Association of CD38+ Immunophenotyping Biomarker With a Better Prognosis in Elderly Acute Myeloid Leukemia Patients.

BACKGROUND/AIM: The relevance of cytogenetic markers as prognostic risk factors has been demonstrated in a vast number of studies, with many prognostication tools utilizing these factors to determine treatment approaches. Patients aged above 60 years represent an important subgroup of acute myeloid leukemia (AML) patients, especially because they usually exhibit a poorer cytogenetic landscape and are less suitable for intensive treatments. The importance of evaluating prognostic parameters in AML, especially in low-income countries, prompted an investigation into CD38 expression and its effects. PATIENTS AND METHODS: Medical records of AML patients aged above 60 years from three hospitals in Brazil's northwest region were analyzed. A total of 67 patients were evaluated in terms of overall survival and factors predicting worse outcomes. The risk stratification was performed based on the European LeukemiaNet 2022 guidelines. The analysis of immunophenotyping markers was conducted using multi-parametric flow cytometry. RESULTS: The overall survival of CD38-positive AML patients was higher than that of patients with CD38-negative AML, with survival rates of 15.6 months versus 4 months, respectively (p-value=0.026). The impact of CD38 positivity was relevant also in multivariable Cox proportional hazards regression, demonstrating a positive effect on overall survival, with a hazard ratio of 0.33 (95%CI=0.13-0.79; p-value=0.014). CONCLUSION: Expression of CD38 in patients with AML was associated with better overall survival and serves as a relevant predictor of improved outcome in patients aged above 60 years.

Clinical outcome and prognosis of patients with acute myeloid leukemia submitted to chemotherapy with 5 years of follow-up

Abstract Objective The purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with acute myeloid leukemia (AML), identifying the main causes of morbidity and mortality and overall survival rate of patients at five years of follow-up. Method This was a retrospective cohort study evaluating the prognosis and clinical outcomes of 222 patients diagnosed with AML at three large hematology centers in Ceará (northeastern Brazil) over a period of five years. Results The mean age at diagnosis was 44.1 ± 16 years, with a female prevalence of 1.3:1. No additional relevant risk factors associated with the development of AML were found, except for the well-established cytogenetic assessment. The overall 5-year survival rate was 39.4% (95%CI: 35.47 - 42.17). The main causes of death were disease progression (37.72%; n = 84) and sepsis (31.58%; n = 70). Conclusion The clinical outcomes in our sample of AML patients were similar to those of other reported groups. Disease progression and infection were the main causes of death. Access to diagnostic flow cytometry and karyotyping was greater in our sample than in the national average. As expected, overall survival differed significantly according to the risk, as determined by cytogenetic testing.

Validation of Endogenous Control Genes by Real-Time Quantitative Reverse Transcriptase Polymerase Chain Reaction for Acute Leukemia Gene Expression Studies.

Reference genes are used as internal reaction controls for gene expression analysis, and for this reason, they are considered reliable and must meet several important criteria. In view of the absence of studies regarding the best reference gene for the analysis of acute leukemia patients, a panel of genes commonly used as endogenous controls was selected from the literature for stability analysis: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Abelson murine leukemia viral oncogene human homolog 1 (ABL), Hypoxanthine phosphoribosyl-transferase 1 (HPRT1), Ribosomal protein lateral stalk subunit P0 (RPLP0), ß-actin (ACTB) and TATA box binding protein (TBP). The stability of candidate reference genes was analyzed according to three statistical methods of assessment, namely, NormFinder, GeNorm and R software (version 4.0.3). From this study's analysis, it was possible to identify that the endogenous set composed of ACTB, ABL, TBP and RPLP0 demonstrated good performances and stable expressions between the analyzed groups. In addition to that, the GAPDH and HPRT genes could not be classified as good reference genes, considering that they presented a high standard deviation and great variability between groups, indicating low stability. Given these findings, this study suggests the main endogenous gene set for use as a control/reference for the gene expression in peripheral blood and bone marrow samples from patients with acute leukemias is composed of the ACTB, ABL, TBP and RPLP0 genes. Researchers may choose two to three of these housekeeping genes to perform data normalization.

Blood components requirement in Brazilian dengue outbreaks: A retrospective analysis between 2008 to 2019.

INTRODUCTION: Dengue is the most fatal virus disease spread by mosquito bites and Aedes aegypti is the main transmitting agent. It is an endemic disease in the tropical and subtropical regions, currently affecting more than 100 countries. Although most patients present mild forms of the disease, a considerable proportion of individuals has severe alterations in the blood count. The aim of this study was to evaluate the consumption pattern of blood components in epidemic and non-epidemic periods and to verify if there was an impact on dengue cases and the death rate. METHOD: This is a retrospective cross-sectional study conducted through the collection and analysis of data from the Brazilian Ministry of Health from 2008 to 2019 on new cases and deaths from dengue, as well as the consumption of blood components in the period mentioned by hemovigilance bulletins of the Brazilian authority. RESULTS: Regarding the results, no significant difference was found between the absolute amount of blood components used in years with an epidemic peak. Regarding the relative values, an important variation was shown among the distributive consumption patterns of blood components in the outbreak years. In the univariate linear regression analysis, there was statistical significance between the increase in the number of dengue cases and deaths from dengue with the increase in the consumption of red blood cell concentrates (RBP), platelet concentrates (PP), fresh frozen plasma (FFP) and cryoprecipitate (Cryo) (p-value < 0.05). The increase in dengue cases was related to the increase in Cryo consumption with clinical significance (R² > 0.5), but dengue deaths were not correlated to the same. In multivariate analysis, all regression models had clinical and statistical significance. CONCLUSION: The data obtained in the present study demonstrate that there is a relevant relationship between the increase in cases and deaths from dengue with the blood components usage, especially PP, FFP and cryoprecipitate.

Association between Immunophenotypic Parameters and Molecular Alterations in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a hematologic malignancy that occurs due to alterations such as genetic mutations, chromosomal translocations, or changes in molecular levels. These alterations can accumulate in stem cells and hematopoietic progenitors, leading to the development of AML, which has a prevalence of 80% of acute leukemias in the adult population. Recurrent cytogenetic abnormalities, in addition to mediating leukemogenesis onset, participate in its evolution and can be used as established diagnostic and prognostic markers. Most of these mutations confer resistance to the traditionally used treatments and, therefore, the aberrant protein products are also considered therapeutic targets. The surface antigens of a cell are characterized through immunophenotyping, which has the ability to identify and differentiate the degrees of maturation and the lineage of the target cell, whether benign or malignant. With this, we seek to establish a relationship according to the molecular aberrations and immunophenotypic alterations that cells with AML present.

Clinical outcome and prognosis of patients with acute myeloid leukemia submitted to chemotherapy with 5 years of follow-up.

OBJECTIVE: The purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with acute myeloid leukemia (AML), identifying the main causes of morbidity and mortality and overall survival rate of patients at five years of follow-up. METHOD: This was a retrospective cohort study evaluating the prognosis and clinical outcomes of 222 patients diagnosed with AML at three large hematology centers in Ceará (northeastern Brazil) over a period of five years. RESULTS: The mean age at diagnosis was 44.1 ± 16 years, with a female prevalence of 1.3:1. No additional relevant risk factors associated with the development of AML were found, except for the well-established cytogenetic assessment. The overall 5-year survival rate was 39.4% (95%CI: 35.47 - 42.17). The main causes of death were disease progression (37.72%; n = 84) and sepsis (31.58%; n = 70). CONCLUSION: The clinical outcomes in our sample of AML patients were similar to those of other reported groups. Disease progression and infection were the main causes of death. Access to diagnostic flow cytometry and karyotyping was greater in our sample than in the national average. As expected, overall survival differed significantly according to the risk, as determined by cytogenetic testing.

Kinase Inhibition in Multiple Myeloma: Current Scenario and Clinical Perspectives.

Multiple myeloma (MM) is a blood cell neoplasm characterized by excessive production of malignant monoclonal plasma cells (activated B lymphocytes) by the bone marrow, which end up synthesizing antibodies or antibody fragments, called M proteins, in excess. The accumulation of this production, both cells themselves and of the immunoglobulins, causes a series of problems for the patient, of a systemic and local nature, such as blood hyperviscosity, renal failure, anemia, bone lesions, and infections due to compromised immunity. MM is the third most common hematological neoplasm, constituting 1% of all cancer cases, and is a disease that is difficult to treat, still being considered an incurable disease. The treatments currently available cannot cure the patient, but only extend their lifespan, and the main and most effective alternative is autologous hematopoietic stem cell transplantation, but not every patient is eligible, often due to age and pre-existing comorbidities. In this context, the search for new therapies that can bring better results to patients is of utmost importance. Protein tyrosine kinases (PTKs) are involved in several biological processes, such as cell growth regulation and proliferation, thus, mutations that affect their functionality can have a great impact on crucial molecular pathways in the cells, leading to tumorigenesis. In the past couple of decades, the use of small-molecule inhibitors, which include tyrosine kinase inhibitors (TKIs), has been a hallmark in the treatment of hematological malignancies, and MM patients may also benefit from TKI-based treatment strategies. In this review, we seek to understand the applicability of TKIs used in MM clinical trials in the last 10 years.

Thrombotic thrombocytopenic purpura associated with dengue and chikungunya virus coinfection: case report during an epidemic period.

The present report shows the occurrence of thrombotic thrombocytopenic purpura (TTP) associated with acute dengue and chikungunya virus coinfection, manifesting as a severe disease with high mortality potential. The patient was a 28 year-old man with clinical and epidemiological diagnosis of arboviruses infections who developed thrombocytopenia and anemia, after which oral corticosteroid therapy was started. On the third day of hospitalization, he showed neurological alterations that simulated a cerebral vascular accident, but the imaging examination did not identify ischemic or hemorrhagic alterations. At that moment, the TTP hypothesis was raised so that plasmapheresis and corticosteroid pulse therapy were started, have been essential for the favorable evolution of the case.

Pancitopenia em pacientes com anemia perniciosa. Estudo descritivo de 33 casos. / Pancytopenia in patients with pernicious anemia. Descriptive study of 33 cases.

Objetivo: Discriminar as variáveis de sexo e idade nos pacientes com anemia perniciosa; estudar seu perfil hematimétrico; verificar a prevalência de outras doenças autoimunes e anemia perniciosa; analisar a incidência da pancitopenia e sua relação com alterações laboratoriais comum na doença; e avaliar a frequência dos autoanticorpos anticélulas parietais e antifator intrínseco. Métodos: Estudo transversal descritivo, de base clínica e laboratorial, de 33 prontuários de pacientes com anemia perniciosa, diagnosticados em um ambulatório de hospital terciário de atenção à saúde, no período de junho de 2009 a junho de 2014. Para analisar a relação da presença e da ausência de pancitopenia com os níveis da enzima lactato desidrogenase e vitamina B12, foi utilizado o teste qui quadrado. O programa utilizado foi o software Epi Info, versão 7. Resultados: Na amostra, 63,6% eram mulheres, e a idade média geral foi de 47,3 anos. Doenças autoimunes estavam associadas em 30,3% dos pacientes. A pancitopenia esteve presente em 39,4% dos pacientes. Houve significância estatística na relação da pancitopenia com os níveis de enzima lactato desidrogenase (p<0,05). A prevalência do antifator intrínseco foi de 69,7% e dos autoanticorpos anticélulas parietais foi de 72,7%. Conclusão: A pancitopenia mostrou-se um achado significante na população com anemia perniciosa, assim como níveis elevado de LDH, acrescentando a anemia perniciosa como um diagnóstico diferencial de tais alterações laboratoriais.(AU)

Objective: To discriminate the gender and age variables in patients with pernicious anemia; to study erythrocyte profile; to check the prevalence of other autoimmune diseases and pernicious anemia; to analyze the incidence of pancytopenia and its relationship with common laboratory abnormalities in the disease; to evaluate the frequency of anti-gastric parietal cell antibodies, and anti-intrinsic factor antibodies. Methods: Descriptive, cross-sectional study of clinical and laboratorybased medical records of 33 patients with pernicious anemia diagnosed in an outpatient's department of a tertiary healthcare center, in the period between June 2009 and June 2014. To analyze the relationship between the presence and absence of pancytopenia with levels of lactate dehydrogenase enzyme and levels of Vitamin B12 we used the chi-squared test. The software used was Epininfo version 7. Results: The sample showed 63.6% women and 36.4% men with a mean age of 47.3 years. Autoimmune diseases were associated in 30.3% of the patients. Pancytopenia was present in 39.4% of patients. There was statistically significant relationship of pancytopenia with lactate dehydrogenase enzyme levels (p <0.05). The frequency of anti-intrinsic factor antibodies was 69.7%, and the antigastric parietal cell antibodies was 72.7%. Conclusion: Pancytopenia proved to be a significant finding among the population with pernicious anemia and high levels of LDH, which includes pernicious anemia as a differential diagnosis of such laboratory alterations.(AU)