Acute myeloid leukemia: challenges for diagnosis and treatment in Latin America.

OBJECTIVE: to review the current diagnostic and therapeutic landscape of AML in Latin America as a reflection of other low- and middle-income countries and regions of the world. Encompassing both acute promyelocytic and non-promyelocytic disease types. METHODS: We reviewed the literature and study registries concerning epidemiological features of patients with AML/APL treated in Latin America, as well as evaluated diagnostic and genetic stratification and patient fitness assessment challenges, the importance of early mortality and supportive care capacity, intensive and non-intensive chemotherapy alternatives, consolidation, and maintenance strategies including novel agents and hematopoietic stem cell transplantation. RESULTS: Although most of the current technologies and treatment options are available in the region, a significant fraction of patients have only limited access to them. In addition, mortality in the first weeks from diagnosis is higher in the region compared to developed countries. CONCLUSIONS: Disparities in access to technologies, supportive care capacity, and availability of novel agents and HSCT hinder results in our region, reflecting barriers common to other LMICs. Recent developments in the diagnosis and treatment of this disease must be implemented through education, collaborative clinical research, and advocacy to improve outcomes.

High ME1 Expression Is a Molecular Predictor of Post-Transplant Survival of Patients with Acute Myeloid Leukemia.

Several laboratory and clinical variables have been reported to be associated with the outcome of intensive chemotherapy for acute myeloid leukemia (AML), but only a few have been tested in the context of hematopoietic stem cell transplant (HSCT). This study aimed to identify genes whose expression of AML at diagnosis were associated with survival after HSCT. For this purpose, three publicly available adult AML cohorts (TCGA, BeatAML, and HOVON), whose patients were treated with intensive chemotherapy and then subjected to allogeneic or autologous HSCT, were included in this study. After whole transcriptome analysis, we identified ME1 as the only gene whose high expression was associated with shorter survival in patients subjected to HSCT. In addition, the inclusion of ME1 expression was able to improve the European LeukemiaNet risk stratification. Pathways related to lipid biosynthesis, mainly fatty acids, and cholesterol were positively correlated with ME1 expression. Furthermore, ME1 expression was associated with an M2 macrophage-enriched microenvironment, mature AML blasts hierarchy, and oxidative phosphorylation metabolism. Therefore, ME1 expression can be used as biomarker of poor response to HSCT in AML.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Transfusion of ABO non-identical platelets increases the severity of trauma patients at ICU admission

ABSTRACT Background: Transfusion of ABO-compatible non-identical platelets (PTLs), fresh plasma (FP) and red blood cells (RBCs) has been associated with increased morbidity and mortality of recipients. Trauma victims are frequently exposed to ABO non-identical products, given the need for emergency transfusions. Our goal was to evaluate the impact of the transfusion of ABO non-identical blood products on the severity and all-cause 30-day mortality of trauma patients. Methods: This was a retrospective single-center cohort, which included trauma patients who received emergency transfusions in the first 24 h of hospitalization. Patients were divided in two groups according to the use of <3 or ≥3 ABO non-identical blood products. The patient severity, measured by the Acute Physiology and Chronic Health Evaluation (APACHEII) score at ICU admission, and the 30-day mortality were compared between groups. Results: Two hundred and sixteen trauma patients were enrolled. Of these, 21.3% received ≥3 ABO non-identical blood products (RBCs, PLTs and FP or cryoprecipitate). The transfusion of ≥3 ABO non-identical blood products in the first 24 h of hospitalization was independently associated with a higher APACHEII score at ICU admission (OR = 3.28 and CI95% = 1.48-7.16). Transfusion of at least one unit of ABO non-identical PTLs was also associated with severity (OR = 10.89 and CI95% = 3.38-38.49). Transfusion of ABO non-identical blood products was not associated with a higher 30-day mortality in the studied cohort. Conclusion: The transfusion of ABO non-identical blood products and, especially, of ABO non-identical PLTs may be associated with the greater severity of trauma patients at ICU admission. The transfusion of ABO non-identical blood products in the trauma setting is not without risks.

Transfusion of ABO non-identical platelets increases the severity of trauma patients at ICU admission.

BACKGROUND: Transfusion of ABO-compatible non-identical platelets (PTLs), fresh plasma (FP) and red blood cells (RBCs) has been associated with increased morbidity and mortality of recipients. Trauma victims are frequently exposed to ABO non-identical products, given the need for emergency transfusions. Our goal was to evaluate the impact of the transfusion of ABO non-identical blood products on the severity and all-cause 30-day mortality of trauma patients. METHODS: This was a retrospective single-center cohort, which included trauma patients who received emergency transfusions in the first 24 h of hospitalization. Patients were divided in two groups according to the use of <3 or ≥3 ABO non-identical blood products. The patient severity, measured by the Acute Physiology and Chronic Health Evaluation (APACHEII) score at ICU admission, and the 30-day mortality were compared between groups. RESULTS: Two hundred and sixteen trauma patients were enrolled. Of these, 21.3% received ≥3 ABO non-identical blood products (RBCs, PLTs and FP or cryoprecipitate). The transfusion of ≥3 ABO non-identical blood products in the first 24 h of hospitalization was independently associated with a higher APACHEII score at ICU admission (OR = 3.28 and CI95% = 1.48-7.16). Transfusion of at least one unit of ABO non-identical PTLs was also associated with severity (OR = 10.89 and CI95% = 3.38-38.49). Transfusion of ABO non-identical blood products was not associated with a higher 30-day mortality in the studied cohort. CONCLUSION: The transfusion of ABO non-identical blood products and, especially, of ABO non-identical PLTs may be associated with the greater severity of trauma patients at ICU admission. The transfusion of ABO non-identical blood products in the trauma setting is not without risks.

FcγR2B B2.4 haplotype predicts increased risk of red blood cell alloimmunization in sickle cell disease patients.

BACKGROUND: Red blood cell (RBC) alloimmunization is an important transfusion complication which is prevalent among sickle cell disease (SCD) patients. Autoimmune diseases are a known risk factor for RBC alloimmunization, suggesting that autoimmunity and post-transfusion alloantibody development occur through similar physiopathological pathways. Polymorphisms in the FcγR2B gene have already been associated with several autoimmune disorders and hypothetically could be associated with RBC alloimmunization. Our goal was to evaluate if important polymorphisms of FcγR2B have an impact on the risk of RBC alloimmunization among SCD patients. STUDY DESIGN AND METHODS: This was a case-control study in which alloimmunized and non-alloimmunized SCD patients were compared in terms of the genotype frequency of the FcγR2B polymorphisms -386G/C, -120 T/A, and 695C/T, genotyped through direct Sanger sequencing. RESULTS: A total of 237 patients met the eligibility criteria, 120 cases (alloimmunized) and 117 controls (non-alloimmunized). RBC alloimmunization was associated with female sex (p < 0.001), lifetime number of RBC units transfused (p = 0.002) and 120 T/A FcγR2B genotype (p = 0.031). The FcγR2B promoter region haplotype 2B.4 (386C120A) was positively associated with RBC alloimunization (p = 0.045). The logistic regression (LR) model identified female sex (OR 10.03, CI 95% 5.16-19.49; p < 0.001) and FcγR2B 2B.4 haplotype (OR 4.55, CI95% 1.1118.65; p = 0.035) as independent predictors of RBC alloimmunization in SCD patients. CONCLUSION: SCD patients with the FcγR2B 2B.4 haplotype had over a fourfold higher risk for RBC alloimmunization. This highlights the role played by FcγR2B on RBC alloimmunization and may be helpful in identifying the immune responders.

SMIM1 intron 2 gene variations leading to variability in Vel antigen expression among Brazilian blood donors.

BACKGROUND: There is a significant inter-individual heterogeneity of Vel antigen expression which can lead to inaccuracies on Vel phenotyping of blood donors and, potentially, to hemolytic post-transfusion reactions. Our aim was to evaluate the impact of genetic variants in the SMIM1 intron 2 on the expression of Vel antigen among Brazilian blood donors harboring the c.64_80del17 deletion in heterozygosity. METHODS: Donors presenting the SMIM1 c.64_80del17 in heterozygosity were included in the study and subjected to SMIM1 intron 2 direct sequencing aiming to genotype the following polymorphisms: rs143702418, rs1181893, rs191041962, rs6673829, rs1175550 and rs9424296. RESULTS: SMIM1 intron 2 sequencing was performed on two hundred donors presenting one c.64_80del17 allele. The rs1175550 polymorphism significantly impacted on Vel antigen expression. Variations in the strength of agglutination on Vel phenotyping were also observed according to the rs6673829 genotype, but this difference did not persist with statistical relevance after multivariate analysis. CONCLUSION: The presence of the rs1175550A allele of SMIM1 is significantly and independently associated with a decrease in Vel antigen expression. Even though the population in Brazil is intensely mixed, the allele frequencies obtained in the current study were very similar to that reported for Europeans.

Associação da quimiotoxicidade com o estado (de la quimiotoxicidad con el estado) nutricional em pacientes oncológicos / Nutritional status and chemotoxicity in oncology patients

Introdução: O câncer é uma enfermidade caracterizada pelo (El cáncer es una enfermedad que se caracteriza por el) crescimento desordenado de células, cujo tratamento com quimioterapia atua no seu controle ou (cuyo tratamiento con quimioterapia actúa en su control o) remissão e pode prolongar a sobrevida. No entanto (Sin embargo), a quimioterapia pode causar uma série de efeitos colaterais, denominados quimiotoxicidade, levando ao déficit nutricional e comprometendo sua tolerância e (llevando al déficit nutricional y comprometiendo su tolerancia y) eficácia. Objetivo: Verificar a associação da quimiotoxicidade com o estado nutricional de pacientes oncológicos. Métodos: Estudo transversal, de caráter retrospectivo, com análise de prontuário (con análisis de historia clínica) de pacientes com neoplasia de tumores sólidos, com 3 ciclos realizados de quimioterapia. Foram coletadas variáveis (Fueron contempladas variables) sociodemográficas, clínicas, antropométricas e a quimiotoxicidade foi categorizada conforme a National Cancer Institute (NCI). Resultados: Foram avaliados 126 pacientes, com idade média 54.6 ± 13.9 anos, predominantemente do sexo feminino (68.3%). As neoplasias mais prevalentes foram mama (51%) e trato gastrointestinal (34.5%) e o estadiamento IV foi prevalente (con prevalencia del estadio IV) (40.5%). A quimiotoxicidade apresentou-se desde o primeiro ciclo, com 52.5% de toxicidade bioquímica. Comparando o primeiro e terceiro ciclo não foi observada associação significativa entre a toxicidade e o índice de massa corporal (IMC), leucócitos, plaquetas e hemoglobina, mas observou-se tendência na toxicidade (pero se observó una tendencia en la toxicidad) de neutrófilos (p = 0.053). A toxicidade gastrointestinal afetou significativamente a perda de peso durante o (la pérdida de peso durante el) tratamento (p = 0.024). Conclusão: A quimiotoxicidade foi observada desde o primeiro ciclo, no entanto apenas a toxicidade do trato gastrointestinal apresentou (sin embargo, solo la toxicidad del tracto gastrointestinal presentó una) associação com a perda de peso corporal.

Introduction: Cancer is a disease characterized by the uncontrolled growth of cells, whose treatment with chemotherapy acts as a control or remission and may prolong survival. However, chemotherapy can cause a number of side effects, called chemotoxicity, leading to malnutrition and compromising its effectiveness and tolerance. Objective: To investigate the association between chemotoxicity and the nutritional status of cancer patients. Methods: Longitudinal and retrospective study with chart analysis of patients with cancer of solid tumors, with at least 3 cycles of chemotherapy performed. Sociodemographic, clinical, anthropometric variables were collected and chemotoxicity was categorized according to the National Cancer Institute (NCI, 1999). Results: We evaluated 126 patients, mean age of 54.6 ± 13.9 years, predominantly female (68.3%). The most common cancers were breast (51%) and gastrointestinal tract (34.5%) and most were classified as stage IV (40.5%). Chemotoxicity showed up from the first cycle, with 52.5% biochemical toxicity. Comparing the first and the third cycles, no difference in toxicity was observed in relation to body mass index (BMI), white blood cells, platelets and hemoglobin; but there was a trend in the association of toxicity with neutrophils (p = 0.053). The GI toxicity significantly affected weight loss during treatment (p = 0.024). Conclusion: chemotoxicity was observed from the first cycle; however only the toxicity of the gastrointestinal tract was associated with weight loss.