RESUMO
Idecabtagene vicleucel (ide-cel), a chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real-world registry-based multicentre observational study in 11 French hospitals to evaluate ide-cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR-T registry. Of these, 159 patients (90%) received ide-cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression-free survival (PFS) from the ide-cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra-medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA-targeted immunoconjugate or T-cell-redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide-cel's feasibility, safety and efficacy in real-life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection.
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BACKGROUND: Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection. METHODS: We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy. RESULTS: Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II-IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II-IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29). CONCLUSION: The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.
Assuntos
Cistite/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Idoso , Doença Enxerto-Hospedeiro/prevenção & controle , Haplótipos , Hemorragia , Humanos , Imunossupressores/farmacologia , Incidência , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
The potentially important role of northern microrefugia during postglacial dispersal is challenging the view of southern Europe as a refuge and source area of European biota. In groundwaters, large geographic ranges of presumably good dispersers are increasingly suspected to consist of assemblages of cryptic species with narrow ranges. Moreover, a large species range, even when confirmed by molecular evidence, tells us little about the spatiotemporal dynamics of dispersal. Here, we used phylogenetic inferences, species delineation methods and Bayesian phylogeographic diffusion models to test for the likelihood of postglacial colonization from distant refugia among five morphospecies of Proasellus (Isopoda, Asellidae). All morphospecies except one were monophyletic, but they comprised a total of 15-17 cryptic species. Three cryptic species retained ranges that spanned a distance >650 km, similar to that of the nominal morphospecies. Bayesian diffusion models based on mitochondrial markers revealed considerable spatiotemporal heterogeneity in dispersal rates, suggesting that short-time dispersal windows were instrumental in shaping species ranges. Only one species was found to experience a recent, presumably postglacial, range expansion. The Jura and Alpine foothills probably played a major role in maintaining diversity within Proasellus in northern regions by acting both as diversification hotspots and Pleistocene refugia. Gaining insight into the spatiotemporal heterogeneity of dispersal rates revealed contrasting colonization dynamics among species that were not consistent with a global postglacial colonization of Europe from distant refugia.
Assuntos
Evolução Molecular , Isópodes/genética , Filogenia , Animais , Teorema de Bayes , DNA Mitocondrial/genética , Ecossistema , Europa (Continente) , Genética Populacional , Água Subterrânea , Modelos Genéticos , Dados de Sequência Molecular , Filogeografia , Análise de Sequência de DNARESUMO
The climate variability hypothesis assumes that the thermal tolerance breadth of a species is primarily determined by temperature variations experienced in its environment. If so, aquatic invertebrates living in thermally buffered environments would be expected to exhibit narrow thermal tolerance breadths (stenothermy). We tested this prediction by studying the thermal physiology of three isopods (Asellidae, Proasellus) colonizing groundwater habitats characterized by an annual temperature amplitude of less than 1°C. The species responses to temperature variation were assessed in the laboratory using five physiological variables: survival, locomotor activity, aerobic respiration, immune defense and concentrations of total free amino acids and sugars. The three species exhibited contrasted thermal physiologies, although all variables were not equally informative. In accordance with the climate variability hypothesis, two species were extremely sensitive even to moderate changes in temperature (2°C) below and above their habitat temperature. In contrast, the third species exhibited a surprisingly high thermal tolerance breadth (11°C). Differences in response to temperature variation among Proasellus species indicated that their thermal physiology was not solely shaped by the current temperature seasonality in their natural habitats. More particularly, recent gene flow among populations living in thermally constant yet contrasted habitats might explain the occurrence of eurytherm species in thermally buffered environments.
Assuntos
Adaptação Fisiológica , Crustáceos/fisiologia , Ecossistema , Água Subterrânea , Temperatura , Aminoácidos/metabolismo , Animais , Metabolismo dos Carboidratos , Crustáceos/imunologia , França , Locomoção/fisiologia , Monofenol Mono-Oxigenase/metabolismo , Consumo de Oxigênio/fisiologia , Análise de Componente Principal , Análise de SobrevidaRESUMO
Nowadays, stormwater infiltration systems are frequently used because of their ability to reduce flows and volumes in downstream sewers, decrease overflows in surface waters and make it possible to recharge groundwater. Moreover, they come in various forms with different uses. Despite these advantages the long term sustainability of these systems is questionable and their real performances have to be assessed taking into account various and sometimes conflicting aspects. To address this problem a decision support system is proposed. It is based on a multicriteria method built to help managers to evaluate the performance of an existing infiltration system at different stages of its lifespan and identify whether it performs correctly or not, according to environmental, socio-economic, technical and sanitary aspects. The paper presents successively: the performance indicators and the way they were built, the multicriteria method to identify if the system works properly and a case study.
Assuntos
Conservação dos Recursos Naturais , Técnicas de Apoio para a Decisão , Drenagem Sanitária/normas , Filtração/normas , Inundações , Modelos Teóricos , Drenagem Sanitária/economia , Drenagem Sanitária/métodos , Filtração/economia , Filtração/métodos , França , Fatores de Tempo , Urbanização , Movimentos da ÁguaRESUMO
Biomarkers are increasingly used for diagnosis and treatment of transplant-related complications including the first biomarker-driven interventional trials of acute graft-versus-host disease (GvHD). In contrast, the development of biomarkers of chronic GvHD (cGvHD) has lagged behind due to a broader variety of manifestations, overlap with acute GvHD, a greater variation in time to onset and maximum severity, and lack of sufficient patient numbers within prospective trials. An international workshop organized by a North-American and European consortium was held in Marseille in March 2017 with the goal to discuss strategies for future biomarker development to guide cGvHD therapy. As a result of this meeting, two areas were prioritized: the development of prognostic biomarkers for subsequent onset of moderate/severe cGvHD, and in parallel, the development of qualified clinical-grade assays for biomarker quantification. The most promising prognostic serum biomarkers are CXCL9, ST2, matrix metalloproteinase-3, osteopontin, CXCL10, CXCL11, and CD163. Urine-proteomics and cellular subsets (CD4+ T-cell subsets, NK cell subsets, and CD19+CD21low B cells) represent additional potential prognostic biomarkers of cGvHD. A joint effort is required to verify the results of numerous exploratory trials before any of the potential candidates is ready for validation and subsequent clinical application.
Assuntos
Biomarcadores/metabolismo , Doença Enxerto-Hospedeiro/diagnóstico , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , PrognósticoRESUMO
Over the past decade, significant advances have been made in the field of multiple myeloma. Introduction of the so-called novel agents, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care have resulted in significantly better outcome. Standard first line treatment in fit patients include PI and IMiD based induction, high dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) and consolidation/maintenance. However, despite these progresses MM remains incurable for the majority of patients and most patients will relapse. Next generation PI (carfilzomib, ixazomib) and IMiD (pomalidomide) and new therapeutic classes: monoclonal antibody (elotuzumab, daratumumab) and pan-deacetylase inhibitors (panobinostat) have been successfully evaluated in relapse multiple myeloma. Some of these new agents are now approved for multiple myeloma treatment at relapse. However choosing the most appropriate treatment at relapse may be difficult. This review sum up the most important studies and provide evidence to choose the most relevant therapeutic strategy for relapse after ASCT, based on disease, patient and previous treatment related parameters.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/terapia , Transplante de Células-Tronco/métodos , Ensaios Clínicos Fase III como Assunto , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Medicina de Precisão/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante AutólogoRESUMO
Transplant-eligible patients with multiple myeloma (MM) now have extended survival after diagnosis owing to effective modern treatment strategies that include new agents in induction therapy, autologous stem cell transplant (ASCT), consolidation therapy and posttransplant maintenance therapy. Standard of care for newly diagnosed, fit patients includes ASCT and, often nowadays, posttransplant maintenance. Several large studies have shown the efficacy of maintenance with thalidomide, lenalidomide and bortezomib in the treatment scheme of MM with regards to prolonging progression-free survival and, to a lesser degree, overall survival. Herein we discuss the data currently available to support the use of maintenance therapy in patients after ASCT as well as the newer available agents that may be a part of its changing landscape in the years to come.
Assuntos
Mieloma Múltiplo/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Bortezomib/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Lenalidomida , Quimioterapia de Manutenção , Terapia de Alvo Molecular , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Cuidados Pós-Operatórios , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Transplante Autólogo , Resultado do TratamentoRESUMO
Allogeneic stem cell transplantation (allo-SCT) is a curative therapy for different life-threatening malignant and non-malignant hematologic disorders. Acute graft-vs.-host disease (aGVHD) and particularly gastrointestinal aGVHD remains a major source of morbidity and mortality following allo-SCT, which limits the use of this treatment in a broader spectrum of patients. Better understanding of aGVHD pathophysiology is indispensable to identify new therapeutic targets for aGVHD prevention and therapy. Growing amount of data suggest a role for T helper (Th)17 cells in aGVHD pathophysiology. In this review, we will discuss the current knowledge in this area in animal models and in humans. We will then describe new potential treatments for aGVHD along the Th17 axis.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Trato Gastrointestinal/efeitos dos fármacos , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Células Th17/efeitos dos fármacos , Doença Aguda , Animais , Ensaios Clínicos como Assunto , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Citocinas/imunologia , Modelos Animais de Doenças , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/patologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doenças Hematológicas/imunologia , Doenças Hematológicas/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Camundongos , Terapia de Alvo Molecular , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Células Th17/imunologia , Células Th17/patologia , Transplante HomólogoRESUMO
Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation, limiting the success of this therapy. We previously reported that interleukin-22 (IL-22) participates to aGVHD development, but the underlying mechanisms of its contribution remain poorly understood. In this study, we analyzed the mechanism of the pathological function of IL-22 in intestinal aGVHD. Ex-vivo colon culture experiments indicated that IL-22 was able to induce Th1-like inflammation via signal transducer and activator of transcription factor-1 (STAT1) and CXCL10 induction in the presence of type I interferon (IFN). To evaluate a potential synergy between IL-22 and type I IFN in aGVHD, we transplanted recipient mice, either wild-type (WT) or type I IFN receptor deficient (IFNAR(-/-)), with bone marrow cells and WT or IL-22 deficient (IL-22(-/-)) T cells. We observed a decreased GVHD severity in IFNAR(-/-) recipient of IL-22(-/-) T cells, which was associated with a lower level of STAT1 activation and reduced CXCL10 expression in the large intestine. Finally, immunohistochemistry staining of STAT1 performed on gastrointestinal biopsies of 20 transplanted patients showed exacerbated STAT1 activation in gastrointestinal tissues of patients with aGVHD as compared with those without aGVHD. Thus, interfering with both IL-22 and type I IFN signaling may provide a novel approach to limit aGVHD.
Assuntos
Transplante de Medula Óssea , Quimiocina CXCL10/imunologia , Doença Enxerto-Hospedeiro/imunologia , Interferon Tipo I/imunologia , Interleucinas/imunologia , Intestino Grosso/imunologia , Fator de Transcrição STAT1/imunologia , Animais , Medula Óssea/imunologia , Medula Óssea/patologia , Quimiocina CXCL10/genética , Regulação da Expressão Gênica , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Interferon Tipo I/genética , Interleucinas/deficiência , Interleucinas/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Intestino Grosso/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Interferon alfa e beta/deficiência , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/imunologia , Fator de Transcrição STAT1/genética , Transdução de Sinais , Células Th1/imunologia , Células Th1/patologia , Doadores de Tecidos , Transplante Homólogo , Irradiação Corporal Total , Interleucina 22RESUMO
Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico , Adulto , Biomarcadores , Diagnóstico Precoce , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
In urban area, management of stormwater leads to the accumulation of polluted sediments at the water-sediment interface of various aquatic ecosystems. In many cases, these sediments are colonised by dense populations of tubificid worms. However, the influence of tubificid worms on the fate of stormwater sediments has never been tackled. The aim of this study was to measure in sediment columns the influence of tubificid worms on sediment reworking, organic matter processing (O(2) uptake and release of NH(4)(+), NO(3)(-), PO(4)(3-), and dissolved organic carbon), release of hydrocarbons and heavy metals, and microbial characteristics. Results showed that tubificid worms increased the release of NH(4)(+), PO(4)(3-), and dissolved organic carbon by 2-, 4-, and 3-fold, respectively. O(2) uptake also increased by more than 35% due to tubificid activity. The increase in the percentages of active bacteria and hydrolytic activity in the presence of worms indicated that the higher sediment respiration was caused by the stimulation of microbial communities. A reduction of the number of sulphate-reducing bacteria in the uppermost layers of the sediment was attributed to the penetration of O(2) due to worm activity. These significant effects of tubificid worms were probably linked to the dense network of burrows, which enhanced the exchange surface between the water column and the sediment. No release of heavy metals and hydrocarbons to the water phase was detected in the sediment columns. Understanding the fate and effect of organic stormwater sediments in the natural environment requires the integration of the role of bioturbation in urban pollution studies.
Assuntos
Helmintos , Poluição da Água , Tempo (Meteorologia) , Animais , Biodegradação Ambiental , Cidades , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Helmintos/metabolismo , Microbiologia da ÁguaRESUMO
Acute myeloid leukemia (AML) with 11q23/MLL rearrangement (MLL-r AML) is allocated to the intermediate- or high-risk cytogenetic prognostic category depending on the MLL fusion partner. A more favorable outcome has been reported in patients receiving an allogeneic hematopoietic stem-cell transplantation (alloHSCT), but this has not been confirmed in large series. We analyzed the outcome of alloHSCT among adult patients reported to the Acute Leukemia Working Party between 2000 and 2010. We identified 159 patients with 11q23/MLL rearranged AML allografted in first complete remission (CR1, n=138) or CR2, mostly corresponding to t(9;11), t(11;19), t(6;11) and t(10;11) translocations. Two-year overall survival (OS), leukemia-free survival (LFS), relapse incidence and non-relapse mortality were 56±4%, 51±4%, 31±3% and 17±4%, respectively. The outcome differed according to 11q23/MLL rearrangement, being more favorable in patients with t(9;11) and t(11;19) compared with t(10;11) and t(6;11) (2-year OS: 64±6% and 73±10% vs 40±13% and 24±11%, respectively; P<0.0001). Multivariate analysis for OS identified t(6;11), t(10;11), age>40 years and CR2 as unfavorable features, whereas t(6;11), t(10;11), CR2 and the use of reduced-intensity conditioning regimen affected poorly the LFS. This study confirms the potential role of alloHSCT for adult patients with 11q23/MLL rearranged AML in CR1.
Assuntos
Rearranjo Gênico , Transplante de Células-Tronco Hematopoéticas , Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/terapia , Proteína de Leucina Linfoide-Mieloide/genética , Adulto , Idoso , Aberrações Cromossômicas , Cromossomos Humanos Par 11 , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Transplante Homólogo , Resultado do TratamentoRESUMO
Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Complicações Pós-Operatórias , Doenças Vasculares , Adulto , Biomarcadores/sangue , Humanos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Fatores de Risco , Doenças Vasculares/sangue , Doenças Vasculares/diagnóstico , Doenças Vasculares/etiologia , Doenças Vasculares/fisiopatologia , Doenças Vasculares/terapiaRESUMO
Artificial recharge of urban aquifers with stormwater has been used extensively in urban areas to dispose of stormwater and compensate for reduced groundwater recharge. However, stormwater-derived sediments accumulating in infiltration beds may act as a source of dissolved contaminants for groundwater. Concentrations of hydrocarbons, heavy metals, nutrients and dissolved oxygen (DO) were monitored at multiple depths in shallow groundwater below a stormwater infiltration basin retaining large amounts of contaminated organic sediments. Multilevel wells and multiparameter loggers were used to examine changes in groundwater chemistry occurring over small spatial and temporal scales. Rainfall events produced a plume of low-salinity stormwater in the first 2 m below the groundwater table, thereby generating steep vertical physico-chemical gradients that resorbed during dry weather. Heavy metals and hydrocarbons were below reference concentrations in groundwater and aquifer sediments, indicating that they remained adsorbed onto the bed sediments. However, mineralization of organic sediments was the most probable cause of elevated concentrations of phosphate and DOC in groundwater. DO supply in groundwater was severely limited by bed respiration which increased with temperature. Cold winter stormwater slightly re-oxygenated groundwater, whereas warm summer stormwater lowered DO concentrations in groundwater. Among several results provided by this study, it is recommended for management purposes that infiltration practices should minimize the contact between inflow stormwater and organic sediments retained in infiltration basins.
RESUMO
Lung function decline is a well-recognized complication following allogeneic SCT (allo-SCT). Reduced-intensity conditioning (RIC) and in vivo T-cell depletion by administration of antithymocyte globulin (ATG) may have a protective role in the occurrence of late pulmonary complications. This retrospective study reported the evolution of lung function parameters within the first 2 years after allo-SCT in a population receiving the same RIC regimen that included fludarabine and i.v. BU in combination with low-dose ATG. The median follow-up was 35.2 months. With a median age of 59 years at the time of transplant, at 2 years, the cumulative incidences of non-relapse mortality was as low as 9.7%. The cumulative incidence of relapse was 33%. At 2 years, the cumulative incidences of extensive chronic GVHD (cGVHD) and of pulmonary cGVHD were 23.1% and 1.9%, respectively. The cumulative incidences of airflow obstruction and restrictive pattern were 3.8% and 9.6%, respectively. Moreover, forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio remained stable from baseline up to 2 years post transplantation (P=0.26, P=0.27 and P=0.07, respectively). These results correspond favorably with the results obtained with other RIC regimens not incorporating ATG, and suggest that ATG may have a protective pulmonary role after allo-SCT.
Assuntos
Doenças Hematológicas/terapia , Pneumopatias/prevenção & controle , Depleção Linfocítica/métodos , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos , Administração Intravenosa , Adulto , Idoso , Soro Antilinfocitário/administração & dosagem , Bussulfano/administração & dosagem , Feminino , Seguimentos , Doenças Hematológicas/mortalidade , Humanos , Imunossupressores/administração & dosagem , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/administração & dosagem , Testes de Função Respiratória , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto JovemAssuntos
Aloenxertos/fisiopatologia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/fisiologia , Reoperação/métodos , Adulto , Idoso , Antígenos CD34/análise , Antígenos CD34/metabolismo , Estudos de Coortes , Função Retardada do Enxerto/fisiopatologia , Função Retardada do Enxerto/terapia , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Células-Tronco Hematopoéticas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Adulto JovemRESUMO
The contribution of Th17 cells to chronic GVHD (cGVHD) has been demonstrated in cGVHD mouse models. However, their contribution to human liver cGVHD remains unclear. We evaluated Th17 cells in biopsies from a cohort of 17 patients with liver cGVHD. We observed a significant increase in Th17 cells in the liver of patients with cGVHD, as demonstrated by an increase in CCR6+, CD161+ and RORγt+ T cells (P=0.03, P=0.0001 and P=0.03, respectively). We also assessed the presence of Th1 and regulatory (Treg) T cells: the numbers of Th1 and Treg cells were very low, with no difference between the two groups (P=0.88 and P=0.12, respectively). Furthermore, Th17/Th1 and Th17/Treg ratios were significantly increased in the liver of patients with liver cGVHD (P=0.005 and P=0.002, respectively). This study provides evidence for an infiltration by Th17 cells in the liver of patients with cGVHD and an increased Th17/Treg ratio, suggesting a defect in the regulatory mechanism driven by Treg cells or an inappropriate activation of effectors cells, especially Th17 cells, or both mechanisms, in human liver cGVHD.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Hepatopatias/imunologia , Linfócitos T Reguladores/patologia , Células Th17/patologia , Adulto , Idoso , Animais , Biópsia , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Hepatopatias/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Células Th17/imunologiaRESUMO
This prospective pilot study aimed to evaluate the predictive value of (18)F-FDG PET/CT for early diagnosis of acute gastrointestinal GVHD (GI-GVHD). In all, 42 consecutive patients who received allo-SCT were included. (18)F-FDG PET/CT was systematically performed at a median of 28 (range, 24-38) days after allo-SCT. (18)F-FDG PET/CT data review was positive in 15 cases (36%) (9 true positive (TP) cases and 6 false positive (FP) cases) and negative in 27 cases (64%; 26 true negative (TN) cases and 1 false negative (FN) case) at visual analysis. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (18)F-FDG PET/CT for the diagnosis of acute GI-GVHD were, respectively, 81%, 90%, 60%, 96% and 83%. There were no significant differences of SUVmax values between grade 1-2 GI-GVHD and severe grade 3-4 GI-GVHD. Overall, these preliminary findings suggested that the inflammatory activity of the gastrointestinal tract associated with acute GI-GVHD could be assessed by (18)F-FDG PET/CT suggesting that noninvasive (18)F-FDG PET/CT could become a valuable examination to be performed shortly before endoscopy to map acute GI-GVHD lesions, guide the biopsy sites and choose the appropriate endoscopic procedure, especially in those asymptomatic patients with a positive (18)F-FDG PET/CT.