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BACKGROUND: Human metapneumovirus (hMPV) epidemiology, clinical characteristics and risk factors for poor outcome after allogeneic stem cell transplantation (allo-HCT) remain a poorly investigated area. METHODS: This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allo-HCT. RESULTS: We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. CONCLUSIONS: These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases.
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Transplante de Células-Tronco Hematopoéticas , Linfopenia , Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Adulto , Humanos , Estudos de Coortes , Estudos Retrospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Infecções Respiratórias/tratamento farmacológico , Infecções por Paramyxoviridae/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Corticosteroides/uso terapêuticoRESUMO
BACKGROUND: We investigated whether donor-recipient mismatch involving one or more cytomegalovirus (CMV) immunodominant (ID) human leukocyte antigen (HLA)-I alleles may impact on the degree of CMV pp65/immediate-early 1 (IE-1) T-cell reconstitution and the incidence of CMV DNAemia in patients undergoing unmanipulated haploidentical hematopoietic stem cell transplantation with high-dose posttransplant cyclophosphamide (PT/Cy-haplo). METHODS: Multicenter observational study including 106 consecutive adult PT/Cy-haplo patients (34 CMV ID HLA-I matched and 72 mismatched). A real-time PCR was used for plasma CMV DNA load monitoring. Enumeration of CMV-specific (pp65/IE-1) interferon (IFN)-γ-producing T cells from several patients was performed by flow cytometry by days +30, +60, +90 and +180 after transplantation. RESULTS: The cumulative incidence of CMV DNAemia, clinically significant CMV DNAemia episodes (cs-CMVi), and recurrent CMV DNAemia was comparable across CMV ID HLA-I matched and mismatched patients (71.8% vs. 80.9%, p = .95; 40.7% vs. 44.2%, p = .85; 16.4% vs. 28.1%; p = .43, respectively). The percentage of patients exhibiting detectable CMV-specific IFN-γ-producing T-cell responses (either CD8+ or CD4+ ) was similar across groups; nevertheless, significantly higher CMV-specific CD8+ T-cell counts were enumerated in the CMV ID HLA-I matched compared to mismatched patients by day +60 (p = .04) and +180 (p = .016) after transplantation. CONCLUSION: CMV ID HLA-I matching may impact on the magnitude of CMV-pp65/IE-1-specific CD8+ T-cell reconstitution; yet, this effect seemed not to have an impact on the incidence of initial, recurrent CMV DNAemia, or cs-CMVi.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Adulto , Humanos , Citomegalovirus , Incidência , Transplante Homólogo , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
BACKGROUND: It has been suggested that patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) have more psycho-emotional disorders than patients with obstructive coronary artery disease (MICAD). The aim of this study is to compare the prevalence of anxiety, insomnia, and type D personality between MINOCA and MICAD and their impact on prognosis. METHODS: Patients with myocardial infarction undergoing coronary angiography were prospectively enrolled. Psychological questionnaires were completed by each patient during admission. RESULTS: Among a total of 533 patients, 56 had MINOCA and 477 had MICAD. There were no differences in the prevalence of anxiety and insomnia between both groups: trait anxiety median value (M) MINOCA = 18 (11-34) vs. MICAD M = 19 (12-27), p = 0.8; state anxiety MINOCA M = 19 (11-29) vs. MICAD M = 19 (12.2-26), p = 0.6; and insomnia MINOCA M = 7 (3-11) vs. MICAD M = 7 (3-12), p = 0.95. More MINOCA patients had type D personality (45.0% vs. 28.5%, p = 0.03). At 3-year follow-up, there were no differences in mortality between MINOCA and MICAD (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.28-2.17) in major adverse cerebral or cardiovascular events (MACCE) (HR 0.71, 95% CI 0.38-1.31). Scores of trait anxiety and negative affectivity were significantly associated with MACCE (HR 1.65, 95% CI [1.05-2.57]; HR 1.75, 95% CI [1.11-2.77], respectively). High insomnia levels were associated with greater mortality (HR 2.72, 95% CI [1.12-6.61]). CONCLUSIONS: Anxiety and insomnia levels were similar between patients with MINOCA and those with MICAD, whilst the prevalence of type D personality was higher in the MINOCA than in the MICAD group. Higher scores in trait anxiety, insomnia, and negative affectivity were related to a worse prognosis at 3-year follow-up.
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Anti-CD19 chimeric antigen receptor T cells (CART) has rapidly been adopted as the standard third-line therapy to treat aggressive B-cell lymphomas (ABCL) after failure of second-line therapy despite the lack of direct comparisons with allogeneic hematopoietic cell transplantation (alloHCT)-based strategies. Using the Grupo Español de Trasplante y Terapia Celular (GETH-TC) registry, we selected patients with the following characteristics: CART or alloHCT performed between 2016 and 2021; ≥18 years old; ABCL diagnosis; ≥2 lines of therapy; and either anti-CD19 CART or alloHCT as therapy at relapse. The analysis included a total of 316 (CART = 215, alloHCT = 101) patients. Median follow-up was 15 and 36 months for the CART and alloHCT cohorts, respectively. In the multivariate analysis, CART was confirmed to be similar to alloHCT for the primary study endpoint (progression-free survival) (hazard ratio [HR] 0.92, CI95%:0.56-1.51, p = 0.75). Furthermore, when the analysis was limited to only patients with chemo-sensitive diseases (complete and partial response) at infusion (CART = 26, alloHCT=93), no differences were reported (progression-free survival at month +18: 65% versus 55%, p = 0.59). However, CART had lower non-relapse mortality (HR 0.34, 95% CI: 0.13-0.85, p = 0.02). Given the lower toxicity and similar survival outcomes, these results suggest the use of CART before alloHCT.
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Transplante de Células-Tronco Hematopoéticas , Linfoma de Células B , Humanos , Adolescente , Transplante de Células-Tronco Hematopoéticas/métodos , Recidiva , Linfoma de Células B/terapiaRESUMO
The kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] (p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.
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COVID-19 , Transplante de Células-Tronco Hematopoéticas , Receptores de Antígenos Quiméricos , Humanos , SARS-CoV-2 , Estudos de Coortes , Estudos Prospectivos , Transplante Autólogo , Anticorpos Antivirais , Vacinação , Infecções Irruptivas , Terapia Baseada em Transplante de Células e Tecidos , TransplantadosRESUMO
Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.
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Antineoplásicos , COVID-19 , Anticorpos Monoclonais , Anticorpos Antivirais , Vacina BNT162 , COVID-19/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Detecção Precoce de Câncer , Humanos , SARS-CoV-2 , VacinaçãoRESUMO
In this study, glass-ceramics based on Sr2MgSi2O7 phosphor co-doped with Eu/Dy were obtained from the sintering and crystallisation of glass powders. The glasses were melted in a gas furnace to simulate an industrial process, and the dopant concentration was varied to optimise the luminescence persistence times. The doped parent glasses showed red emission under UV light excitation due to the doping of Eu3+ ions, while the corresponding glass-ceramics showed persistent blue emission corresponding to the presence of Eu2+ in the crystalline environment. The dopant concentration had a strong impact on the sintering/crystallisation kinetics affecting the final glass-ceramic microstructure. The microstructures and morphology of the crystals responsible for the blue emission were observed by scanning electron microscopy-cathodoluminescence. The composition of the crystallised phases and the distribution of rare-earth (RE) ions in the crystals and in the residual glassy phase were determined by X-ray diffraction and energy dispersive X-ray analysis. The emission and persistence of phosphorescence were studied by photoluminescence.
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Aim: Whether Takotsubo syndrome (TTS) should be classified within myocardial infarction with non-obstructive coronary arteries (MINOCAs) is still controversial. The aim of this work was to evaluate the main differences between TTS and non-TTS MINOCAs. Methods and Results: A cohort study based on two prospective registries: TTS from the RETAKO registry (N:1,015) and patients with non-TTS MINOCAs from contemporary records of acute myocardial infarction from five 5 national centers (N:1,080). Definitions and management recommended by the ESC were used. Survival analysis was based on the Cox regression analysis; propensity score matching (PS) was created to adjust prognostic variables. Takotsubo syndrome were more often women (85.9 vs. 51.9%; p < 0.001) and older (69.4 ± 12.5 vs. 64.5 ± 14.1 years; p < 0.001). Atrial fibrillation (AF) was more frequent in non-TTS MINOCAs (10.4 vs. 14.4%; p = 0.007). Psychiatric disorders were more prevalent in TTS (15.5 vs. 10.2%, p < 0.001). In-hospital mortality and complications were higher in TTS: 3.4 vs. 1.8%, (p = 0.015), and 25.8 vs. 11.5%, (p < 0.001). Global mortality before PS matching was 16.1% in non-TTS MINOCAs and 8.1% in TTS. Median follow-up was 32.4 months; after PS matching, TTS had fewer major adverse cardiovascular events (MACEs): hazard ratio (HR) 0.59; 95% CI 0.42-0.83. There were no differences in global mortality (HR 0.87; CI: 0.64-1.19), but TTS had lower cardiovascular mortality (HR 0.58; CI: 0.35-0.98). Conclusion: Compared to the rest of MINOCAs, TTS presents a different patient profile and a more aggressive acute phase. However, its long-term cardiovascular prognosis is better. These results support that TTS should be considered a separate entity with unique characteristics and prognosis.
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This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3-6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109 /ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16-0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27-0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15-0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02-0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02-0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.
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Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/imunologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia , Adulto JovemRESUMO
BACKGROUND: A definition of myocardial infarction with non-obstructive coronary arteries (MINOCA) was published by European Society of Cardiology in 2016. The aim of this study is to analyze the clinical profile and prognosis of these patients in a prospective single-center study and compare it with the literature data. METHODS: During a 3-year period, information from every consecutive MINOCA patient was gathered (n = 109). It was then compared with 412 contemporaneous patients with myocardial infarction and obstructive coronary arteries (MIOCA). Univariate and multivariate analyses were performed. Prognosis analysis was adjusted by age and cardiovascular risk factors (CVRF). RESULTS: MINOCA represented 16.9% of the total of patients admitted for myocardial infarction (MI). Compared with MIOCA, they had more psychosocial disorders (22.9% vs. 10.7%; p < 0.01) and more pro-inflammatory conditions (34.9% vs. 14.0%; p < 0.01). Atrial fibrillation was twice as frequent in MINOCA (14.7% vs. 7.3%; p = 0.016). Predictors of MINOCA were as follows: female gender, absence of diabetes, absence of tobacco use, tachycardia, troponin above 10 times the 99th percentile, and proinflammatory conditions. Median follow-up was 17.3 ± 9.3 months. Major adverse cardiovascular events (MACE; a composite of a recurrence of acute MI, transient ischemic attack/stroke, or death from cardiovascular cause and death from any cause) occurred in 10.8% of the MINOCA group as compared with 10.7% in the MIOCA group (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.58-2.45; p = 0.645). Cardiovascular re-admission rates were higher in the MINOCA group: 19.8% vs. 13.9% (HR 1.85; CI 1.06-3.21; p = 0.030). CONCLUSIONS: The frequency of MINOCA is high, with fewer CVRF, and it is linked to atrial fibrillation, psychosocial disorders, and pro-inflammatory conditions. Mid-term prognosis is worse than previously thought, with a similar proportion of MACE as compared to MIOCA, and even a higher rate of cardiovascular re-admissions.
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Fibrilação Atrial , Doença da Artéria Coronariana , Infarto do Miocárdio , Angiografia Coronária/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Vasos Coronários , Feminino , Humanos , MINOCA , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , TroponinaRESUMO
Severe infections and their attributable mortality are major complications in recipients of allogeneic hematopoietic stem cell transplantation (alloSCT). We herein report 236 adult patients who received haploSCT with PTCy. The median follow-up for survivors was 37 months. The overall incidence of bloodstream infections by gram-positive and gram-negative bacteria at 37 months was 51% and 46%, respectively. The incidence of cytomegalovirus infection was 69%, while Epstein Barr virus infections occurred in 10% of patients and hemorrhagic cystitis in 35% of cases. Invasive fungal infections occurred in 11% at 17 months. The 3-year incidence of infection-related mortality was 19%. The median interval from transplant to IRM was 3 months (range 1-30), 53% of IRM occurred >100 days post-haploSCT. Risk factors for IRM included age >50 years, lymphoid malignancy, and developing grade III-IV acute GvHD. Bacterial infections were the most common causes of IRM (51%), mainly due to gram-negative bacilli BSI. In conclusion, severe infections are the most common causes of NRM after haploSCT with PTCy, with a reemergence of gram-negative bacilli as the most lethal pathogens. More studies focusing on the severe infections after haploSCT with PTCy and differences with other types of alloSCT in adults are clearly warranted.
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Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Antibacterianos/uso terapêutico , Ciclofosfamida , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4 , Humanos , Pessoa de Meia-Idade , Condicionamento Pré-TransplanteRESUMO
One hundred and sixty-one patients underwent haploidentical stem cell transplantation (haploSCT) with thiotepa, busulfan, and fludarabine conditioning followed by post-transplantation cyclophosphamide (PTCy) (on days +3 and +4) and tacrolimus as graft-versus-host disease prophylaxis. Forty-two percent of patients had a high or very high revised Disease Risk Index (rDRI), 55% had an European Society for Blood and Marrow Transplantation risk score (EBMT-RS) ≥4, and 36% had an age-adjusted Hematopoietic Cell Transplant Comorbidity Index (HCT-CI-age) score ≥3. Each of these was considered an unfavorable score. Using the pretransplantation unfavorable scores that had an independent impact on each transplantation outcome studied in multivariate analysis allowed for better stratification of patient outcomes. Thus, the 3-year overall survival (OS) in patients with 0, 1, 2, and 3 unfavorable scores was 86%, 56%, 36%, and 24%, respectively. Nonrelapse mortality (NRM) was negatively impacted by the EBMT-RS and the HCT-CI-age score (3-year NRM in patients with 0, 1, and 2 unfavorable scores was 12%, 33%, and 43%, respectively), whereas the EBMT-RS and the rDRI had an impact on the 3-year relapse incidence (8%, 18%, and 41% in patients with 0, 1, and 2 unfavorable scores, respectively). In conclusion, our study shows that combining 2 or 3 of these well-defined pretransplantation scores improves the ability to predict transplantation outcomes in the setting of haploSCT with PTCy.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Bussulfano/uso terapêutico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Tiotepa/uso terapêutico , Condicionamento Pré-Transplante , Vidarabina/análogos & derivadosRESUMO
Accurate prognostic tools are crucial to assess the risk/benefit ratio of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with myelofibrosis (MF). We aimed to evaluate the performance of the Myelofibrosis Transplant Scoring System (MTSS) and identify risk factors for survival in a multicenter series of 197 patients with MF undergoing allo-HCT. After a median follow-up of 3.1 years, 47% of patients had died, and the estimated 5-year survival rate was 51%. Projected 5-year risk of nonrelapse mortality and relapse incidence was 30% and 20%, respectively. Factors independently associated with increased mortality were a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) ≥3 and receiving a graft from an HLA-mismatched unrelated donor or cord blood, whereas post-transplant cyclophosphamide (PT-Cy) was associated with improved survival. Donor type was the only parameter included in the MTSS model with independent prognostic value for survival. According to the MTSS, 3-year survival was 62%, 66%, 37%, and 17% for low-, intermediate-, high-, and very high-risk groups, respectively. By pooling together the low- and intermediate-risk groups, as well as the high- and very high-risk groups, we pinpointed 2 categories: standard risk and high risk (25% of the series). Three-year survival was 62% in standard-risk and 25% in high-risk categories (P < .001). We derived a risk score based on the 3 independent risk factors for survival in our series (donor type, HCT-CI, and PT-Cy). The corresponding 5-year survival for the low-, intermediate-, and high-risk categories was 79%, 55%, and 32%, respectively (P < .001). In conclusion, the MTSS model failed to clearly delineate 4 prognostic groups in our series but may still be useful to identify a subset of patients with poor outcome. We provide a simple prognostic scoring system for risk/benefit considerations before transplantation in patients with MF.
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Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Humanos , Mielofibrose Primária/terapia , Prognóstico , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do TratamentoRESUMO
Cytomegalovirus (CMV) DNAemia and CMV disease have been reported as more frequent in patients undergoing haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) than in those receiving HLA-matched allografts. This could be due to impaired CMV-specific T-cell reconstitution. Here, we conducted a multicenter observational study to assess CMV pp65 and IE-1-specific T cells kinetics in patients undergoing unmanipulated Haplo-HSCT with posttransplant cyclophosphamide (PT/Cy-haplo) and compared it with patients allografted with HLA-matched donors. Plasma CMV DNA load was monitored by real-time PCR and enumeration of CMV-specific IFN-γ-producing CD8+ and CD4+ T cells was performed by flow cytometry for intracellular cytokine staining at days +30, +60, +90, and +180 after transplantation. CMV DNAemia developed in 62 patients, occurring with comparable frequency in PT/Cy-haplo and MRD/MUD recipients (P = 0.14). There were no significant differences across groups in the number of patients either displaying detectable CMV-specific CD8+ and CD4+ T-cell responses or acquiring CMV-specific T-cell levels conferring protection against subsequent infection. CMV-specific T-cell counts were comparable between groups at most time points examined, irrespective of whether CMV DNAemia occurred or not prior to monitoring. Collectively the data suggest that PT/Cy-haplo recipients may reconstitute CMV-specific T-cell immunity to the same extent as patients undergoing HLA-matched allo-HSCT.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Linfócitos T CD8-Positivos , Ciclofosfamida , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfócitos TRESUMO
Precise identification of patients at highest risk for developing Cytomegalovirus (CMV) DNAemia may improve CMV infection management in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting. Here, we studied the potential use of detecting free CMV micro(mi)RNAs circulating in plasma for predicting CMV DNAemia in this clinical scenario. A total of 62 adult allo-HSCT recipients were included in this prospective observational multicenter study. Plasma CMV DNA load was monitored using the CMV RealTime CMV PCR (Abbott Molecular, Des Plaines, IL, USA). Detection of mature CMV miRNAs in plasma drawn by days + 7, + 14 and + 30 after allo-HSCT was performed using the miScript PCR System (Qiagen, Hilden, Germany). Assays could be optimized for five out of the seven targeted CMV miRNAs: UL36-5p, US33-5p, UL148D, UL22A-5p and UL112-3p. Of the 62 patients included in the study, 42 developed a first episode of CMV DNAemia at a median of 35 days after allo-HSCT. All targeted CMV miRNA were detected early after transplantation, with CMV miRNA US33-5p and UL112-3p the most commonly found species at any time point; nevertheless, neither the detection rate of CMV miRNAs nor their abundance allowed discrimination between patients with subsequent CMV DNAemia and those with no CMV DNAemia. The data presented herein do not support any predictive utility of these CMV miRNAs for first episodes of CMV DNAemia in a cohort consisting primarily of allo-HSCT patients receiving haploidentical allografts.
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Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Citomegalovirus/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , MicroRNAs , RNA Viral , Viremia/diagnóstico , Viremia/virologia , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Adulto JovemRESUMO
BACKGROUND: Conflicting data have been published as to the risk of cytomegalovirus (CMV) DNAemia and CMV disease in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide. METHODS: We conducted a multicenter retrospective study including 118 patients subjected to unmanipulated haplo-HSCT to further clarify this issue. An historic cohort comprising 165 patients undergoing other transplant modalities (HLA-matched related, matched unrelated or mismatched) was built for comparison purposes. Plasma CMV DNA monitoring was performed using two highly sensitive real-time PCR assays. RESULTS: Overall, the cumulative incidence of CMV DNAemia, recurrent CMV DNAemia, and CMV DNAemia requiring preemptive antiviral therapy in patients undergoing haplo-HSCT was 63.9%, 34.9%, and 50.1%, respectively. These figures were rather comparable for other transplant modalities (P = .22, P = .13 and P = .72, respectively). A trend toward longer duration of episodes and shorter CMV DNA doubling times was observed in haplo-HSCT patients in comparison with other transplant modalities. Furthermore, median CMV DNA peak load was significantly higher in haplo-HSCTs (P = .008), yet overall mortality by day 180 and 365 was the same across comparison groups. There were five cases of CMV disease, and all occurred in haplo-HSCT patients. This latter observation is worrying and merits further investigation. CONCLUSIONS: The incidence of initial and recurrent episodes of CMV DNAemia either requiring or not antiviral therapy in unmanipulated haplo-HSCT was comparable to other transplant modalities in our cohort.
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Ciclofosfamida/uso terapêutico , Infecções por Citomegalovirus/sangue , DNA Viral/sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Adolescente , Adulto , Idoso , Citomegalovirus , Infecções por Citomegalovirus/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Transplante Homólogo/efeitos adversos , Carga Viral , Adulto JovemRESUMO
BACKGROUND: There is an emerging field underlying the myocardial infarction (MI) with non-obstruc-tive coronary arteries (MINOCA). The aim of this study was to evaluate the impact of psycho-emotional disorders and social habits in MINOCA patients. METHODS: The study included 95 consecutive patients diagnosed of MINOCA and 178 patients with MI and obstructive lesions. MINOCA patients were included when they fulfilled the three main criteria: accomplishment of the Third Universal Definition of Myocardial Infarction, absence of obstructive coronary arteries and no clinically overt specific cause for the acute presentation. RESULTS: MINOCA patients had a higher frequency of previous psychiatric illnesses than the obstructive coronary arteries group (29.7% vs. 12.9%, p = 0.001). MINOCA patients recognized emotional stress in 75.7% of the cases, while only 32.1% of the obstructive related group did (p < 0.001). The relation-ship remained after excluding takotsubo syndrome from the analysis (26 cases, 27.4%): psychiatric diseases (27.9% vs. 12.9%, p < 0.01) and recognition of emotional stress (70.8% vs. 32.1%, p < 0.001). Social habits which could act as stress modulating showed no significant relation with MINOCA. CONCLUSIONS: Psycho-emotional disorders are related to MINOCA and they could act as risk fac-tor. This relationship is maintained after excluding takotsubo from the analysis. (Cardiol J 2018; 25, 1: 24-31).
Assuntos
Doença da Artéria Coronariana/complicações , Vasos Coronários/diagnóstico por imagem , Transtornos do Humor/complicações , Infarto do Miocárdio/etiologia , Sistema de Registros , Medição de Risco/métodos , Idoso , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Transtornos do Humor/psicologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Fatores de Risco , Espanha/epidemiologiaRESUMO
BACKGROUND AIMS: Despite the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the procedure is still associated with high toxicity in patients with refractory graft-versus-host disease (GvHD). Mesenchymal stromal cells (MSCs) are a new mode of therapy in the context of allo-HSCT. The objective of this study was to evaluate the safety and feasibility of the use of adipose tissue-derived MSCs (AT-MSCs) in patients with chronic GvHD. METHODS: Fourteen patients with moderate (n = 7) or severe (n = 7) chronic GvHD received 1 × 106/kg (group A, n = 9) or 3 × 106/kg (group B, n = 5) AT-MSCs with cyclosporine and prednisone as first-line therapy. RESULTS: Ten of the 14 patients were able to continue under the protocol: 80% were in complete remission, and 100% were off of steroids at week 56. The remaining 4 patients either worsened from chronic GvHD (n = 3) or abandoned the study (n = 1). At the end of the study, 11 of 14 patients are alive (overall survival 71.4%, median survival of 45.3 weeks). No suspected unexpected serious adverse reactions occurred during the trial. Neither relapse of underlying disease nor mortality due to infection was observed in this cohort. Biological studies showed increased CD19, CD4 and tumor necrosis factor-α with a temporary decrease in natural killer cells. DISCUSSION: AT-MSCs, in combination with immunosuppressive therapy, may be considered feasible and safe and likely would have an impact on the course of chronic GvHD. More studies are warranted to understand the potential benefits of AT-MSCs in these patients.