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ABSTRACT Introduction: Hematologic abnormalities are common in HIV and involve all blood cell lineages. A study on cytopenias, as correlated with disease progression, can be valuable in resource-limited settings. This study aimed to determine the hematologic profile of HIV patients and its association with CD4 count and antiretroviral (ARV) treatment. Methods: This is a retrospective cohort study involving adult Filipino HIV patients with complete blood count (CBC) and CD4 count determinations prior to the initiation of ARV treatment and after ≥6 months of ARV treatment. Logistic regression was performed to determine the association between cytopenias and a CD4 count <200 cells/μL. Results: The study included 302 patients. Anemia was the most common cytopenia. Anemia and leukopenia were associated with an increased likelihood of having a CD4 count <200 cells/μL in ARV-naïve patients. In ARV-treated patients, leukopenia was associated with an increased probability of having a CD4 count <200 cells/μL. An increase in hemoglobin, white blood cell (WBC) and platelet counts was observed after ≥6 months of ARV treatment. Conclusion: Anemia and leukopenia can be used as markers of immune status in HIV-infected individuals and improvement in the CBC parameters can be used to assess response to ARV treatment. Routine monitoring of hematologic parameters is recommended.

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ABSTRACT Background: The date of acute lymphoblastic leukemia (ALL) diagnosis has been studied regarding potential etiologic roles with contrasting results and the issue remains controversial. The principal aim of this study was to analyze monthly variation of ALL diagnosis in a large homogenous Hispanic Latin American cohort over 15 years; its association with survival rates was also assessed. Methods: Clinical files and electronic records of 501 consecutive patients of all ages with ALL in northeastern Mexico over the years of 2004–2018 were scrutinized. Patients were divided into children <18 and adults >18 years. The Chi-square heterogeneity analysis was used to test for non-uniform variation. The Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data, using the month of diagnosis as a covariate in a separate model. Results: During the study period 363 children (72.5%) and 138 adults (27.5%) (p < 0.001) were diagnosed with ALL. Heterogeneity across the months of diagnosis was confirmed (p = 0.019) and the Poisson regression analysis confirmed a significant monthly variation (p < 0.001) (95% CI, 3.024–3.745), a higher annual peak being observed in the month of March (p = 0.002), followed by a second peak in October (p = 0.026). The five-year OS for children was 68.2% (95% CI, 67.64–68.74) and for adults, 43.7% (95% CI, 42.67–44.71) (p < 0.001). No significant association between the month of diagnosis and OS was found (p = 0.789). Conclusion: The monthly variation of ALL diagnosis was documented; these results confirm the heterogeneous behavior of the disease and appear to be consistent with an interplay of environmental and biologic factors. Further studies are needed to examine putative candidate agents.

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ABSTRACT Introduction: Constitutional symptoms and thrombohemorrhagic events are common in patients with myeloproliferative neoplasms (MPNs). Hence, the treatment’s primary goal is to control symptoms and improve the quality of life (QoL). In order to assess response to therapy, symptom burden, and QoL among patients with MPN, the “Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)” questionnaire was developed in the USA in 2012. Herein, we translated and validated the MPN-SAF TSS questionnaire to Brazilian Portuguese. Methods: The ten-item questionnaire was translated from the English language and its psychometric properties (reliability, convergent and construct validities) were evaluated in 101 MPN patients. Results: There were 41 patients with essential thrombocythemia, 39 with myelofibrosis and 21 with polycythemia vera. The median age of all patients at diagnosis was 68 years and 59% were female. The Cronbach’s alpha coefficient for the overall questionnaire was 0.78, ranging from 0.73 to 0.79, if each item was deleted. Validity analyses showed that the strongest item-item correlation were between early satiety and abdominal discomfort. Strong correlations were also found between physician and patient perceptions of itching (r = 0.81) and fatigue (r = 0.70). The Pearson coefficient correlation between the MPN-SAF TSS global score and the EORTC QLQ-C30 functional scales ranged from 0.51 to 0.64. The exploratory factor analysis showed that seven of the ten symptoms loaded into one single factor. Conclusion: The Brazilian Portuguese version of the MPN-SAF-TSS showed good psychometric properties and can be an available tool to assess symptom burden in this group of patients.

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ABSTRACT Introduction: One of the most critical complications in myelodysplastic syndromes (MDS) is the progression to acute myeloid leukemia (AML). The dynamics of clonal evolution in MDS and how acquired mutations can be used as biomarkers to track disease progression remains under investigation. Objective and method: Herein, we investigated the frequency of common myeloid clonal mutations (FLT3, NPM1, JAK2, IDH1 and IDH2) in 88 patients with MDS and 35 AML patients with myelodysplasia-related changes, followed at a single reference center in northeastern Brazil. Results: Overall, 9/88 (10%) ofthe MDSpatients and 9/35 (26%) of the secondary AML patients had at least one mutation. While the JAK2 V617F mutation was the most frequent in the MDS patients, the FLT3, NPM1, IDH1 and IDH2 mutations were more frequently found in the secondary AML group. Furthermore, there was a higher frequency of FLT3, NPM1, IDH1 and IDH2 mutations in MDS patients classified as high-risk subtypes than in those of lower risk. Conclusion: Despite the limited sample size, our data suggest that mutations in FLT3, NPM1, IDH1 and IDH2 genes could be potential biomarkers to detect early disease progression in MDS.

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ABSTRACT Introduction: The myelodysplastic syndrome (MDS) represents a group of hematopoietic neoplasms that is characterized by clonal hematopoiesis, cytopenia and abnormal cellular maturation. Red cell distribution width (RDW) refers to the variation degree of erythrocyte size and it is a reflection of anisocytosis. Higher values have been linked to adverse outcomes, such as increased mortality, vascular events, kidney and liver disease and demonstrated to harbor poor prognosis in solid and hematological malignancies. The RDW value can be used as a contributing parameter for MDS diagnosis, as well as its prognosis. In this study, we essentially aimed to demonstrate the correlation between the RDW and MDS prognostic indexes. Materials and methods: Ninety-four MDS patients at the Aydın Adnan Menderes University Hematology Division were included in the study. The correlations between the RDW and laboratory values (either lactate dehydrogenase, albumin, globulin or ferritin) and the RDW prognostic scoring indexes (IPSS, WPSS, IPSS-R and LR-PSS) were investigated. The PASW for Windows, version 21.0 (SPSS Inc., Chicago, IL, USA), was used for statistical assessment. A p-value below 0.05 was the cut-off for the statistical significance. Results: The mean age of all the patients was 73 ±10 years. Patients were observed for 41.88 ± 25 months. The mean RDW value for all cases was 15.5 ± 2.39. We found a statistically significant difference of survival between RDW values below and above 15.5% (p = 0.016). A significant difference was also observed according to the prognostic scoring indexes (see below). Conclusion: An increase in RDW is probably related to dysplasia in the MDS and this constitutes a possible explanation for the poor outcome. Prognostic indexes might incorporate the RDW as a parameter in the future.

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ABSTRACT Introduction: In Brazil, the sickle cell trait (SCT) has an average prevalence of 4% in the general population and 6-10% among Afro-descendants. Although SCT is highly prevalent, a large segment of the population ignores their status. The Therapeutic Guidelines prohibit the transfusion of SCT red blood cells into patients with hemoglobin disorders or severe acidosis and newborns. Methods: This was a cross-sectional study with data from 37,310 blood donation candidates. The study included only eligible first-time donors qualified to be tested for the presence of hemoglobin S (HbS) at the Fundação Hemominas Juiz de Fora, Brazil. The variables studied were gender, skin color, age, type of donation, place of birth, blood type, result of the solubility test for hemoglobin S (HbST) and hemoglobin electrophoresis (HbEF). Statistical analysis was performed using the Q square test and the Kappa index of agreement for comparing biochemical methods. This project was approved by the National Research Ethics Committee. Results: The analysis of first-time donor data showed that 7166 were considered eligible. A total of 127 of the 7166 donors were carriers of SCT (1.77%). Among the blood donors, 73.23% were from the local area. The HbST and HbEF were found to be 100% in concordance. Sensitivity was not tested in the present study. Conclusions: The HbST is highly specific for identifying the HbS, but sensitivity was not tested in this study. The screening of blood donors for abnormal hemoglobins is useful, helping to detect and counsel heterozygous people. The study seeks to identify the prevalence of SCT in a region of Brazil.

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ABSTRACT Introduction: By providing timely actionable results for prompt management, point-of-care testing (POCT) kits have revolutionised medical care for various diseases, ranging from infectious diseases like malaria to genetic disorders, such as sickle cell disease (SCD). They are, however, underutilised in the diagnosis of SCD in developing countries, where the need is greatest. Objective: The study was aimed at assessing the sensitivity of HemoTypeSC POCT among a cohort of children with SCD, previously diagnosed by Alkaline cellulose acetate hemoglobin electrophoresis (ACAE), with or without high-performance liquid chromatography (HPLC). Methods: In this descriptive cross-sectional study, HemoTypeSC test was conducted on all participants and its sensitivity was determined by comparing results with those obtained using ACAE. Discordance was verified with HPLC. Results: One hundred and forty-five children aged one to 19 years were studied. There were 84 males and 61 females (male: female ratio = 1.4:1). The HemoTypeSC was able to correctly diagnose sickle cell anemia (SCA) and hemoglobin SC in all (100%) of the children tested. Conclusion: The HemoTypeSC shows high sensitivity in detecting SCA and hemoglobin SC. Hence, it is useful for targeted screening of individuals suspected of having SCD, leading to rapid diagnosis of these hemoglobinopathies, even in resource-constrained settings.

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ABSTRACT Introduction: Telomere length (TL) is a biomarker of cellular proliferative history. In healthy individuals, leukocyte TL shortens with age and associates with the lifespan of men and women. However, most of studies had used linear regression models to address the association of the TL attrition, aging and sex. Methods: We evaluated the association between the TL, aging and sex in a cohort of 180 healthy subjects by quantile regression. The TL of nucleated blood cells was measured by fluorescent in situ hypridization (flow-FISH) in a cohort of 89 men, 81 women, and 10 umbilical cord samples. The results were validated by quantitative polymerase chain reaction (qPCR) and compared to a linear regression analysis. Results: By quantile regression, telomere dynamics slightly differed between sexes with aging: women had longer telomeres at birth and slower attrition rate than men until the sixth decade of life; after that, TL eroded faster and became shorter than that in men. These differences were not observed by linear regression analysis, as the overall telomere attrition rates in women and men were similar (42 pb per year, p < 0.0001 vs. 45 pb kb per year, p < 0.0001). Also, qPCR did not recapitulate flow-FISH findings, as the telomere dynamics by qPCR followed a linear model. Conclusion: The quantile regression analysis accurately reproduced a third-orderpolynomial TL attrition rate in both women and men, but it depended on the technique applied to measure TL. The Flow-FISH reproduced the expected telomere dynamics through life and, differently from the qPCR, was able to detect the subtle TL variations associated with sex and aging.

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ABSTRACT Introduction: Erythrocyte phenotyping is a very important test in the adoption of prophylactic measures to reduce transfusion reactions/alloimmunizations in polytransfused patients. The blood group Diego, in its current, form has 22 antigens, of which 4 are immunogenic, being Dia/Dib and Wra/Wrb, while the others are less expressive. The antigen Dia is of low incidence among whites and blacks, however, it is common in the South American indigenous and Asian Mongolian populations. It is also considered a system of clinical importance for its immunogenicity. Method: The present study aimed to carry out a retrospective and descriptive survey of the frequency of the Dia antigen in the blood donor population at the HEMOPA Foundation Coordinating Blood Center from 12/2018 to 1/2000. The data obtained were from the HEMOPA Foundation SBS Progress and SBS WEB Systems databases. Results: During this period, 941,744 blood bags were collected and, of these, 930 bags were phenotyped for the Dia antigen, of which 842 were negative and 88 (9.7%) positive. The research showed that, among the positive donors for the antigen Dia, 88.6% were brown, 3.4%, black and 8%, white. In the statistical analysis, the frequency observed was higher in browns. Conclusion: In the present investigation, we concluded that our region has a relatively higher frequency of the Dia antigen, when compared to the rest of Brazil, and it occurs more often in browns.

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ABSTRACT Introduction: Although several combination therapies for acute myeloid leukemia (AML) have emerged recently, there has been a lack of published surveys and educational projects focused on these important treatment options. We aimed to improve the oncology team members’ knowledge and awareness of several FDA approved combination therapies for AML, including glasdegib (DAURISMO®), venetoclax (VENCLEXTA®), GO (MYOLOTARG®),CPX-351 (VYXEOS®), and midostaurin (RYDAPT®). Additionally, we aimed to examine these teams’ perspectives, views, and attitudes towards these topics and finally identify barriers to the implementationof such therapies in clinical practice. Method: Initially, we developed booklets and then distributed them to each participating oncology and hematology office. Subsequently, all participating oncology and hematology team members were asked to complete an anonymous online survey to test their knowledge of and attitudes toward the subjects. Main results: There was a total of 52 survey respondents. The correct answer regarding various combination therapies for AML was identified by nearly 70% or more of survey takers. The level of awareness of project subjects significantly improved after reading our printing materials. Many survey respondents were motivated to learn more about combination therapies for AML as well as discuss these topics with others. Conclusions: Our booklets effectively improved understanding and awareness of combination therapies for AML. Future studies should explore awareness, knowledge, and perception of other new and emerging combination therapies for AML amongoncology and hematology team members in other areas.

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ABSTRACT Introduction: Platelet antibody identification is indispensable for diagnosing the human platelet antigen (HPA) or human leukocyte antigen (HLA) immunization, mostly because it can restrict the compatibility and results of transfusions. Correct detection of these antibodies is of utmost importance for the diagnosis and treatment. Method: We present 16 platelet alloimmunization results, comparing two tests with different technologies: the MAIPA (monoclonal antibody immobilization of platelet antigens), as a reference technique, and a bead-based assay, the Pak-Lx. Results: Eleven samples (68.75%) showed agreement in both techniques. Two tests were false negatives in the Pak-Lx: a pan-reactivity in GPIIbIIIa and an anti-HPA-9b. On the other hand, the Pak-Lx was more sensitive to detect a decreasing anti-HPA-5b. The Pak-Lx found an anti-HPA-2b positive, but with a low median fluorescent intensity (MFI), suggesting a false-positive result. Moreover, in one case, the MAIPA was negative for a positive Pak-Lx HLA. Conclusion: Antibody platelet diagnosis can sometimes be challenging. The methods seemed similar, the Pak-Lx being faster and simpler than the MAIPA, and they can be complementary to solve clinical issues.

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ABSTRACT Introduction: The aim of this study was to describe maternal and perinatal outcomes in pregnant women with sickle cell disease (SCD) followed at Santa Casa de Sao Paulo over a 10-year period (between 2010 and 2019). Method: Fifty-five records of pregnancies were analyzed among 35 women with SCD. Results: Among 29 newborns, 19 (65.5%) were full-term and 10 pre-term; 24 (82.7%) caesareans and 5 (17.2%) natural births were observed. The mean gestational age at birth and mother‘s age were 36.6 weeks (30–40) and 26.7 years (17–39), respectively. No maternal death was observed. The main maternal obstetric and non-obstetric complications were: preeclampsia and gestational diabetes, and vaso-occlusive crisis, urinary tract infection and acute chest syndrome, respectively. Twenty-six (47.0%) fetal deaths were observed, 24 being intrauterine fetal (14 early abortions, 10 late abortions and 2 stillbirths). Regarding the red blood cell transfusion history, 40 (72.7%) out of 55 pregnancies received transfusion. Pregnant women who received 6 or more transfusions throughout pregnancy had a significantly lower number of abortions, i.e., no cases of early abortion and only 1 case of late abortion, versus 14 and 9 cases in pregnancies with 0-5 transfusions, respectively. Despite advances in the management of SCD, pregnant women with SCD (particularly those with HbSS) are at a high risk for maternal and fetal complications, even though they are followed in reference centers. Conclusion: The lower risk of intrauterine fetal death for those women who received more transfusions throughout pregnancy observed in the current study leads us once more to raise the need for prospective, multicenter, randomized trials to determine whether the potential benefits balance the risks of prophylactic transfusions.

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ABSTRACT Introduction: Patient blood management (PBM) programs are associated with better patient outcomes, a reduced number of transfusions and cost-savings The Clinical Decision Support (CDS) systems are valuable tools in this process, but their availability is limited in developing countries This study assesses the feasibility and effectiveness of an adapted CDS system for low-income countries. Methods: This was a prospective study of the PBM program implementation, in a 200-bed tertiary hospital, between February 2019 and May 2020. Outcome measures were red blood cell (RBC), fresh frozen plasma (FFP) and platelet unit transfusions, the transfusion of a single unit of red blood cells and an RBC adequacy index (RAI). Results: Comparing the post-PBM program era with the pre-PBM system era, there was a decrease in red blood cell transfusions (p = 0.05), with an increase in single unit red blood cell transfusions (p = 0.005) and RAI (p < 0.001). Conclusions: The PBM programs, including electronic transfusion guidelines with pre-transfusion medical auditing, was associated with improved transfusion practices and reduced product acquisition-related costs.

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ABSTRACT Introduction: Thromboembolic events occur due to an imbalance in the hemostasis and some factors associated with this condition can be inherited. In order to evaluate the frequency of genotypes considered to be common hereditary risk factors for thrombophilia associated with venous thrombosis (g.1691G>A and g.20210G>A) and hyperhomocysteinemia (g.677C>T and g.1298A>C), samples from voluntary healthy blood donors at the Hospital de Clínicas de Porto Alegre were tested. Methods: We examined 325 blood samples from blood donors collected from October 2017 to July 2018. Blood was collected on filter paper and the DNA was extracted for single nucleotide polymorphisms (SNPs) analysis using the qualitative real time polymerase chain reaction. Results: The calculated frequencies of each genetic variant in heterozygosity were 4% for the FV gene (g.1691G> A), 4% for the F2 gene (g.20210G> A) and 42% and 39% for methylenetetrahydrofolate reductase (MTHFR), g.677C>T and g.1298A>C, respectively. Only the genetic variants of MTHFR were found in homozygosity, with frequencies of 14% and 6% (g.677C>T and g.1298A>C), respectively. Discussion: Altogether, these results describe the frequencies of genetic variants associated with venous thrombosis and hyperhomocysteinemia in the analyzed group and are important to enhance our current knowledge about the genetic profiles of Brazilian blood donors.

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ABSTRACT Introduction: Prevalence of RhD negative phenotype in Nigeria is low; this leads to scarcity of RhD negative red cells for transfusion. Serological and molecular genotyping of RhD negative individuals for weak D types could reduce this scarcity. The aim of this study was to determine the serological prevalence and molecular types of weak D phenotypes among blood donors and pregnant women in Kano, Nigeria. Methods: A total of 4482 blood donors and pregnant women from three hospitals in Kano were recruited. An indirect antiglobulin test was used to determine weak D phenotypes. Molecular genotyping was performed on genomic DNA from whole blood amplified by polymerase chain reaction sequence-specific primers (PCR-SSP) with agarose gel electrophoresis. Results: The mean age of the participants was 26.50 ±5.79 years. The prevalence of the RhD negative phenotype was 4.2% (189/4482). Of the 189 RhD negative phenotypes, 20 (10.6%) were weak D positive. Molecular genotyping of the 20 Weak D positive phenotypes revealed 15 (75%) weak D type 4, of which 11 were due to the RHD*09.03 and RHD*DAR3 (T201R, F223V) polymorphisms and 4, due to RHD* 08.01 and RHD* DFV polymorphisms; 2 (10%) were due to the 602 C>G polymorphism, while the remaining 3 (15%) constituted partial D or other rare weak D types. Conclusion: The prevalence of weak D positive phenotypes is high in this study; weak D type 4 is the most common RhD genetic variant. Routine serologic weak D testing of RhD negative blood and molecular genotyping should be encouraged in resource-limited settings.

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ABSTRACT Introduction: The oral cavity can present the first clinical manifestations of leukemia, therefore; it is important to recognize their principal characteristics. Objective: To identify oral manifestations as the first clinical signs of leukemia. Methods: This is an integrative review, that gathered data from articles with oral manifestations of leukemia as part of its first clinical features. The were included case reports, case series, clinical research, or reviews with case reports. The variables that were considered relevant: age, sex, sites of the oral lesions, characteristics of the oral lesions, medical history and physical examination, time of evolution, radiographic examination, blood test results, initial diagnosis, differential diagnosis and final diagnosis. Results: A total of 31 studies were included, with a total of 33 individuals identified. There were 19 (57.57%) males and 14 (42.42%) females. The age range was from 1.6 to 74 years. Acute myeloid leukemia (72.72%) and acute lymphoid leukemia (18.18%) presented more oral manifestations as the first clinical signs of the disease. All individuals with leukemia presented lesions, such as ulcer, erosion, bleeding, ecchymosis, color change of the bluish or pale mucous membranes and areas of tissue necrosis. Hard tissue lesions were less frequent, being 6 (18.18%). Conclusion: The first clinical manifestations of leukemia can be present in the oral cavity, mainly in acute myeloid leukemia. The principal oral tissues affected were gingival tissue, buccal mucosa and hard and/or soft palate. When hard tissues, such as the maxilla bone or mandible bone were affected, dental mobility was the principal clinical sign.

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ABSTRACT Introduction: Treatment-free remission (TFR) is a new goal of chronic myeloid leukemia (CML) therapy. TFR is feasible when the patient has achieved a deep and stable molecular response and met the criteria required to ensure its success. Treatment discontinuation should not be proposed to the CML patient if minimum conditions are not met. In Brazil, for example, molecular tests (BCR::ABL1) are not broadly available, making it difficult to monitor the patients adequately. Objective: In this sense, providing TFR recommendations for Brazilian physicians are therefore necessary. These recommendations include the main criteria checklist to start the TKIs treatment discontinuing process in patients diagnosed with CML and the population-eligible characteristics for treatment discontinuation. Method: Age, risk score at diagnosis, TKI treatment duration, BCR::ABL1 transcripts type, depth of the molecular response for treatment discontinuation, treatment adherence, patient monitoring and withdrawal syndrome are essential factors to consider in TFR. After TKI discontinuation, BCR::ABL1 transcripts monitoring should be more frequent. When a major molecular response loss is observed during the monitoring of a patient in TFR, the TKI treatment should be resumed. Conclusion: These recommendations should serve as a basis for medical professionals interested in proposing TKI discontinuation for CML patients in clinical practice. It is important to highlight that, despite the benefits of TFR for the patients and the health system, it should only be feasible following the minimum standards proposed in this recommendation.

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ABSTRACT Introduction: Involvement of the peritoneum occurs very rarely and is exceptional as an exclusive extranodal presentation of lymphomas. In most cases lymphomas associated with this rare entity are high-grade ones. PL secondary to high-grade nodal lymphoma is more frequent than primary peritoneal lymphoma, and there are only a few cases of the latter described in the literature. Description of the case: We present the case of a patient with constitutional syndrome and imaging findings suggestive of peritoneal carcinomatosis who was finally diagnosed with a Diffuse Large B-cell Lymphoma (DLBCL) by an ultrasound-guided core needle biopsy (CNB) of peritoneum. The patient received one polychemotherapy cycle; however tumor lysis syndrome occurred with death of the patient in the following days. This case tries to show the existence of a PL without other radiological findings of lymphoma, a fact that is very exceptionally described in the literature. Discussion: The differential diagnosis between PL and others peritoneum diseases such as peritoneal carcinomatosis, malignant primary peritoneal mesotheliomas, tuberculous peritonitis, sarcomatosis, diffuse peritoneal leiomyomatosis or benign splenosis, constitutes a major problem in imaging techniques. An exhaustive analysis of the radiological characteristics as well as a clinical-analytical context allows the differential diagnosis against peritoneal carcinomatosis and the rest of the entities previously referred although the final diagnosis will always be a biopsy. Conclusion: PL usually manifests as an aggressive histological subtype of high-grade lymphomas leading to a rapid progression and deterioration of the patient. It is crucial for the radiologist and the clinician to be aware of this rare entity providing the earliest possible diagnosis and optimal treatment to prolong the patient’s life.