RESUMO
Patients who undergo autologous hematopoietic stem cell transplantation (autoHSCT) often experience reduced oral intake and wasting. We examined their daily nutritional intake, assessed alterations in body composition and muscle strength, and explored associations between decreased nutritional intake and treatment outcomes. This retrospective study included 64 patients. Their food record charts and parenteral nutrition (PN) prescriptions from medical records were used to assess nutritional intake. Body composition and handgrip strength data were obtained from dietitian records. Patients consumed >75% of their nutritional requirements through an oral diet in 6.7 days, 50-75% in 4.8 days, 25-50% in 5.0 days, and <25% in 3.1 days. The average oral intake was 62% of the requirement and was partially supplemented with PN. Patients experienced a mean decrease in body weight of 2.9 ± 3.0 kg, with 2.3 ± 3.4 kg of lean mass, and a mean reduction in handgrip strength of 3.5 ± 3.6 kg. We found a positive correlation of caloric deficits with weight loss and handgrip strength reduction and negative correlation with time to neutrophil engraftment and duration of hospitalization. This study highlighted a notable reduction in oral nutritional intake following autoHSCT. While caloric deficits might affect outcomes, further investigation is warranted to explore this observation.
Assuntos
Força da Mão , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Retrospectivos , Composição Corporal , Ingestão de Alimentos , Suplementos NutricionaisRESUMO
Mesenchymal stem cell (MSCs) therapy has already been studied in kidney transplant recipients (KTRs), and the available data showed that it is safe and well tolerated. The aim of this study was to evaluate the safety and efficacy of autologous MSCs in combination with standard therapy in KTRs with biopsy-proven chronic active antibody-mediated rejection (AMR). Patients with biopsy-proven chronic active AMR received treatment with autologous bone marrow-derived MSCs (3 × 106 cells/kg iv) after completion of standard therapy and were followed for up to 12 months. The primary endpoints were safety by assessment of adverse events. Secondary endpoints included assessment of kidney graft function, immunological and histological changes related to AMR activity and chronicity assessed by conventional microscopy and molecular transcripts. A total of 3 patients were enrolled in the study before it was terminated prematurely because of adverse events. We found that AMR did not improve in any of the patients after treatment with MSCs. In addition, serious adverse events were observed in one case when autologous MSCs therapy was administered in the late phase after kidney transplantation, which requires further elucidation.
Assuntos
Rejeição de Enxerto , Células-Tronco Mesenquimais , Humanos , RimRESUMO
Erythrocytosis has a diverse background. While polycythaemia vera has well defined criteria, the diagnostic approach and management of other types of erythrocytosis are more challenging. The aim of study was to retrospectively analyse the aetiology and management of non-clonal erythrocytosis patients referred to a haematology outpatient clinic in an 8-year period using a 3-step algorithm. The first step was inclusion of patients with Hb > 185 g/L and/or Hct > 0.52 in men and Hb > 165 g/L and/or Hct > 0.48 in women on two visits ≥ two months apart, thus confirming true erythrocytosis. Secondly, polycythaemia vera was excluded and secondary causes of erythrocytosis (SE) identified. Thirdly, idiopathic erythrocytosis patients (IE) were referred to next-generation sequencing for possible genetic background evaluation. Of the 116 patients, 75 (65%) are men and 41 (35%) women, with non-clonal erythrocytosis 34/116 (29%) had SE, 15/116 (13%) IE and 67/116 (58%) stayed incompletely characterized (ICE). Patients with SE were significantly older and had significantly higher Hb and Hct compared to patients with IE. Most frequently, SE was attributed to obstructive sleep apnoea and smoking. Phlebotomies were performed in 56, 53 and 40% of patients in the SE, IE, and ICE group, respectively. Approx. 70% of patients in each group received aspirin. Thrombotic events were registered in 12, 20 and 15% of SE, IE and ICE patients, respectively. Congenital erythrocytosis type 4 (ECYT4) was diagnosed in one patient. The study demonstrates real-life management of non-clonal erythrocytosis which could be optimized using a 3-step diagnostic algorithm.
Assuntos
Policitemia/diagnóstico , Policitemia/terapia , Adulto , Gerenciamento Clínico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Flebotomia , Policitemia/congênito , Policitemia/genética , Estudos RetrospectivosRESUMO
CALR mutations are a revolutionary discovery and represent an important hallmark of myeloproliferative neoplasms (MPN), especially essential thrombocythemia and primary myelofibrosis. To date, several CALR mutations were identified, with only frameshift mutations linked to the diseased phenotype. It is of diagnostic and prognostic importance to properly define the type of CALR mutation and subclassify it according to its structural similarities to the classical mutations, a 52-bp deletion (type 1 mutation) and a 5-bp insertion (type 2 mutation), using a statistical approximation algorithm (AGADIR). Today, the knowledge on the pathogenesis of CALR-positive MPN is expanding and several cellular mechanisms have been recognized that finally cause a clonal hematopoietic expansion. In this review, we discuss the current basis of the cellular effects of CALR mutants and the understanding of its implementation in the current diagnostic laboratorial and medical practice. Different methods of CALR detection are explained and a diagnostic algorithm is shown that aids in the approach to CALR-positive MPN. Finally, contemporary methods joining artificial intelligence in accordance with molecular-genetic biomarkers in the approach to MPN are presented.
Assuntos
Calreticulina/genética , Mutação , Transtornos Mieloproliferativos/genética , Algoritmos , Animais , Inteligência Artificial , Biomarcadores/metabolismo , Calreticulina/metabolismo , Análise Mutacional de DNA , Deleção de Genes , Hematologia , Humanos , Ligantes , Aprendizado de Máquina , Chaperonas Moleculares/metabolismo , Fenótipo , Prognóstico , Transdução de Sinais , Trombocitose/metabolismoRESUMO
BACKGROUND: Prehabilitation with regular exercise and nutritional care for patients undergoing surgeries for malignant disease was recently introduced to increase physiologic reserve prior to the procedure, accelerate recovery and improve outcomes. This study aimed to investigate the feasibility and safety of combined exercise training and nutritional support in patients with haematologic malignancies prior to haematopoietic stem cell transplantation (HSCT). METHODS: In this single-arm pilot study, 34 HSCT candidates were enrolled at least two weeks before admission for the procedure. Patients performed aerobic exercises at least 4 days per week for 20-30 min and strength exercises 3 days per week for 10-20 min. They received daily supplements of whey protein (0.3-0.4 g/kg body weight) and oral nutritional supplements if needed. The primary endpoints were feasibility (acceptability > 75%, attrition < 20%, adherence > 66%) and safety. The secondary endpoints were fat-free mass (FFM), muscle strength, physical performance and health-related quality of life (HRQoL) at HSCT. RESULTS: The rate of acceptability, attrition and adherence to aerobic exercise, strength exercise and protein supplement consumption was 82.4, 17.8, 71, 78 and 80%, respectively. No severe adverse events were reported. Twenty-eight patients participated in the study for a median of 6.0 weeks (range, 2-14). They performed aerobic exercises 4.5 days per week for 132 min per week and strength exercises 3.0 times per week. Patients consumed 20.7 g of extra protein daily. At the end of the programme, we recorded increases of 1.1 kg in FFM (p = 0.011), 50 m in walking distance in the 6-min walking test (6MWT) (p < 0.001), 3.3 repetitions in the 30-s chair-stand test (30sCST) score (p < 0.001) and 2.6 kg in handgrip strength (p = 0.006). The EORTC QLQ-C30 scores improved by 8.6 (p < 0.006) for global health status, 8.3 (p = 0.009) for emotional functioning, and 12.1 (p = 0.014) for social functioning. There was less fatigue, nausea and insomnia (p < 0.05). CONCLUSIONS: Our study shows that a multimodal intervention programme with partially supervised exercise training combined with nutritional support prior to HSCT is feasible and safe. Patients showed improvements in FFM, physical performance and HRQoL. Additional research is needed to assess the possible positive effects of such interventions.
Assuntos
Terapia por Exercício/métodos , Neoplasias Hematológicas/reabilitação , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Apoio Nutricional , Estudos de Viabilidade , Feminino , Seguimentos , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , PrognósticoRESUMO
One hundred and eight consecutive acute myeloid leukemia (AML) patients aged 60 or less treated with two different induction regimens were retrospectively analyzed. Induction regimen for the first 50 consecutive patients was DA3+7, and the following 58 patients received cladribine 5 mg/m2 on days 1 through 5 in addition to DA3+7 (DAC). There were no significant differences in the median age and the proportion of patients with unfavorable characteristics between the two groups. Remission after induction chemotherapy was achieved in 30/50 (60%) patients in DA3+7 and in 46/58 (79%) in DAC group (p = 0.028). The median survival in the DA3+7 group was 18 months, while in the DAC group it was not reached (p = 0.034). We confirmed results from other research groups by demonstrating improved remission induction rate and overall survival of AML patients aged 60 years or less treated with DAC induction compared with standard DA3+7 induction chemotherapy.
Assuntos
Cladribina/administração & dosagem , Quimioterapia de Indução , Leucemia Mieloide Aguda , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
RATIONALE: Preclinical data in heart failure models suggest that repetitive stem cell therapy may be superior to single-dose cell administration. OBJECTIVE: We investigated whether repetitive administration of CD34+ cells is superior to single-dose administration in patients with nonischemic dilated cardiomyopathy. METHODS AND RESULTS: Of 66 patients with dilated cardiomyopathy, New York Heart Association functional class III, and left ventricular ejection fraction (LVEF) <40% enrolled in the study, 60 were randomly allocated to repetitive cell therapy (group A, n=30) or single-cell therapy (group B, n=30). Patients received G-CSF (granulocyte colony-stimulating factor) for 5 days, and 80 million CD34+ cells were collected by apheresis and injected transendocardially. In group A, cell therapy was repeated at 6 months. All patients were followed for 1 year, and the primary end point was the difference in change in LVEF between the groups. At baseline, the groups did not differ in age, sex, LVEF, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or 6-minute walk test distance. When directly comparing groups A and B at 1 year, there was no significant difference in change in LVEF (from 32.2±9.3% to 41.2±6.5% in group A and from 30.0±7.0% to 37.9±5.3% in group B, P=0.40). From baseline to 6 months, both groups improved in LVEF (+6.9±3.3% in group A, P=0.001 and +7.1±3.5% in group B, P=0.001), NT-proBNP (-578±211 pg/mL, P=0.02 and -633±305 pg/mL, P=0.01), and 6-minute walk test (+87±21 m, P=0.03 and +92±25 m, P=0.02). In contrast, we observed no significant changes between 6 months and 1 year (LVEF: +2.1±2.3% in group A, P=0.19 and +0.8±3.1% in group B, P=0.56; NT-proBNP: -215±125 pg/mL, P=0.26 and -33±205 pg/mL, P=0.77; 6-minute walk test: +27±11 m, P=0.2 and +12±18 m, P=0.42). CONCLUSIONS: In patients with dilated cardiomyopathy, repetitive CD34+ cell administration does not seem to be associated with superior improvements in LVEF, NT-proBNP, or 6-minute walk test when compared with single-dose cell therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02248532.
Assuntos
Cardiomiopatia Dilatada/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Idoso , Antígenos CD34/genética , Antígenos CD34/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Although the use of commercially manufactured hormone therapy (HT) to treat menopausal symptoms has declined during the past 12 years, the use of custom compounded HT seems to have increased. A 39-year-old woman with refractory anemia sustained premature ovarian insufficiency following allogeneic stem cell transplantation. After systemic biologic treatment (azacitidine) and corticosteroid therapy, besides extreme climacteric symptoms (Green Climacteric Scale, 59) and impaired quality of life, she also had elevated liver enzymes. Therefore, she was not a candidate for oral HT. Treatment was started with 17-beta estradiol patch 0.5 mg (Climara) together with micronized progesterone intravaginally, 2x100 mg (Utrogestan) for 3 months. She was not satisfied, so the custom compound HT started with 17-beta estradiol 0.5 mg gel 2x/day and micronized progesterone in liposomal gel 100 mg/daily. She was much better but she complained of low libido, decreased sex drive and emotional instability, so 1% testosterone gel was added. Now she was completely satisfied, Green Climacteric Scale was 8 and liver enzymes were normal. In conclusion, custom compound HT has the possibility of tailoring and adjusting therapy to the individual need, which has been the everlasting goal in menopause medicine and should be a good option for special clinical cases.
Assuntos
Terapia de Reposição de Estrogênios/métodos , Estrogênios/administração & dosagem , Insuficiência Ovariana Primária/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Composição de Medicamentos , Feminino , Humanos , Insuficiência Ovariana Primária/induzido quimicamente , Progesterona/administração & dosagem , Progesterona/análogos & derivados , Qualidade de VidaRESUMO
OBJECTIVES: To present the Central European Myeloproliferative Neoplasm Organisation (CEMPO) treatment recommendations for polycythaemia vera (PV). METHODS: During meetings held from 2015 through 2017, CEMPO discussed PV and its treatment and recent data. RESULTS: PV is associated with increased risks of thrombosis/thrombo-haemorrhagic complications, fibrotic progression and leukaemic transformation. Presence of Janus kinase (JAK)-2 gene mutations is a diagnostic marker and standard diagnostic criterion. World Health Organization 2016 diagnostic criteria for PV, focusing on haemoglobin levels and bone marrow morphology, are mandatory. PV therapy aims at managing long-term risks of vascular complications and progression towards transformation to acute myeloid leukaemia and myelodysplastic syndrome. Risk stratification for thrombotic complications guides therapeutic decisions. Low-risk patients are treated first line with low-dose aspirin and phlebotomy. Cytoreduction is considered for low-risk (phlebotomy intolerance, severe/progressive symptoms, cardiovascular risk factors) and high-risk patients. Hydroxyurea is suspected of leukaemogenic potential. IFN-α has demonstrated efficacy in many clinical trials; its pegylated form is best tolerated, enabling less frequent administration than standard interferon. Ropeginterferon alfa-2b has been shown to be more efficacious than hydroxyurea. JAK1/JAK2 inhibitor ruxolitinib is approved for hydroxyurea resistant/intolerant patients. CONCLUSIONS: Greater understanding of PV is serving as a platform for new therapy development and treatment response predictors.
RESUMO
BACKGROUND: We investigated a correlation between electromechanical properties of the myocardium and response to CD34+ cell therapy in patients with chronic heart failure. METHODS AND RESULTS: We enrolled 40 patients with ischemic cardiomyopathy (ICM) and 40 with nonischemic dilated cardiomyopathy (DCM). All patients were in New York Heart Association functional class III and had a left ventricular ejection fraction (LVEF) <40%. CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Electroanatomic mapping was performed to define areas of myocardial scar and hibernation, and CD34+ cells were injected transendocardially in the hibernating areas. Patient were followed for 6 months; responders were defined as patients with LVEF increase of >5%. At baseline, the groups did not differ in sex, LVEF, creatinine, N-terminal pro-B-type natriuretic peptide or electroanatomic parameters (scar area: 53 ± 18% in ICM vs 55 ± 23% in DCM [P = .83]; hibernating area: 23 ± 13% vs 22 ± 12% [P = .56]). At 6 months we found similar rates of responders in both groups (60% in ICM vs 65% in DCM [P = .95]). When compared with nonresponders, responders had less myocardial scar (47 ± 17% vs 58 ± 15% [P = .003]). CONCLUSIONS: In patients with chronic heart failure due to ICM and DCM we observed similar electroanatomic properties of the myocardium. In both groups, lower myocardial scar burden was associated with better clinical response to CD34+ cell therapy.
Assuntos
Antígenos CD34/administração & dosagem , Cardiomiopatia Dilatada/complicações , Terapia Baseada em Transplante de Células e Tecidos/métodos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Isquemia Miocárdica/complicações , Adulto , Idoso , Análise de Variância , Cardiomiopatia Dilatada/diagnóstico , Doença Crônica , Ecocardiografia , Teste de Esforço/métodos , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Imageamento Tridimensional , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Isquemia Miocárdica/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Índice de Gravidade de Doença , Volume Sistólico/fisiologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Remodelação Ventricular/fisiologiaRESUMO
BACKGROUND: Although stem cell therapy (SCT) is emerging as a potential treatment for patients with dilated cardiomyopathy (DCM), clinical response remains variable. Our objective was to determine whether baseline differences in circulating immunologic and nonimmunologic biomarkers may help to identify patients more likely to respond to intramyocardial injection of CD34(+)-based SCT. METHODS AND RESULTS: We enrolled from January 3, 2011 to March 5, 2012 37 patients with longstanding DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral CD34(+) stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) and collection by means of apheresis. CD34(+) cells were labeled with (99m)Tc-hexamethylpropyleneamine oxime to allow assessment of stem cell retention at 18 hours. Response to SCT was predefined as an increase in LVEF of ≥5% at 3 months. The majority (84%) of patients were male with an overall mean LVEF of 27 ± 7% and a median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of 2,774 pg/mL. Nineteen patients (51%) were responders to SCT. There was no significant difference between responders and nonresponders regarding to age, sex, baseline LVEF, NT-proBNP levels, or 6-minute walking distance. With the use of a partial least squares (PLS) predictive model, we identified 9 baseline factors that were associated with both stem cell response and stem cell retention (mechanistic validation). Among the baseline factors positively associated with both clinical response and stem cell retention were G-CSF, SDF-1, LIF, MCP-1, and MCP-3. Among baseline factors negatively associated with both clinical response and retention were IL-12p70, FASL, ICAM-1, and GGT. A decrease in G-CSF at 3-month follow-up was also observed in responders compared with nonresponders (P = .02). CONCLUSIONS: If further validated, baseline immunologic and nonimmunologic biomarkers may help to identify patients with DCM who are more likely to respond to CD34(+)-based SCT.
Assuntos
Cardiomiopatia Dilatada , Quimiocina CXCL12/sangue , Fator Estimulador de Colônias de Granulócitos , Molécula 1 de Adesão Intercelular/sangue , Fator Inibidor de Leucemia/sangue , Transplante de Células-Tronco de Sangue Periférico/métodos , Adulto , Antígenos CD34/imunologia , Biomarcadores/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/imunologia , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/imunologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Imunológica/métodos , Imagem de Perfusão do Miocárdio/métodos , Compostos Radiofarmacêuticos/farmacologia , Volume Sistólico , Tecnécio Tc 99m Exametazima/farmacologiaRESUMO
BACKGROUND: We investigated the effects of intracoronary transplantation of CD34(+) cells on myocardial perfusion in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We enrolled 21 patients with DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral stem cell mobilization with granulocyte-colony stimulating factor (G-CSF). CD34(+) cells were collected by means of apheresis. Patients underwent myocardial perfusion imaging, and CD34(+) cells were injected in the coronary artery supplying viable segments with reduced myocardial perfusion and regional dysfunction. Myocardial perfusion imaging was repeated 6 months later. Clinical response to stem cell therapy was predefined as a change in LVEF >5%. The majority of patients were men (81%) with an overall mean age 53 ± 9 years, LVEF 25 ± 5%, and 6-minute walking distance 354 ± 71 m. Myocardial perfusion defects at rest were observed in 86% of patients and were more common in the left anterior descending territory (50%). At 6 months' follow-up, there was a significant improvement in rest myocardial perfusion scores (6.3 ± 5.8 vs 3.1 ± 4.3; P < .001), LVEF (25 ± 7% vs 29 ± 8%; P = .005), and 6-minute walking distance (354 ± 71 m vs 404 ± 91 m; P < .001). Responders to stem cell therapy had lower summed rest perfusion score at both baseline (3.2 ± 3.0 vs 9.1 ± 6.3; P = .015) and follow-up (1.0 ± 1.5 vs 5.0 ± 5.1; P = .028). CONCLUSIONS: CD34(+) cell transplantation may lead to improved myocardial perfusion in patients with nonischemic DCM. Patients with less severe myocardial perfusion defects at baseline may have an increased likelihood to respond to intracoronary CD34(+) cell transplantation.
Assuntos
Antígenos CD34 , Cardiomiopatia Dilatada/terapia , Vasos Coronários , Imagem de Perfusão do Miocárdio/tendências , Transplante de Células-Tronco/tendências , Adulto , Antígenos CD34/sangue , Cardiomiopatia Dilatada/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reperfusão Miocárdica/tendências , Projetos Piloto , Estudos Prospectivos , Método Simples-CegoRESUMO
RATIONALE: CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance. OBJECTIVE: We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response. METHODS AND RESULTS: Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34+ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P=0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P<0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P<0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P=0.01). The same was true of pump failure (5% vs. 18%; P=0.03), but not of sudden cardiac death (9% vs. 16%; P=0.39). CONCLUSIONS: Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.
Assuntos
Antígenos CD34/metabolismo , Cardiomiopatia Dilatada/cirurgia , Miocárdio/patologia , Transplante de Células-Tronco , Células-Tronco/imunologia , Função Ventricular Esquerda , Biomarcadores/metabolismo , California , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/imunologia , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Causas de Morte , Movimento Celular , Rastreamento de Células , Distribuição de Qui-Quadrado , Circulação Coronária , Ecocardiografia , Teste de Esforço , Tolerância ao Exercício , Feminino , Seguimentos , Humanos , Injeções Intra-Arteriais , Interleucina-6/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Imagem de Perfusão do Miocárdio , Miocárdio/imunologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Modelos de Riscos Proporcionais , Recuperação de Função Fisiológica , Eslovênia , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Volume Sistólico , Texas , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangueRESUMO
Parameters associated with poor CD34(+) stem cell mobilization in advanced chronic heart failure (CHF) patients were investigated. Forty-four CHF patients underwent bone marrow stimulation with granulocyte colony stimulating factor. Poor cell mobilization presents in 32% of patients. Poor and good mobilizers did not differ significantly regarding age, gender, left ventricular ejection fraction, kidney or liver function and exercise capacity. Significant differences were found regarding NT-proBNP levels and red cell distribution width (RDW). Increased RDW was the only independent predictor of poor CD34(+) stem cell mobilization on multivariable analysis and may serve as a biomarker of poor stem cell mobilization in CHF patients.
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Índices de Eritrócitos , Insuficiência Cardíaca/sangue , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/metabolismo , Adulto , Idoso , Antígenos CD34/metabolismo , Biomarcadores/sangue , Doença Crônica , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Insuficiência Cardíaca/terapia , Mobilização de Células-Tronco Hematopoéticas/estatística & dados numéricos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricosRESUMO
BACKGROUND: In an open-label blinded study, we compared intracoronary and transendocardial CD34(+) cell transplantation in patients with nonischemic dilated cardiomyopathy. METHODS AND RESULTS: Of the 40 patients with dilated cardiomyopathy, 20 were randomized to receive intracoronary injection and 20 received transendocardial CD34(+) cell delivery. In both groups, CD34(+) cells were mobilized by filgrastim, collected via apheresis, and labeled with technetium-99m radioisotope for single-photon emission computed tomographic imaging. In the intracoronary group, cells were injected intracoronarily in the artery supplying segments of greater perfusion defect on myocardial perfusion scintigraphy. In the transendocardial group, electroanatomic mapping was used to identify viable but dysfunctional myocardium, and transendocardial cell injections were performed. Nuclear single-photon emission computed tomographic imaging for quantification of myocardial retention was performed 18 hours thereafter. At baseline, groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal pro-brain natriuretic peptide levels. The number of CD34(+) cells was also comparable (105 ± 31 × 10(6) in the transendocardial group versus 103 ± 27 × 10(6) in the intracoronary group, P=0.62). At 18 hours after procedure, myocardial retention was higher in the transendocardial group (19.2 ± 4.8%) than in the intracoronary group (4.4 ± 1.2%, P<0.01). At 6 months, left ventricular ejection fraction improved more in the transendocardial group (+8.1 ± 4.3%) than in the intracoronary group (+4.2 ± 2.3%, P=0.03). The same pattern was observed for the 6-minute walk test distance (+125 ± 33 m in the transendocardial group versus +86 ± 13 m in the intracoronary group, P=0.03) and N-terminal pro-brain natriuretic peptide (-628 ± 211 versus -315 ± 133 pg/mL, P=0.04). CONCLUSIONS: In patients with dilated cardiomyopathy, transendocardial CD34(+) cell transplantation is associated with higher myocardial retention rates and greater improvement in ventricular function, N-terminal pro-brain natriuretic peptide, and exercise capacity compared with intracoronary route. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01350310.
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Antígenos CD34/biossíntese , Transplante de Medula Óssea/métodos , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/cirurgia , Endocárdio/cirurgia , Isquemia Miocárdica , Transplante de Células-Tronco/métodos , Idoso , Antígenos CD34/administração & dosagem , Cardiomiopatia Dilatada/metabolismo , Endocárdio/patologia , Feminino , Seguimentos , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Isquemia Miocárdica/cirurgia , Resultado do TratamentoRESUMO
AIMS AND OBJECTIVES: To establish the availability of High Efficiency Particulate Air (HEPA)- and nonHEPA-filtered rooms in eastern European transplant centres and to investigate the impact on incidence of pneumonia and mortality after haematopoietic stem cell transplantation (HSCT). BACKGROUND: Barrier nursing in HEPA-filtered rooms is generally recommended for patients undergoing HSCT. There are only limited data on the availability of HEPA-filtered rooms and the impact on incidence of pneumonia and mortality. DESIGN: A prospective, observational, international study. METHODS: Monitoring cards were distributed within the East Forum EBMT-Nurses Group cooperating centres, and 689 consecutive patients were registered in 1/2010-6/2012. Patients were monitored for 100 days post-transplant. RESULTS: In patients undergoing autologous HSCT, pneumonia developed in 14/400 (3·5%) and was the cause of death in 2/14 (14%) of patients. There was no significant difference in mortality between HEPA-filtered and nonHEPA-filtered groups (4·5% vs. 4·9%, respectively). 239/400 (59%) transplantations were performed in single-bed rooms [190/239 (79%) HEPA-filtered] and 161 (41%) in two-bed rooms [28/161 (17%) HEPA-filtered]. In allogeneic transplantation, pneumonia developed in 24/289 (8·3%) and was the cause of death in 11/24 (45%) of patients. There was no significant difference in mortality between HEPA-filtered and non-HEPA-filtered groups (14% vs. 17%, respectively). 281/289 (97%) of allogeneic transplantations were performed in single-bed rooms [254/281 (90%) HEPA-filtered], and pneumonia was more frequent in patients on corticosteroids and in rooms without HEPA. CONCLUSION: The incidence of pneumonia in the autologous transplantation setting is low. More pneumonia was observed in the allogeneic HSCT group, especially in patients on corticosteroids. There was a trend towards a lower incidence of pneumonia in allogeneic HSCT patients treated in HEPA-filtered rooms. RELEVANCE TO CLINICAL PRACTICE: Autologous HSCT transplantation may safely be performed without HEPA filtration. HEPA filtration might be preferable in patients undergoing allogeneic transplantation.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Isolamento de Pacientes , Quartos de Pacientes , Pneumonia/epidemiologia , Adolescente , Adulto , Idoso , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia/etiologia , Pneumonia/enfermagem , Pneumonia/prevenção & controle , Estudos Prospectivos , Adulto JovemRESUMO
(1) Background: Relapsed/refractory (r/r) and secondary acute myeloid leukemia are highlighted by chemoresistance and poor outcomes. The aim of the study was to assess the efficacy and toxicity of fludarabine, cytarabine, and granulocyte-colony stimulation factor (FLAG) with or without idarubicin (-Ida) and to discuss novel therapies in this setting. (2) Methods: Clinical and cytogenetic data on 130 consecutive patients with r/r and secondary AML treated at our center were retrospectively analyzed. (3) Results: There were 48, 56, and 26 patients with relapsed, refractory, and secondary AML, respectively. The median age was 60 years. The overall response was achieved in 70% of patients. The median overall survival (OS) time for the whole group was 9.4 months. In total, 47% of patients proceeded to allogeneic hematopoietic stem cell transplantation (aHSCT) and these patients had significantly prolonged OS compared to the others (63 months vs. 4.2 months; p < 0.001). Among the variables, including age, FLT3 mutation status, European LeukemiaNet (ELN) 2022 classification risk, FLAG vs. FLAG-Ida, and aHSCT, a multivariate analysis revealed that only aHSCT significantly influenced overall survival. (4) Conclusions: FLAG(-Ida) chemotherapy remains an effective salvage chemotherapy for patients with r/r and secondary AML with a plan of proceeding to aHSCT.
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Chimeric antigen receptor (CAR) T cell therapy has emerged as a powerful therapeutic approach against a range of hematologic malignancies. While the incorporation of CD28 or 4-1BB costimulatory signaling domains into CARs revolutionized immune responses, there is an exciting prospect of further enhancing CAR functionality. Here, we investigated the design of CD19 CARs enriched with distinct Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), or Toll/IL-1 domain-containing adaptor-inducing interferon (IFN)-ß (TRIF) costimulatory domains. Screening of various designs identified several candidates with no tonic activity but with increased CD19 target cell-dependent interleukin (IL)-2 production. Human T cells transduced with the selected CAR construct exhibited augmented hIL-2 and hIFN-γ induction and cytotoxicity when cocultured with CD19-positive lymphoma and solid-tumor cell lines. RNA sequencing (RNA-seq) analysis demonstrated the upregulation of some genes involved in the innate immune response and T cell activation and proliferation. In experiments on a xenogeneic solid-tumor mice model, MyD88 and TLR4 CAR T cells exhibited prolonged remission. This study demonstrates that the integration of a truncated TLR4 signaling costimulatory domain could provide immunotherapeutic potential against both hematologic malignancies and solid tumors.
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Immune thrombocytopenia (ITP) is an autoimmune blood disorder characterised by isolated severe thrombocytopenia. Arterial thrombotic events, such as acute ischaemic stroke (AIS), are rare complications. A 56-year-old woman with chronic ITP on eltrombopag and dexamethasone therapy presented to the emergency department due to AIS in the vertebrobasilar territory, and lower abdominal pain. The computed tomography (CT) scan of the head was unremarkable, whereas CT angiography revealed left vertebral artery occlusion. As the platelet count was sufficient, intravenous thrombolysis (IVT) was initiated. However, after 15 min, an anaphylactic reaction occurred, which was appropriately solved. Although the IVT was prematurely stopped, the NIHSS score improved from 7 to 2, and the follow-up head CT scan remained unremarkable. CT angiography of the thoracoabdominal aorta revealed multiple thrombi in the infrarenal aorta, inferior mesenteric artery (IMA), and left renal artery. The abdominal pain subsided after IVT, but recurred within 24 h. Repeated CT angiography showed ischaemia of the descending colon, with persistent IMA occlusion. After the hemicolectomy condition stabilised. Discrete left-sided ataxia and impaired sensation were the only neurological sequelae. We found two articles reporting only three patients with ITP who suffered AIS and were treated with IVT. A favourable outcome was observed in two cases, while one patient suffered an intracranial haemorrhage (ICH) and died. A review of AIS cases with undefined thrombocytopenia treated with IVT reported ICH in up to 6.8% of patients. Our case suggests that IVT for AIS may be effective in patients with ITP. Further data are needed to better clarify this issue.
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The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2 (82%), and >140 mg/m2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5-42.2) and the median OS 102 months (95% CI: 70.4-129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3-14%), 13% (6-20%), and 20% (12-29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.