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1.
Environ Res ; 242: 117735, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38000630

RESUMEN

Biogas methanation emerges as a prominent technology for converting biogas into biomethane in a single step. Furthermore, this technology can be implemented at biogas plant locations, supporting local economies and reducing dependence on large energy producers. However, there is a lack of comprehensive studies on biogas methanation, particularly regarding the technical optimization of operational parameters and the profitability analysis of the overall process. To address this gap, our study represents a seminal work on the technical optimization of biogas methanation obtaining an empirical model to predict the performance of biogas methanation. We investigate the influence of operational parameters, such as reaction temperature, H2/CO2 ratio, space velocity, and CO2 share in the biogas stream through an experimental design. Based on previous research we selected a nickel supported on ceria-alumina catalyst; being nickel a benchmark system for methanation process such selection permits a reliable data extrapolation to commercial units. We showcase the remarkable impact of studied key operation parameters, being the temperature, the most critical factor affecting the reaction performance (ca. 2 to 5 times higher than the second most influencing parameter). The impact of the H2/CO2 ratio is also noticeable. The response surfaces and contour maps suggest that a temperature between 350 and 450 °C and an H2/CO2 ratio between 2.5 and 3.2 optimize the reaction performance. Further experimental tests were performed for model validation and optimization leading to a reliable predictive model. Overall, this study provides validated equations for technology scaling-up and techno-economic analysis, thus representing a step ahead towards real-world applications for bio-methane production.


Asunto(s)
Biocombustibles , Dióxido de Carbono , Níquel , Óxido de Aluminio , Biomasa
2.
Clin Exp Obstet Gynecol ; 41(6): 638-40, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25551954

RESUMEN

OBJECTIVE: To assess the indications and possible underlying causes of emergency peripartum hysterectomy (EPH) at the present hos- pital during the 2001-2011 period. MATERIALS AND METHODS: A revision of the charts and pathology reports corresponding to 42,728 parturients. RESULTS: During the study period, 25 peripartum hysterectomies were performed (0.61/1.000), of which 23 were EPHs (0.54/1.000) and two were planned cesarean hysterectomies. The indication for EPH was acute postpartum hemorrhage in 22 of 23 instances (95.7%). Roughly two-thirds of the operated uteri (16/25, 64%) showed placental site anomalies, half corresponding to different degrees of placental accretism and half to anomalies derived from the implantation site intermediate trophoblast. In five cases (31%), the anomaly was an exaggerated placental site and three cases corresponded to placental site trophoblastic tumors. Of the 16 cases showing placental site anomalies, ten (62.5%) were associated with one or more previous cesarean sections. CONCLUSIONS: Roughly one-third of EPHs performed at the present center during the last ten years were associated with placental site anomalies originating in the implantation site intermediate trophoblast (exaggerated placental site and placental site trophoblastic tumor). This association has not been described before, and should be taken into consideration when facing acute peripartum hemorrhage predisposing to EPH.


Asunto(s)
Histerectomía , Tumor Trofoblástico Localizado en la Placenta/cirugía , Neoplasias Uterinas/cirugía , Adulto , Cesárea , Urgencias Médicas , Femenino , Humanos , Periodo Periparto , Hemorragia Posparto/cirugía , Embarazo , Factores de Riesgo
3.
RSC Adv ; 13(30): 21071-21079, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37448636

RESUMEN

Today's rising energy costs, coupled with increasing energy demand, make it necessary to search for more efficient energy processes. In recent years, there have been increasing efforts to develop efficient catalysts based on waste-derived char, by a single step where the carbon precursor and the metallic active phase one undergo a single common thermal process under a reductant atmosphere at high temperature. The use of a reductant atmosphere drives the formation of carbonaceous materials with different characteristics than those obtained under the standard nitrogen-inert one. Our work evaluates the influence of the residence time and the heating rate on the physicochemical properties of the biochar obtained. Relatively long residence times and slow heating rates, improve the yield to the resulting biochar, without increasing production cost, making the subsequent char-based metallic catalyst synthesis more efficient. The heating rate was shown to be key in improving the properties of the char in a smoother and more controlled way, unlocking a new working pathway for the efficient design and production of char-based catalysts in a one-pot synthesis.

4.
Front Chem ; 9: 785571, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34869232

RESUMEN

The exponential growth of greenhouse gas emissions and their associated climate change problems have motivated the development of strategies to reduce CO2 levels via CO2 capture and conversion. Reverse water gas shift (RWGS) reaction has been targeted as a promising pathway to convert CO2 into syngas which is the primary reactive in several reactions to obtain high-value chemicals. Among the different catalysts reported for RWGS, the nickel-based catalyst has been proposed as an alternative to the expensive noble metal catalyst. However, Ni-based catalysts tend to be less active in RWGS reaction conditions due to preference to CO2 methanation reaction and to the sintering and coke formation. Due to this, the aim of this work is to study the effect of the potassium (K) in Ni/CeO2 catalyst seeking the optimal catalyst for low-temperature RWGS reaction. We synthesised Ni-based catalyst with different amounts of K:Ni ratio (0.5:10, 1:10, and 2:10) and fully characterised using different physicochemical techniques where was observed the modification on the surface characteristics as a function of the amount of K. Furthermore, it was observed an improvement in the CO selectivity at a lower temperature as a result of the K-Ni-support interactions but also a decrease on the CO2 conversion. The 1K catalyst presented the best compromise between CO2 conversion, suppression of CO2 methanation and enhancing CO selectivity. Finally, the experimental results were contrasted with the trends obtained from the thermodynamics process modelling observing that the result follows in good agreement with the modelling trends giving evidence of the promising behaviour of the designed catalysts in CO2 high-scale units.

5.
Methods Find Exp Clin Pharmacol ; 32 Suppl A: 19-23, 2010 Dec.
Artículo en Español | MEDLINE | ID: mdl-21381284

RESUMEN

Graft-versus-host disease (GVHD) remains the greatest source of morbidity-mortality in allogenic transplant patients. Although in most cases the more easily obtainable clinical and laboratory test parameters suffice to confirm the diagnosis and establish the stage of the disease biopsies of the affected organ are sometimes needed. At present there is great Interest in the study of factors allowing a prognosis of the course and type of response to treatment in patients with CVHD. In this sense, It would be necessary to objectively Identify and validate biomarkers capable of predicting biological or pathological processes in patients with cVHD. To this effect we have performed serial analyses of skin tissue using peripheral blood and tissue biomarkers in a prospective observational study conducted in three transplant centers. The still preliminary results Indicate that certain histopathological findings classically attributed to CVHD ore also seen in patients not clinically affected by the disease--this probably being related to other physiopathological phenomena occurring during transplantation. The study of these findings, combined with biomarker analysis, will allow improved understanding of the underlying etiopathogenesis, as well as the definition of new diagnostic, prognostic and response-evaluating criteria.


Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Trasplante de Órganos/efectos adversos , Enfermedades de la Piel/etiología , Piel/química , Piel/patología , Biomarcadores/análisis , Biopsia , Enfermedad Injerto contra Huésped/metabolismo , Enfermedad Injerto contra Huésped/patología , Humanos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/patología , España , Trasplante Homólogo
6.
J Nanosci Nanotechnol ; 9(6): 3837-42, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19504928

RESUMEN

Manganese oxides having 2 x 2 tunnel structures (cryptomelanes) have been synthesized by a milling method in order to test their efficiency as catalysts for the abatement of volatile organic compounds, using toluene as probe molecule. These materials present excellent textural properties, arising from the nanofiber morphology and were active for toluene total oxidation. DRIFTS of the adsorbed phase allow proposing the role of lattice oxygen in the catalytic reaction.

7.
J Nanosci Nanotechnol ; 8(12): 6414-8, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19205214

RESUMEN

Photocatalytic oxidation of 2,4-dichlorophenoxyacetic acid was performed over ZrO2, Cu/ZrO2 and Fe/ZrO2 catalysts prepared by the sol-gel method. The samples were annealed at 400 degrees C. Textural and electronic characterization was carried out using BET and UV-Vis in order to establish the relationship between surface, pore volume and E(g) with the photoactivity of the materials. The degradation of the acid was followed by UV-Vis spectroscopy. The disappearance of the herbicide in solution follows approximately pseudo-first order kinetics. The apparent rate constants were calculated for the three catalysts. The results reveal that Fe/ZrO2 exhibits the best photoactivity for the degradation of 2,4-dichlorophenoxyacetic acid.

8.
J Hazard Mater ; 150(1): 99-108, 2008 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-17532119

RESUMEN

Apatite and Portland/apatite composite cements containing steelwork dusts have been prepared using a low temperature hydrothermal method (200 degrees C, 48h). The produced solids were characterized by means of XRD, IR, and SEM-EDX, and the remaining liquid was analyzed by ICP. The results clearly show the capability of these cements to inertise the heavy metals contained in steelwork dusts, that is Fe, Pb, Mo, Cr, Mn, Ni, and Zn. In the case of apatitic cements, Fe, Mg, Cr, Mn, and Pb coming from steel dust replaced Ca in the divalent cation position of the apatite structure, while Si and Mo replaced P in tetrahedral position. The average crystal size of the apatite-containing dust is smaller than in pure apatite synthesized using the same procedure, which is related to the magnesium content of the dust, since magnesium seems to inhibit the crystal growth. XRD diagrams of composite cements show only peaks corresponding to phases observed in the single cements, and in that no new phases are found. However, EDX analysis reveals the introduction of cations coming from Portland cement into the apatite structure. From the results of water analysis it could be concluded that the capability of retention is higher in composite matrices than in the pure apatite one. In conclusion, the obtained data allow stating that the proposed method, the hydrothermal synthesis of steelwork dust containing cement, is a reliable one for immobilization of toxic residues containing heavy leachable cations.


Asunto(s)
Apatitas/química , Metales Pesados/química , Administración de Residuos/métodos , Contaminantes Químicos del Agua/química , Contaminación del Agua/prevención & control , Apatitas/análisis , Polvo , Calor , Microscopía Electrónica de Rastreo , Acero Inoxidable/química , Contaminantes Químicos del Agua/análisis
9.
Leukemia ; 20(6): 1047-54, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16598311

RESUMEN

The use of the tyrosine kinase inhibitor imatinib, which blocks the enzymatic action of the BCR-ABL fusion protein, has represented a critical advance in chronic myeloid leukemia (CML) treatment. However, a subset of patients initially fails to respond to this treatment. Use of complementary DNA (cDNA) microarray expression profiling allows the identification of genes whose expression is associated with imatinib resistance. Thirty-two CML bone marrow samples, collected before imatinib treatment, were hybridized to a cDNA microarray containing 6500 cancer genes, and analyzed using bootstrap statistics. Patients refractory to interferon-alpha treatment were evaluated for cytogenetic and molecular responses for a minimum of 12 months. A set of 46 genes was differentially expressed in imatinib responders and non-responders. This set includes genes involved in cell adhesion (TNC and SCAM-1), drug metabolism (cyclooxygenase 1), protein tyrosine kinases and phosphatases (BTK and PTPN22). A six-gene prediction model was constructed, which was capable of distinguishing cytogenetic response with an accuracy of 80%. This study identifies a set of genes that may be involved in primary resistance to imatinib, suggesting BCR-ABL-independent mechanisms.


Asunto(s)
Resistencia a Antineoplásicos/genética , Perfilación de la Expresión Génica , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adolescente , Adulto , Anciano , Benzamidas , Análisis Citogenético , Femenino , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Proteínas de Fusión bcr-abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo
10.
Acta Biomater ; 2(2): 173-9, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16701875

RESUMEN

A novel biomaterial (HA-SBA-15) has been developed based on the growth of calcium phosphate hydroxyapatite (HA) nanoparticles within an organized silica structure (SBA-15). Characterization of the material was carried out using a combination of X-ray diffraction, X-ray fluorescence, transmission electron microscopy, N2 adsorption-desorption isotherms and nuclear magnetic resonance. Transmission electron microscopy observations and N2 porosimetry revealed the crystallization of hydroxyapatite nanoparticles inside the mesopore cavities of the silica structure. Specific surface areas of 760 m2 g(-1) and 260 m2 g(-1) were measured for the SBA-15 and the HA-SBA-15 material, respectively. The hydroxyl groups present in the silica nanostructure surface have brought about cationic defects in the silicium sites, mainly with those of tetrahedral symmetry, and promoted the formation of siloxanes. 29Si MAS-NMR analysis shows a significant reduction of the silanol groups concentration with HA growing within the base (SBA-15) material. Studies and brain tissue biocompatibility tests were carried out. Histopathological studies on the SBA-15 implant material showed no changes to the tissue nearby. The results confirmed the synthesis of a silica-based composite containing HA nanoparticles with the potential for biomedical applications.


Asunto(s)
Durapatita/química , Dióxido de Silicio/química , Adsorción , Materiales Biocompatibles , Calcio , Espectroscopía de Resonancia Magnética , Ensayo de Materiales , Microscopía Electrónica , Silicio , Termodinámica
11.
Biochim Biophys Acta ; 488(2): 207-17, 1977 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-196658

RESUMEN

Mycobacterium smegmatis extracts contain two fatty acyl synthetase systems (Brindley, D.N., Matsumura, S. and Bloch, K. (1966) Nature 224, 666-669). One is the extensively studied multienzyme complex, (molecular weight 1.39 - 10(6)) which produces shorter C16 and C18) and longer (C24 and higher) fatty acids in a bimodal pattern. The second synthetase is acyl carrier-protein (ACP) dependent and elongates the CoA derivatives of C12 and longer chains. In contrast to the type I synthetase which also extends long fatty acyl chains, the ACP-dependent system produces homologous fatty acids up to 30 carbon atoms long in approximately equal proportions. Other properties which distinguish the ACP-dependent system from the multienzyme complex include the resistance to high concentrations of palmitoyl-CoA and to low ionic strength and the lack of stimulation by mycobacterial polysaccharides. The possibility that the two fatty acid synthetases are complimentary in their function is discussed.


Asunto(s)
Proteínas Portadoras , Ácido Graso Sintasas , Mycobacterium/enzimología , Adenosina Trifosfato , Proteínas Portadoras/aislamiento & purificación , Proteínas Portadoras/metabolismo , Ácido Graso Sintasas/aislamiento & purificación , Ácido Graso Sintasas/metabolismo , Isoenzimas/aislamiento & purificación , Isoenzimas/metabolismo , Cinética , Magnesio , NAD , Concentración Osmolar , Oxidación-Reducción , Relación Estructura-Actividad
12.
J Clin Oncol ; 21(11): 2123-37, 2003 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-12775738

RESUMEN

PURPOSE: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries. PATIENTS AND METHODS: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients. RESULTS: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin's lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine-based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years. CONCLUSION: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II-targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.


Asunto(s)
Antineoplásicos/efectos adversos , Leucemia Promielocítica Aguda/etiología , Leucemia Inducida por Radiación , Adulto , Anciano , Anciano de 80 o más Años , Antibióticos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bélgica/epidemiología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Niño , ADN-Topoisomerasas de Tipo II , Femenino , Francia/epidemiología , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/epidemiología , Leucemia Promielocítica Aguda/genética , Leucemia Inducida por Radiación/tratamiento farmacológico , Leucemia Inducida por Radiación/epidemiología , Leucemia Inducida por Radiación/genética , Linfoma/tratamiento farmacológico , Linfoma/radioterapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España/epidemiología , Resultado del Tratamiento , Tretinoina/administración & dosificación
13.
Exp Hematol ; 25(6): 516-20, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9197330

RESUMEN

We evaluated the role of high-dose granulocyte colony stimulating factor (G-CSF) in vitro, in inducing the generation of high-proliferative potential colony forming cells (HPP-CFC), from either mononuclear cells or purified CD34+ cells. Both normal controls and patients undergoing peripheral blood stem cell (PBSC) mobilization and transplantation were studied. In serum-driven agar cultures, G-CSF stimulated the proliferation of HPP-CFC in a dose dependent manner (r = 0.92). The number of HPP-CFC was four-fold greater in mobilized patients than in normal controls. Purified CD34+ cells yielded 11-fold more colonies than mononuclear cells. HPP-CFC from mobilized patients showed replating capacity, giving rise to secondary colonies of more mature appearance. In serum-free cultures, the effect of G-CSF appeared to be mediated by synergistic interaction with stem cell factor. Our results suggest that G-CSF stimulates primitive hematopoietic cells that are detectable in increased amounts in patients receiving mobilization therapy. Therefore, determination of G-CSF induced HPP-CFC could be a useful tool in the evaluation of mobilization strategies.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Hematopoyesis/efectos de los fármacos , Células Madre Hematopoyéticas/citología , Antígenos CD34/análisis , Sangre , Separación Celular , Células Cultivadas , Medios de Cultivo , Relación Dosis-Respuesta a Droga , Humanos
14.
Bone Marrow Transplant ; 20(3): 243-5, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9257893

RESUMEN

We report the case of a BMT recipient who developed blindness 22 months after BMT. Microvascular retinopathy, cortical blindness and other ocular pathologies were excluded with appropriate tests. Electrophysiological studies showed retinal damage without excluding an optic nerve lesion. The patient, who had several risk factors for neurologic-induced cyclosporine toxicity, improved with cyclosporine withdrawal. Our findings stress the need of electrophysiological tests to exclude neuroretinal damage in patients receiving cyclosporine after BMT.


Asunto(s)
Ceguera/inducido químicamente , Trasplante de Médula Ósea , Ciclosporina/efectos adversos , Rechazo de Injerto/prevención & control , Inmunosupresores/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adulto , Ceguera/patología , Ciclosporina/administración & dosificación , Femenino , Humanos , Inmunosupresores/administración & dosificación , Retina/efectos de los fármacos , Retina/patología , Trasplante Homólogo
15.
Bone Marrow Transplant ; 10(3): 297-9, 1992 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1384901

RESUMEN

A 20-year-old male with severe bone marrow failure associated with paroxysmal nocturnal haemoglobinuria (PNH) underwent an allogeneic bone marrow transplantation (BMT). Flow cytometric analysis of phosphatidylinositol (PI) anchored membrane proteins prior to BMT showed a markedly reduced expression of monocyte CD14 and neutrophil CD16 molecules. On day +17 after BMT expression of both antigens reached normal values and remained stable throughout a follow-up period of 10 months, thus confirming the eradication of the PNH clone. To date, this is the first case in which normal expression of PI-anchored proteins after BMT is reported.


Asunto(s)
Trasplante de Médula Ósea , Hemoglobinuria Paroxística/metabolismo , Hemoglobinuria Paroxística/cirugía , Proteínas de la Membrana/metabolismo , Fosfatidilinositoles/metabolismo , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Trasplante de Médula Ósea/inmunología , Trasplante de Médula Ósea/fisiología , Hemoglobinuria Paroxística/inmunología , Humanos , Receptores de Lipopolisacáridos , Masculino , Proteínas de la Membrana/inmunología , Monocitos/inmunología , Monocitos/metabolismo , Neutrófilos/inmunología , Neutrófilos/metabolismo , Receptores de IgG/metabolismo
16.
Bone Marrow Transplant ; 18(5): 899-905, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8932843

RESUMEN

IL-2 therapy may be useful in situations with a low tumour burden, such as after autologous transplantation. However, conflicting reports about the deleterious effects of this cytokine on haemopoiesis have precluded its widespread use. To study IL-2 effects on haemopoietic transplant progenitors we established long-term cultures (Dexter-type) with cells from allogeneic marrow and marrow/peripheral blood cell infusates of autologous transplants with different concentrations of IL-2 (0-1000 IU/ml). Percentage of CD56+ cells was also determined in cultures. IL-2 induced an inhibitory effect on stroma and an increase in the percentage of CD56+ cells compared with controls. No deleterious effect either in the production of BFU-E or CFU-GM weekly or over the whole period of culture was observed. Our results suggest that IL-2 is able to induce an increase in CD56+ cells early after transplantation without a deleterious effect on long-term haemopoiesis.


Asunto(s)
Trasplante de Médula Ósea , Médula Ósea/patología , Células Madre Hematopoyéticas/patología , Interleucina-2/farmacología , Antígeno CD56/análisis , Recuento de Células/efectos de los fármacos , Células Cultivadas , Células Madre Hematopoyéticas/inmunología , Humanos , Trasplante Autólogo , Trasplante Homólogo
17.
Hematol J ; 1(6): 374-81, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11920217

RESUMEN

INTRODUCTION: This study analyses the factors affecting mobilisation and engraftment in autologous peripheral blood progenitor cell transplantation according to the number of CD34(+) re-infused. MATERIALS AND METHODS: A total of 190 patients underwent mobilisation with G-CSF alone (n=113) or in combination with chemotherapy (n=77). A total of 116 patients (61%) were autografted with <2 x 10(6) CD34(+) cells/kg and 74 patients were transplanted with >2 x 10(6) CD34(+) cells/kg. Rates of granulocyte and platelet recovery were estimated using the product-limit method of Kaplan-Meier and compared using a log-rank test. The Cox regression model was used for the multivariate analysis of factors influencing engraftment. Differences between cohorts were evaluated by one-way ANOVA or Mann-Whitney tests, and multivariate analysis was performed using a stepwise lineal regression. RESULTS: Neutrophil and platelet engraftment was significantly longer with <2 x 10(6)/CD34(+)/kg (12 vs 10 days, P=0.014 and 16 vs 13 days, P=0.0001 respectively). Platelet recovery was affected by exposure to alkylating agents (P=0.04), refractory disease (P=0.02) and AML (P=0.0001), but only the last two variables remained significant in Cox regression (P<0.01). Granulocyte engraftment was longer in CML (univariate, P=0.04) and in refractory disease (multivariate, P=0.02). In patients re-infused with >2 x 10(6)/CD34(+)/kg, the Cox model did not identify prognostic factors for haematopoietic recovery. CONCLUSION: Although mobilisation schedules and disease status influenced not only the yield of progenitor cells, but also the engraftment kinetics, the number of CD34(+) re-infused was the main predictor of haematopoietic recovery. While engraftment succeeded in most of the cases, the re-infusion of >2 x 10(6)/CD34(+)/kg resulted in significantly shorter recovery times.


Asunto(s)
Neoplasias Hematológicas/terapia , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Adulto , Anciano , Antígenos CD34/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Células Sanguíneas , Caspasa 14 , Caspasas/administración & dosificación , Hemorragia Cerebral/etiología , Estudios de Cohortes , Terapia Combinada , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Eritropoyetina/farmacología , Etopósido/administración & dosificación , Femenino , Supervivencia de Injerto , Factor Estimulante de Colonias de Granulocitos/farmacología , Neoplasias Hematológicas/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Hidroxiurea/administración & dosificación , Infecciones/etiología , Infecciones/mortalidad , Leucaféresis/métodos , Tablas de Vida , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Modelos de Riesgos Proporcionales , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/mortalidad , Trasplante Autólogo
18.
Bone Marrow Transplant ; 30(2): 63-8, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12132043

RESUMEN

Standard allogeneic stem cell transplantation (SCT) has been associated with a high transplant-related mortality (TRM) in patients who have failed a prior autologous SCT (ASCT). Reduced-intensity conditioning (RIC) regimens may reduce the toxicities and TRM of traditional myeloablative transplants. We report 46 adults who received a RIC peripheral blood SCT from an HLA-identical sibling in two multicenter prospective studies. The median interval between ASCT and allograft was 16 months, and the patients were allografted due to disease progression (n = 43) and/or secondary myelodysplasia (n = 4). Conditioning regimens consisted of fludarabine plus melphalan (n = 41) or busulphan (n = 5). The 100-day incidence of grade II-IV acute graft-versus-host disease (GVHD) was 42% (24% grade III-IV), and 10/30 evaluable patients developed chronic extensive GVHD. Early complete donor chimerism in bone marrow and peripheral blood was observed in 35/42 (83%) patients, and 16 evaluable patients had complete chimerism 1 year post transplant. With a median follow-up of 358 days (450 in 29 survivors), the 1-year incidence of TRM was 24%, and the 1-year overall (OS) and progression-free survival were 63% and 57%, respectively. Patients who had chemorefractory/ progressive disease, a low performance status or received GVHD prophylaxis with cyclosporine A alone (n = 32) had a 1-year TRM of 35% and an OS of 46%, while patients who had none of these characteristics (n = 32) had a 1-year TRM of 35% and an OS of 46% while patients who had none of these characteristics (n = 14) had a TRM of 0% and an OS of 100%. Our results suggest that adult patients who fail a prior ASCT can be salvaged with a RIC allogeneic PBSCT with a low risk of TRM, although patient selection has a profound influence on early outcome.


Asunto(s)
Trasplante de Células Madre de Sangre Periférica/mortalidad , Acondicionamiento Pretrasplante/métodos , Adulto , Femenino , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Hematopoyesis , Humanos , Masculino , Persona de Mediana Edad , Infecciones Oportunistas , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Estudios Prospectivos , Recurrencia , Quimera por Trasplante , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Autólogo , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/mortalidad , Insuficiencia del Tratamiento , Resultado del Tratamiento
19.
Bone Marrow Transplant ; 19(5): 429-34, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9052907

RESUMEN

Use of IL-2 therapy after autologous transplantation is currently being explored to reduce relapse rate. Low doses of the cytokine induce significant immunomodulation avoiding the severe side-effects associated with high-dose IL-2 therapy. However, low-dose IL-2 is usually given by continuous infusion through central venous lines with the consequent risks of thrombosis and infections. Twenty-six consecutive patients who received autologous transplants received low-dose IL-2 after stable engraftment had been achieved. The first 13 patients (group A) were scheduled to receive 400,000/IU/m2/day for 3 months by continuous intravenous infusion. Ten of these patients suffered infectious episodes, mainly bacteriemias that often necessitated delaying IL-2 therapy (median delivered dose: 32% of planned). The next 13 patients were then assigned to receive IL-2 (800,000-1,000,000 IU/m2/day for 3 months) subcutaneously (group B). For group B patients, median dose intensity was 84% (P = 0.01 when compared with group A patients). Only one severe infectious episode was observed in these patients. Clinical toxicity in group B patients consisted mainly of s.c. nodules. Immunomodulation, measured as an increase in the absolute number of CD56+ cells and CD56+(bright) cells, was higher in patients who received the cytokine by the subcutaneous route (median peak increase of CD56+ cells: 160 and 220% for group A and B patients respectively; median peak increase of CD56+(bright) cells: 210% and 310% for group A and B respectively, P < 0.05 between groups A and B). No statistically significant increment of T lymphocytes was observed in any group. No hematologic toxicity was observed apart from eosinophilia, which was very marked in group B (P < 0.01). Our results show that low-dose s.c. IL-2 therapy is associated with low clinical and hematologic toxicity after autologous transplantation. The immunomodulation achieved is no less than that achieved with the i.v. approach.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Trasplante de Médula Ósea , Trasplante de Células Madre Hematopoyéticas , Interleucina-2/administración & dosificación , Lesión Renal Aguda/inducido químicamente , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Síndrome de Fuga Capilar/inducido químicamente , Cateterismo Venoso Central , Terapia Combinada , Estudios de Seguimiento , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Hipotensión/inducido químicamente , Infecciones/etiología , Infusiones Intravenosas , Inyecciones Subcutáneas , Interleucina-2/efectos adversos , Interleucina-2/sangre , Interleucina-2/uso terapéutico , Recuento de Linfocitos , Subgrupos Linfocitarios , Neoplasias/terapia , Estudios Prospectivos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Autólogo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisis
20.
Bone Marrow Transplant ; 22(6): 519-25, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9758337

RESUMEN

The objective of this study was to analyze CD34+ cell recovery and T cell depletion (TCD) achieved in CD34+ cell grafts using either immunoadsorption or immunomagnetic methods applied to leukapheresis products from healthy donors. We also wanted to determine the kinetics of engraftment and incidence and severity of graft-versus-host disease (GVHD) after allogeneic transplantation of selected CD34+ cells. HLA-identical sibling donors received G-CSF. After leukapheresis, peripheral blood progenitor cells were selected using immunoadsorption (Ceprate SC) (n = 38) or immunomagnetic (Isolex 300) (n = 24) methods. Sixty-two patients, with a median age of 42 years (range 17-60) diagnosed with hematological malignancies were conditioned with either cyclophosphamide and total body irradiation (n = 43) or busulphan and cyclophosphamide (n = 19). GVHD prophylaxis consisted of cyclosporin A (CsA) and prednisone (n = 48), CsA alone (n = 11) and CsA and methotrexate (n = 3). The median yield and purity of CD34+ cells after the procedure was 65 and 66% with immunoadsorption, and 48 and 86% with immunomagnetic method, respectively. The median number (range) of CD34+ cells infused into the patients was 3.5 x 10(6)/kg (1-9.6). The median number (range) of CD3+ cells administered was 0.4 x 10(6)/kg (0.01-2) using immunoadsorption and 0.14 x 10(6)/kg (0.03-2.5) using immunomagnetic methods. Neutrophil recovery >500 and >1000/microl was achieved at a median (range) of 13 days (8-22) and 14 days (9-31), respectively. Platelets recovered to >20000 and >50000/microl at a median (range) of 13 days (0-128) and 18 days (0-180), respectively. Two patients developed graft failure. Acute GVHD in patients at risk was clinical grade 0 (n = 43), I (n = 8), II (n = 4) and III (n = 1). No patient developed acute GVHD grade IV. Chronic GVHD was limited in two cases and extensive in four cases. The actuarial probability of acute GVHD II-IV was 10% (95% CI, 1-19%), and of extensive chronic GVHD was 12% (95% CI, 11-13%). The cumulative incidence of transplant-related mortality was 12.6%, and this figure was 9% at 6 months. In conclusion, with the immunomagnetic procedure, a lower recovery and higher purity of CD34+ cells, and stronger TCD is obtained as compared to immunoadsorption (P = 0.008, P < 0.0001 and P = 0.0002, respectively). Our results also indicate that allogeneic transplantation of selected CD34+ cells is associated with a very rapid engraftment and with a low incidence of severe GVHD.


Asunto(s)
Antígenos CD34/sangre , Trasplante de Células Madre Hematopoyéticas , Enfermedad Aguda , Adolescente , Adulto , Enfermedad Crónica , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Células Madre Hematopoyéticas/inmunología , Humanos , Separación Inmunomagnética , Técnicas de Inmunoadsorción , Cinética , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Linfocitos T/inmunología , Trasplante Homólogo
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