Un nuevo modelo predictivo basado en variables clínicas y en polimorfismos en genes de citocinas permite predecir la incidencia de EICR grave post-trasplante hematopoyético alogénico

Un nuevo modelo predictivo basado en variables clínicas y en polimorfismos en genes de citocinas permite predecir la incidencia de EICR grave post-trasplante hematopoyético alogénico. El trasplante alogénico de progenitores hematopoyéticos (alo-TPH) es el tratamiento de elección para la curación de enfermedades como las leucemias agudas y otras neoplasias hematológicas, inmunodeficiencias severas o errores congénitos del metabolismo y la enfermedad de injerto contra receptor (EICR), reacción aloinmune de las células del donante contra células sanas de distintos tejidos del receptor, es una de las complicaciones más relevantes post-TPH y la principal causa de morbilidad y mortalidad del mismo. Entre un 30 y un 50% de los pacientes que reciben un trasplante alogénico desarrollan la EICR pero el anticipar dicha complicación sigue siendo un tema aún no resuelto. Hasta ahora se hace principalmente usando variables clínicas como la edad del paciente en el momento del TPH, la fuente de progenitores hematopoyéticos, la disparidad de sexo entre donante y receptor, la profilaxis de la EICR o el acondicionamiento. Sin embargo, en los últimos años, se está viendo también la importancia de las variables genéticas y, aunque la selección de donantes adecuados para el TPH se basa fundamentalmente en la compatibilidad del sistema HLA entre donante y receptor, se está estudiando la influencia de otros genes en los fenómenos alorreactivos ya que aún en trasplantes HLA idénticos se observan complicaciones como la EICR o el rechazo del injerto. Es necesario, por tanto, un mejor conocimiento de otros factores que influyen en las reacciones de alorreactividad donante/receptor entre los que se encuentran los antígenos menores de histocompatibilidad, las citocinas y sus receptores, las quimiocinas y sus receptores y otras proteínas relacionadas con el sistema inmunitario o con el metabolismo de fármacos. A pesar de la existencia de varios trabajos que intentan relacionar uno o dos polimorfismos genéticos en donantes o receptores con el éxito del trasplante alogénico, no existen trabajos que analicen de forma global un número elevado de polimorfismos con la aparición de la EICR..

The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation

The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients

Semi-longitudinal analysis of physical status in madrilenian adolescents

La condición física tiene gran importancia sobre la salud de los sujetos, pero también es primordial ajustar la carga del entrenamiento y adecuarla a la edad de los individuos. El profesorado de Educación Física puede evaluar la condición física de su alumnado a partir de siete pruebas que forman parte de los contenidos curriculares de la mencionada asignatura. Los objetivos de este trabajo son, por un lado, conocer la condición física de los estudiantes madrileños de ambos sexos de 13 a 18 años y, por otro, elaborar unos patrones actualizados que sirvan de referencia al profesorado de Educación Física para su alumnado de ESO y Bachillerato. Se ha efectuado un análisis semilongitudinal, ya que cada sujeto ha sido evaluado entre dos y ocho ocasiones. La muestra se compone de 4.271 registros (2.333 de chicos y 1.938 de chicas) de más de 500 escolares de 13 a 18 años. Los ejercicios examinados determinan las capacidades físicas de los estudiantes, fuerza, resistencia, velocidad y flexibilidad. Estas pruebas son: abdominales en 30 segundos, carrera de 9 m x 4, salto horizontal, carrera de 50 m lisos, lanzamiento del balón medicinal de 3 kg, flexión del tronco y carrera de 1.000 m. Los resultados presentados permiten caracterizar la aptitud física de los escolares madrileños. Se ha examinado la variabilidad ontogénica y sexual y se aportan las correspondientes tablas con la media, desviación estándar y la distribución percentilar para cada una de las pruebas, según sexo y edad en años cumplidos. En el análisis efectuado con el paquete estadístico SPSS (versión 20.0) se manifiesta un dimorfismo sexual significativo (p < 0,001) para todos los ejercicios estudiados. Asimismo los valores aportados por esta investigación muestran que los varones obtienen mejores resultados que las mujeres en todas las pruebas físicas, excepto en aquellas que miden la flexibilidad.Physical fitness is very important for health, but is also essential to adjust the training load and adapt it to the age of individuals. The Physical Education teachers can assess the fitness of their students, from seven tests that are part of the curricular contents of that subject. The aim of the present work was to determine the physical aptitude of Madrilenian students of both sexes aged 13 to 18, and to develop an updated reference patterns that could serving to assess the physical fitness in High Schools students. Longitudinal study was performed, since each individual was evaluated among two and eight times. The sample consisted of 4271 records (2333 boys and 1938 girls) from more than 500 individuals between 13 and 18 years old. The tested exercises determine the physical capabilities of students, strength, endurance, speed and flexibility. These tests are the following: SitUps in 30 seconds, 4 x 9 meter Shuttle Run test, 50 m shuttle-run test, Standing Broad Jump, medicine ball explosive power test and trunk flexion test. Results allow characterizing the physical fitness of the Madrilenian students. Ontogenic and sexual variability were examined and the corresponding tables are provided with mean, standard deviation and percentile distribution for each test, according to sex and age. The statistical analysis, made using the SPSS v.20.0, shows a significant sexual dimorphism (p < 0.001) for all the studied tests.Depto. de Biodiversidad, Ecología y EvoluciónFac. de Ciencias BiológicasTRUEpu

A novel predictive approach for GVHD after allogeneic SCT based on clinical variables and cytokine gene polymorphisms.

Despite considerable advances in our understanding of the pathophysiology of graft-versus-host disease (GVHD), its prediction remains unresolved and depends mainly on clinical data. The aim of this study is to build a predictive model based on clinical variables and cytokine gene polymorphism for predicting acute GVHD (aGVHD) and chronic GVHD (cGVHD) from the analysis of a large cohort of HLA-identical sibling donor allogeneic stem cell transplant (allo-SCT) patients. A total of 25 SNPs in 12 cytokine genes were evaluated in 509 patients. Data were analyzed using a linear regression model and the least absolute shrinkage and selection operator (LASSO). The statistical model was constructed by randomly selecting 85% of cases (training set), and the predictive ability was confirmed based on the remaining 15% of cases (test set). Models including clinical and genetic variables (CG-M) predicted severe aGVHD significantly better than models including only clinical variables (C-M) or only genetic variables (G-M). For grades 3-4 aGVHD, the correct classification rates (CCR1) were: 100% for CG-M, 88% for G-M, and 50% for C-M. On the other hand, CG-M and G-M predicted extensive cGVHD better than C-M (CCR1: 80% vs. 66.7%, respectively). A risk score was calculated based on LASSO multivariate analyses. It was able to correctly stratify patients who developed grades 3-4 aGVHD (

The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation.

Journal Article; Research Support, Non-U.S. Gov't;The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients.This work was partially supported by the Ministry of Economy and Competitiveness ISCIII-FIS grants PI08/1463, PI11/00708, PI14-01731 and RD12/0036/0061, co-financed by ERDF (FEDER) Funds from the European Commission, the Fundación LAIR and Asociación Madrileña de Hematología y Hemoterapia (AMHH). ISCIII-FIS grants PI01-3624, PI08- 36173 and The Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM).Ye

The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation

The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients

Influence of the genotype of the donor for the polymorphism (GT)_n in the promoter/enhancer of <i>FOXP3</i> on the outcome of allo-SCT.

<p><b>(A)</b> Cumulative incidence of grade III-IV GVHD. <b>(B)</b> Cumulative incidence of relapse. <b>(C-D)</b> Kaplan-Meier curves of event free survival (B) and overall survival (C).</p