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1.
Ann Hematol ; 101(10): 2263-2270, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35997804

RESUMEN

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.


Asunto(s)
Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva , Piridazinas , Antineoplásicos/efectos adversos , Resistencia a Antineoplásicos , Proteínas de Fusión bcr-abl/genética , Humanos , Imidazoles , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Niacinamida/análogos & derivados , Inhibidores de Proteínas Quinasas/efectos adversos , Pirazoles , Piridazinas/efectos adversos , Estudios Retrospectivos
2.
Phys Rev Lett ; 124(24): 244801, 2020 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-32639812

RESUMEN

Continuous-wave photoinjectors operating at high accelerating gradients promise to revolutionize many areas of science and applications. They can establish the basis for a new generation of monochromatic x-ray free electron lasers, high-brightness hadron beams, or a new generation of microchip production. In this Letter we report on the record-performing superconducting rf electron gun with CsK_{2}Sb photocathode. The gun is generating high charge electron bunches (up to 10 nC/bunch) and low transverse emittances, while operating for months with a single photocathode. This achievement opens a new era in generating high-power beams with a very high average brightness.

3.
J Environ Manage ; 213: 159-167, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29494932

RESUMEN

The anaerobic biodegradation of ethanol-glycol ether mixtures as 1-ethoxy-2-propanol (E2P) and 1-methoxy-2-propanol (M2P), widely used in printing facilities, was investigated by means of two laboratory-scale anaerobic bioreactors at 25oC: an expanded granular sludge bed (EGSB) reactor and an anaerobic hybrid reactor (AHR), which incorporated a packed bed to improve biomass retention. Despite AHR showed almost half of solid leakages compared to EGSB, both reactors obtained practically the same performance for the operating conditions studied with global removal efficiencies (REs) higher than 92% for organic loading rates (OLRs) as high as 54 kg of chemical oxygen demand (COD) m-3 d-1 (REs of 70% and 100% for OLRs of 10.6 and 8.3 kg COD m-3 d-1 for E2P and M2P, respectively). Identified byproducts allowed clarifying the anaerobic degradation pathways of these glycol ethers. Thus, this study shows that anaerobic scrubber can be a feasible treatment for printing emissions.


Asunto(s)
Etanol , Éter , Eliminación de Residuos Líquidos , Anaerobiosis , Reactores Biológicos , Éteres , Aguas del Alcantarillado
4.
Actas Dermosifiliogr ; 106(7): 569-77, 2015 Sep.
Artículo en Inglés, Español | MEDLINE | ID: mdl-25935194

RESUMEN

INTRODUCTION: In biologic therapy, dose modification in carefully selected patients when psoriasis is in remission could reduce treatment costs and the risks associated with drug exposure. MATERIAL AND METHODS: Observational, descriptive, crosssectional study, performed in January 2014, of 112 patients with moderate to severe psoriasis who had been on biologic therapy for at least 6 months. The therapeutic objective in all cases was to achieve and maintain a 75% reduction in Psoriasis Area and Severity Index (PASI 75). All the patients had started treatment with the standard regimen. During treatment, the dose had been reduced in patients who achieved the therapeutic objective and escalated in those who failed to respond adequately to standard doses. RESULTS: At the time of the study, 42.9% of the patients were receiving the standard dose, 50% were on a reduced dose, and 7.1% were on an escalated regimen. The agent with which the dose was most often reduced was adalimumab (57.7%), and the agents with which therapy was most often escalated were ustekinumab (17.9%) and infliximab (12.5%). Patients who received reduced doses had significantly longer-standing disease (P=.049) and longer treatment duration with the same biologic agent (P=.009). In the group that did not fulfill the criteria for dose reduction, the proportion of patients with psoriatic arthritis was significantly higher (P=.023). Cost savings were as follows: 21.5% with adalimumab, 13.8% with etanercept, .9% with ustekinumab, and .55% with infliximab. CONCLUSIONS: Patients with longer-standing disease and longer treatment duration with the same biologic agent were significantly more likely to be candidates for dose reduction. The proportion of patients with psoriatic arthritis was greater in the group of patients who did not fulfill the conditions for dose reduction. The overall cost saving achieved using the dose modification algorithm described in this study was 13%. Controlled studies are needed to define the profile of the patients best suited for dose reduction strategies without loss of treatment efficacy.


Asunto(s)
Adalimumab/uso terapéutico , Terapia Biológica/métodos , Fármacos Dermatológicos/uso terapéutico , Etanercept/uso terapéutico , Infliximab/uso terapéutico , Psoriasis/tratamiento farmacológico , Ustekinumab/uso terapéutico , Adalimumab/administración & dosificación , Adalimumab/economía , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Terapia Biológica/economía , Ahorro de Costo , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/economía , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Costos de los Medicamentos , Etanercept/administración & dosificación , Etanercept/economía , Femenino , Humanos , Infliximab/administración & dosificación , Infliximab/economía , Masculino , Persona de Mediana Edad , Psoriasis/economía , Resultado del Tratamiento , Ustekinumab/administración & dosificación , Ustekinumab/economía , Adulto Joven
5.
J Affect Disord ; 333: 365-376, 2023 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-37094658

RESUMEN

BACKGROUND: The study of Obsessive-Compulsive Disorder (OCD) genomics has primarily been tackled by Genome-wide association studies (GWAS), which have encountered troubles in identifying replicable single nucleotide polymorphisms (SNPs). Endophenotypes have emerged as a promising avenue of study in trying to elucidate the genomic bases of complex traits such as OCD. METHODS: We analyzed the association of SNPs across the whole genome with the construction of visuospatial information and executive performance through four neurocognitive variables assessed by the Rey-Osterrieth Complex Figure Test (ROCFT) in a sample of 133 OCD probands. Analyses were performed at SNP- and gene-level. RESULTS: No SNP reached genome-wide significance, although there was one SNP almost reaching significant association with copy organization (rs60360940; P = 9.98E-08). Suggestive signals were found for the four variables at both SNP- (P < 1E-05) and gene-levels (P < 1E-04). Most of the suggestive signals pointed to genes and genomic regions previously associated with neurological function and neuropsychological traits. LIMITATIONS: Our main limitations were the sample size, which was limited to identify associated signals at a genome-wide level, and the composition of the sample, more representative of rather severe OCD cases than a population-based OCD sample with a broad severity spectrum. CONCLUSIONS: Our results suggest that studying neurocognitive variables in GWAS would be more informative on the genetic basis of OCD than the classical case/control GWAS, facilitating the genetic characterization of OCD and its different clinical profiles, the development of individualized treatment approaches, and the improvement of prognosis and treatment response.


Asunto(s)
Estudio de Asociación del Genoma Completo , Trastorno Obsesivo Compulsivo , Humanos , Trastorno Obsesivo Compulsivo/genética , Trastorno Obsesivo Compulsivo/psicología , Polimorfismo de Nucleótido Simple/genética , Endofenotipos , Genómica
6.
Water Sci Technol ; 65(1): 177-82, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22173423

RESUMEN

The study of an industrial unit of biotrickling filter for the treatment of the exhaust gases of a flexographic facility was investigated over a 2-year period with the objective to meet the volatile organic compound (VOC) regulatory emission limits. Increasing the water flow rate from 2 to 40 m(3) h(-1) improved the performance of the process, meeting the VOC regulation when 40 m(3) h(-1) were used. An empty bed residence time (EBRT) of 36 s was used when the inlet air temperature was 18.7 °C, and an EBRT as low as 26 s was set when the inlet temperature was 26.8 °C. During this long-term operation, the pressure drop over the column of the bioreactor was completely controlled avoiding clogging problems and the system could perfectly handle the non-working periods without VOC emission, demonstrating its robustness and feasibility to treat the emission of the flexographic sector.


Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire/prevención & control , Reactores Biológicos , Filtración/instrumentación , Impresión , Compuestos Orgánicos Volátiles/análisis , Presión , Aguas del Alcantarillado
7.
J Environ Manage ; 92(8): 1978-85, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21531069

RESUMEN

The effect of using ground tire rubber (GTR) as an adsorptive material in the removal of a 2:1:1 weight mixture of n-butyl acetate, toluene and m-xylene by using a peat biofilter under different intermittent conditions was investigated. The performance of two identical size biofilters, one packed with fibrous peat alone and the other with a 3:1 (vol) fibrous peat and GTR mixture, was examined for a period of four months. Partition coefficients of both materials were measured. Values of 53, 118 and 402 L kg(-1) were determined for n-butyl acetate, toluene and m-xylene in peat, respectively; and values of 40, 609 and 3035 L kg(-1) were measured for the same compounds in GTR. Intermittent load feeding of 16 h per day, 5 days per week working at an EBRT of 60 s and an inlet VOC concentration of 0.3 g C m(-1), resulted in removal efficiencies higher than 90% for both biofilters, indicating that the addition of GTR did not adversely affect the behavior of the bioreactor. Full removal of n-butyl acetate was obtained for both biofilters. GTR improved the removal of the aromatics in the first part of the biofilter, facilitating lower penetration of the toluene and m-xylene into the bed. A 31-day starvation period was applied and intermittent operation subsequently restarted. In both biofilters, high removal efficiencies after a re-acclimation period of two days were achieved. A shock loading test related to 1-h peaks of three- and four-fold increases in its baseline concentration (0.30 g C m(-3)) was applied in both biofilters. For the biofilter packed with the peat and GTR mixture, attenuation greater than 60% was observed in the maximum outlet concentration when compared to the biofilter packed with peat alone.


Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire/prevención & control , Filtración/métodos , Goma/química , Suelo/química , Compuestos Orgánicos Volátiles/análisis , Acetatos/análisis , Adsorción , Cromatografía de Gases , Tolueno/análisis , Xilenos/análisis
9.
Pharmacogenomics J ; 8(2): 101-12, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17505499

RESUMEN

Brain-derived neurotrophic factor (BDNF) has been studied extensively in relation to the susceptibility to mood disorders (MD), although it remains to be clarified whether BDNF is a susceptibility locus for MD phenotypes, including therapeutic response to antidepressants. We have performed a single-marker and haplotype association study of eight TagSNPs polymorphisms in the genomic region containing the BDNF gene in 342 control subjects and 374 patients with MD, and have tested the association with antidepressant treatment outcome. None of the eight single nucleotide polymorphisms (TagSNPs) was significantly associated with MD phenotype after Bonferroni correction. In the single-marker analysis, a SNP was found to be associated with the patient's state of 'remitter' after adequate trial with a single antidepressant phenotype (odds ratio (OR)=2.95; P=0.0025). We also identified a haplotype associated with this phenotype. This study supports the implication of BDNF in antidepressant treatment outcome in MD, with specific association with 5' upstream region of BDNF gene.


Asunto(s)
Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/genética , Haplotipos , Trastornos del Humor/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Regiones no Traducidas 5' , Adulto , Anciano , Estudios de Casos y Controles , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/genética , Oportunidad Relativa , Fenotipo , Factores de Riesgo , España , Resultado del Tratamiento
10.
Bioresour Technol ; 99(2): 269-76, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17317157

RESUMEN

In order to investigate suitable packing materials, a soil amendment composed of granular high mineralized peat (35% organic content) locally available has been evaluated as carrier material for biofiltration of volatile organic compounds in air by comparison with a fibrous peat (95% organic content). Both supports were tested to eliminate ethylbenzene from air streams in laboratory-scale reactors inoculated with a two-month conditioned culture. In pseudo-steady state operation, experiments at various ethylbenzene inlet loads (ILs) were carried out. Maximum elimination capacity of about 120 g m(-3) h(-1) for an IL of 135 g m(-3) h(-1) was obtained for the fibrous peat. The soil amendment reactor achieved a maximum elimination capacity of about 45 g m(-3) h(-1) for an inlet load of 55 g m(-3) h(-1). Ottengraf-van den Oever model was applied to the prediction of the performance of both biofilters. The influence of gas flow rate was also studied: the fibrous peat reactor kept near complete removal efficiency for empty bed residence times greater than 1 min. For the soil amendment reactor, an empty bed residence time greater than 2 min was needed to achieve adequate removal efficiency. Concentration profiles along the biofilter were also compared: elimination occurred in the whole fibrous peat biofilter, while in the soil amendment reactor the biodegradation only occurred in the first 65% part of the biofilter. Results indicated that soil amendment material, previously selected to increase the organic content, would have potential application as biofilter carrier to treat moderate VOC inlet loads.


Asunto(s)
Derivados del Benceno/aislamiento & purificación , Filtración/métodos , Suelo/análisis , Filtración/instrumentación , Modelos Teóricos , España
11.
Bone Marrow Transplant ; 52(5): 745-752, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28112745

RESUMEN

The pathogenesis of GvHD involves migration of donor T-cells into the secondary lymphoid organs in the recipient, which is steered by two homing molecules, CD62L and CCR7. Therefore, we investigated whether the migratory capacity of donor T-cells is associated with GvHD. This single center prospective study included 85 donor-recipient pairs. In vitro chemotaxis assays of the lymphocytes of the apheresis product were performed in parallel to the analysis of CD62L and CCR7 by flow cytometry. The migratory index to the CCR7 ligands, CCL19 and CCL21, was higher in T-cells from donors whose recipients will develop GvHD. Similarly, the acute GvHD (aGvHD) group received higher percentage of CD4+CCR7+ T-cells, whereas chronic GvHD (cGvHD) patients were transplanted with higher percentages of CD8+CCR7+ T-cells compared with the non-GvHD group. These results were confirmed when patients were subdivided according to degrees of severity. Further, multivariate analysis confirmed that the proportions of CCR7+ CD4+ and CCR7+ CD8+ T-cells are risk factors for the development and severity of aGvHD and cGvHD, respectively. Functional experiments demonstrated that CCR7+ T-cells exhibited higher potential for activation than CCR7- T-cells did. We therefore propose that the selective depletion of CCR7-expressing T-cells may be an effective preventive therapy for GvHD.


Asunto(s)
Linfocitos T CD4-Positivos/citología , Quimiotaxis , Enfermedad Injerto contra Huésped/patología , Receptores CCR7/análisis , Adolescente , Adulto , Anciano , Relación CD4-CD8 , Linfocitos T CD4-Positivos/trasplante , Quimiocina CCL19/análisis , Quimiocina CCL21/análisis , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Incidencia , Selectina L/análisis , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Receptores CCR7/inmunología , Receptores Mensajeros de Linfocitos/fisiología , Índice de Severidad de la Enfermedad , Donantes de Tejidos , Trasplante Homólogo/efectos adversos , Adulto Joven
12.
Int J Oncol ; 28(1): 143-8, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16327990

RESUMEN

Invasiveness and metastatic potential are the two most important properties defining malignancy. The adeno-virus E1A (Ad-E1A) gene has a dual effect as a proliferative gene and as a tumor-suppressor gene, decreasing tumor growth and the metastatic potential of malignant cells. In order to study genes related with the antimetastatic effect of Ad-E1A in human cells, we performed a microarray analysis using OncoChiptrade mark. In three independent experiments, NIH3T3, IMR90 and MDA MB 435 cells were infected with pLPC retroviruses carrying the adenovirus 12S E1A gene or the GFP gene. We analyzed cDNA expression by using the CNIO OncoChipTM, a cDNA microarray containing a total of 6386 genes represented by 7237 clones. uPA, uPAr, tPA, PAI-1 and PAI-2 were also studied at RNA and protein levels. Microarrays of cDNA expression, RT-PCR and Western blot performed in IMR90 E1A-expressing cells showed downregulation of uPA, uPAr, tPA, PAI-1 and upregulation of PAI-2. These results were confirmed in NIH3T3 and MDA MB 435 breast carcinoma cells, with PAI-2 upregulation by RT-PCR and Western blot. In addition, zymographic analysis demonstrated that E1A expression greatly reduced the gelatinase activity of the pro-MMP2 and -MMP9 proteins. We propose that adenovirus E1A may orchestrate the expression of most members of the urokinase-plasminogen activation system, downregulating potentially invasive genes and upregulating PAI-2, which is associated with a better prognosis in human tumors.


Asunto(s)
Adenoviridae/genética , Proteínas Precoces de Adenovirus/fisiología , Neoplasias de la Mama/patología , Carcinoma/patología , Regulación Neoplásica de la Expresión Génica , Inhibidor 1 de Activador Plasminogénico/biosíntesis , Adenoviridae/fisiología , Western Blotting , Femenino , Perfilación de la Expresión Génica , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Regulación hacia Arriba
13.
Neurocirugia (Astur) ; 16(5): 441-6, 2005 Oct.
Artículo en Español | MEDLINE | ID: mdl-16276452

RESUMEN

BACKGROUND: In the surgical approaches to the posterior fossa, the accurate location of the transverse-sigmoid sinus (TS-SS) complex is of great importance. The asterion is a referral landmark to the transverse sinus location. METHOD: Twenty-five skulls of adult cadavers were studied. We seek for the relationships of the asterion with: TS location, mastoid emissary vein, suprametal crest and inion. RESULTS: The asterion was found in 49 cases. In the great majority of cases (87.8%) the asterion was over the TS (72.2% over the sinus proper, 27.8% over the TS-SS transition). The mastoid emissary vein was present in 46 cases, and in 36% we found two veins. DISCUSSION AND CONCLUSIONS: The burr hole for posterolateral approaches to the posterior fossa must be located below and behind the asterion.


Asunto(s)
Fosa Craneal Posterior/anatomía & histología , Senos Craneales/anatomía & histología , Adulto , Cadáver , Fosa Craneal Posterior/cirugía , Humanos , Procedimientos Neuroquirúrgicos , Cráneo/anatomía & histología , Propiedades de Superficie
14.
Thromb Haemost ; 81(6): 887-90, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10404762

RESUMEN

We present the case of a full-term newborn in whom purpura fulminans developed shortly after birth. A diagnosis of homozygous protein C deficiency was established based upon undetectable plasma protein C activity and antigenemia in the newborn infant, and was later confirmed by protein C gene analysis. Specific replacement therapy with intravenous protein C concentrate was started 9 days after birth. This rapidly led to the complete regression of cutaneous lesions and consumption coagulopathy. After stabilization, oral anticoagulation was initiated in association with prophylactic treatment with intravenous protein C concentrate. However, oral anticoagulation was finally abandoned as the patient presented several thrombotic and hemorrhagic episodes clearly related to difficulties with anticoagulation. Due to the hazards related to prolonged venous access, we are currently using subcutaneous infusion of protein C concentrate for the long-term management of this condition, with satisfactory results.


Asunto(s)
Deficiencia de Proteína C/tratamiento farmacológico , Proteína C/administración & dosificación , Administración Oral , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Femenino , Homocigoto , Humanos , Recién Nacido , Inyecciones Subcutáneas , Deficiencia de Proteína C/genética
15.
Bone Marrow Transplant ; 26(11): 1199-204, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11149731

RESUMEN

Acute renal failure and veno-occlusive disease of the liver are serious complications following stem cell transplantation (SCT) and contribute to the non-relapse mortality associated with this procedure. Endothelins, a family of vasoconstrictor peptides, may be involved in the pathogenesis of a variety of renal and hepatic diseases, including CsA-associated hypertension and the hepatorenal syndrome. In order to study the relevance of endothelins to SCT-related liver and kidney dysfunction, we determined endothelin-1 (ET-1) levels in plasma samples obtained from 65 patients (38 autologous, 27 allogeneic) 7 days before and 7, 14 and 28 days after SCT. A steady increase in plasma ET-1 was observed after SCT (5.36 pg/ml, 95% CI 4.30-6.43 on day +28 vs 3.82 pg/ml, 95% CI 3.21-4.43 on day -7; P = 0.020). No differences in ET-1 levels existed between autologous and allogeneic SCT recipients at any of the time points studied (P = 0.561). In addition, no significant differences were observed among patients with renal dysfunction vs those without (P = 0.187), nor in patient groups with or without hepatic dysfunction (P = 0.075). In conclusion, even though plasma ET-1 levels showed a steady increase following SCT, no correlation could be found with development of SCT-related kidney or liver dysfunction.


Asunto(s)
Endotelina-1/sangre , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Adolescente , Adulto , Ciclosporina/sangre , Ciclosporina/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/etiología , Enfermedad Veno-Oclusiva Hepática/sangre , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Inmunosupresores/sangre , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad
16.
Bone Marrow Transplant ; 17(6): 979-84, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8807103

RESUMEN

Between May 1983 and March 1994, 31 patients with AML in second CR underwent BMT. Fifteen underwent allogeneic BMT from an HLA-identical sibling donor and 16 without a donor, unpurged ABMT. Two different preparative regimens were used: CY (120 mg/kg) and 12 Gy of fractioned TBI (19 patients), and Bu (16 mg/kg) and Cy (120 mg/kg) (BuCy2) in 12 patients. Main clinical characteristics including age, sex, length of first remission, FAB type, and number of leukocytes at diagnosis were similar in both groups. A combination of MTX and CsA was used in 13 cases whereas either CsA or MTX alone was employed in the other two patients. With a median follow-up of 5 years the actuarial 5 year probability of disease-free survival (DFS) for the whole group was 39.8% (95% CI: 29.5-50.1%). The 5 year DFS was equivalent for those who received either ABMT (41.6 +/- 14.2%) or allogeneic BMT (40 +/- 15%). Probabilities of relapse and non-relapse mortality for ABMT and allo BMT patients were 48.7 +/- 16.1 and 18.7 +/- 14.3, and 30.1 +/- 19.2 and 40.7 +/- 16.9, respectively. DFS was better in those patients with a longer duration of first CR (> 18 months) 62.5 +/- 14.4 vs 30.4 +/- 17.9%, attributable to a significantly lower relapse rate in this group of patients 16.6 +/- 12.8 vs 57.8 +/- 22.7 (P 0.05). In conclusion, similar results were observed when ABMT and allo BMT were compared for AML in CR2. A higher antileukemic effect associated with the allo BMT is balanced by an increase in transplant-related mortality. Duration of first remission was the most important factor affecting DFS and better outcome was observed for patients with longer CR1.


Asunto(s)
Trasplante de Médula Ósea , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Niño , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia , Factores de Tiempo , Trasplante Autólogo , Trasplante Homólogo
17.
Med Clin (Barc) ; 109(1): 12-5, 1997 May 31.
Artículo en Español | MEDLINE | ID: mdl-9303971

RESUMEN

BACKGROUND: A single-center experience review about accessibility to bone marrow transplantation (BMT) as postremission therapy for acute myeloid leukemia (AML) is analyzed. PATIENTS AND METHODS: From January 1988 to December 1994, 86 patients were diagnosed from de novo AML in our institution. A BMT was the treatment of choice for all patients younger than 55 years. An allogenic BMT (Allo-BMT) was offered for all patients younger than 35 years with a compatible sibling donor or those older patients, 35-55 years, with bad prognosis features. An autologus BMT (ABMT) was offered to those patients older than 35 years or those younger than 35 without an histocompatible donor. RESULTS: 52 out of 86 diagnosed patients were younger than 50 years (60%). 29 of them were candidates to Allo-BMT (24 patients younger than 35 years and 5 patients older than 35 with refractory disease) and the rest 23 to ABMT. 22 out of the 24 candidates to Allo-BMT entered complete remission (CR) and 12 of them had an HLA-identical donor. The Allo-BMT was performed in CR1 in 7 patients in CR2 in three patients and with refractory disease in two cases. An ABMT was finally planned in 30 patients, 18 patients older than 35 who entered CR and the rest 12 patients younger than 35 years in CR without a sibling donor. Only 11 out of this 30 patients underwent an ABMT in first CR. Reasons for this low number were: early relapse (B), toxicity (6), refuse (2), lost of follow-up (2) and suicide (1). Five out of this early relapse patients underwent an ABMT in CR2. Disease-free survival (DFS) at three years was 23 +/- 10% for the 52 patients included in the study. DFS obtained with Allo-BMT and AMBT were 39 +/- 16% and 63 +/- 22% respectively. CONCLUSIONS: In spite of the new postremission treatment modalities available for AML the rate of longer survivals are still low. When data from BMT is analyzed we must be awared because only a small fraction of patients assigned to BMT will finally access to this treatment.


Asunto(s)
Trasplante de Médula Ósea/estadística & datos numéricos , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Supervivencia
18.
Med Clin (Barc) ; 105(16): 605-11, 1995 Nov 11.
Artículo en Español | MEDLINE | ID: mdl-8523939

RESUMEN

BACKGROUND: The 10 year experience of a single center performing allogeneic bone marrow transplantation in 70 patients with chronic myeloid leukemia (CML) is analyzed. METHODS: Seventy patients transplanted for CML between November 1982 and October 1992 were evaluated. Fifty-two patients were in the first chronic phase (FC), 10 in an accelerated phase, 4 in blast crisis and 4 in the second chronic phase. The combination of cyclosporin and methotrexate was the most commonly used prophylactic schedule for graft versus host disease (GVHD) (60 cases) and T depletion was not performed in any case. The combination of cyclophosphamide (120 mg/kg) and total body irradiation was used in 48 patients with the remaining patients received busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The estimation of survival was performed using the Kaplan-Meier limit product method. The prognostic factors influencing survival, disease free period and relapse were evaluated by Cox multivariate models of proportional risk. RESULTS: Actuarial survival at four years was 40% (95% Cl: 26-58%). Multivariate analysis selected variables associated with lower survival, the presence of acute GVHD (relative risk-RR-4.75), advanced disease phase (RR: 3.26) and age over 30 years (RR: 3.57). Eleven patients had relapsed. Multivariate analysis found the absence of chronic GVHD (RR: 5.3) and advanced phase (RR: 1.91) to be associated to a higher probability of relapse. In a separate analysis of the 48 patients transplanted in chronic phase who received cyclosporin and methotrexate, the disease free survival was longer for those under the age of 30 years (71.4% vs. 36%) without acute GVHD (68.8% vs. 39.6%) and those transplanted from a male donor (64.6% vs. 30%). CONCLUSIONS: Advanced phase of the disease, the presence of acute graft versus host disease and the age and female sex of the donor are the main factors associated to shorter survival in allogeneic bone marrow transplant for chronic myeloid leukemia. In contrast, the presence of chronic graft versus host disease decreases the possibilities of relapse.


Asunto(s)
Trasplante de Médula Ósea , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/métodos , Trasplante de Médula Ósea/estadística & datos numéricos , Niño , Preescolar , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Inducción de Remisión , Factores de Riesgo , España/epidemiología , Trasplante Homólogo , Resultado del Tratamiento
19.
Med Clin (Barc) ; 108(6): 201-6, 1997 Feb 15.
Artículo en Español | MEDLINE | ID: mdl-9102484

RESUMEN

BACKGROUND: A single-center experience using autologous bone marrow transplantation (ABMT) as postremission therapy for acute myeloid leukemia (AML) in first complete remission (CR1) in 41 patients is analyzed. PATIENTS AND METHODS: From July 1986 to March 1994, 41 patients with AML in CR1 underwent an ABMT. Source of hematopoietic stem cells was bone marrow in all cases. In eleven patients the marrow was purged with mafosfamide (ASTA-Z 7654). Median age was 31 years (17-59) and median time from CR to ABMT was 7 months (3-27). Busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) was employed as conditioning regimen in 36 patients. The rest 5 patients were prepared with cyclophosphamide (120 mg/kg) and fractioned total body irradiation (12 Gy). Eleven patients received G-CSF after AMBT because of an absolute neutrophil count lower than 0.5 x 10(9) on day +30. Survival analysis was performed according to the methods of Kaplan and Meier and comparison between groups used the log-rank test. RESULTS: With a median follow-up of 26 months (12-75) 21 patients remain alive in CR. Disease-free survival (DFS) at five years was 40% (95% CI: 25-55%). Transplant-related mortality, mainly for infection and hemorrhage, occurred in 6/41 patients (16%). Leukemia relapse was the main cause of treatment failure: 14/35 (40%). Probability of DFS and relapse was similar for those patients with purged ABMT on unpurged ABMT 45 +/- 23% vs 38 +/- 16% and 37 +/- 14% vs 54 +/- 22% respectively. A significantly longer engraftment time for neutrophils (> 0.5 x 10(9)) and platelets (> 20 x 10(9)) was observed in those patients who received a bone marrow treated with mafosfamide compared with the unpurged group (54 vs 29 days for neutrophils and 102 vs 58 for platelets respectively) (p < 0.05). CONCLUSIONS: ABMT is a feasible treatment for AML in CR1. Using bone marrow as hematopoietic stem cell support we observed that delayed engraftment was a common finding among AML patients, specially when the marrow was treatment with mafosfamide. Leukemia relapse remains as the main cause of treatment failure for ABMT.


Asunto(s)
Trasplante de Médula Ósea , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Trasplante de Médula Ósea/métodos , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , España/epidemiología , Análisis de Supervivencia , Factores de Tiempo , Trasplante Autólogo
20.
Neurochirurgie ; 34(6): 361-73, 1988.
Artículo en Francés | MEDLINE | ID: mdl-3070419

RESUMEN

UNLABELLED: During the period January 1975-October 1987, we performed stereotactic ventriculocisternostomy (V.C.S.) on 23 patients (13 M., 10 F.; age: 11-73 years, m: 33). Sometimes used as an isolated therapeutic procedure, V.C.S. may also follow stereotactic biopsies using Talairach's methodology. Serial stereotactic biopsies were performed in 15 out of 23 patients showing 11 tumoral lesion, two arachnoïdal cysts and two cryptic vascular malformations. Eight patients presented with an isolated aqueductal stenosis. Among the 12 non tumoral patients, seven had very large triventricular hydrocephalus (6 with a retroclival dilatation of the third ventricle) and 5 showed significant dilatation. Of the 11 tumoral patients, 7 had significant ventricular dilatation (1 with a protrusion of the floor of the third ventricle) and 4 with modest dilation. V.C.S. is done by creating an opening (diameter: 5-6 mm) in the floor of third ventricle with a fine forceps introduced through a tubular guide (diameter: 2.45 mm). The percutaneous double oblique transfrontal trajectory (drill-hole: 2.5 mm of diameter) passing through the foramina of Monro, avoids superficial and deep vessels visualised on the previous Stereoscopic Tele-Angiographic and Ventriculographic study. A systematic verification of the V.C.S. patency is made intraoperatively by injection of iodine contrast medium into the third ventricle. RESULTS: (non tumoral patients: 12) (m follow-up: 4 years): two patients needed a ventricular shunt after 3 and 1 months respectively, the first one because of an associated communicant hydrocephalus, the second because of a post-operative meningeal infection. Long-term clinical and CT-Scan follow-up showed that complete resolution (7 cases) or partial (2 cases) improvement of symptoms and signs was not accompanied by normalization of ventricular size, even though the dilatation was significantly reduced in 8 cases and to a lesser extent in 2. RESULTS: (tumoral patients: 11) (m follow-up: 3 years). Hydrocephalus was reduced in 6 cases and remained unchanged in 5. Two patients needed a ventricular shunt 2 years after the V.C.S.: 1 patient, because of a tumoral recurrence involving the region of the fenestration, the second patient because of adhesive arachnoiditis following reoperation for suspicion of recurrence, though this was found to be granulomatous inflammation. Two patients died as a result of their tumors at 2 and 6 years. CONCLUSION: Stereotactic V.C.S. is the treatment of choice for triventricular obstructive hydrocephalus even when there is no retroclival dilatation of the floor of the third ventricle.


Asunto(s)
Ventrículos Cerebrales , Derivaciones del Líquido Cefalorraquídeo/métodos , Hidrocefalia/cirugía , Técnicas Estereotáxicas , Ventriculostomía/métodos , Adolescente , Adulto , Anciano , Biopsia , Ventrículos Cerebrales/patología , Niño , Femenino , Humanos , Hidrocefalia/etiología , Hidrocefalia/patología , Masculino , Persona de Mediana Edad
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