Abstract in English:

ABSTRACT Background: Screening of transfusion-transmissible infectious agents of blood components is carried out in order to guarantee the safety of the transfusion process. The objective of this investigation was to characterize cases positive for transfusion-transmissible infectious agents in blood donations in the North ofPortugal. Method: Data from 2010 to 2022 of the Local Health Unit-Santo Antonio were used for this study. In specific epidemiological situations, malaria, Chagas disease and West Nile virus were screened. Main results: Over 12 years, the health unit, received 137,751 donations with 108 positive tests. The proportions of human immunodeficiency viruses, syphilis, human hepatitis viruses type B and C varied between 0 and 44/100,000 donations. In this period, two cases of malaria were detected in 2020-2021, and 21 were detected in 2022 corresponding to 52.1/1000 donations screened. In 2022, two cases of Chagas disease and no cases of West Nile virus were detected. Conclusion: These results highlight the importance of a rigorous investigation at the time of donation in which the donor’s history, including origin and movement in areas of greater geographic risk, are assessed. The recent and increasing detection of cases of malaria and Chagas disease confirms the presence of emerging infectious diseases transmitted by vectors, including mosquitoes, in blood donors. The increased risk of vector-borne diseases in Europe is a public health problem and represents a new challenge in screening donations.

Abstract in English:

ABSTRACT Introduction: Granulocyte colony-stimulating factor (G-CSF) is the most prevalently used growth factor for peripheral blood hematopoietic stem cell (HSC) mobilization. Most centers split the granulocyte colony-stimulating factor in two daily doses, whereas some centers administer one dose per day. This study aims to investigate the effect of the filgrastim dosing schedule on the quantity of hematopoietic stem cells collected after mobilization in healthy donors. Methods: A total of 251 healthy donors mobilized in our center were included in the study. Mobilization was either once a day (filgrastim 1 x 10 mg/kg/day) or twice a day (filgrastim 2 × 5 mg/kg/day). Results: White blood cell and peripheral CD34+ cell numbers were significantly higher in the Twice-a-day Group on the fifth day compared to the Once-a-day Group. No statistically significant difference was shown between the two groups regarding the number of CD34+ cells collected on the first apheresis day or the number of apheresis procedures needed to achieve the targeted number ofCD34+ cells. Conclusion: This study revealed that one daily dose of 10 mg/kg filgrastim is as effective as administering the same dose split on two days for an adequate amount of CD34+ cells in healthy donors.

Abstract in English:

ABSTRACT Objective: To elucidate the molecular basis, hematological features, and electrophoretic and chromatographic mobility behavior of an unstable α2-globin chain variant, and to describe the diagnostic approach. Methods: A Thai patient with unexplained chronic anemia and her daughter were investigated. Hematological data were analyzed using a standard automated cell counter. Hemoglobin was analyzed using high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Mutational analysis was performed using appropriate polymerase chain reaction (PCR) techniques and direct sequencing. Additionally, α-globin haplotype analysis was conducted. Simple and rapid diagnostic methods were developed. Results: Hemoglobin analysis in the patient revealed anomalous peaks separated from normal hemoglobin visible using the HPLC technique. These peaks were virtually absent in the daughter. DNA analysis identified a G to C mutation at codon 14 of the α2-globin gene responsible for hemoglobin Jax in trans to the α0-thalassemia gene in the patient. Heterozygosity of this mutation was identified in her daughter. Hematological analysis showed mild thalassemia-like changes in simple heterozygotes and exhibited a hemoglobin H-like phenotype when combined with (α0-thalassemia. Isopropanol stability testing and bioinformatic software indicated that the variant was unstable and potentially damaging. This mutation was confirmed using allele-specific PCR. Hemoglobin Jax was strongly associated with the haplotype [+ - S + - + -]. Conclusions: Hemoglobin Jax, a pathological α-globin variant, is asymptomatic in simple heterozygotes and demonstrates more pronounced clinical effects when associated with deletional ( -thalassemia. This knowledge can help develop strategies to prevent hemoglobinopathies in regions of high prevalence. Accurate identification requires DNA level analysis.

Abstract in English:

Abstract The German Hodgkin Study Group developed the escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) protocol as a treatment strategy for advanced-stage Hodgkin's lymphoma. In Brazil, as well as in other countries, procarbazine has been replaced with dacarbazine due to the limited availability of procarbazine. The Hematology Center at Irmandade da Santa Casa de Misericórdia in São Paulo adopted and modified the escalated BEACOPP protocol, substituting prednisone with dexamethasone and incorporating two different doses of dacarbazine: 375 mg/m2/day on Day 8 or the original dose of 250 mg/m2/day on Days 2 and 3. This adjustment was made in response to the anticipated toxicity profile. This study aimed to compare the two different doses in the protocols (375 mg/m2/cycle versus 500 mg/m2/cycle) administered to patients with advanced Hodgkin's lymphoma in similar periods. This retrospective study analyzed the data of 31 patients at a single center in Brazil from 2019 to 2021. Seventeen of the 31 patients received 500 mg/m2/cycle (500 Group), while 14 received 375 mg/m2/cycle (375 Group). At the end of the protocol, 71% of the patients in the 375 Group and 76% in the 500 Group achieved complete remission. On analyzing the number of cycles that patients presented with febrile neutropenia, the 500 Group had three times more events (17.9%) than the 375 Group (6.09% - p-value = 0.04). In the 500 Group, 47.1% needed to change the protocol to ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine) due to toxicity. In this limited cohort from a single public center in Brazil, the use of 375 mg/m2 of dacarbazine per cycle of the modified escalated BEACOPP protocol emerged as a safer strategy, maintaining treatment efficacy without compromising response in patients with advanced Hodgkin's lymphoma.

Abstract in English:

Abstract Objective To evaluate the accuracy of the galactomannan serum test in diagnosing oral invasive aspergillosis. Methods This prospective observational study included oncohematological neutropenic patients with suspected invasive aspergillosis, but without signs of pulmonary involvement. These patients underwent nasofibroscopy, biopsy, galactomannan serum testing, and maxillofacial high-resolution computed tomography to diagnose invasive aspergillosis. Patients were divided into two groups: Group 1 consisted of those with proven invasive aspergillosis, while Group 2 included patients without proven invasive aspergillosis. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results Thirteen patients were included in Group 1 and four in Group 2. The sensitivity, specificity, positive predictive and negative predictive values were 0.69, 1.0, 1.0 and 0.5, respectively. Sensitivity was higher in cases with Aspergillus sinusitis than in cases with exclusive oral lesions (0.77 versus 0.5, respectively). The galactomannan serum test optical density index was higher in Group 1 (2.4; range 0.2-3.5) than in Group 2 (0.2; range: 0.1-0.3; P-value = 0.007. Conclusions The galactomannan serum test is a valuable tool for screening invasive aspergillosis, especially in cases with nasal or sinus involvement, but biopsy is still the gold standard for diagnosis.

Abstract in English:

Abstract Background and objectives Stem cell mobilization is a well-known procedure to harvest hematopoietic stem cells for autologous stem cell transplantation in certain hematologic diseases. Numerous studies have been conducted to identify risk factors for poor mobilization but there are no studies that identify good mobilizers. In our hospital, we decided to explore good mobilizers, defining them as those with ≥40 CD34+ cells/μL on Day +4 in order to start early apheresis. Material and methods A descriptive retrospective study was performed at Hospital Universitari Son Espases. A total of 198 patients mobilized with doses of around 10 µg/kg of granulocyte colony-stimulating factor (G-CSF) every 12 h were analyzed for autologous collection between January 2015 and September 2022. Fifty patients who had ≥40 CD34+ cells/μL on Day +4 started early apheresis; the rest continued mobilization as planned. Success was defined as obtaining over 2.5 × 106 CD34+ cells/kg in a single apheresis. Results The necessary number of CD34+ cells/kg to perform an autologous stem cell transplantation was reached in a single apheresis session in 62 % of patients with ≥40 CD34+ cells/μL in peripheral blood. A cutoff of 102 CD34+ cells/μL on Day +4 was shown to have the best success rate (94 %). In an analysis of success, age, previously failed mobilization and having one or more adverse factors for bad mobilization were statistically significant. Conclusion Patients considered as good mobilizers were matched with our factors of poor mobilization, revealing that most patients (79 %) had none or only one risk factor for poor mobilization. Apheresis on Day +4 in good mobilizers was shown to be an effective alternative to reduce mobilization duration and decrease the amount of granulocyte-colony stimulating factor administered.

Abstract in English:

Abstract Background Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia associated with ADAMTS-13 deficiency, a cleaving protease of von Willebrand factor (vWF). According to the literature, blood group O tends to be less common among these patients than in the general population. This study aimed to investigate whether the decreasing trend of blood group O in thrombotic thrombocytopenic purpura patients is observed in a Turkish cohort and to analyze the relationship between clinical outcomes and blood groups. Patients and Methods A total of 65 patients with acquired and five patients with congenital thrombotic thrombocytopenic purpura from two university hospitals were enrolled in this study. As a control group, the blood group data of 136,231 individuals who were not diagnosed without anemia were obtained from the archives of the Istanbul Medical Faculty Blood Centre. The blood groups were compared between cases and the Control Group using the chi-square test. Subsequently, the clinical outcomes of patients and categorized blood groups were compared by the chi-square test, Mann Whitney U test and Cox regression with Kaplan Meier analysis. Results This study shows that the decreasing trend of blood group O was not observed in this Turkish cohort. Regarding the relationship between blood groups and clinical outcomes, the AB blood group is associated with a good prognosis and blood group O is associated with a poor prognosis. In addition, relapses were more common with blood group A patients but less common in blood group B. Conclusion The current study shows the association between thrombotic thrombocytopenic purpura and blood groups in the Turkish cohort. This study also contributes by analyzing the relationship between blood groups and clinical outcomes.

Abstract in English:

Abstract Mesenchymal stromal cells are multipotent cells present in various tissues that are widely studied for relevant therapeutic potential due to their paracrine immunomodulatory and tissue regenerating properties. Many mesenchymal stromal cell-based products are under investigation for the treatment of different clinical conditions. Recently, the therapeutic potential of the extracellular vesicles released by these cells has been under focus, with emphasis on clinical translation. Sterility testing during manufacture and before the final release of the advanced therapy medicinal products to markets is a critical quality control measure. Therefore, analytical methods for sterility testing in addition to complying with pharmacopeial standards must validate the adequacy of each product and evaluate matrix interference. Here, an automated system for sterility control of reagents used in the bioprocessing of mesenchymal stromal cells and their extracellular vesicles was validated. Reagents (culture media, antibiotics, and excipients in the final product) were inoculated with 10 or 50 colony forming units of microorganisms in BACTEC™ Peds Plus™ T/F aerobic/anaerobic bottles. Under aerobic conditions (BACTEC™ Peds Plus™ T/F aerobic bottles), microbial growth was detected within an acceptable incubation time according to regulatory guidelines. The results of this study corroborate other studies that use automated sterility testing as an alternative to the manual USP<71> compendial method to detect microorganisms close to the limit of detection within an acceptable incubation time.

Abstract in English:

Abstract Introduction Venous thromboembolism, a common complication associated with cancer, causes increased morbidity and mortality. D-dimer levels are often increased non-specifically in cancer which limits their use to diagnose venous thromboembolism. The current study aimed to investigate the role of the serum soluble suppression of tumorigenicity 2 (sST2) as a new biomarker to diagnose venous thromboembolism in cancer. Methods Eighty-eight patients with different types of cancer were enrolled and divided into two groups: Group I: 44 cancer patients with confirmed diagnosis of venous thromboembolism and Group II: 44 age- and sex-matched cancer patients without any thrombotic complications. The D-dimer test and sST2 measurement were performed for all study subjects. Results Serum sST2 levels were significantly higher in Group I than in Group II (p-value < 0.001); the median serum sST2 was 13.02 ng/mL (range: 7.65-117.9 ng/mL) in Group I versus 8.56 ng/mL (range: 5.59-10.33 ng/mL) in Group II. There was a significant positive correlation between serum sST2 and the D-dimer level. Using a receiver operating characteristic curve, sST2 had a greater area under the curve than the D-dimer test (0.974 versus 0.869, respectively). Although the D-dimer test was more sensitive, sST2 had a greater specificity than D-dimer (95.45 % versus 27.3 %, respectively) and a higher positive predictive value (95.3 % versus 56.8 %, respectively). Conclusion The results of the current study support a potential role of soluble ST2 to aid in diagnosing venous thromboembolism in cancer patients.

Abstract in English:

Abstract Introduction Bronchoscopy is frequently performed in the management of patients with acute leukemia due to their high susceptibility to infections. In this setting, it is performed in the context of lung infiltrates on imaging and persistent fever in immunocompromised subjects. This study aimed to evaluate the utility of bronchoscopy in patients with acute leukemia, its diagnostic yield, and its impact on management decisions. Methods This is a single-center cross-sectional study that included patients diagnosed with acute leukemia of any phenotype who received intensive chemotherapy. Consecutive patients who underwent bronchoscopy as part of a work-up for associated infections were selected, while patients who had undergone bone marrow transplant were excluded. This study investigated patient characteristics and the impact of bronchoscopy on changes in clinical management. Results Seventy-nine patients who underwent bronchoscopy at various stages of treatment were analyzed. The most frequent type of acute leukemia was acute myeloid leukemia, accounting for 68.3 % of cases. The induction phase was the most prevalent (29.1 %) treatment stage. Bacterial cultures were positive in 17 out of the 74 patients evaluated, with Pseudomonas aeruginosa being the most frequently identified microorganism. A change in medical management was observed in 18.2 % of cases, and only six patients experienced secondary complications. Conclusions This is the first Brazilian study to evaluate the utility of bronchoscopy in managing infectious complications in patients with acute leukemia. The impact of bronchoscopy on clinical management was less than anticipated, largely due to its low yield in identifying causative agents. Nevertheless, it remains a safe procedure and can be useful in specific situations.

Abstract in English:

Abstract The objective of this study was to explore the therapeutic effect of blueberries on hematological parameters, oxidative stress, and interleukin-10 levels in acute hemolytic anemia induced by the administration of an intraperitoneal injection of 40 mg/kg phenylhydrazine. Male Wistar rats were divided into three groups: Control, anemia (PHZ), and anemia plus blueberries (PHZ+BB). Blueberries were administered via oral gavage (250 mg/day). The erythrocyte osmotic fragility, splenomegaly, iron metabolism, hematological analysis, reactive oxygens species, sulfhydryl group, and interleukin-10 levels were evaluated. The erythrocyte osmotic fragility (in 0.85% and 0.55% sodium chloride solution) and spleen weight-to-body weight ratio (∼400%) were elevated in the PHZ and PHZ+BB Groups compared to the controls (p-value < 0.05). Increased transferrin and reactive oxygens species levels were found in the PHZ (15%) compared to the Control Group (p-value < 0.05). There was an immune inflammatory response in the PHZ Group due to increases in the total leukocyte (300%), lymphocyte (100%), and neutrophil (400%) counts compared to the Control Group (p-value < 0.05); the PHZ Group showed increased interleukin-10 levels (100%) compared to the Control Group (p-value < 0.05). Blueberries showed a partial protective effect on these parameters, since there were lower neutrophil and lymphocyte counts and diminished interleukin-10 levels in the PHZ+BB Group compared to the PHZ Group (p-value < 0.05). In addition, blueberries increased sulfhydryl group levels (p-value < 0.05). These data suggest a protective role of blueberries against inflammatory response and oxidative stress in an acute hemolytic anemia model.

Abstract in English:

Abstract The introduction of tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia vastly improving the prognosis and clinical outcome of most patients. It was estimated that approximately 40-50 % of patients treated with imatinib will require treatment with a second-generation or third-generation tyrosine kinase inhibitor to achieve an optimal response. The treatment duration, increased patient survival, and aging of the population receiving tyrosine kinase inhibitors raise concerns as to long-term toxicities, such as an elevated cardiovascular risk and a higher rate of comorbidities. Ponatinib is a highly potent third-generation tyrosine kinase inhibitor that was shown to be effective in patients with a wide range of ABL mutations, including T315I. The use of ponatinib is associated with significant vascular toxicity, including peripheral arterial occlusive disease, ischemic heart disease, cerebrovascular accidents, and venous thromboembolism. This review discusses the vascular toxicity of ponatinib and presents a comprehensive panel of tests for the evaluation of patients requiring ponatinib therapy. Moreover, the management of patients with cardiovascular risk factors who receive ponatinib is discussed. Finally, the strategy for establishing the optimal dose of ponatinib in patients with chronic myeloid leukemia is described.

Abstract in English:

Abstract The first step in innovation is to identify a problem of real relevance and systematically address it to deliver a sophisticated and viable solution. Disruptive innovation is a process where technology, products, or services are transformed or replaced by a better innovative solution. This superiority must be perceived by users as being more accessible, simple, or convenient. Patient Blood Management (PBM) suggests the notion of the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis and minimize blood loss thus improving patient outcomes, that is, they are aimed at changing patient care, assisting healthcare professionals in disease treatment and cure as well as risk reduction. Thus, innovation in PBM is a new frontier to be pursued. The management of patient's blood and preparation for surgical procedures is an enormous challenge that helps minimize anemia and control blood loss during hospitalization, ensuring they are discharged in adequate clinical conditions. Until 2016, there was no standard definition or classification for the severity of intraoperative bleeding or hemostasis. The development of a PBM program when combined to the development of a bleeding scale such as the validated Intraoperative Bleeding (VIBe) Scale, represents a new solution that balances perioperative blood loss and more importantly, enables a critical cultural change which can be useful to help surgeons communicate anticipated hemostatic needs throughout a case and therefore enhance efficiency leading to better outcomes.

Abstract in English:

Abstract Chimeric antigen receptor T-cell therapy represents an innovative approach to immunotherapy and currently stands out, particularly for oncohematological patients refractory to traditional treatments. Ongoing trials are further expanding its clinical use for new oncological and non-oncological indications, potentially leading to newer treatment options soon. This new approach, however, also presents challenges, including cardiovascular toxicity. Little is reported in pivotal studies, and some recent retrospective observations suggest a non-negligible incidence of side effects with presentation ranging from mild adverse cardiovascular events to fatal complications in which, in most cases, there is a direct or indirect association with cytokine release syndrome. In this literature review, the hypotheses of an important interface between cytokine release syndrome and cardiotoxicity by chimeric antigen receptor T-cell therapy will be addressed, as will current knowledge about risk factors for cardiotoxicity and recommendations for pre-therapy evaluation, post-infusion monitoring and clinical management of these complications.