Cistitis hemorrágica tras trasplante alogénico de progenitores hematopoyéticos: experiencia en un centro oncológico pediátrico / Hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation: experience in a pediatric oncological institution

Objetivos: Analizar factores de riesgo asociados a la gravedad de lacistitis hemorrágica (CH) y estrategias de tratamiento en pacientes conCH tras trasplante alogénico de progenitores hematopoyéticos (TAPH).Material y métodos: Estudio retrospectivo de historias clínicas. Lospacientes con CH tras TAPH tratados entre 2017 y 2021 se dividieronen dos grupos según la gravedad del cuadro (leve y grave). Se compararon datos demográficos, características específicas de la enfermedad,secuelas urológicas y mortalidad global entre ambos grupos. Se utilizóel protocolo del hospital para el manejo de los pacientes. Resultados: Se recogieron 33 episodios de CH en 27 pacientes, delos cuales el 72,7% fueron varones. La incidencia de CH tras TAPH fuedel 23,4% (33/141). El 51,5% de las CH fueron graves (grados III-IV).La enfermedad de injerto contra huésped (EICH) grave (grados III-IV) yla trombopenia al inicio se asociaron a CH grave (p= 0,043 y p= 0,039,respectivamente). Este grupo tuvo mayor tiempo de hematuria (p<0,001)y necesitó más transfusiones de plaquetas (p= 0,003). Además, el 70,6%precisó sondaje vesical, pero solo un caso cistostomía percutánea. Ningún paciente con CH leve precisó sondaje. No hubo diferencias en lassecuelas urológicas ni en la mortalidad global. Conclusiones: Una CH más grave podría predecirse por la presenciade EICH grave o trombopenia al inicio del cuadro. La CH grave puedemanejarse con sondaje vesical en la mayoría de estos pacientes. Seguirun protocolo estandarizado puede reducir la necesidad de procedimientosinvasivos en pacientes con CH leve.(AU)

Objective: To analyze the risk factors associated with hemorrhagiccystitis (HC) severity and the treatment strategies available in HC patientsfollowing allogeneic hematopoietic stem cell transplantation (AHSCT). Materials and methods: A retrospective study of medical recordswas carried out. Patients with HC following AHSCT treated from 2017to 2021 were divided into two groups according to severity –mild andsevere. Demographic data, disease-specific characteristics, urologicalsequelae, and overall mortality were compared between both groups.The hospital’s protocol was used for patient management. Results: 33 episodes of HC were collected in 27 patients, 72.7% ofwhom were male. HC incidence following AHSCT was 23.4% (33/141).51.5% of HCs were severe (grades III-IV). Severe graft host disease(GHD) (grades III-IV) and thrombopenia at HC onset were associatedwith severe HC (p= 0.043 and p= 0.039, respectively). This group hadlonger hematuria times (p< 0.001) and required more platelet transfusions (p= 0.003). In addition, 70.6% required bladder catheterization,but only 1 case needed percutaneous cystostomy. None of the patientswith mild HC required catheterization. No differences were found interms of urological sequelae or overall mortality. Conclusions: Severe HC could be predicted thanks to the presenceof severe GHD or thrombopenia at HC onset. Severe HC can be managedwith bladder catheterization in most of these patients. A standardizedprotocol may help reduce the need for invasive procedures in patientswith mild HC.(AU)

A research review of experimental animal models with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) consists of a group of hematologic tumors that are derived from the clonal proliferation of hematopoietic stem cells, featuring abnormal hematopoietic cell development and ineffective hematopoiesis. Animal models are an important scientific research platform that has been widely applied in the research of human diseases, especially tumors. Animal models with MDS can simulate characteristic human genetic variations and tumor phenotypes. They also provide a reliable platform for the exploration of the pathogenesis and diagnostic markers of MDS as well as for a drug efficacy evaluation. This paper reviews the research status of three animal models and a new spontaneous mouse model with MDS (AU)

Acute kidney injury after allogeneic hematopoietic stem cell transplantation – Predictors and survival impact: A single center retrospective study / Lesión renal aguda después de trasplante de células madre hematopoyéticas alogénicas, factores predictivos e impacto en la supervivencia: un estudio retrospectivo en un solo centro

Introduction and objectives: Acute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting. Patients and methods: We performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019. Results: AKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p=0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p=0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p<0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p=0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p=0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p=0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p=0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p=0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p=0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival. Conclusion: Patients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit. (AU)

Introducción y objetivos: La lesión renal aguda (LRA) es una complicación frecuente del trasplante de células madre hematopoyéticas (TCMH) y parece estar asociado a un incremento en la morbilidad y la mortalidad. El objetivo de este estudio fue evaluar la incidencia, la etiología, los factores predictivos y el impacto en la supervivencia de la LRA temprana en el contexto posterior al TCMH alogénico. Pacientes y métodos: Se realizó un estudio retrospectivo en un único centro que incluyó 155 procedimientos de trasplante alogénico desde junio de 2017 hasta septiembre de 2019. Resultados: Se observó LRA en 50 pacientes (32%). En el análisis de múltiples variables, la edad (OR 31,55, IC del 95% [3,42; 290,80], p=0,002), la evidencia de enfermedad en el momento del trasplante (OR 2,54, IC del 95% [1,12; 5,75], p=0,025), reactivación de citomegalovirus (OR 5,77, IC del 95% [2,43; 13,72], p<0,001) y estancia hospitalaria>35 días (OR 2,66, IC del 95% [1,08; 6,52], p=0,033) fueron los factores predictivos independientes para LRA. La mayor edad (HR 1,02, IC del 95% [1,00; 1,04], p=0,029), la mayor duración de la estancia hospitalaria (HR 1,02, IC del 95% [1,01; 1,03], p=0,002), TCMH con acondicionamiento de intensidad reducida no relacionados emparejados (HR 1,91, IC del 95% [1,10; 3,33], p=0,022), aparición de enfermedad injerto contra huésped aguda de grado iii/iv (HR 2,41, IC del 95% [1,15; 5,03], p=0,019) y necesidad de ventilación mecánica (HR 3,49, IC del 95% [1,54; 7,92], p=0,003) predijeron una supervivencia inferior en el análisis de múltiples variables. La LRA temprana de cualquier etiología no se asoció con una peor supervivencia. Conclusión: Los pacientes sometidos a TCMH presentan un mayor riesgo de LRA, cuya etiología es con frecuencia multifactorial. Debido a la incidencia de LRA, la consulta a un nefrólogo especializado como parte del equipo multidisciplinario podría ser beneficiosa. (AU)

Suppressive effect of tamarixetin, isolated from Inula japonica, on degranulation and eicosanoid production in bone marrow-derived mast cells

Background: The aim of this study was to evaluate the inhibitory effect of tamarixetin on the production of inflammatory mediators in IgE/antigen-induced mouse bone marrow-derived mast cells (BMMCs). Materials and methods: The effects of tamarixetin on mast cell activation were investigated with regard to degranulation, eicosanoid generation, Ca2+ influx, and immunoblotting of various signaling molecules. Results: Tamarixetin effectively decreased degranulation and the eicosanoid generation such as leukotriene C4 and prostaglandin D2 in BMMCs. To elucidate the mechanism involved, we investigated the effect of tamarixetin on the phosphorylation of signal molecules. Tamarixetin inhibited the phosphorylation of Akt and its downstream signal molecules including IKK and nuclear factor κB. In addition, tamarixetin downregulated the phosphorylation of cytosolic phospholipase A2 (cPLA2) and p38 mitogen-activated protein kinase. Conclusions: Taken together, this study suggests that tamarixetin inhibits degranulation and eicosanoid generation through the PLCγ1 as well as Akt pathways in BMMCs, which would be potential for the prevention of allergic inflammatory diseases (AU)

Tratamiento de rescate de pacientes con leucemia aguda en recaída después de un primer trasplante alogénico de progenitores hematopoyéticos / Rescue treatment of patients with relapsed acute leukemia after first allogeneic hematopoietic stem cell transplantation

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Expression differences of genes in the PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways in CD34+ hematopoietic cells obtained from chronic phase patients with chronic myeloid leukemia and from healthy controls

Purpose. The fusion gene BCR-ABL has an important role to the progression of chronic myeloid leukemia (CML) and several signaling pathways have been characterized as responsible for the terminal blastic phase (BP). However, the initial phase, the chronic phase (CP), is long lasting and there is much yet to be understood about the critical role of BCR-ABL in this phase. This study aims to evaluate transcriptional deregulation in CD34+ hematopoietic cells (CD34+ cells) from patients with untreated newly diagnosed CML compared with CD34+HC from healthy controls. Methods. Gene expression profiling in CML-CD34 cells and CD34 cells from healthy controls were used for this purpose with emphasis on five main pathways important for enhanced proliferation/survival, enhanced self-renewal and block of myeloid differentiation. Results. We found 835 genes with changed expression levels (fold change ≥ ±2) in CML-CD34 cells compared with CD34 cells. These include genes belonging to PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways. Four of these pathways converge to MYC activation. We also identified five transcripts upregulated in CD34-CML patients named OSBPL9, MEK2, p90RSK, TCF4 and FZD7 that can be potential biomarkers in CD34-CML-CP. Conclusion. We show several mRNAs up- or downregulated in CD34-CML during the chronic phase (AU)

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Agotamiento de las células madre hematopoyéticas y productos finales de la glicación avanzada en la anemia inexplicada de la persona mayor / Hematopoietic stem cell exhaustion and advanced glycation end-products in the unexplained anemia of the elderly

Introducción. En occidente, más del 10% de las personas mayores de 65 años padecen anemia. Hasta en un tercio de los mismos esta es inexplicada. La anemia inexplicada de la persona mayor (AI) se considera un diagnóstico de exclusión, sin que exista un consenso en los criterios para su abordaje clínico o experimental. En estudios en animales y humanos se ha evidenciado que existe un vínculo entre envejecimiento y anemia. Objetivos. Conocer si existe evidencia en la literatura que soporte como causa de AI al agotamiento de células madre hematopoyéticas (CMH) y al acúmulo de productos finales de la glicación avanzada (AGE). Método. Tras una revisión exhaustiva de la literatura se seleccionaron 32 trabajos de investigación (28 para agotamiento de CMH y 4 para AGE). Se vincularon sus conclusiones a los mecanismos y efectos tanto del agotamiento de CMH como del acúmulo de AGE sobre el envejecimiento y la anemia. Resultados. Únicamente 3 trabajos relacionaron la AI con el agotamiento de CMH y 2 de ellos difirieron en sus conclusiones, el tercero difirió en el tipo de estudio. Existe relación del incremento y acúmulo de AGE con anemia en la persona mayor. Conclusión. Existe evidencia en la literatura que vincula los mecanismos moleculares y celulares del envejecimiento con el agotamiento de CMH y el acúmulo de AGE, también existe evidencia de que ambas entidades condicionan anemia relacionada a la edad en animales y humanos. Hay una pobre evidencia en la literatura que determine una relación entre envejecimiento y AI (AU)

Introduction. More than 10% of the aged 65 years and over in the western world suffers anemia and in one third of them the cause of the anemia remains obscure. The unexplained anemia of the elderly (UAE) is considered an exclusion diagnosis, without the existence of a clear consensus to its clinical or experimental approach. There is an association between aging and anemia in studies performed in animals and in humans. Objectives. To determine if there is evidence in the literature that supports hematopoietic stem cells (HSC) exhaustion and the advanced glycation end-products (AGE's) as a cause of UAE. Method. A total of 32 combined texts (28 for HSC exhaustion and 4 for AGEs) were selected after an intensive review. Conclusions were associated with causes and effects of the HSC exhaustion and circulating AGE's over aging and anemia. Results. Only three works try to establish an association between UAE and HSC exhaustion, two of them disagreed in their conclusions, with the third one differing in the type of study. There is a relationship between anemia and AGEs increase and accumulation. Conclusions. There is evidence in the literature that links the aging molecular and cellular mechanisms with the HSC exhaustion and the increase of AGE's. Furthermore; there is some evidence that both conditions determine the emergence of anemia associated with age in animals and in humans. There is little evidence in the literature to clarify the relationship between aging and UAE (AU)

Estudio de incidencia de las neoplasias hematopoyéticas en Castilla y León / Incidence of haematological neoplasms in Castilla y León, Spain

Fundamento y objetivo: Conocer la incidencia de las neoplasias hematopoyéticas (NH) en Castilla y León, una región de 2,5 millones de habitantes, y su distribución en función de la edad, el sexo y el subtipo histológico. Pacientes y método: Se ha analizado el perfil epidemiológico en función de las variables descritas de las 10.943 NH diagnosticadas durante un período de 10 años, comparándolo con el de otros estudios. Resultados: La incidencia ajustada por edad alcanzó 29,4 casos/105 habitantes-año, con ciertas variaciones geográficas. La edad media fue de 67,3 años, con un punto de inflexión entre la sexta y séptima décadas de la vida, a partir del cual se produjo un aumento muy importante de la incidencia. A medida que avanzaba la edad, ocurrieron de forma paralela otros 2 hechos relevantes: una disminución de la incidencia de los procesos linfoides y el aumento de la de las neoplasias de bajo grado de agresividad. Los procesos linfoides de bajo grado representaron la mitad de los casos del registro, mostraron una mayor preferencia por el sexo masculino y alcanzaron la moda antes que el resto de las NH. La incidencia de neoplasias mieloides (9,5) fue superior a la descrita en otros registros europeos, especialmente en los países del sur de Europa, contrariamente a lo observado con las neoplasias linfoides (20,0). Conclusiones: Se observó una mayor incidencia de neoplasias mieloides y menor de linfoides de lo esperado. El punto de inflexión de incidencia se situó entre la sexta y séptima décadas de la vida, con predominio del sexo masculino, que se reduce con el aumento de la edad. La mayor incidencia de NH se observó en la zona donde se concentra una mayor densidad de industrias potencialmente contaminantes (AU)

Background and objective: We aimed to assess the incidence of haematological neoplasms (HNs) in Castilla y León (2,5 million inhabitants) and its distribution by age, gender and histological type. Patients and method: The epidemiological profile based on the described variables of the 10,943 HNs diagnosed during a 10-years period was analyzed, compared with other studies. Results: The overall age-adjusted incidence was 29.4 cases/105 inhabitants-year, with some geographical differences. The mean age was 67.3 years, with a turning point between the 6th-7th decades of life from which there was a very significant increase of incidence. Two relevant facts where simultaneous with advancing age: decreased lymphoid neoplasms incidence and increased low degree neoplasms incidence. Lymphoid low degree neoplasms accounted for half of the registered processes, showed the greatest preference for male and reached the mode before the rest of neoplasms. Myeloid neoplasms incidence (9.5) was higher than that reported in other European registries, specially compared to southern European countries, opposite to lymphoid neoplasms incidence (20.0). Conclusions: A higher myeloid neoplasms incidence and lower lymphoid one than expected was observed. The turning point of incidence is between the 6th-7th decades of life, with a preference for male that decreases with age. There is an increased incidence of HNs in the area where a higher density of potentially polluting facilities is concentrated (AU)

Potencial terapéutico de las células madre derivadas de la médula ósea en el infarto cerebral / Therapeutic potential of bone marrow stem cells in cerebral infarction

Introducción. Las células madre constituyen una alternativa terapéutica que se encuentra en fase de experimentación para el infarto cerebral. Objetivo. Mostrar la evidencia científica existente sobre el potencial terapéutico de las células madre de la médula ósea en esta enfermedad. Desarrollo. El infarto cerebral representa el 80% de las enfermedades cerebrovasculares. La trombólisis constituye la única terapia aprobada, pero, por su estrecha ventana terapéutica, sólo se aplica a un bajo porcentaje de los pacientes. De manera alternativa, los tratamientos neurorrestauradores, como el de células madre, pueden aplicarse en períodos más prolongados. Por esta razón se efectuó una búsqueda bibliográfica en PubMed con el empleo de las palabras clave ‘stem cells’, ‘bone marrow derived mononuclear cells’ y ‘stroke’. Se encontraron evidencias de seguridad y eficacia de dichas cé- lulas en diferentes momentos evolutivos del infarto cerebral. Se identificaron estudios que en clínica y preclínica las recolectaron por punción medular y en sangre periférica, y las trasplantaron directamente en el área infartada o por vía intravascular. El efecto terapéutico se relaciona con sus propiedades de plasticidad celular y liberación de factores tróficos. Conclusiones. El concentrado de células mononucleares autólogas, obtenido en sangre periférica o por punción de la médula ósea, y trasplantado por vía intravenosa, es una factible opción metodológica que permitirá rápidamente incrementar el número de ensayos clínicos en diferentes etapas evolutivas del infarto cerebral. Esta terapia muestra seguridad y eficacia; sin embargo, deben ampliarse las evidencias que avalen su generalización en humanos (AU)

Introduction. Stem cells are an alternative therapy for cerebral infarction that is still in the experimental phase. Aims. To report on the existing scientific evidence on the therapeutic potential of bone marrow stem cells in this disease. Development. Cerebral infarction accounts for 80% of cerebrovascular diseases. Thrombolysis is the only approved therapy, but, owing to its narrow therapeutic window, it is only applied to a low percentage of patients. Conversely, neurorestorative treatments, such as stem cells, can be applied over longer periods of time. For this reason a literature search was conducted on PubMed using the key words ‘stem cells’, ‘bone marrow derived mononuclear cells’ and ‘stroke’. Evidence was found of the safety and effectiveness of such cells at different points in the development of the completed stroke. Results included studies that, in the clinical and preclinical period, collected them by spinal puncture and in peripheral blood, and transplanted them either directly into the infarcted area or intravenously. The therapeutic effect is related with their cell plasticity and trophic-factor releasing properties. Conclusions. Autologous mononuclear cell concentrate, obtained from peripheral blood or by puncturing the bone marrow and transplanted intravenously, is a feasible methodological option that will make it possible to quickly increase the number of clinical trials conducted at different stages of the development of a completed stroke. This therapy has proved itself to be safe and effective; nevertheless, further evidence is needed to endorse its generalised use in humans (AU)

Nitric oxide regulates multiple functions and fate of adult progenitor and stem cells

Nitric oxide is an endogenous gas which exerts autocrine/paracrine actions by different signaling pathways and/or direct interactions with intracellular compounds and structures. Several processes are regulated by nitric oxide in stem cells including self-renewal, viability, migration, proliferation, and differentiation. The modulation of cell functions depends on its concentrations because opposite effects can be observed when low and high levels of nitric oxide are compared. Here, the responses to nitric oxide of adult stem/progenitor cells which are often used in regenerative medicine, including mesenchymal stem cells, hematopoietic stem cells, neural stem cells, endothelial progenitor cells, satellite cells, and fibro-adipogenic precursor cells, are reviewed. Therapeutic strategies which employ drugs releasing nitric oxide or modulating nitric oxide intracellular pathways are suggested to perform new ex vivo preconditioning or in vivo treatments suitable for stem/progenitor cell therapy and tissue engineering applications

Statin use and peripheral blood progenitor cells mobilization in patients with multiple myeloma

PURPOSE: Statins have beneficial effects in patients after myocardial infarction and at least part of the benefit results from mobilization of marrow endothelial progenitors to repopulate damaged myocardial tissues. This study examines if statins may have the same effect in mobilizing marrow progenitors to be harvested and subsequently used in high-dose chemotherapy with progenitor cell rescue in multiple myeloma. METHODS: From 2006 to 2012, 86 patients with multiple myeloma were mobilized with the use of G-CSF and were retrospectively analyzed. Patients with other malignancies or mobilized with the use of chemotherapy or with plerixafor were excluded. RESULTS: The median age of the patients was 60 years. 72 patients had received one line of chemotherapy and 14 patients two or more lines of chemotherapy. Twenty patients were taking statins at the time of the harvest while 66 patients were not. In the group of patients taking statins the success rate of first leukapheresis (obtaining the target number of 4 × 10(6) CD34+ cells/kg) was 85 % while in the group not taking statins this rate was 63.6 %. Despite the comparatively small number of patients this difference approached statistical significance (χ (2) = 0.07). CONCLUSION: This retrospective analysis of 86 patients shows for the first time a possible benefit of statins for peripheral blood progenitor cells mobilization in patients with multiple myeloma. Larger studies would be required to clarify the issue. If their effectiveness is confirmed, statins could be a safe and cheaper addition to chemotherapy and plerixafor for peripheral hematopoietic stem cell mobilization (AU)

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Morphological comparison of bone marrow derived mesenchymal stem cell from albino rats and Indian chicken

The bone marrow is a complex tissue containing stem cells with hematopoietic properties. These bone-marrow mesenchymal stem cells have been identified as the source of multipotent stem cells. Bone-marrow-derived mesenchymal stem cells (BM-MSCs) are also referred to as stromal progenitor cells which are self-renewing and expandable stem cells used for regenerative studies. Basically, the mesenchymal stem cell (MSC) has the unique property of plasticity and adherence. In this study we discuss the bone-marrow-MSC isolation and their cultural characterization based on plasticity, proliferation, and CD44 cell surface marker identification in Albino Rats and Indian Chicken. The results of comparative study in the two different species indicate that there are differences in the cell morphology and proliferation rate of MSC. This article provides general understanding of the cellular morphological difference of stem cells in the lower animal models, and paves the way for future research work into the selection of species (AU)

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Tratamiento de Enfermedades neurológicas basado en Células Madre / Stem cell-based treatment of neurologic diseases

Las estrategias terapéuticas basadas en células madre se están empleando cada vez más para el tratamiento de un amplio número de enfermedades neurológicas. Aunque dichas estrategias se diseñaron inicialmente con la finalidad de reemplazar las células muertas en el tejido lesionado, el potencial de las células madre para migrar, secretar factores tróficos e inmunomodular permite en la actualidad su uso terapéutico como vehículo para la terapia génica, como en el caso de la enfermedad de Parkinson, o como inmunomoduladores y neuroprotectores, como por ejemplo en la esclerosis múltiple. En esta revisión se discute la evidencia clínica y experimental actual existente en relación con el tratamiento de enfermedades neurológicas empleando estrategias basadas en células madre (AU)

Therapeutic strategies based on stem cells are being increasingly used to treat a wide range of neurological diseases. Although these strategies were initially designed to replace dead cells in injured tissue, the potential of stem cells to migrate, secrete trophic factors, and immunomodulate allows their therapeutic use as a vehicle for gene therapy, as in Parkinson's disease, or as immunomodulators and neuroprotectors in diseases such as multiple sclerosis. This review will focus on current clinical and experimental evidence on the treatment of neurological disorders with strategies based on stem cells (AU)

Nuevas estrategias terapéuticas en el tratamiento del mieloma múltiple. Análisis de su eficacia y coste-efectividad / New therapeutic strategies for multiple myeloma. Efficacy and cost-effectiveness analyses

El objetivo del presente artículo es revisar las principales innovaciones terapéuticas en el tratamiento del mieloma múltiple, desde el punto de vista de su eficacia y coste-efectividad. Aparte del autotrasplante de progenitores hematopoyéticos, la talidomida se establece como uno de los principales recursos terapéuticos en el tratamiento de inducción y de extensión de la respuesta, conjuntamente con la lenalidomida y el bortezomib en el tratamiento de rescate en el mieloma múltiple refractario/recidivante. Con respecto al tratamiento de este último, la talidomida puede ser una opción adecuada en combinación con la dexametasona. Desde un punto de vista estrictamente farmacoeconómico, la lenalidomida y el bortezomib constituyen alternativas especialmente válidas en pacientes tratados previamente con talidomida

The objective of the present article is the review of the most important therapeutic innovations in the treatment of multiple myeloma in terms of efficacy and cost-efectiveness. Besides autologous transplant with peripheral-blood stem-cell, thalidomide establishes as one of the most powerful therapeutic tools in induction and maintenance treatment and together with lenalidomide and bortezomib as therapy for relapsing/refractory multiple myeloma. Considering, the last named situation thalidomide can be an adequate therapeutical option in combination with dexamethasone. Under a strictly pharmacoeconomic point of view, lenalidomide and bortezomib seem to be additional alternatives in patients previously treated with thalidomide (AU)

Hematopoietic stem cell homing: The long, winding and adhesive road to the bone marow

En mamíferos adultos, una población celular muy restringida que da origen al tejido hematopoyético se localiza en nichos dentro de la médula ósea en los que recibe sustento y protección. Estas célulasmadre hematopoiéticas de la sangre pueden salir de estos nichos en condiciones fisiológicas y, en el contexto del transplante de médula ósea, migrar a la médula del recipiente para regenerar su sistema hematopoyético. En esta revisión se describen las evidencias que hanpermitido caracterizar los mecanismos por los cuales estas células madre migran a los nichos medulares siguiendo un camino largo y tortuoso: Desde la circulación periférica, y mediante interacciones conla vasculatura medular, hasta nichos localizados en el espacio intramedular. También se discute cómo se han generado nuevas herramientas que nos permitirán manipular el tráfico de células madre

In adult mammals, a rare population of cells that gives rise to the hematopoietic compartment dwells in niches within the bone marrow where they are nourished and protected. These blood stem cells can, however, exit these niches under physiological conditions and, in thecontext of bone marrow transplantation, migrate to the recipient’s marrow to regenerate hematopoiesis. This review will address old and new discoveries regarding the mechanisms that allow these stem cells to find their way home through long and winding roads: From the peripheral circulation, through interactions with the vessel-lining endothelial cells in the bone marrow, and into their niches located in the intramedullary space. It will also address how these discoveries have provided us with new tools to manipulate stem cell trafficking

Quimioterapia intensiva y de rescate con progenitores hematopoyéticos autólogos en el tratamiento de los linfomas no hodgkinianos / High-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin’s lymphoma

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Normal development of fetal hepatic haematopoiesis during the second trimester of gestation is upregulated by fibronectin expression in the stromal cells of the portal triads

Objetivo: en el segundo trimestre de la gestación, el principalfoco de hematopoyesis del feto es el hígado. En los órganoshematopoyéticos, las células del estroma, como fibroblastos,células epiteliales y células de tipo macrófago, desarrollan redespara mantener la hematopoyesis, es decir, la auto-renovación,la proliferación y el crecimiento de las células madre hematopoyéticas,al interactuar con las células progenitoras hematopoyéticas.Se sabe que las glucoproteínas de la MEC producidaspor las células del estroma desempeñan un papel crítico enla regulación del crecimiento y la diferenciación celulares. Sehan documentado numerosos factores solubles y de membranaque regulan directamente la hematopoyesis, pero se sabe pocode la actividad de las células del estroma hepático y de laproteína (fibronectina) de la matriz extracelular en el feto en relacióncon la hematopoyesis hepática. La unión de las célulaseritroides tardías a la fibronectina está bien tipificada y se creeque es crítica para las etapas terminales de la diferenciación eritroide.La intención de este artículo es determinar el papel dela fibronectina en la proliferación y diferenciación hematopoyéticadel hígado fetal en las distintas etapas del desarrollo.Material y método: examinamos y comparamos la expresióninmunohistoquímica de fibronectina en los campos portalesdel estroma hepático durante los trimestres primero, segundoy tercero del embarazo en relación con la aparición decélulas progenitoras hematopoyéticas CD34, progenitoras delestroma y endoteliales vasculares, respectivamente.Resultados: nuestros resultados mostraron una diferenciacuantitativa en cuanto a expresión de fibronectina en el estromadel tejido conjuntivo de los campos portales en el segundotrimestre de embarazo respecto al primero (p < 0,0001, pruebade la t) y respecto al tercero (p < 0,0001, prueba de la t). Sehallaron también cambios similares en cuanto a la expresión deCD34 respecto al primer (p < 0,0001, prueba de la t) y el tercertrimestres (p < 0,0001, prueba de la t), lo que indica la participacióndirecta de la fibronectina en el mantenimiento de laactividad hematopoyética

Objective: in midtrimester fetuses the principal site ofhematopoiesis is the liver. In hematopoietic organs, stromal cellssuch as fibroblasts, epithelial cells, and macrophage-like cells developnetworks to maintain hematopoiesis, i.e. hematopoietic stemcell self-renewal, proliferation, and growth, by interaction withhematopoietic progenitor cells. ECM glycoproteins produced by thestromal cells are known to play a critical role in the regulation of cellgrowth and differentiation. Numerous soluble and membraneboundfactors directly regulating haematopoiesis have been documented,but little is known about fetal hepatic stromal cell activityand stromal extracellular matrix protein-fibronectin, on fetal hepatichaematopoiesis. The binding of late stage erythroid cells to fibronectinhas been well characterized and is believed to be criticalfor the terminal stages of erythroid differentiation. The intention ofthis article is to determine the role of fibronectin in fetal hepatichematopoietic proliferation and differentiation in different stages ofdevelopment.Material and method: we examined and compared the immunohistochemicalexpression of fibronectin in the hepatic stromalportal fields in the 1st, 2nd, and 3rd trimester of gestation respectively,in relation to the appearance of CD34 progenitor hematopoietic,stromal progenitor and vascular endothelial positive cells.Results: our results demonstrated a quantitative difference inthe second trimester of gestation concerning the expression of fibronectinin the connective tissue stroma of the hepatic portalfields over the equivalent expression of the protein in the first (p <0.0001, t-test) and third trimester (p < 0.0001, t-test). Similarchanges in the above period were found concerning the expressionof CD34 during the second trimester of gestation, over thefirst (p < 0.0001, t-test) and third trimesters (p < 0.0001, t-test),suggesting a direct involvement of fibronectin in the sustaining ofhematopoietic activity

Selección de donantes y recogida de las unidades en un banco de sangre de cordón umbilical / Donors selection and retrieval of units in an umbilical cord blood bank

Fundamento y objetivo: El contenido cualitativo y cuantitativo de la fracción celular es el factor principal que limita el uso clínico de progenitores hematopoyéticos de sangre de cordón umbilical (SCU). Con el fin de optimizar la calidad de la SCU, se ha llevado a cabo un estudio sobre los criterios de selección de donantes en nuestro entorno geográfico, comparando además diferentes métodos de recogida. Material y método: Se analizaron 391 donaciones potenciales de SCU en la maternidad del Hospital Universitario La Fe. Se evaluaron diversos factores obstétricos relativos a 2.000 unidades de SCU. También se analizó el valor del peso placentario y del recién nacido. Resultados: Se excluyó al 32,5% de las donantes potenciales, principalmente por factores obstétricos. El 56% de las unidades recogidas se rechazó antes de la criopreservación, debido al insuficiente número de células. En el análisis multivariante se demostró que el peso de la placenta fue el único factor predictivo que influyó en la cantidad de células nucleadas totales, células CD34+ y unidades formadoras de colonias, mientras que el modo de recogida también influyó en las cifras de células nucleadas totales y células CD34+. Conclusiones: Nuestro estudio demuestra que, teniendo en cuenta diversos factores obstétricos previamente a la recogida de SCU, se puede optimizar su contenido en progenitores hematopoyéticos. La recogida intraútero es, según nuestros resultados, la mejor estrategia para obtener unidades de SCU eficientemente

Background and objective: Umbilical cord blood (UCB) contains hematopoietic stem cells that can be used as an alternative to bone marrow transplantation in certain cases. This study was designed to investigate the influence of obstetric, neonatal and collection factors on the hematopoietic content of UCB donations. Material and method: A total of 391 consecutive maternal-neonatal pairs were evaluated during the prepartum period in the maternity ward at La Fe University Hospital. Maternal, neonatal and collection factors influencing cord blood quality measured as volume, total nucleated cells count, CD34+ cells and colony forming units were analyzed in 2,000 UCB collections. Results: 32.5% of UCB potential donors were excluded, mainly due to obstetrical reasons. Among the collected units, 56% were discarded before cryopreservation, mainly due to low cell counts. In the multivariate analysis, placental weight was a predictor variable for total nucleated cells, CD34+ cells and colony forming units, while the mode of collection influenced the total nucleated cells and CD34+ cell counts. Conclusions: The collection of UCB units before placental delivery (using the birth weight as an estimation of the placental weight) could be added to standard cord blood donors criteria in order to improve the bank efficiency

Optimización en la recogida de sangre del cordón umbilical / Optimization of umbilical cord blood collection

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Linfopoyesis temprana en médula ósea adulta / Early lymphopoiesis in adult bone marrow

El desarrollo de las células linfoides a partir de células troncaleshematopoyéticas es un proceso organizado en el que se pierdengradualmente múltiples potenciales de diferenciación alternos;y coinciden el compromiso de linaje y la ganancia de funcionesespecializadas. En los últimos años se han registrado avancesnotables en la caracterización de los progenitores primitivosque dan inicio al programa linfoide, y en la definición de los patronesde actividad transcripcional que controlan las decisiones dellinaje, aunque está poco definida la relación entre las señalesambientales y la estabilidad de la ruta de diferenciación linfoide.Esta revisión bibliográfica pretende proporcionar un panoramaclaro del conocimiento actual en los eventos tempranos de la linfopoyesisy su interrelación con el microambiente hematopoyético

Development of lymphoid cells from hematopoietic stem cellsis an ordered process where multiple alternate lineage potentialsare gradually lost and lineage commitment is coincident with gainof specialized functions. Over the last few years remarkableadvances have been made in characterizing primitive progenitorsthat initiate the lymphoid program, and patterns of transcriptionalactivity controlling lineage fate decisions during normalhematopoiesis, but less is known about environmental signalsthat may influence the differentiation pathway stability. Thisreview discusses the current knowledge with relevance to hierarchyand early events in lymphopoiesis and their relationship tohematopoietic microenvironment