Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients.

Background and aims: Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico. Methods: Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined. Results: Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS. Conclusion: Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

Factores epidemiológicos asociados a los accidentes cerebrovasculares en el municipio San Juan y Martínez / Epidemiological factors associated with strokes in San Juan y Martinez municipality

RESUMEN Introducción: los accidentes cerebrovasculares pueden cursar de forma silente o expresarse clínicamente como un evento agudo de déficit neurológico con secuelas permanentes. Objetivo: caracterizar los factores epidemiológicos asociados a los accidentes cerebrovasculares en el municipio San Juan y Martínez, durante el período noviembre 2017 a mayo 2018. Métodos: se realizó un estudio observacional, descriptiva y transversal. El universo estuvo constituido por los 706 pacientes diagnosticados con accidente vascular encefálico en el período estudiado. La muestra quedó integrada por 200 pacientes que cumplieron con los criterios de inclusión establecidos en la investigación. Resultados: según grupos de edades y sexo, el 62 % pertenecían al sexo masculino y la edad que predominó fue de 70 a 79 años, el 43 % de los pacientes eran fumadores, el 55 % tenían antecedentes patológicos personales de accidentes cerebrovasculares, en el 97 % de los casos se presentó un accidente cerebrovascular isquémico y entre las enfermedades asociadas, predominó la hipertensión arterial en el 43.1 % de los pacientes. Conclusiones: la prevención de los accidentes cerebrovasculares está en el mantenimiento de hábitos y estilos de vida saludables y con factores de bajo riesgo. Se asocia con un menor riesgo de múltiples enfermedades crónicas y también puede ser beneficioso en la prevención de los accidentes cerebrovasculares, en especial de tipo isquémico.

ABSTRACT Introduction: silent stroke can occur or be clinically expressed as an acute event of neurological deficit with permanent sequelae. Objective: to characterize the epidemiological factors associated with strokes in San Juan y Martínez municipality during the period of November 2017 to May 2018. Methods: an observational, descriptive and cross-sectional study was conducted. The target group comprised 706 patients diagnosed with cerebrovascular accident in the period studied. The sample consisted of 200 patients who met the inclusion criteria established in the research. Results: according to age groups and sex, 62 % belonged to male sex and the predominant age was from 70 to 79 years, 43 % of patients were smokers, 55 % had a personal pathological history of strokes, in 97 % of the cases there was an ischemic cerebrovascular accident and among the associated diseases hypertension predominated in 43,1 % of the patients. Conclusions: stroke prevention is based on the maintenance of healthy habits and lifestyles, the standard of living should be associated with low risk factors, which in turn should be linked to a lower risk of suffering from multiple chronic diseases and may also be favorable in the prevention of strokes, especially those of ischemic types.

Comportamiento del riesgo preconcepcional genético / Behavior of genetic pre-conception risk

Introducción: el riesgo genético reproductivo en las mujeres comprende factores de variada naturaleza que implican un peligro potencial para la descendencia. Se considera riesgo preconcepcional genético a la existencia de factores de diversa índole, que constituyen un peligro potencial para la salud reproductiva, identificados en mujeres comprendidas en edad fértil no gestante. Objetivo: describir el comportamiento del riesgo preconcepcional genético en el municipio de San Juan y Martínez en el año 2011. Material y método: se realizó una investigación descriptiva, retrospectiva y de corte transversal. El universo estuvo constituido por el total de pacientes con riesgo preconcepcional del municipio, y la muestra por las mujeres clasificadas como riesgo preconcepcional genético durante el año 2011. Se revisaron todas las fichas individuales de riesgo genético preconcepcional existentes en el servicio municipal de genética médica comunitaria de San Juan y Martínez, previo consentimiento informado; se realizó además una entrevista médica con la finalidad de obtener los datos con mayor certeza y profundidad. Resultados: el 62,5% de las mujeres clasificadas como riesgo preconcepcional genético fue por cromosomopatías, representado por las adolescentes seguidas por la edad materna avanzada. Los defectos del cierre del tubo neural fueron los defectos congénitos más frecuentes, seguidos de los cardíacos. Un elevado número de las pacientes estudiadas no conocían la efectividad del ácido fólico antes de la concepción del embarazo. Conclusiones: se debe promover en los profesionales de la salud el programa del manejo y control del riesgo preconcepcional, con la realización de actividades educativas para disminuir el riesgo genético antes del embarazo.

Introduction: reproductive genetic risk in women involves factors of a varied nature which imply a potential risk for the descendants. Genetic pre-conception refers to the existence of diverse factors which constitute a potential hazard to the reproductive health, identified in non-pregnant women in fertile ages. Objective: to describe the behavior of genetic pre-conception risk in San Juan y Martinez municipality during 2011. Material and method: a descriptive, retrospective and cross-sectional study, which target group was comprised of the total of patients having pre-conception risk in the municipality, the sample included women classified with genetic pre-conception risk at Community Genetics Service, previous an informed consent; along with a medical interview aimed at obtaining data with absolute certainty and in-depth analysis. Results: 62% of women classified of having pre-conception risk included chromosomal anomalies, represented by adolescents followed by advanced maternal ages. Neural tube defects were the most frequent congenital defects followed by cardiac ones. A great number of patients participating in the study knew nothing of the effectiveness of folic acid intake before the conception. Conclusions: the program for the management and control of pre-conception risk should be promoted in health professionals, performing educational activities in order to reduce genetic risk before the pregnancy.

Comportamiento del riesgo preconcepcional genético / Behavior of genetic pre-conception risk

El riesgo genético reproductivo en las mujeres comprende factores de variada naturaleza que implican un peligro potencial para la descendencia. Se considera riesgo preconcepcional genético a la existencia de factores de diversa índole, que constituyen un peligro potencial para la salud reproductiva, identificados en mujeres comprendidas en edad fértil no gestante. El objetivo fue describir el comportamiento del riesgo preconcepcional genético en el municipio de San Juan y Martínez en el año 2011. Se realizó una investigación descriptiva, retrospectiva y de corte transversal. El universo estuvo constituido por el total de pacientes con riesgo preconcepcional del municipio, y la muestra por las mujeres clasificadas como riesgo preconcepcional genético durante el año 2011. Se revisaron todas las fichas individuales de riesgo genético preconcepcional existentes en el servicio municipal de genética médica comunitaria de San Juan y Martínez, previo consentimiento informado; se realizó además una entrevista médica con la finalidad de obtener los datos con mayor certeza y profundidad. El 62,5 por ciento de las mujeres clasificadas como riesgo preconcepcional genético fue por cromosomopatías, representado por las adolescentes seguidas por la edad materna avanzada. Los defectos del cierre del tubo neural fueron los defectos congénitos más frecuentes, seguidos de los cardíacos. Un elevado número de las pacientes estudiadas no conocían la efectividad del ácido fólico antes de la concepción del embarazo. Se debe promover en los profesionales de la salud el programa del manejo y control del riesgo preconcepcional, con la realización de actividades educativas para disminuir el riesgo genético antes del embarazo(AU)

Reproductive genetic risk in women involves factors of a varied nature which imply a potential risk for the descendants. Genetic pre-conception refers to the existence of diverse factors which constitute a potential hazard to the reproductive health, identified in non-pregnant women in fertile ages. The objective was to describe the behavior of genetic pre-conception risk in San Juan y Martinez municipality during 2011. A descriptive, retrospective and cross-sectional study was carried out, which target group was comprised of the total of patients having pre-conception risk in the municipality. The sample included women classified with genetic pre-conception risk at Community Genetics Service, previous an informed consent; along with a medical interview aimed at obtaining data with absolute certainty and in-depth analysis. 62 per cent of women classified of having pre-conception risk included chromosomal anomalies, represented by adolescents followed by advanced maternal ages. Neural tube defects were the most frequent congenital defects followed by cardiac ones. A great number of patients participating in the study knew nothing of the effectiveness of folic acid intake before the conception. The program for the management and control of pre-conception risk should be promoted in health professionals, performing educational activities in order to reduce genetic risk before the pregnancy(AU)

Clinical prognostic factors for survival and risk of progression to acute myeloid leukemia in patients with myelodysplastic syndromes with < 10% marrow blasts and non-unfavorable cytogenetic categories.

UNLABELLED: Prognosis of myelodysplastic syndromes (MDS) is an area of ongoing interest. Identification of patients with poor outcome in the categories of lower risk disease is critical. In this study, we classify a cohort of 332 lower risk MDS into 3 groups with differences in survival and risk for leukemic progression that could drive treatment approaches to improve prognosis in a fraction of these patients. BACKGROUND: Prognosis of MDS and particularly in patients categorized as lower risk (< 10% blasts or low and intermediate-1 International Prognostic Scoring System [IPSS]) is very heterogeneous and includes patients with very different outcomes with current scoring systems. Recently, a new cytogenetic classification has been proposed for the revised IPSS in predicting the outcome for MDS. PATIENTS AND METHODS: To evaluate the prognostic significance of multiple variables for survival and risk of progression to acute myeloid leukemia, we analyzed baseline characteristics of 332 lower risk MDS patients within the lower risk cytogenetic categories by IPSS and the recent proposal for the new cytogenetic classification. RESULTS: In multivariate analysis, severity of cytopenias, age > 60 years, bone marrow blasts (5%-9%) and transfusion dependency significantly influenced outcome. The combination of these variables allowed development of a model which categorizes patients in 3 different groups with median survival of 95, 44, and 13 months for groups 1, 2, and 3, respectively (P < .001). In addition, this score also stratified patients for their risk for leukemic progression, estimated at 2 years in 3.1%, 7.6%, and 21.3% for each group (P = .024). CONCLUSION: Although karyotype remains the main prognostic factor in MDS, the current study identifies clinical parameters predicting outcome among patients with the better cytogenetic profile. Degree of cytopenias, blasts 5%-9% and transfusion dependence might identify a subset of patients within the nonadverse karyotype, in which early or more aggressive approaches could possibly be required to improve survival or prevent disease progression.

Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project.

There are few published data from real-world clinical experience with miglustat (Zavesca), an oral inhibitor of glucosylceramide synthase, in type 1 Gaucher disease. We report data from a prospective, open-label investigational study that evaluated substrate reduction therapy with miglustat 100 mg t.i.d. as a maintenance therapy in patients with Type 1 Gaucher disease who had been switched from previous enzyme replacement therapy. Long-term data on changes in organ size, blood counts, disease severity bio-markers, bone marrow infiltration, overall clinical status and safety/tolerability were analyzed from 28 patients with Type 1 Gaucher disease who were attending routine clinic visits. Assessments were performed at six, 12, 24, 36 and 48 months of therapy. Disease severity biomarkers improved up to 48 months after initiation of miglustat, while other disease parameters remained stable. Miglustat showed an acceptable profile of safety and tolerability throughout treatment. In conclusion, miglustat is an effective therapy for the long-term maintenance of patients with Type 1 Gaucher disease previously stabilized with enzyme replacement therapy.

Short-term effect of miglustat in every day clinical use in treatment-naïve or previously treated patients with type 1 Gaucher's disease.

In a prospective, open-label study, 25 patients with mild-to-moderate type 1 Gaucher's disease (GD1) were treated with miglustat (Zavesca), an oral glucosylceramide synthase inhibitor, over 12 months. Of the 25 patients, 10 were therapy-naïve and 15 had previously received enzyme replacement therapy (ERT). Clinical status, blood parameters, biomarkers, and organomegaly were assessed at baseline at 6 months and at 12 months. At 6 months the previously untreated patients showed a mean increase in hemoglobin of 0.77 g/dL, platelet counts improved or remaining stable, chitotriosidase and CCL18 decreased. These results were similar to those observed in 40 Spanish GD1 patients on ERT. Bone marrow infiltration cleared at 12 months. In the previously treated group, clinical and hematologic parameters and biomarkers were maintained/ improved at 12 months. Miglustat was well tolerated. The efficacy of miglustat treatment after 6 months was comparable to that of ERT.

[Study of deferoxamine in subcutaneous profusion treatment of iron overload in myelodysplastic syndromes]. / Estudio del tratamiento con desferroxamina en perfusión subcutánea para la sobrecarga de hierro en pacientes con síndrome mielodisplásico.

BACKGROUND AND OBJECTIVE: The progressive accumulation of iron in the organism contribute to one of the most important problems of morbidity and mortality in patients with myelodysplastic syndrome (MDS). We present an observational protocol, multicentre, open and non-aleatheorised, in patients diagnosed with MDS on transfusional regime with iron overload. The study was meant to prove the effectiveness of the parenteral treatment with desferrioxamine using continuous devices of subcutaneous profusion and evaluate the evolution of iron overload as well as transfusional requirements. PATIENTS AND METHOD: There were 28 patients (12 men and 16 women), 12 AR, 15 AS and 1 unknown. Average monitoring lasted 13.5 months and there was a gradual loss of patients. 11 of them had gone during the first year. RESULTS: After 12 months the average of ferritin decreased by 258.51 ng/dl (DE 1208.04; p = 9.4) and after 24 months, it decreased by 979.6 ng/dl (DE 810.31; p = 0.1). After 12 months the average of requirements increased by 60.57 gHb/month (DE 183.7; p = 0.029) and after 24 months, it increased by 167.3 g/Hb/month (DE 406.5; p = 0.36). CONCLUSIONS: Desferroxiamine treatment is effective at least to prevent an iron overload in these patients, and therefore should be incorporated in the clinical practice.

Estudio del tratamiento con desferroxamina en perfusión subcutánea para la sobrecarga de hierro en pacientes con síndrome mielodisplásico / Study of deferoxamine in subcutaneous profusion treatment of iron overload in myelodysplastic syndromes

FUNDAMENTO Y OBJETIVO: En los pacientes con síndromes mielodisplásicos (SMD) la acumulación progresiva de hierro en el organismo representa uno de los problemas más importantes de morbilidad y mortalidad. Presentamos un protocolo de diseño observacional, abierto, multicéntrico y no aleatorizado, en pacientes diagnosticados de SMD en régimen transfusional con sobrecarga de hierro. En este estudio se pretende comprobar la eficacia del tratamiento parenteral con desferrioxamina, utilizando dispositivos de perfusión continua subcutánea, y valorar la evolución de la sobrecarga de hierro y los requerimientos tranfusionales. PACIENTES Y MÉTODO: Se incluyeron 28 pacientes (12 varones, 16 mujeres), 12 con anemia refractaria(AR), 15 con anemia sideroblástica (AS) y 1 con un SMD no especificado. El seguimiento medio fue de 13,5 meses con pérdidas paulatinas de pacientes, 11 de ellas durante el primer año. RESULTADOS: A los 12 meses, la media (desviación estándar [DE]) de ferritina disminuyó en258,51 (1.208,04) ng/ml (p = 0,4) y a los 24 meses, en 979,6 (810,31) ng/dl (p = 0,1). A los 12 meses la media de transfundidos aumentó en 60,57 (183,7) g Hb/mes (p = 0,029) y a los 24 meses, en 167,3 (406,5) g Hb/mes (p = 0,36). CONCLUSIONES: La administración de desferrioxamina es eficaz en prevenir el aumento de la sobrecarga férrica en los pacientes con síndromes mielodisplásicos y debería incorporarse en su tratamiento

BACKGROUND AND OBJECTIVE: The progressive accumulation of iron in the organism contribute toone of the most important problems of morbidity and mortality in patients with myelodysplasticsyndrome (MDS). We present an observational protocol, multicentre, open and non-aleatheorised,I n patients diagnosed with MDS on transfusional regime with iron overload. The study was meant to prove the effectiveness of the parenteral treatment with desferrioxamine using continuous devices of subcutaneous profusion and evaluate the evolution of iron overload as well as transfusional requirements. PATIENTS AND METHOD: There were 28 patients (12 men and 16 women), 12 AR, 15 AS and 1unknown. Average monitoring lasted 13.5 months and there was a gradual loss of patients. 11of them had gone during the first year. RESULTS: After 12 months the average of ferritin decreased by 258.51 ng/dl (DE 1208.04; p =9.4) and after 24 months, it decreased by 979.6 ng/dl (DE 810.31; p = 0.1). After 12 months the average of requirements increased by 60.57 gHb/month (DE 183.7; p = 0.029) and after24 months, it increased by 167.3 g/Hb/month (DE 406.5; p = 0.36).CONCLUSIONS: Desferroxiamine treatment is effective at least to prevent an iron overload in these patients, and therefore should be incorporated in the clinical practice