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ABSTRACT Introduction: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) patients are exposed to acute and chronic nephrotoxic events (drugs, hypotension, infections, and microangiopathy). The need for hemodialysis (HD) may be associated with high mortality rates. However, the risk factors and clinical impact of HD are poorly understood. Aim: To analyze survival and risk factors associated with HD in allo-HSCT Patients and methods: single-center cohort study 185 (34 HD cases versus 151 controls) consecutive adult allo-HSCT patients from 2007-2019. We performed univariate statistical analysis, then logistic regression and competing risk regression were used to multivariate analysis. Survival was analyzed by Kaplan-Meier and Cox proportional-hazards models. Results: The one-year HD cumulative incidence was 17.6%. Univariate analysis revealed that HD was significantly associated with male gender, age (p 0.056), haploidentical donor, grade II-IV acute GVHD, polymyxin B, amikacin, cidofovir, microangiopathy, septic shock (norepinephrine use) and steroid exposure. The median days of glycopeptides exposure (teicoplanin/vancomycin) was 16 (HD) versus 10 (no HD) (p 0.088). In multivariate analysis, we found: norepinephrine (hazard ratio, HR:3.3; 95% confidence interval, 95%CI:1.2-8.9; p 0.024), cidofovir drug (HR:11.0; 95%CI:4.6 - 26.0; p < 0.001), haploidentical HSCT (HR:1.94; 95%CI:0.81-4.65; p 0.14) and Age (HR:1.01; 95%CI: 0.99-1.03; p 0.18). The HD group had higher mortality rate (HR:6.68; 95% CI: 4.1-10.9; p < 0.001). Conclusion: HD was associated with decreased survival in allo-HSCT. Carefully use of nephrotoxic drugs and improving immune reconstitution could reduce severe infections (shock) and patients requiring cidofovir, which taken together may result in lower rates of HD, therefore improving survival.
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ABSTRACT Objective To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. Methods Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. Results A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). Conclusion The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.
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ABSTRACT Autoimmune diseases are an important field for the development of bone marrow transplantation, or hematopoietic stem cell transplantation. In Europe alone, almost 3000 procedures have been registered so far. The Brazilian Society for Bone Marrow Transplantation (Sociedade Brasileira de Transplantes de Medula Óssea) organized consensus meetings for the Autoimmune Diseases Group, to review the available literature on hematopoietic stem cell transplantation for autoimmune diseases, aiming to gather data that support the procedure for these patients. Three autoimmune diseases for which there are evidence-based indications for hematopoietic stem cell transplantation are multiple sclerosis, systemic sclerosis and Crohn's disease. The professional stem cell transplant societies in America, Europe and Brazil (Sociedade Brasileira de Transplantes de Medula Óssea) currently consider hematopoietic stem cell transplantation as a therapeutic modality for these three autoimmune diseases. This article reviews the evidence available.
Subject(s)
Humans , Scleroderma, Systemic , Crohn Disease , Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Scleroderma, Diffuse , Multiple SclerosisABSTRACT
ABSTRACT The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Elderly was elaborated by nutritionists, nutrologists and hematologists physicians from 15 Brazilians reference centers in hematopoietic stem cell transplantation, in order to emphasize the importancy of nutritional status and the body composition during the treatment, as well as the main characteristics related to patient's nutritional assessment. Establishing the consensus, we intended to improve and standardize the nutritional therapy during the hematopoietic stem cell transplantation. The Consensus was approved by the Brazilian Society of Bone Marrow Transplantation.
RESUMO O Consenso Brasileiro de Nutrição em Transplante de Células-Tronco Hematopoiéticas: Idoso foi elaborado com a participação de nutricionistas, médicos nutrólogos e médicos hematologistas de 15 centros brasileiros referência em transplante de células-tronco hematopoiéticas, com o objetivo de salientar a importância do estado nutricional e da composição corporal durante o tratamento, bem como as principais características relacionadas à avaliação nutricional do paciente. As intenções, ao se estabelecer o consenso, foram aprimorar e padronizar a terapia nutricional durante o transplante de células-tronco hematopoiéticas. O consenso foi aprovado pela Sociedade Brasileira de Transplante de Médula Óssea.
Subject(s)
Humans , Aged , Hematopoietic Stem Cell Transplantation , Hematologic Neoplasms/therapy , Transplantation Conditioning , Consensus , Body Composition , Brazil , Aging , Comorbidity , Geriatric Assessment , Nutrition Assessment , Nutritional StatusABSTRACT
OBJETIVO: Comparar as células-tronco mesenquimais humanas obtidas de filtros de coleta reutilizáveis àquelas coletadas em filtros descartáveis e caracterizá-las utilizando os critérios da International Society for Cellular Therapy. MÉTODOS: Foram isoladas células-tronco mesenquimais humanas de kits de coleta de medula óssea reutilizáveis e descartáveis, pela lavagem dos filtros com meio de cultura. As células isoladas foram caracterizadas de acordo com os critérios estabelecidos pela International Society for Cellular Therapy, por meio das técnicas de citometria de fluxo, diferenciação in vitro e citoquímica. RESULTADOS: As amostras foram obtidas de filtro descartável (n=3) e reutilizável (n=3). Todas as amostras obtidas de filtros descartáveis produziram células-tronco mesenquimais, e todas as células-tronco mesenquimais humanas derivadas de medula óssea preencheram os critérios estabelecidos pela International Society for Cellular Therapy. CONCLUSÃO: Este estudo mostrou que as células-tronco mesenquimais também podem ser obtidas de kits de coleta reutilizáveis (que permanecem em uso em vários centros, no mundo inteiro), para serem empregadas em pesquisa como uma fonte alternativa e ética.
OBJECTIVE: To compare human mesenchymal stem cells obtained from reusable and disposable filters and to characterize them according to the criteria of the International Society of Cellular Therapy. METHODS: Human mesenchymal stem cells were isolated from bone marrow collection reusable sets and compared with those obtained from disposable sets by washing the filters with cell culture media. The isolated cells were characterized according to the criteria of the International Society of Cellular Therapy using flow cytometry, differentiation in vitro, and cytochemistry techniques. RESULTS: Samples were obtained from disposable (n=3) and from reusable collection sets (n=3). All samples obtained from bone marrow disposable sets successfully produced mesenchymal stem cells. All bone marrow derived mesenchymal stem cells were characterized and fulfilled the criteria established by International Society of Cellular Therapy. CONCLUSION: This study showed that mesenchymal stem cells can also be obtained from reusable collection sets (which are still used in several centers around the world) to be employed in research as an alternative and ethical source.
Subject(s)
Bone Marrow , Conservation of Natural Resources , Disposable Equipment , Filtration , Mesenchymal Stem CellsABSTRACT
Objective: To determine the 5-year post-transplant survival of patients with multiple myeloma. Methods: A retrospective study in patients diagnosed with multiple myeloma submitted to autologous bone marrow transplantation at a Brazilian institution, during the period of 1993 to 2007. Results: Seventy-three patients were evaluated with a median age of 55 years. Survival in 5 years was 75% (2.4 to 60 months). Statistical analysis demonstrated statistical significance for the applied grade of response prior to treatment with autologous bone marrow transplantation (p = 0.01). There was no statistical significance for clinical staging or time of diagnosis (before or after the year 2000). Conclusion: Experience in autologous bone marrow transplantation for multiple myeloma at a Brazilian institution demonstrated an evolution consistent with that of medical literature and highlighted the importance of a response to treatment prior to transplantation in the survival of these patients.
Objetivo: Determinar a sobrevida de pacientes portadores de mieloma múltiplo em 5 anos pós-transplante. Métodos: Estudo retrospectivo em pacientes com diagnóstico de mieloma múltiplo submetidos a transplante autólogo de medula óssea em umainstituição brasileira, no período de 1993 a 2007 . Resultados: Foram avaliados 73 pacientes com mediana de idade de 55 anos. A sobrevida encontrada em 5 anos foi de 75% (2,4 a 60 meses). A análise estatística demonstrou significância estatística para o grau de resposta ao tratamento aplicado previamente ao transplante autólogo de medula óssea (p = 0,01). Não houve significância estatística para o estadiamento clínico ou período de diagnóstico (antes ou após o ano 2000). Conclusão: A experiência na realização de transplante autólogo de medula para mileoma múltiplo, em uma instituição brasileira, demonstrou uma evolução concordante com a literatura médica e destacou a importância da resposta prévia ao transplante na sobrevida desses pacientes.
Subject(s)
Bone Marrow Transplantation , Multiple Myeloma , Survival , Transplantation, AutologousABSTRACT
Objective: To report the experience of a tertiary care hospital with allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiencies. Methods: Seven pediatric patients with primary immunodeficiencies (severe combined immunodeficiency: n = 2; combined immunodeficiency: n = 1; chronic granulomatous disease: n = 1; hyper-IgM syndrome: n = 2; and IPEX syndrome: n = 1) who underwent eight hematopoietic stem cell transplants in a single center, from 2007 to 2010, were studied. Results: Two patients received transplants from HLA-identical siblings; the other six transplants were done with unrelated donors (bone marrow: n = 1; cord blood:n = 5). All patients had pre-existing infections before hematopoietic stem cell transplants. One patient received only anti-thymocyte globulin prior to transplant, three transplants were done with reduced intensity conditioning regimens and four transplants were done after myeloablative therapy. Two patients were not evaluated for engraftmentdue to early death. Three patients engrafted, two had primary graft failure and one received a second transplant with posterior engraftment. Two patients died of regimen related toxicity (hepatic sinusoidal obstruction syndrome); one patient died of progressive respiratory failure due to Parainfluenza infection present prior to transplant. Four patients are alive and well from 60 days to 14 months after transplant. Conclusion: Patients' status prior to transplant is the most important risk factor on the outcome of hematopoietic stem cell transplants in the treatment of these diseases. Early diagnosis and the possibility of a faster referral of these patients for treatment in reference centers may substantially improve their survival and quality of life.
Objetivo: Relatar a experiência de um hospital terciário no tratamento de pacientes pediátricos com imunodeficiências primárias com transplante de células-tronco hematopoéticas. Métodos: De 2007 a 2010, foram realizados oito transplantes em sete pacientes pediátricos com imunodeficiências primárias: imunodeficiência combinada grave (n = 2); imunodeficiência combinada (n = 1); doença granulomatosa crônica (n = 1); síndrome hiper-IgM (n = 2); síndrome IPEX (n=1). Resultados: Dois pacientes foram transplantados com medula óssea de irmãos HLA-idênticos; seis transplantes foram feitos com doadores não aparentados (medula óssea: n = 1; sangue de cordão umbilical: n = 5). Todos os pacientes haviam tido episódios de infecção grave previamente ao tratamento. Um paciente recebeu apenas globulina antitimocítica antes do transplante de células-tronco hematopoéticas, três transplantes foram feitos com quimioterapia de intensidade reduzida e quatro após quimioterapia mieloablativa. Dois pacientes morreram precocemente e não foram avaliados em relação à enxertia. Três pacientes tiveram enxertia completa, dois evoluíram com falha primária de pega, um deles recebeu um segundo transplante com pega do enxerto. Dois pacientes morreram de toxicidade do transplante (síndrome da obstrução sinusoidal hepática), um paciente morreu de insuficiência respiratória por infecção por parainfluenza já existente antes do transplante. Quatro pacientes estão vivos e bem entre 60 dias e 14 meses após o transplante. Conclusão: A condição do paciente ao transplante é o fator mais importante no sucesso do tratamento. O diagnóstico precoce dos pacientes e a possibilidade de encaminhá-los mais rapidamente para tratamento em centros de referência podem melhorar substancialmente a sobrevida e a qualidade de vida deles.
Subject(s)
Humans , Male , Female , Child , Acquired Immunodeficiency Syndrome , Hematopoietic Stem Cell TransplantationABSTRACT
Objectives: To evaluate the use of magnetic resonance imaging in patients with Beta-thalassemia and to compare T2* magnetic resonance imaging results with serum ferritin levels and the redox active fraction of labile plasma iron. Methods: We have retrospectively evaluated 115 chronically transfused patients (65 women). We tested serum ferritin with chemiluminescence, fraction of labile plasma iron by cellular fluorescence and used T2* MRI to assess iron content in the heart, liver, and pancreas. Hepatic iron concentration was determined in liver biopsies of 11 patients and the results were compared with liver T2* magnetic resonance imaging. Results: The mean serum ferritin was 2,676.5+/- 2,051.7ng/mL. A fraction of labile plasma iron was abnormal (> 0,6 Units/mL) in 48/83 patients (57%). The mean liver T2* value was 3.91 ± 3.95 ms, suggesting liver siderosis in most patients (92.1%). The mean myocardial T2* value was 24.96 ± 14.17 ms and the incidence of cardiac siderosis (T2* < 20 ms) was 36%, of which 19% (22/115) were severe cases (T2* < 10 ms). The mean pancreas T2* value was 11.12 ± 11.20 ms, and 83.5% of patients had pancreatic iron deposition (T2* < 21 ms). There was significant curvilinear and inverse correlation between liver T2* magnetic resonance imaging and hepatic iron concentration (r= -0.878; p < 0.001) and moderate correlation between pancreas and myocardial T2* MRI (r = 0.546; p < 0.0001). Conclusion: A high rate of hepatic, pancreatic and cardiac impairment by iron overload was demonstrated. Ferritin levels could not predict liver, heart or pancreas iron overload as measured by T2* magnetic resonance imaging. Therewas no correlation between liver, pancreas, liver and myocardial iron overload, neither between ferritin and fraction of labile plasma iron with liver, heart and pancreas T2* values.
Objetivo: Avaliar o acúmulo de ferro em diferentes órgãos por meio da ressonância nuclear magnética T2* e correlacionar os resultados aos níveis de ferritina sérica, ferro plasmático lábil e outros órgãos envolvidos. Métodos: Foram avaliados retrospectivamente 115 pacientes talassêmicos (sendo 65 mulheres). A concentração hepática de ferro foi determinada em biópsia de 11 pacientes; os resultados foram comparados com os valores de T2* fígado. Resultados: a ferritina sérica média foi de 2.676,5 +/- 2.051,7 ng/mL. O ferro plasmático lábil foi anormal (> 0,6 Unidades/mL) em 48/83 pacientes (57%). A média dos valores de T2* no fígado foi 3,91 ± 3,95 ms, sugerindo siderose hepática em 92,1% pacientes. A média do T2* cardíaco foi de 24,96 ± 14,17 ms e 36% dos pacientes apresentavam siderose cardíaca (T2* < 20ms), dos quais 19% (22/115) já apresentavam sobrecarga cardíaca grave (T2* < 10 ms). A média de T2* no pâncreas foi de 11,12 ± 11,20 ms, perfazendo um total de 83,5% de pacientes com sobrecarga de ferro pancreático (T2* < 21 ms). Houve correlação significativa, curvilínea e inversa entre T2* fígado e a concentração de ferro hepática (r = -0,878; p <0,001) e correlação moderada entre T2* pâncreas e T2* miocárdio (r = 0,546; p<0,0001). Conclusão: Uma elevada taxa de acometimento hepático, pancreático e cardíaco por sobrecarga férrica foi demonstrada. Os níveis de ferritina não puderam prever sobrecarga de ferro hepático, cardíaco ou pancreáticos medidos por meio da ressonância nuclear magnética T2*. Não houve correlação entre a sobrecarga de ferro no fígado, pâncreas e miocárdio, nem entre a ferritina e os níveis plasmáticos de ferro sérico e os valores de T2* no fígado, coração e pâncreas.
Subject(s)
Biopsy , Blood Transfusion , Iron Overload , Magnetic Resonance ImagingABSTRACT
Objective: To evaluate factors affecting peripheral blood hematopoietic stem cell yield in patients undergoing large-volume leukapheresis for autologous peripheral blood stem cell collection. Methods: Data from 304 consecutive autologous peripheral blood stem cell donors mobilized with hematopoietic growth factor (usually G-CSF), associated or not with chemotherapy, at Hospital Israelita Albert Einstein between February 1999 and June 2010 were retrospectively analyzed. The objective was to obtain at least 2 x 106 CD34+ cells/kg of body weight. Pre-mobilization factors analyzed included patient?s age, gender and diagnosis. Post mobilization parameters evaluated were pre-apheresis peripheral white blood cell count, immature circulating cell count, mononuclear cell count, peripheral blood CD34+ cell count, platelet count, and hemoglobin level. The effect of pre and post-mobilization factors on hematopoietic stem cell collection yield was investigated using logistic regression analysis (univariate and multivariate approaches). Results: Premobilization factors correlating to poor CD34+ cell yield in univariate analysis were acute myeloid leukemia (p = 0.017) and other hematological diseases (p = 0.023). Significant post-mobilization factors included peripheral blood immature circulating cells (p = 0.001), granulocytes (p = 0.002), hemoglobin level (p = 0.016), and CD34+ cell concentration (p < 0.001) in the first harvesting day. However, according to multivariate analysis, peripheral blood CD34+ cell content (p < 0.001) was the only independentfactor that significantly correlated to poor hematopoietic stem cell yield. Conclusion: In this study, peripheral blood CD34+ cell concentration was the only factor significantly correlated to yield in patients submitted to for autologous collection.
Objetivo: Avaliar fatores que afetam o rendimento da coleta em pacientes submetidos à leucaférese de grande volume para obtenção de células-tronco hematopoiéticas do sangue periférico para autotransplante. Métodos: Análise retrospectiva de 304 doadores de células-tronco hematopoiéticas de sangue periférico para autotransplante submetidos à mobilização com fator de crescimento hematopoiético (geralmente G-CSF), associado ou não à quimioterapia, no Hospital Israelita Albert Einstein de Fevereiro de 1999 a Junho de 2010. O objetivo da coleta foi obter pelo menos 2x106 CD34+ células/kg peso. Os fatores pré-mobilização incluíam idade, sexo e diagnóstico do paciente. Os parâmetros pós-mobilização avaliados foram contagem de leucócitos, células imaturas, células mononucleares e células CD34+, plaquetas e nível de hemoglobina no sangue periférico. O efeito desses fatores no rendimento da coleta de CTH foi investigado por meio de regressão logística (análise univariada e multivariada). Resultados: A análise univariada revelou os seguintes fatores pré-mobilização estatisticamente significantes: diagnóstico de leucemia mieloide aguda (p = 0,017) e outras doenças hematológicas (p = 0,023), células imaturas circulantes (p = 0,001), granulócitos (p = 0,002), nível de hemoglobina (p = 0,016) e contagem de células CD34+ (p <0,001) no primeiro dia de coleta. Entretanto, só a contagem de células CD34+ no sangue periférico manteve-se associada de forma significante ao rendimento ruim da coleta de células-tronco hematopoiéticas na análise multivariada. Conclusão: Neste estudo, a contagem de células CD34+ no sangue periférico foi o único fator significantemente associado ao rendimento da coleta de células-tronco hematopoiéticas com leucaférese de grande volume para autotransplante.
Subject(s)
Humans , Male , Female , Blood Specimen Collection , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cells , Leukapheresis , Transplantation, AutologousABSTRACT
Mesenchymal stem cells represent an adult population of nonhematopoietic cells, which can differentiate into a variety of cell types such as osteocytes, chondrocytes, adipocytes, and myocytes. They display immunomodulatory properties that have led to the consideration of their use for the inhibition of immune responses. In this context, mesenchymal stem cells efficiently inhibit maturation, cytokine production, and the T cell stimulatory capacity of dendritic cells. They also can impair proliferation, cytokine secretion, and cytotoxic potential of T lymphocytes. Moreover, mesenchymal stem cells are able to inhibit the differentiation of B cells to plasma cells by inhibiting their capacity to produce antibodies. A variety of animal models confirm the immunomodulatory properties of mesenchymal stem cells. Clinical studies including patients with severe acute graft-versus-host disease have revealed that the administration of mesenchymal stem cells results in significant clinical responses. Therefore, mesenchymal stem cells improve acute graft-versus-host disease and represent a promising candidate for the prevention and treatment of immune-mediated diseases, due to their immunomodulatory capability and their low immunogenicity.
As células-tronco mesenquimais são uma população adulta de células não hematopoiéticas, que podem se diferenciar em uma variedade de tipos celulares, como osteócitos, condrócitos, adipócitos e miócitos. Apresentam propriedades imunomoduladoras, que levaram a considerar seu uso para inibir as respostas imunes. Nesse contexto, as células-tronco mesenquimais inibem com eficiência a maturação, a produção de citocinas, e a capacidade de estimular as células T das células dendríticas. Podem também impedir a proliferação, secreção de citocina e o potencial citotóxicodos linfócitos T. Além disso, as células-tronco mesenquimais são capazes de inibir a diferenciação de células B em plasmócitos ao inibir sua capacidade de produzir anticorpos. Uma variedade de modelos animais confirma as propriedades imunomoduladoras das células-tronco mesenquimais. Alguns estudos clínicos que incluíram pacientes com doença do enxerto contra hospedeiro mostraram que a administração de células-tronco mesenquimais resultou em respostas clínicas significativas. Portanto, as célulastronco mesenquimais parecem melhorar a doença do enxerto contra hospedeiro e são candidatas promissoras na prevenção e tratamento de doenças imunomediadas devido à sua capacidade imunomoduladora à baixa imunogenicidade.
Subject(s)
Immunologic Factors , Mesenchymal Stem CellsABSTRACT
Objective: To analyze the outcome of patients treated with gemtuzumab ozogamycin combined with conventional therapy treated at Hospital Israelita Albert Einstein. Methods: 14 patients who had high risk features (secondary leukemia, unfavorable cytogenetics, and refractory disease) were treated with gemtuzumab ozogamycincombined with conventional therapy and their outcome was analysed by reviewing their medical records. Results: Overall response rate was 58%, with 43% achieving complete response, with a median followup of 11 months, event-free survival was 3 months. Eleven patients died, 6 of them due to refractory acute myeloid leukemia. Only four patients presented with grade 3 to 4 toxicities and only one patient had sinusoidal obstruction syndrome after bone marrow transplant. Conclusion: gemtuzumab ozogamycin combined with chemotherapy is a feasible treatment regimen in acute myeloid leukemia patients. However, further studies are necessary to clarify which subgroup of patients may benefit from this treatment.
Objetivo: Analisar a evolução de pacientes tratados com gemtuzumabe ozogamicina combinado à terapêutica convencional no Hospital Israelita Albert Einstein. Métodos: 14 pacientes que tinham alto risco (leucemia secundária, citogenética desfavorávele doença refratária) foram tratados com gentuzumabe ozogamicina associado à terapêutica convencional, e sua evolução foi analisada por meio de seus prontuários médicos. Resultados: A taxa total de resposta foi de 58%, com 43% chegando a resposta completa, em acompanhamento médio de 11 meses, e três meses com intervalo de sobrevivência livre. Foram a óbito 11 pacientes, 6 deles por leucemia mieloide aguda. Somente quatro pacientes apresentaram graus 3 a 4 de toxicidade e apenas um paciente teve síndrome de obstrução sinusoidal após transplante de medula. Conclusão: Gemtuzumabe ozogamicina associado à terapêutica quimioterápica convencional éum tratamento factível em pacientes com leucemia mieloide aguda. Contudo, novos estudos são necessários para esclarecer qual o subgrupo de pacientes que pode se beneficiar desse tratamento.
Subject(s)
Humans , Male , Female , Aged , Antineoplastic Agents/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , RadiotherapyABSTRACT
Mesenchymal stem cells represent an adult population of nonhematopoietic cells, which can differentiate into a variety of cell types such as osteocytes, chondrocytes, adipocytes, and myocytes. They display immunomodulatory properties that have led to the consideration of their use for the inhibition of immune responses. In this context, mesenchymal stem cells efficiently inhibit maturation, cytokine production, and the T cell stimulatory capacity of dendritic cells. They also can impair proliferation, cytokine secretion, and cytotoxic potential of T lymphocytes. Moreover, mesenchymal stem cells are able to inhibit the differentiation of B cells to plasma cells by inhibiting their capacity to produce antibodies. A variety of animal models confirm the immunomodulatory properties of mesenchymal stem cells. Clinical studies including patients with severe acute graft-versus-host disease have revealed that the administration of mesenchymal stem cells results in significant clinical responses. Therefore, mesenchymal stem cells improve acute graft-versus-host disease and represent a promising candidate for the prevention and treatment of immune-mediated diseases, due to their immunomodulatory capability and their low immunogenicity.
As células-tronco mesenquimais são uma população adulta de células não hematopoiéticas, que podem se diferenciar em uma variedade de tipos celulares, como osteócitos, condrócitos, adipócitos e miócitos. Apresentam propriedades imunomoduladoras, que levaram a considerar seu uso para inibir as respostas imunes. Nesse contexto, as células-tronco mesenquimais inibem com eficiência a maturação, a produção de citocinas, e a capacidade de estimular as células T das células dendríticas. Podem também impedir a proliferação, secreção de citocina e o potencial citotóxico dos linfócitos T. Além disso, as células-tronco mesenquimais são capazes de inibir a diferenciação de células B em plasmócitos ao inibir sua capacidade de produzir anticorpos. Uma variedade de modelos animais confirma as propriedades imunomoduladoras das células-tronco mesenquimais. Alguns estudos clínicos que incluíram pacientes com doença do enxerto contra hospedeiro mostraram que a administração de células-tronco mesenquimais resultou em respostas clínicas significativas. Portanto, as célulastronco mesenquimais parecem melhorar a doença do enxerto contra hospedeiro e são candidatas promissoras na prevenção e tratamento de doenças imunomediadas devido à sua capacidade imunomoduladora à baixa imunogenicidade.
ABSTRACT
A amiloidose é uma síndrome caracterizada pela deposição no meio extracelular de material protéico altamente insolúvel e que pode afetar vários órgãos. Pode ocorrer como doença generalizada e pode ser idiopática (amiloidose primária). Descrevemos o caso de mulher de 48 anos com neuropatia axonal associada a proteinúria na qual a investigação final resultou no diagnóstico de amiloidose primária (AL). Foi submetida a transplante autólogo de medula óssea sem complicações. Discutiremos aspectos relacionados ao diagnóstico da neuropatia e do tratamento atual da AL.
Subject(s)
Humans , Female , Middle Aged , Amyloid Neuropathies/diagnosis , Amyloid Neuropathies/surgery , Amyloidosis/diagnosis , Amyloidosis/surgery , Bone Marrow Transplantation , Amyloid Neuropathies/pathology , Amyloidosis/pathology , Diagnosis, DifferentialABSTRACT
Células mononucleares de sangue de cordão umbilical (SCU) e sangue periférico mobilizado (SPM) com G-CSF, foram cultivadas in vitro com citocinas, na presença ou não de estroma de medula óssea. Os objetivos foram avaliar a capacidade proliferativa de células progenitoras, a ocorrência de apoptose e expressão de integrina. Nas culturas sem estroma, a celularidade aumentou 5 vezes (SCU) e não se alterou nas de SPM. O total de células CD34+ caiu em ambas culturas. Com estroma, o total de células nucleadas aumentou 7 vezes (SCU) e 2,3 vezes (SPM). O total de células CD34+ permaneceu o mesmo. A apoptose foi menor nas culturas de SCU. A expressão de integrina caiu, na população de células CD34+ e de CD45+ / Mononuclear cells from umbilical cord blood (UCB) and G-CSF mobilized peripheral blood (MPB), were cultured in vitro, in the presence of cytokines, with or without bone marrow stroma. The aims were to evaluate the proliferative response of progenitor cells, occurrence of apoptosis and expression of adhesion molecule. In cultures without stroma, cellularity increased 5-fold for UCB, but has not changed for MPB. The number of CD34+ cells has dropped in both culture. With stroma, total nucleated cells had a 7-fold increse (UCB) and a 2,3-fold (MBP), however, CD34+ cells number has not changed. Apoptosis was lower in UCB culture. The expression of integrin decreased, in the...
Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , Apoptosis/physiology , Umbilical Cord/transplantation , Leukocytes, Mononuclear/immunology , Stromal Cells/physiology , Cytokines/agonists , Cell Division/immunology , Hematopoietic Cell Growth Factors/agonists , Cell Adhesion Molecules/bloodABSTRACT
Os autores estudaram a autotransfusäo intra-operatória em artroplastias totais de joelho, unilaterais, cimentadas, primárias. Os pacientes foram divididos em dois grupos. No primeiro grupo foram selecionados os pacientes que receberam sangue autólogo de pré-depósito e utilizaram o sistema de salvamento sanguíneo. O grupo-controle foi composto de 16 pacientes tratados com sangue homólogo. Concluem que o uso de sangue autólogo pré-depositado e salvamento sanguíneo intra-operatório é útil para diminuir a necessidade de transfusäo de sangue homólogo. Com relaçäo ao custo, o salvamento sanguíneo intra-operatório só é efetivo quando ocorre o salvamento de 2,5 unidades de sangue. Os componentes do sangue salvado säo semelhantes aos do sangue obtido em veia periférica.