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1.
Circ J ; 82(6): 1688-1698, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29576595

RESUMO

BACKGROUND: The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC-treated patients, there was a positive correlation between injected CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients. CONCLUSIONS: This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.


Assuntos
Transplante de Medula Óssea/métodos , Células Progenitoras Endoteliais/transplante , Isquemia/terapia , Transplante Autólogo/métodos , Idoso , Amputação Cirúrgica , Células da Medula Óssea , Transplante de Medula Óssea/normas , Extremidades/patologia , Feminino , Humanos , Leucócitos Mononucleares/transplante , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Transplante Autólogo/normas
2.
Biol Blood Marrow Transplant ; 19(9): 1387-92, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23850652

RESUMO

Myeloablative single-unit umbilical cord blood transplantation (sUCBT) using busulfan, thiotepa, fludarabine, and antithymocyte globulin (Grupo Español de Trasplante Hematopoyético [GETH]-2005 protocol) resulted in high rates of engraftment and high antitumor activity. We designed a new graft-versus-host disease prophylaxis, substituting long-term steroids with mycophenolate mofetil together with a slight reduction of antithymocyte globulin (GETH/Gruppo Italiano Trapianto Midollo Osseo [GITMO]-2008 protocol). The results in 145 consecutive patients were compared with those obtained in 88 patients from the previous GETH-2005 trial. The cumulative incidence (CI) of myeloid engraftment at 60 days for patients in the GETH-2005 and GETH/GITMO-2008 trials was 94% and 88%, respectively, at a median time to neutrophil recovery of 19 and 23 days, respectively (P < .0001). In the multivariable analyses, platelet engraftment, acute and chronic graft-versus-host disease, nonrelapse mortality, relapse, and event-free survival were not significantly different. The 3-year event-free survival rate in the GETH/GITMO-2008 trial was 66%, 31%, and 25% for patients transplanted in early, intermediate, and advanced stages of the disease, respectively (P < .0001). This study confirms that myeloablative sUCBT using busulfan-based conditioning is a valuable strategy for patients with hematological malignancies. The use of mycophenolate mofetil apparently had an adverse effect on myeloid engraftment, and therefore a cautious use of this agent is warranted in the UCBT setting.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Condicionamento Pré-Transplante/métodos , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Fatores de Risco , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Adulto Jovem
3.
Biol Blood Marrow Transplant ; 15(8): 938-47, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19589483

RESUMO

In animal models, CD4+/CD25+ T-regulatory cells (Tregs) have been reported to prevent/delay the onset of graft-versus-host disease (GVHD). Recently, an insufficient upregulation of Tregs was found in target organ (intestinal) biopsies from patients with GVHD. We have analyzed by immunohistochemistry the number of CD3+ T lymphocytes and FOXP3+ Tregs in skin biopsies from (1) recipients of allogeneic hematopoietic stem cell transplantation (HSCT, n = 26), (2) nontransplanted patients diagnosed with cutaneous drug reaction (n = 12), and (3) healthy donors (n = 10). Infiltrating CD3+ cells were significantly higher in both transplanted patients showing acute GVHD (aGVHD) and drug reaction when compared to healthy donors and patients without GVHD. Tregs number in aGVHD was higher than in patients without GVHD or healthy subjects and lower than in drug reaction. Interestingly, the number of infiltrating FOXP3+ Tregs was significantly higher in patients responding to GVHD treatment and with a low GVHD grade. Increase in FOXP3+ Tregs in GVHD skin biopsies correlates with less severe GVHD and is associated with response to GVHD treatment. Larger studies are required to confirm that evaluation of Tregs in minimally invasive skin biopsies assists the diagnosis and prognosis of GVHD patients.


Assuntos
Fatores de Transcrição Forkhead , Doença Enxerto-Hospedeiro/patologia , Linfócitos T Reguladores/patologia , Adulto , Idoso , Biópsia , Complexo CD3 , Estudos de Casos e Controles , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Dermatopatias/patologia , Linfócitos T , Transplante Homólogo , Adulto Jovem
4.
J Clin Microbiol ; 47(10): 3246-54, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19656984

RESUMO

In this study we report the results of analysis of 253 isolates of Staphylococcus aureus (132 methicillin [meticillin]-resistant S. aureus [MRSA] isolates and 121 methicillin-susceptible S. aureus [MSSA] isolates) from 209 patients admitted to 18 high-risk wards of six hospitals located in Florence, Italy, over an 8-month period during which a program of epidemiological surveillance of hospital-acquired infections was conducted. The majority (69%) of the 87 reported S. aureus infections were caused by MRSA. No outbreak events have been reported. All the isolates were typed by amplified fragment length polymorphism (AFLP), and AFLP profiles were analyzed in order to define similarity groups. The discriminatory power of AFLP is very high with MSSA (Simpson index of diversity [D], 95.9%), whereas its resolution capability with MRSA (D, 44.7%) is hampered by the well-known high clonality of these populations (the main MRSA group accounted for 74% of the MRSA isolates). Combining AFLP, improved by visual inspection of polymorphisms, with multiplex PCR greatly increases MRSA resolution (D, 85.5%), resolving the MRSA population to a level that is one of the highest reported in the literature. Widespread and sporadic clones of MSSA and MRSA were identified, and their diffusion in the different hospitals and wards over the surveillance period was studied. The understanding of MSSA and MRSA population structures should be the starting point for the design of a more rational surveillance program for S. aureus species, maximizing benefits and reducing the cost of infection control strategies.


Assuntos
Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Técnicas de Tipagem Bacteriana , Criança , Pré-Escolar , Análise por Conglomerados , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Impressões Digitais de DNA , DNA Bacteriano/genética , Feminino , Genótipo , Hospitais , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Epidemiologia Molecular , Polimorfismo Genético , Fatores de Risco , Staphylococcus aureus/classificação , Adulto Jovem
5.
Blood Transfus ; 11(1): 94-101, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23114516

RESUMO

BACKGROUND: Early identification of predictive factors of failure to mobilise CD34+ cells could enable rational use of plerixafor during first mobilisation, avoiding the need for a second mobilisation course. However, "on demand" administration of plerixafor needs to be driven by established parameters to avoid inappropriate use. MATERIALS AND METHODS: To address this issue, we studied the value of the peripheral blood CD34+ count, measured early (on days +10, +11, +12 and +13), in predicting the mobilisation outcome in the ensuing days. We retrospectively collected data from three Italian centres on 233 patients affected by multiple myeloma or lymphoma who underwent a first or second attempt at mobilisation with cyclophosphamide 4 g/m(2) and granulocyte colony-stimulating factor. To assess the diagnostic value of peripheral blood white blood cell and CD34+ cell counts with respect to "mobilisation failure", we considered failed mobilisation as "disease" and the CD34+ cell count in peripheral blood, on a specific day, as a "diagnostic test". For various thresholds, we measured sensitivity, false positive rate, specificity and positive predictive value (PPV) as well as the area under the receiver-operating characteristic curves (AUC). RESULTS: A CD34+ cell count <10 × 10(6)/L on day 13 had high sensitivity (1.00) and high specificity (1.00) for predicting subsequent mobilisation failure, with an AUC of 1.0. However, good prediction was also obtained using a lower threshold (CD34+ cell count: <6 × 10(6)/L) at an earlier time (day 12). The PPV of the day 13 threshold was 1.00 while that of the day 12 one was 0.87. DISCUSSION: We propose that patients with <6 × 10(6)/L CD34+ cells in peripheral blood on day 12 and <10 × 10(6)/L on day 13 following mobilisation with cyclophosphamide 4 g/m(2) and granulocyte colony-stimulating factor are candidates for "on demand" use of plerixafor, making the administration of this expensive agent more efficient and avoiding its inappropriate use.


Assuntos
Fármacos Anti-HIV , Antígenos CD34 , Ciclofosfamida/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Agonistas Mieloablativos/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Benzilaminas , Ciclamos , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/terapia , Humanos , Contagem de Leucócitos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo
6.
Exp Neurol ; 222(1): 30-41, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20026043

RESUMO

Rebuilding brain structure and neural circuitries by transplantation of fetal tissue is a strategy to repair the damaged nervous system and is currently being investigated using striatal primordium in Huntington's disease (HD) patients. Four HD patients underwent bilateral transplantation with human fetal striatal tissues (9-12 week gestation). Small blocks of whole ganglionic eminencies were processed to obtain cell suspension and then stereotactically grafted in the caudate head and in the putamen. Follow-up period ranged between 18 and 34 months (mean, 24.7 months). Surgery was uneventful. Starting from the fourth month after grafting, neo-generation of metabolically active tissue with striatal-like MRI features was observed in 6 out of 8 grafts. The increase in D2 receptor binding suggested striatal differentiation of the neo-generated tissue in 3 patients. New tissue, connecting the developing grafts with the frontal cortex and, in one case, with the ventral striatum, was also observed. The new tissue growth halted after the ninth month post transplantation. All patients showed stabilization or improvement in some neurological indices. No clinical and imaging signs, suggestive of graft uncontrolled growth, were seen. This study provides the first evidence in humans that neuroblasts of a striatal primordium can develop and move into the brain after neurotransplantation. Primordium development resulted in the building of a new structure with the same imaging features as the corresponding mature structure, combined with short- and long-distance targeted migration of neuroblasts. The results of this study support both the reconstructive potential of fetal tissue and the remarkably retained plasticity of adult brain. Further studies are necessary to assess the clinical efficacy of the human fetal striatal transplantation.


Assuntos
Transplante de Tecido Encefálico/métodos , Corpo Estriado/transplante , Doença de Huntington/fisiopatologia , Doença de Huntington/cirurgia , Adulto , Movimento Celular/fisiologia , Corpo Estriado/citologia , Corpo Estriado/diagnóstico por imagem , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Feto , Fluordesoxiglucose F18 , Seguimentos , Regulação da Expressão Gênica/fisiologia , Antígenos HLA/metabolismo , Humanos , Doença de Huntington/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Exame Neurológico/métodos , Ligação Proteica/fisiologia , RNA Mensageiro/metabolismo , Receptores de Dopamina D2/metabolismo , Índice de Gravidade de Doença , Tomografia Computadorizada de Emissão de Fóton Único/métodos
7.
Blood ; 110(4): 1238-50, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17420287

RESUMO

Leukemia cell motility and transendothelial migration into extramedullary sites are regulated by angiogenic factors and are considered unfavorable prognostic factors in acute leukemias. We have studied cross talk among (1) the vascular endothelial growth factor receptor-1, FLT-1; (2) the human eag-related gene 1 (hERG1) K(+) channels; and (3) integrin receptors in acute myeloid leukemia (AML) cells. FLT-1, hERG1, and the beta(1) integrin were found to form a macromolecular signaling complex. The latter mostly recruited the hERG1B isoform of hERG1 channels, and its assembly was necessary for FLT-1 signaling activation and AML cell migration. Both effects were inhibited when hERG1 channels were specifically blocked. A FLT-1/hERG1/beta(1) complex was also observed in primary AML blasts, obtained from a population of human patients. The co-expression of FLT-1 and hERG1 conferred a pro-migratory phenotype to AML blasts. Such a phenotype was also observed in vivo. The hERG1-positive blasts were more efficient in invading the peripheral circulation and the extramedullary sites after engraftment into immunodeficient mice. Moreover, hERG1 expression in leukemia patients correlated with a higher probability of relapse and shorter survival periods. We conclude that in AML, hERG1 channels mediate the FLT-1-dependent cell migration and invasion, and hence confer a greater malignancy.


Assuntos
Movimento Celular , Canais de Potássio Éter-A-Go-Go/metabolismo , Integrina beta1/metabolismo , Leucemia Mieloide/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Doença Aguda , Adulto , Idoso , Adesão Celular , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/farmacologia , Transdução de Sinais , Células Tumorais Cultivadas
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