Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America.

Objectives: Venetoclax combinations are a new standard for patients with acute myeloid leukemia (AML). We aimed to evaluate the safety and efficacy of these combinations in a period of accelerated approval in Latin-America.Methods: This observational study evaluated adults with acute myeloid leukemia who received venetoclax-based therapy in 11 public or private centers in Mexico and Peru for both newly diagnosed or relapsed and refractory AML.Results: Fifty patients were included; 28 with newly diagnosed (ND) AML and 22 with relapsed/refractory (RR) disease. ND patients were older (64 vs. 40 years; p < 0.001) with a lower functional capacity (ECOG ≥2 64.3% vs 9%; p < 0.001). Venetoclax was frequently combined with azacytidine (60%) and prophylactic azoles (82%) with a median maximum dose of 200 mg (range, 100-600 mg). Hematologic toxicities were common. Complete response rates including patients with incomplete hematopoietic recovery were 78.6% in ND and 45.5% in RR patients, with a median overall survival of 9.6 (95% CI 3.7-15.5) and 8 months (95% CI 4.8-11.2).Discussion: Our study showed a preferred use of venetoclax plus azacytidine over cyatrabine. Patients in the first-line setting were similar to those in the landmark studies, while most patients with relapsed disease had received prior intensive therapies. Responses were favorable, with a median survival in agreement to other reports, albeit shorter than that observed in the randomized phase-3 trials.Conclusion: Venetoclax-based therapy in AML was effective despite dose reductions and prophylactic antifungals in two middle-income countries outside of a clinical trial setting.

Diagnostic concordance of pathological methods and reports of hematopathologists compared to local nonspecialized pathologists in the diagnosis of lymphoma in Mexico.

OBJECTIVES: To assess the concordance between lymphoma diagnoses made via tissue biopsy by local pathologists and also to assess the after review of these specimens by more specialized hematopathologists. METHODS: A prospective, non-interventional and multicenter study was conducted at seven sites in Mexico from January 2017 to October 2017. Eligible biopsies were sampled from patients with a previous diagnosis of lymphoma on lymph node biopsy or a diagnosis of extranodal lymphoma, with adequate amount and tissue preservation for the review analysis. The biopsy tissues reviewed by local pathologists were also reviewed by hematopathologists participating in the study. The concordance in diagnosis results was classified into three categories: diagnostic agreement, minor discrepancy and major discrepancy. RESULTS: Out of 111 samples received, 105 samples met the eligibility criteria and were included for full analysis. The median patient age (range) was 54 (16-94) years. A diagnostic agreement was observed in 23 (21.9%) biopsies, minor discrepancies were observed in 32 (30.5%) biopsies and major discrepancies were observed in 50 (47.6%) biopsies. Diagnostic concordance varied across the seven study sites; the rate of major discrepancies ranged from 0% to 100% and the rate of diagnostic agreement ranged from 0% to 81.8%. Out of the 105 reviewed biopsies, a total of 89 cases were diagnosed as lymphoma by hematopathologists. CONCLUSIONS: This study showed that major discrepancies were observed following the review by hematopathologists compared with that of the local pathologist's initial diagnosis in nearly one-half cases. In addition, there was a wide variation in the percentage of diagnostic agreements and discrepancies among different study sites.

Intervalos de referencia para 25-hidroxivitamina D en población autóctona y aparentemente sana de Yucatán / Reference values for 25-hydroxy-vitamin D in a native and apparently healthy population from Yucatan, Mexico

Introducción: La 25-hidroxivitamina D [25(OH)D] se considera un marcador del estado general de salud y su deficiencia es un problema a nivel mundial. En la actualidad no existe un consenso para definir sus niveles óptimos, siendo necesario establecerlos para cada población de acuerdo con sus características étnicas y factores ambientales a los que está expuesta. Objetivo: Determinar los intervalos de referencia para 25(OH)D en población autóctona y aparentemente sana de Yucatán. Métodos: Se estudiaron 71 voluntarios aparentemente sanos, de uno u otro sexo, de uno a 65 años, originarios y residentes en Yucatán. Se determinaron los niveles séricos de 25(OH)D, así como los de calcio, fósforo y paratohormona por su relación con el metabolismo de la vitamina D. Los intervalos de referencia se calcularon con los métodos paramétrico y consistente. Se registró el fototipo de piel y se aplicó el test de Garabédian para determinar el consumo diario de calcio y vitamina D. Resultados: El valor medio de 25(OH)D fue de 23,49±5,60ng/mL. Los límites de referencia para 25(OH)D total y por sexos fueron más estrechos y significativamente diferentes a los propuestos por el fabricante. Se encontró correlación directa entre los niveles de 25(OH)D y el calcio sérico (r=0,36; p=0,003) e inversa con la paratohormona intacta (r=−0,44; p<0,001). Una dieta rica en calcio y vitamina D no es suficiente para mantener los requerimientos normales de 25(OH)D en esta población. Conclusiones: Los intervalos de referencia propuestos están adecuados a las peculiaridades de la población de Yucatán, y pudieran mejorar la exactitud de la medición del estado de salud con base en los niveles séricos de vitamina D

Introduction: 25-hydroxyvitamin D [25(OH)D] is considered a marker of general health and its deficiency is a problem worldwide. There is still no consensus to define their optimal levels, with it being necessary to establish them for each population according to their ethnic characteristics and environmental factors to which they are exposed. Objective: To determine the reference intervals for 25(OH)D in the native and apparently healthy population of Yucatan. Methods:The study included 71 apparently healthy volunteers, female and male, between one and 65 years old, and originally from Yucatan. Serum levels of 25(OH)D were measured along with the determination of calcium, phosphorus, and parathormone levels due to their relationship with vitamin D metabolism. Reference intervals were calculated using parametric and robust methods. The skin phototype was recorded and the Garabedian test was applied to determine the daily intake of calcium and vitamin D. Results: The mean value of 25(OH)D was 23.49±5.60ng/mL. The reference limits for total and gender-related 25(OH)D, and by gender were narrower and significantly different from those proposed by the manufacturer. A direct correlation was found between 25(OH)D levels and serum calcium (r=0.36; P=.003) and an inverse one with intact parathormone (r=−0.44; P<.001). A diet rich in calcium and vitamin D is not sufficient to maintain the normal requirements of 25(OH)D in this population. Conclusions: The proposed reference intervals are adequate to the peculiarities of the population of Yucatan and could improve the accuracy of health status measurement based on serum levels of vitamin D

Análisis de epistasia de polimorfismos de genes metabólicos asociados a cardiopatía isquémica en Yucatán / Epistasis analysis of metabolic genes polymorphisms associated with ischemic heart disease in Yucatan

Objetivo: La epistasia es un tipo de interacción genética que podría explicar gran parte de la variabilidad fenotípica que muestran las enfermedades complejas. En este trabajo se determinó el efecto de la epistasia de genes metabólicos y los factores de riesgo cardiovascular en la susceptibilidad al desarrollo de cardiopatía isquémica en Yucatán. Métodos: Estudio de casos y controles en 79 pacientes yucatecos con cardiopatía isquémica y 101 controles sanos pareados por edad y origen con los casos. Se genotipificaron los polimorfismos -108CT, Q192R, L55M (paraoxonasa 1, PON1), C677T, A1298C (5,10 metilentetrahidrofolato reductasa, MTHFR) y la presencia/ausencia del gen glutatión S-transferasa T1 (GSTT1). El análisis de epistasia se realizó con el método de reducción dimensional multifactorial (MDR). El mejor modelo de predicción de riesgo se seleccionó con base en la precisión (%), la significación estadística (p < 0,05) y la consistencia de la validación cruzada. Resultados: Se encontró asociación independiente del genotipo nulo GSTT1*0/0 (OR = 3,39; IC: 1,29-8,87; p = 0,017) y el alelo nulo (OR = 1,86; IC: 1,19-2,91; p = 0,007) con la cardiopatía isquémica. La deleción GSTT1*0 y el genotipo 677TT (MTHFR) se identificaron de alto riesgo cardiovascular, mientras que el genotipo silvestre GSTT1*1 y la variante CC677 se clasificaron de bajo riesgo. La interacción gen-ambiente identificó al gen GSTT1, al polimorfismo C677T (MTHFR) y a la hipertensión arterial como los factores que mejor explican la cardiopatía isquémica en la población estudiada. Conclusiones: La interacción de los genes GSTT1 y MTHFR conjuntamente con la hipertensión arterial puede constituir un modelo de predicción de riesgo para el inicio temprano de cardiopatía isquémica en la población de Yucatán

Objective: Epistasis is a type of genetic interaction that could explain much of the phenotypic variability of complex diseases. In this work, the effect of epistasis of metabolic genes and cardiovascular risk on the susceptibility to the development of ischemic heart disease in Yucatan was determined. Methods: Case-control study in 79 Yucatecan patients with ischemic heart disease and 101 healthy controls matched by age and origin with cases. The polymorphisms -108CT, Q192R, L55M (paraoxonase 1; PON1), C677T, A1298C (methylenetetrahydrofolate reductase; MTHFR), and the presence/absence of the glutathione S-transferase T1 (GSTT1) gene were genotyped. Epistasis analysis was performed using the multifactorial dimensional reduction method. The best risk prediction model was selected based on precision (%), statistical significance (P<0.05), and cross-validation consistency. Results: We found an independent association of the null genotype GSTT1*0/0 (OR=3.39, CI: 1.29-8.87, P=0.017) and the null allele (OR=1.86, CI: 1.19-2.91, P=0.007) with ischemic heart disease. The GSTT1*0 deletion and the 677TT genotype (MTHFR) were identified as being at a high cardiovascular risk, whereas the GSTT1*1 wild type genotype and the CC677 variant were at low risk. The gene-environment interaction identified the GSTT1 gene, C677T polymorphism (MTHFR), and hypertension as the factors that best explain ischemic heart disease in the study population. Conclusions: The interaction of the MTHFR, GSTT1 and hypertension may constitute a predictive model of risk for early onset ischemic heart disease in the population of Yucatan

Epistasis analysis of metabolic genes polymorphisms associated with ischemic heart disease in Yucatan. / Análisis de epistasia de polimorfismos de genes metabólicos asociados a cardiopatía isquémica en Yucatán.

OBJECTIVE: Epistasis is a type of genetic interaction that could explain much of the phenotypic variability of complex diseases. In this work, the effect of epistasis of metabolic genes and cardiovascular risk on the susceptibility to the development of ischemic heart disease in Yucatan was determined. METHODS: Case-control study in 79 Yucatecan patients with ischemic heart disease and 101 healthy controls matched by age and origin with cases. The polymorphisms -108CT, Q192R, L55M (paraoxonase 1; PON1), C677T, A1298C (methylenetetrahydrofolate reductase; MTHFR), and the presence/absence of the glutathione S-transferase T1 (GSTT1) gene were genotyped. Epistasis analysis was performed using the multifactorial dimensional reduction method. The best risk prediction model was selected based on precision (%), statistical significance (P<0.05), and cross-validation consistency. RESULTS: We found an independent association of the null genotype GSTT1*0/0 (OR=3.39, CI: 1.29-8.87, P=0.017) and the null allele (OR=1.86, CI: 1.19-2.91, P=0.007) with ischemic heart disease. The GSTT1*0 deletion and the 677TT genotype (MTHFR) were identified as being at a high cardiovascular risk, whereas the GSTT1*1 wild type genotype and the CC677 variant were at low risk. The gene-environment interaction identified the GSTT1 gene, C677T polymorphism (MTHFR), and hypertension as the factors that best explain ischemic heart disease in the study population. CONCLUSIONS: The interaction of the MTHFR, GSTT1 and hypertension may constitute a predictive model of risk for early onset ischemic heart disease in the population of Yucatan.

Prevalencia de infecciones de transmisión sexual en pacientes sintomáticos y asintomáticos de Yucatán / Prevalence of sexually transmitted infections in symptomatic and asymptomatic patients from Yucatan

Introducción. Los datos epidemiológicos sobre infecciones de transmisión sexual (ITS) no virales en Yucatán son limitados y provienen de pruebas serológicas. Material y métodos. Estudio retrospectivo para estimar la prevalencia de ITS no virales en pacientes de Yucatán utilizando un método molecular. Se tomaron muestras urogenitales en 147 pacientes (53 hombres y 94 mujeres) para la extracción de los ácidos nucleicos. Se utilizó la reacción en cadena de la polimerasa en tiempo real para la detección simultánea de Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum y Trichomonas vaginalis. El análisis estadístico se realizó con el test exacto de Fisher. Resultados. La prevalencia de ITS fue de 45,6%. Ureaplasma spp. fue el patógeno más frecuente y el sexo femenino el más afectado (p=0,022). Se detectó un 12,2% de coinfecciones con mayor frecuencia en mujeres (16,0 vs. 3,7%, p=0,035). No se encontraron diferencias significativas entre los pacientes sintomáticos (n=138) con reacción en cadena de la polimerasa positivo (n=64) y negativo (n=74). Las mujeres entre 21-40 años fueron las más expuestas a ITS (p <0,05). Conclusiones. Estos datos confirman la alta prevalencia de ITS no virales en Yucatán, siendo el primer reporte epidemiológico aplicando un método molecular (AU)

Introduction. Epidemiological data about non-viral sexually transmitted infections (STI) in Yucatan are limited and come from serological methods. Material and methods. Retrospective study to estimate the prevalence of STI in symptomatic and asymptomatic patients from Yucatan based on a molecular method. The urogenital samples were taken from 147 patients (53 men and 94 women) to extracted nucleic acids. Real-time polymerase chain reaction was used to simultaneous detection of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum y Trichomonas vaginalis. Statistical analysis was performed with the Fisher's exact test. Results. The prevalence of STIs was 45.6%. Ureaplasma spp. was the pathogen most frequent and the females the most affected (p=.022). It was detected 12.2% of coinfections being more frequent in women (16.0 vs. 3.7%, p=.035). No significant differences were found between symptomatic patients (n=138) with positive polymerase chain reaction (n=64) and negative (n=74). Women 21-40 years were the most exposed to STIs (p<.05). Conclusions. These data confirm the high prevalence of non-viral STIs in Yucatán, being the first epidemiological report based on a molecular method (AU)

High response rate to low-dose rituximab plus high-dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia.

UNLABELLED: Corticosteroids as initial therapy for primary immune thrombocytopenia achieve a low rate of sustained remission. METHODS: We prospectively evaluated the efficacy, safety, and response duration of low-dose rituximab plus high-dose dexamethasone as frontline therapy in newly diagnosed primary immune thrombocytopenia patients. One cycle of dexamethasone, 40 mg/d/intravenously for four consecutive days, plus weekly intravenous rituximab, 100 mg for four doses, was delivered. RESULTS: Twenty-one consecutive adults were enrolled. The overall response at day +28 was 90.5%. Complete sustained response at 6 months and relapse rate were 76.2% and 15.8%, respectively, compared with 30% and 62.5% for a historical group who had received standard treatment with prednisone (P = 0.005 and P = 0.004). There was a 9.5% incidence of adverse effects. CONCLUSIONS: The combination of low-dose rituximab and high-dose dexamethasone as frontline therapy for adults with primary immune thrombocytopenia was effective and had a high overall response rate and a low incidence of relapse.