68 research outputs found
Multiple myeloma: Available therapies and causes of drug resistance
No full textMultiple myeloma (MM) is the second most common blood cancer. Treatments for MM include corticosteroids, alkylating agents, anthracyclines, proteasome inhibitors, immunomodulatory drugs, histone deacetylase inhibitors and monoclonal antibodies. Survival outcomes have improved substantially due to the introduction of many of these drugs allied with their rational use. Nonetheless, MM patients successively relapse after one or more treatment regimens or become refractory, mostly due to drug resistance. This review focuses on the main drugs used in MM treatment and on causes of drug resistance, including cytogenetic, genetic and epigenetic alterations, abnormal drug transport and metabolism, dysregulation of apoptosis, autophagy activation and other intracellular signaling pathways, the presence of cancer stem cells, and the tumor microenvironment. Furthermore, we highlight the areas that need to be further clarified in an attempt to identify novel therapeutic targets to counteract drug resistance in MM patients.The work of our laboratory is funded by project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); also by FEDER?Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020?Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT?Funda??o para a Ci?ncia e a Tecnologia/Minist?rio da Ci?ncia, Tecnologia e Ensino Superior in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274)". The authors also thank ?Sociedade Portuguesa de Hematologia? for a grant to Rui Bergantim
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis
No full textMultiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy’s efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy
Searching for biomarkers of measurable residual disease and drug resistance in liquid biopsies from multiple myeloma patients
No full textPB2162: EVALUATION OF IMMUNE RECONSTITUTION IN MULTIPLE MYELOMA PATIENTS ON MAINTENANCE THERAPY WITH LENALIDOMIDE - THE ROLE OF HEAVYLITE CHAINS
No full texta preliminary study
No full textFunding Information: The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors acknowledge Sociedade Portuguesa de Hematologia/Associa\u00E7\u00E3o Portuguesa contra a Leucemia/AMGEN for funding this work (\u201CBOLSA DE INVESTIGA\u00C7\u00C3O 2017 EM MIELOMA M\u00DALTIPLO\u201D). Funding Information: The authors acknowledge the support of the i3S Bioinformatics Platform, the Flow Cytometry Laboratory of the Clinical Pathology Department, and the Hematology Laboratory of the Clinical Hematology Department of Centro Hospital S\u00E3o Jo\u00E3o, Porto, Portugal. SP is supported by FCT through PhD fellowship 2021.07467. BD. Publisher Copyright: Copyright © 2025 Bergantim, Peixoto da Silva, Pinto, Pereira, Sousa, Trigo, Matthiesen, Guimarães and Vasconcelos.Background: Multiple myeloma (MM) is a complex hematological malignancy with heterogeneous clinical and pathophysiological backgrounds that influence treatment responses and outcomes. Identifying biomarkers to predict drug response and guide treatment decisions, particularly regarding drug combinations, is essential to improve therapeutic efficacy and patient outcomes. This study explores the role of microRNAs (miRNAs/miRs) derived from bone marrow (BM) and peripheral blood (PB) in responses to treatment and survival outcomes in newly diagnosed MM (ndMM) patients. Methods: This study included twenty patients with ndMM undergoing first-line treatment with bortezomib, thalidomide, and dexamethasone. The miRNAs were isolated from BM and PB, and their profiles were analyzed using Next-Generation Sequencing (NGS), followed by validation of differentially expressed miRNAs by quantitative real-time PCR (qPCR). Clinical and response data were collected to assess correlations between miRNA levels, clinical characteristics, and patient outcomes. In silico analysis for target-prediction and gene ontology (GO) enrichment was performed to explore the potential biological and functional role of the identified miRNAs. Results: NGS profiling revealed several miRNAs differently expressed between treatment-refractory and sensitive patients, as well as between PB and BM. Among these, miR-665, miR-483-5p, miR-143-3p and miR-145-5p were selected for further validation by qPCR. It was observed that miR-665 was significantly elevated in treatment-refractory patients compared to treatment-sensitive patients. Additionally, miR-665 levels were higher in PB than in BM. Elevated miR-665 levels were associated with more aggressive disease characteristics and poorer clinical outcomes, including reduced overall survival. Discussion: Our preliminary findings suggest that miR-665 could potentially serve as a non-invasive tool for predicting drug resistance and guiding treatment decisions in MM. These findings also highlight the potential utility of miRNAs in liquid biopsies as a predictive tool of drug response in MM and could pave the way for personalized treatment strategies, improving patient outcomes. Future research is needed to validate these results in larger cohorts and explore the underlying mechanisms of miR-665 in MM pathogenesis and drug resistance.publishersversionpublishe
O processo de formação de palavras e a estilística na obra “Por que Lulu Bergantim não atravessou o Rubicon” de José Cândido de Carvalho
No full textThis Labor Course Completion tries to analyze stylistic and expressive processes of formation of some words present in the work Why Lulu Brigantine not crossed the Rubicon, José Cândido de Carvalho. For this analysis were applied theoretical and analytical tools of stylistics, which will help us understand how the processes of word formation work in affective stylistic expression. Picked out the author José Cândido de Carvalho, because it appropriates the morphological processes to satirize the speech of rustics, and using the same processes, criticizes the civil service, bringing a bit of the comic for your text. This work was divided into three stages: first, seeking the Stylistics, the parses style transcending intelectivo plan for the affective, as well as observing the Stylistics can act within the morphology of Brazilian Portuguese and Portuguese-language literature; Next analyzes were made of the occurrences of the process of word formation in traditional grammars, such as Evanildo Bechara and Napoleon Mendes and last, we analyzed the expression of some words found in José Cândido.O presente Trabalho de Conclusão de Curso busca a análise estilística e expressiva dos processos de formação de algumas palavras presentes na obra Por que Lulu Bergantim não atravessou o Rubicon, de José Cândido de Carvalho. Para esta análise foram aplicadas ferramentas teórico- analíticas da Estilística, que nos auxiliarão a perceber como os processos de formação de palavras atuam na expressão afetiva estilística. Foi escolhido o autor José Cândido de Carvalho, pois o mesmo apropria-se dos processos morfológicos para satirizar a fala do caipira, e, utilizando os mesmos processos, critica o funcionalismo público, trazendo um pouco do cômico para seu texto. Este trabalho foi dividido em três momentos: primeiramente, buscando na Estilística, que a analisa o estilo transcendendo do plano intelectivo para o plano afetivo, observando assim como a Estilística pode atuar dentro da morfologia do português brasileiro e da literatura de língua portuguesa; Em seguida foram feitas análises das ocorrências do processo de formação de palavras em gramáticas tradicionais, como a de Evanildo Bechara e Napoleão Mendes e por último, foram analisadas a expressividade de algumas palavras presentes em José Cândido
Severe neutropenia and thrombocytopenia in a young adult: a case-report
No full textWe present the case of a 20-year-old male hospitalized with severe neutropenia and thrombocytopenia. After exclusion of other etiologies, it was concluded
to be of autoimmune etiology. The prompt and sustained response of both cell lines to corticosteroids, reinforced this diagnosis. This case illustrates a very
rare association of severe primary neutropenia and thrombocytopenia. The lack of serological marker makes this diagnosis delayed and resource-consuming
Impact of hematologic complete response in the treatment of sporadic late‐onset nemaline myopathy associated with monoclonal gammopathy
No full textAbstract Monoclonal gammopathy of undetermined significance (MGUS) may be associated with pathologies with severe neuromuscular manifestations such as sporadic late‐onset nemaline myopathy (SLONM). We describe a difficult to diagnose case of SLNOM with marked clinical improvement after achieving gammopathy complete hematologic response
Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry
No full textCOVID-19; SARS-CoV-2; Multiple myelomaCOVID-19; SARS-CoV-2; Mieloma múltipleCOVID-19; SARS-CoV-2; Mieloma múltiplePatients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109/L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020–8223)
Prognostic value of unrelated atypical serum immunofixation patterns during Multiple Myeloma therapy
No full textAbstract Autologous stem cell transplantation (ASCT) is the gold standard therapy for suitable multiple myeloma (MM) patients after induction with high dose therapy. To date, the evidence of a reliable marker of prognosis in these cases remains scarce. Our aim was to evaluate appearance of unrelated atypical serum immunofixation patterns (ASIPs) as a marker of prognosis in MM patients submitted to ASCT. We retrospectively analysed data from 65 patients. Interestingly, we observed that presence of ASIPs was associated with longer progression-free survival and longer overall survival. Our results suggested that presence of ASIPs could be a novel marker of good prognosis in MM patients submitted to ASCT.</p
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