RESUMEN
We evaluated the impact of recipient and cord blood unit (CBU) genetic polymorphisms related to immune response on outcomes after unrelated cord blood transplantations (CBTs). Pretransplant DNA samples from 696 CBUs with malignant diseases were genotyped for NLRP1, NLRP2, NLRP3, TIRAP/Mal, IL10, REL, TNFRSF1B, and CTLA4. HLA compatibility was 6 of 6 in 10%, 5 of 6 in 39%, and ≥4 of 6 in 51% of transplants. Myeloablative conditioning was used in 80%, and in vivo T-cell depletion in 81%, of cases. The median number of total nucleated cells infused was 3.4 × 107/kg. In multivariable analysis, patients receiving CBUs with GG-CTLA4 genotype had poorer neutrophil recovery (hazard ratio [HR], 1.33; P = .02), increased nonrelapse mortality (NRM) (HR, 1.50; P < .01), and inferior disease-free survival (HR, 1.41; P = .02). We performed the same analysis in a more homogeneous subset of cohort 1 (cohort 2, n = 305) of patients who received transplants for acute leukemia, all given a myeloablative conditioning regimen, and with available allele HLA typing (HLA-A, -B, -C, and -DRB1). In this more homogeneous but smaller cohort, we were able to demonstrate that GG-CTLA4-CBU was associated with increased NRM (HR, 1.85; P = .01). Use of GG-CTLA4-CBU was associated with higher mortality after CBT, which may be a useful criterion for CBU selection, when multiple CBUs are available.
Asunto(s)
Antígeno CTLA-4/inmunología , Trasplante de Células Madre de Sangre del Cordón Umbilical , Antígenos HLA/inmunología , Neoplasias Hematológicas/genética , Polimorfismo Genético , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Adolescente , Adulto , Alelos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/inmunología , Antígeno CTLA-4/genética , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Sangre Fetal/citología , Sangre Fetal/inmunología , Sangre Fetal/trasplante , Expresión Génica , Genotipo , Antígenos HLA/genética , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/terapia , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Proteínas NLR , Modelos de Riesgos Proporcionales , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Donante no EmparentadoRESUMEN
OBJECTIVES: To determine the best anthropometric index in relation to cardiovascular disease risk factors among children and adolescents. METHODS: This cross-sectional school-based study was conducted among a random sample of 3179 students, aged 6 to 18 years, in three large cities in Brazil. RESULTS: The prevalence of overweight and obesity was 10% and 5%, respectively. In relation to the students in the lower quartile (Q1) of the distribution of subscapular skinfold, the students in the upper quartile (Q4) presented a 2.0 times higher risk (odds ratio) of having elevated total cholesterol levels. Overweight and obese students had a 3.3 times higher risk of having elevated systolic blood pressure, and a 1.9 times higher risk of elevated diastolic blood pressure than other students. The less active students presented a 1.58 times higher risk of having waist-to-height ratio (WHtR) above the upper tertile (Q3). WHtR mean values was 0.46 (SE 0.00) presented the largest area under the curve (AUC) [0.613 (CI995%:0.578-0.647)] for high total cholesterol levels, [0.546 (CI995%: 0.515-0.578)] for low HDL-C levels, and [0.614 (CI95%: 0.577-0.651)] for high LDL-C levels, while body mass index presented the largest AUC [0.669 (CI95%: 0.64-0.699)] for increased diastolic blood pressure followed by the waist circumference for increased systolic blood pressure [0.761 (CI95%: 0.735-0.787)]. CONCLUSIONS: WHtR is considered as a simple and accurate anthropometric parameter that identifies youth with cardiovascular risk factors. In this study, WHtR above 0.44 was indicative of risk factors in children and adolescents. These findings can be applied in future preventive strategies against CVDs, and screening programs.