administration and management of CAR-T cell therapy patients.
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Clé DV, Hirayama AV, Alencar AJ, Costa LJ, Feliciano JVP, Mattos ER, Cordeiro AC, Salvino MA, Barros GMN, de Lima M, Scheinberg P, and Guerino-Cunha RL
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Chimeric antigen receptor T-cells (CAR-T cells) are a new modality of oncological treatment which has demonstrated impressive response in refractory or relapsed diseases, such as acute lymphoblastic leukemia (ALL), lymphomas, and myeloma but is also associated with unique and potentially life-threatening toxicities. The most common adverse events (AEs) include cytokine release syndrome (CRS), neurological toxicities, such as the immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, infections, and hypogammaglobulinemia. These may be severe and require admission of the patient to an intensive care unit. However, these AEs are manageable when recognized early and treated by a duly trained team. The objective of this article is to report a consensus compiled by specialists in the fields of oncohematology, bone marrow transplantation, and cellular therapy describing recommendations on the Clinical Centers preparation, training of teams that will use CAR-T cells, and leading clinical questions as to their use and the management of potential complications., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)
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- 2021
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13. Molecular surveillance of the on-going SARS-COV-2 epidemic in Ribeirao Preto City, Brazil.
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Slavov SN, Giovanetti M, Dos Santos Bezerra R, Fonseca V, Santos EV, Rodrigues ES, Adelino T, Xavier J, Borges JS, Evaristo M, Lima MT, de Carvalho Pereira G, Yamamoto AY, Clé DV, Calado RT, Covas DT, Alcantara LCJ, and Kashima S
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- Adult, Brazil epidemiology, COVID-19 virology, Evolution, Molecular, Female, Genome, Viral, Humans, Male, Middle Aged, Phylogeny, SARS-CoV-2 isolation & purification, COVID-19 epidemiology, SARS-CoV-2 genetics
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The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of an unprecedented worldwide pandemic. Brazil demonstrates one of the highest numbers of confirmed SARS-CoV-2 cases, and São Paulo State is the epicenter of the pandemics in the country. Nevertheless, little is known about the SARS-CoV-2 circulation in other cities in the State than São Paulo city. The objective of this study was to analyze phylogenetically SARS-CoV-2 strains circulating in city of Ribeirão Preto at the beginning of the pandemic and during the actual second wave. Twenty-nine nasopharyngeal SARS-CoV-2 RNA positive samples were sequenced by nanopore technology (18 obtained at the initial period of the pandemic and 11 during the second wave) and analyzed them phylogenetically. The performed analysis demonstrated that the majority of the strains obtained in the initial period of the pandemic in Ribeirão Preto belonged mainly to the B1.1.33 lineage (61.1%), but B.1.1 (27.8%) and B.1.1.28 (11.1%) lineages were also identified. In contrast, the second wave strains were composed exclusively by the Brazilian variant of concern (VOC) P.1 (91%) and P.2 (9%) lineages. The obtained phylogenetic results were suggestive of successive SARS-CoV-2 lineage substitution in this Brazilian region by the P.1 VOC. The performed study examines the SARS-CoV-2 genotypes in Ribeirão Preto city via genomic surveillance data. The obtained findings can contribute for continuous long-term genomic surveillance of SARS-CoV-2 due to the accelerated dynamics of viral lineage substitution, predict further waves and examine lineage behavior during SARS-CoV-2 vaccination., (Copyright © 2021. Published by Elsevier B.V.)
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- 2021
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14. Prevalence of virological and serological markers of SARS-CoV-2 infection in the population of Ribeirão Preto, Southeast Brazil: an epidemiological survey.
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Martinez EZ, Passos ADC, Fabbro ALD, Silva ASD, Escarso AC, Pazin-Filho A, Fonseca BALD, Maciel BC, Araújo DCAE, Clé DV, Gaspar GG, Santos JLFD, Ferreira JBB, Souza JP, Mello LM, Santos LLD, Passos LMR, Siconelli MJL, Cavalli RC, Santana RC, Calado RDT, Scarpelini S, Bollela VR, Floriano VG, and Bellissimo-Rodrigues F
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- Brazil epidemiology, Humans, Pandemics, Prevalence, COVID-19, SARS-CoV-2
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Introduction: This epidemiological household survey aimed to estimate the prevalence of the current and past SARS-CoV-2 infections in Ribeirão Preto, a municipality of southeast Brazil., Methods: The survey was conducted in two phases using a clustered sampling scheme. The first phase spanned May 1-3 and involved 709 participants. The second phase spanned June 11-14, 2020, and involved 646 participants., Results: During the first phase, RT-PCR performed on nasopharyngeal swabs was positive at 0.14%. The serological tests were positive in 1.27% of the patients during the first phase and 2.79% during the second phase. People living in households with more than five members had a prevalence of 10.83% (95%CI: 1.58-74.27) higher than those living alone or with someone other. Considering the proportion of the positive serological test results with sex and age adjustments, approximately 2.37% (95%CI: 1.32-3.42) of the population had been cumulatively infected by mid-June 2020, which is equivalent to 16,670 people (95%CI: 9,267-24,074). Considering that 68 deaths from the disease in the residents of the city had been confirmed as at the date of the second phase of the survey, the infection fatality rate was estimated to be 0.41% (95%CI: 0.28-0.73). Our results suggest that approximately 88% of the cases of SARS-CoV-2 infection at the time of the survey were not reported to the local epidemiological surveillance service., Conclusions: The findings of this study provide in-depth knowledge of the COVID-19 pandemic in Brazil and are helpful for the preventive and decision-making policies of public managers.
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- 2021
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15. Somatic genetic rescue in hematopoietic cells in GATA2 deficiency.
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Catto LFB, Borges G, Pinto AL, Clé DV, Chahud F, Santana BA, Donaires FS, and Calado RT
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- Adult, Asymptomatic Diseases, Codon, Nonsense genetics, GATA2 Deficiency blood, GATA2 Deficiency diagnosis, Germ-Line Mutation, Hematopoietic Stem Cells pathology, Heterozygote, Humans, Male, Middle Aged, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Young Adult, Zinc Fingers genetics, GATA2 Deficiency genetics, GATA2 Transcription Factor genetics, Genes, Recessive genetics, Hematopoietic Stem Cells metabolism
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- 2020
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16. Outcomes of HIV-associated Burkitt Lymphoma in Brazil: High treatment toxicity and refractoriness rates - A multicenter cohort study.
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Silva WFD, Garibaldi PMM, Rosa LID, Bellesso M, Clé DV, Delamain MT, Rego EM, Pereira J, and Rocha V
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- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Brazil epidemiology, Burkitt Lymphoma diagnosis, Burkitt Lymphoma therapy, Comorbidity, Disease Management, Disease Susceptibility, Drug Resistance, Neoplasm, Female, HIV Infections virology, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Patient Outcome Assessment, Public Health Surveillance, Retrospective Studies, Young Adult, Burkitt Lymphoma epidemiology, Burkitt Lymphoma etiology, HIV Infections complications, HIV Infections epidemiology
- Abstract
Background: Although the increased use of combined antiretroviral therapy (cART) has decreased the incidence of lymphomas HIV-associated, Burkitt lymphoma (BL) incidence remains stable. Reported outcomes on HIV-associated BL from developed countries seem to corroborate that the regimens do not need to be tailored to the HIV-positive population., Materials and Methods: This is a retrospective multicenter cohort study from Brazil, including HIV-positive patients aged 15 years and above diagnosed with BL., Results: A total of 54 patients were included. Median age was 39 years (range, 15-64). At diagnosis, advanced disease was found in 86% and 52% had a CD4+ count lower than 200 cells/mm
3 . Five patients died before starting any regimen. Among the remaining 49 patients, most were treated with Hyper-CVAD (53%) and CODOX-M IVAC (18%). Rituximab was used in frontline in only 16% of the patients. Primary refractory disease was found in 14%. A treatment-related mortality of 38.7% and a complete response rate of 44.9% were found. At 4 years, estimated overall survival (OS) was 39.8%. All relapsed and primary refractory patients eventually died. Remaining patients died from infections (24/34), despite antimicrobial prophylaxis and associated cART., Conclusion: Early mortality and toxicity were higher in our cohort than in developed countries. A faster diagnosis, better understanding of the biology of the disease, establishment of low toxicity regimens, inclusion of rituximab and improvement of supportive care may decrease the mortality of HIV-associated BL in developing countries., Competing Interests: Declarations of Competing Interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2020
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17. Pathogenic TERT promoter variants in telomere diseases.
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Gutierrez-Rodrigues F, Donaires FS, Pinto A, Vicente A, Dillon LW, Clé DV, Santana BA, Pirooznia M, Ibanez MDPF, Townsley DM, Kajigaya S, Hourigan CS, Cooper JN, Calado RT, and Young NS
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- Adolescent, Adult, Aged, Anemia, Aplastic genetics, Blood Cell Count, Bone Marrow Diseases genetics, Child, Child, Preschool, Cohort Studies, Female, Humans, Idiopathic Pulmonary Fibrosis genetics, Liver Diseases genetics, Male, Middle Aged, Retrospective Studies, Telomerase deficiency, Young Adult, Promoter Regions, Genetic, Telomerase genetics, Telomere pathology
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Purpose: The acquisition of pathogenic variants in the TERT promoter (TERTp) region is a mechanism of tumorigenesis. In nonmalignant diseases, TERTp variants have been reported only in patients with idiopathic pulmonary fibrosis (IPF) due to germline variants in telomere biology genes., Methods: We screened patients with a broad spectrum of telomeropathies (n = 136), their relatives (n = 52), and controls (n = 195) for TERTp variants using a customized massively parallel amplicon-based sequencing assay., Results: Pathogenic -124 and -146 TERTp variants were identified in nine (7%) unrelated patients diagnosed with IPF (28%) or moderate aplastic anemia (4.6%); five of them also presented cirrhosis. Five (10%) relatives were also found with these variants, all harboring a pathogenic germline variant in telomere biology genes. TERTp clone selection did not associate with peripheral blood counts, telomere length, and response to danazol treatment. However, it was specific for patients with telomeropathies, more frequently co-occurring with TERT germline variants and associated with aging., Conclusion: We extend the spectrum of nonmalignant diseases associated with pathogenic TERTp variants to marrow failure and liver disease due to inherited telomerase deficiency. Specificity of pathogenic TERTp variants for telomerase dysfunction may help to assess the pathogenicity of unclear constitutional variants in the telomere diseases.
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- 2019
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18. Short telomere length in peripheral blood leukocytes in head and neck cancer: Findings in a Brazilian cohort.
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Alves-Paiva RM, Gutierrez-Rodrigues F, Pereira-Martins DA, Figueiredo DLA, Clé DV, Conti-Freitas LC, Mamede RCM, and Calado RT
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- Adult, Aged, Aged, 80 and over, Brazil, Case-Control Studies, Cohort Studies, Female, Head and Neck Neoplasms mortality, Humans, Male, Middle Aged, Risk Factors, Survival Rate, Telomere Homeostasis, Head and Neck Neoplasms pathology, Leukocytes pathology, Telomere Shortening
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Background: Telomeres are specialized DNA structures that are critical to maintain cell homeostasis and to avoid genomic instability. Epidemiological studies have examined the association between leukocyte telomere length (LTL) and risk of cancers, but the findings remain conflicting., Methods: Mean LTL was measured by quantitative PCR in 97 patients with head and neck cancer (HNC) and 262 healthy controls. The association between LTL and patients' clinical status, such as smoke, alcoholism, and overall survival, were also evaluated., Results: The age-adjusted LTL was significantly shorter in patients with HNC in comparison to healthy controls (P = .0003). Patients with shortest LTL had an increased risk to develop HNC (P < 0.0001). No significant correlation was observed between LTL and patients' clinical features and personal habits., Conclusions: Our data support the hypothesis that LTL is a risk factor for HNC. The use of LTL as a biomarker can help physicians to identify high-risk individuals for HNC., (© 2018 Wiley Periodicals, Inc.)
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- 2019
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19. Rabbit antithymocyte globulin dose does not affect response or survival as first-line therapy for acquired aplastic anemia: a multicenter retrospective study.
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Clé DV, Atta EH, Dias DSP, Lima CBL, Bonduel M, Sciuccati G, Medeiros LA, de Oliveira MM, Blum Fonseca PB, Saad STO, Hamerschlak N, Salvino MA, Garanito MP, Pazin-Filho A, Scheinberg P, and Calado RT
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- Adolescent, Adult, Aged, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Infant, Male, Middle Aged, Retrospective Studies, Survival Rate, Anemia, Aplastic drug therapy, Anemia, Aplastic mortality, Antilymphocyte Serum administration & dosage, Cyclosporine administration & dosage
- Abstract
In a prospective randomized study, treatment for aplastic anemia (AA) with rabbit antithymocyte globulin (r-ATG) and cyclosporine showed inferior hematological response and survival in comparison to horse antithymocyte globulin (h-ATG) and cyclosporine. However, h-ATG was discontinued in most Asian, South American, and European countries, where r-ATG became the only ATG formulation available. We retrospectively evaluated consecutive patients with acquired AA who received either rabbit (n = 170) or horse (n = 85) ATG and cyclosporine for first-line treatment from 1992 to 2014 in seven referral centers in Brazil and Argentina. Overall response at 3 months was 17% (95%CI, 11-23%) for r-ATG and 44% (95%CI, 33-55%) for h-ATG (p < 0.001). At 6 months, it was 31% (95%CI, 34-39%) for r-ATG and 59% (95%CI, 48-69%) for h-ATG (p < 0.001). Overall survival at 5 years was 57% (95%CI, 47-65%) for r-ATG and 80% (95%CI, 69-87%) for h-ATG (log-rank = 0.001). Relapse was significantly higher in patients receiving h-ATG (28%; 95%CI, 17-43%) as compared to r-ATG (9.4%; 95%CI, 4-21%; log-rank, p = 0.01). The type of ATG was the only factor associated with both response and survival. The r-ATG dose varied from 1 to 5 mg/kg/day, but it did not correlate with outcomes. In summary, this is the largest multicenter study comparing the two ATG formulations in AA. Our results indicate that the dose of r-ATG does not influence hematologic response or survival in first-line therapy for acquired AA. Considering the toxicity and costs of r-ATG, our findings challenge its aggregate benefit to cyclosporine therapy and further strengthen that h-ATG should remain standard therapy in AA.
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- 2018
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20. Treatment of inherited bone marrow failure syndromes beyond transplantation.
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Calado RT and Clé DV
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- Androgens adverse effects, Androgens therapeutic use, Bone Marrow Diseases genetics, Bone Marrow Diseases metabolism, Chemical and Drug Induced Liver Injury, Danazol adverse effects, Danazol therapeutic use, Female, Genetic Diseases, Inborn genetics, Genetic Diseases, Inborn metabolism, Genetic Therapy, Humans, Leucine therapeutic use, Oxymetholone adverse effects, Oxymetholone therapeutic use, Quercetin therapeutic use, Stem Cell Transplantation, Syndrome, Virilism chemically induced, Bone Marrow Diseases therapy, Genetic Diseases, Inborn therapy
- Abstract
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists, leucine, quercetin, and novel gene therapy approaches may benefit inherited cases in the future., Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests., (© 2016 by The American Society of Hematology. All rights reserved.)
- Published
- 2017
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21. Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia.
- Author
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Atta EH, Lima CBL, Dias DSP, Clé DV, Bonduel MM, Sciuccati GB, Medeiros LA, Oliveira MM, Salvino MA, Garanito MP, Blum Fonseca PB, Saad STO, Calado RT, and Scheinberg P
- Subjects
- Adolescent, Adult, Aged, Anemia, Aplastic diagnosis, Animals, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Male, Middle Aged, Mortality trends, Predictive Value of Tests, Rabbits, Retrospective Studies, Treatment Outcome, Young Adult, Anemia, Aplastic drug therapy, Anemia, Aplastic mortality, Antilymphocyte Serum administration & dosage, Immunosuppressive Agents administration & dosage, Severity of Illness Index
- Abstract
Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 10
9 /L (OR 7.64, P < 0.001) were independent risk factors for early mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 109 /L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.- Published
- 2017
- Full Text
- View/download PDF
22. Blood film in the era of streaming cells.
- Author
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Clé DV
- Published
- 2017
- Full Text
- View/download PDF
23. Intravenous infusion of allogeneic mesenchymal stromal cells in refractory or relapsed aplastic anemia.
- Author
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Clé DV, Santana-Lemos B, Tellechea MF, Prata KL, Orellana MD, Covas DT, and Calado RT
- Subjects
- Adult, Female, Humans, Immunosuppression Therapy methods, In Situ Hybridization, Fluorescence, Infusions, Intravenous, Male, Middle Aged, Transplantation, Homologous, Treatment Outcome, Young Adult, Anemia, Aplastic therapy, Antilymphocyte Serum therapeutic use, Cyclosporine therapeutic use, Immunologic Factors therapeutic use, Immunosuppressive Agents therapeutic use, Mesenchymal Stem Cell Transplantation adverse effects, Mesenchymal Stem Cells
- Abstract
Background Aims: For patients with aplastic anemia (AA) who are refractory to anti-thymocyte globulin (ATG) and cyclosporine, a second course of immunosuppression is successful in only one-fourth to one-third of cases., Methods: We conducted a phase 1/2 study to evaluate the addition of two to five weekly intravenous infusions of allogeneic unrelated non-human leukocyte antigen-matched bone marrow-derived mesenchymal stromal cells (MSCs) (median, 2.7 × 10(6) cells/kg/infusion; range, 1.3-4.5) to standard rabbit ATG and cyclosporine in nine patients with refractory or relapsed AA., Results: After a median follow-up of 20 months, no infusion-related adverse event was observed, but four deaths occurred as the result of heart failure and bacterial or invasive fungal infections; only two patients achieved partial hematologic responses at 6 months. We failed to demonstrate by fluorescence in situ hybridization or variable number tandem repeat any MSC engraftment in patient marrow 30, 90 or 180 days after infusions., Conclusions: Infusion of allogeneic MSCs in AA is safe but does not improve clinical hematologic response or engraft in recipient bone marrow. This study was registered at clinicaltrials.gov, identifier: NCT01297972., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
24. Repeat course of rabbit antithymocyte globulin as salvage following initial therapy with rabbit antithymocyte globulin in acquired aplastic anemia.
- Author
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Clé DV, Atta EH, Dias DS, Lima CB, Bonduel M, Sciuccati G, Medeiros LA, de Oliveira MM, Salvino MA, Garanito M, Saad ST, Calado RT, and Scheinberg P
- Subjects
- Anemia, Aplastic mortality, Anemia, Aplastic pathology, Animals, Disease-Free Survival, Female, Humans, Male, Rabbits, Survival Rate, Anemia, Aplastic drug therapy, Antilymphocyte Serum administration & dosage, Immunologic Factors administration & dosage, Salvage Therapy
- Published
- 2015
- Full Text
- View/download PDF
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