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ABSTRACT Objective: Intraoperative blood salvage (cell saver technique) in cardiac surgery is universally used in surgical procedures with a marked risk of blood loss. The primary objectives of this study were to determine the concentration of residual heparin in the final product that is reinfused into the patient in the operating room and to evaluate the efficacy and safety of the cell saver technique. Method: Twelve patients undergoing elective cardiac surgery were enrolled in this study. Using the XTRA Autotransfusion System, blood samples were collected from the cardiotomy reservoir, both prior to blood processing (pre-sample) and after it, directly from the bag with processed product (post-sample). Hematocrit and hemoglobin levels, the protein, albumin and residual heparin concentrations, hemolysis index, and the platelet, erythrocyte and leukocyte counts were measured. Results: Hematocrit and hemoglobin levels and red blood cell counts were higher in post-processing samples, with a mean variation of 54.78%, 19.81 g/dl and 6.84 × 106/mm3, respectively (p < 0.001). The mean hematocrit of the processed bag was 63.49 g/dl (range: 57.2-67.5). The residual heparin levels were ≤0.1 IU/ml in all post-treatment analyses (p = 0.003). No related adverse events were observed. Conclusion: The reduced residual heparin values (≤0.1 IU/ml) in processed blood found in this study are extremely important, as they are consistent with the American Association of Blood Banks guidelines, which establish target values below 0.5 IU/ml. The procedure was effective, safe and compliant with legal requirements and the available international literature.

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ABSTRACT Introduction: To assess the frequency of allergic reactions to asparaginase (ASP) and possible risk factors for reactions in a cohort of pediatric patients. Method: The study was performed based on retrospective data from patients under acute lymphoid leukemia treatment in a general university hospital located in southern Brazil. Information on patients who used ASP from 2010 to 2017 was collected. Allergic reactions were identified in electronic medical records. Results: Among the 98 patients included in the study, 16 (16.3 %) experienced an allergic reaction to native l-asparaginase (L-ASP). Of the 22 patients (22.4 %) that received only intravenous (IV) administration of l-ASP, 10 (62.5 %) had allergic reactions, while 48 patients (49 %) received intramuscular (IM) administration and 28 (28.6 %) received IV and IM administrations. The occurrence of allergic reactions differed between the groups (p < 0.001), and IV administration was associated with allergic reactions. Association was also observed between the severity of the reaction and the route of administration, with the IM route associated with grade 2 and IV route associated with grade 3. Occurrence of allergic reactions was higher when the commercial formulation of l-ASP, Leuginase®, was used (p = 0.0009 in the analysis per patient and p = 0.0003 in the analysis per administration). Conclusions: The IV administration and commercial Leuginase® presentation were associated with more allergic reactions in the study population, which corroborates the findings in the literature. The IV route was also associated with higher severity of reactions in the present study.

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ABSTRACT Introduction: The radiosynovectomy (RS) is one treatment option for recurrent hemarthrosis in patients with hemophilia (PWH). A prospective cohort study was designed to evaluate the effects of the RS on the synovial membrane volume in the ankles and knees of PWH and patient characteristics related to the RS outcome. Methods: In a one-year follow-up, 25 joints of 22 PWH who presented 3 bleeds or more in the same joint over the last 6 months (target joints) were subjected to the RS. Two groups were compared: those who retained target joints following the RS and those who did not (less than 3 bleeds/6 months after the RS). The groups were analyzed according to age, hemophilia type/severity, joint, body mass index (BMI), inhibitor and Hemophilia Joint Health Score 2.1 (HJHS). The magnetic resonance images (MRI) of six ankles and six knees were acquired prior to, and 6 months after, the RS. The synovial membrane volume and arthropathy MRI scale were accessed and volumes were compared and correlated with the Yttrium-90 dose injected. Results: Patients with a mean age of 12 years and a mean HJHS of 6.7 (p < 0.05) retained target joints after the RS. The inhibitor, joint, type/severity of disease and BMI showed no significant differences between groups. The synovial membrane volume had a significant reduction after the RS (p = 0.03), but no correlation with the Yttrium-90 dose. In proportion to the synovial membrane volume, doses injected to the ankles were larger than those injected to the knees. Conclusion: The synovial membrane volume is reduced after the RS, regardless of the effective 90Y dose.

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ABSTRACT Acute promyelocytic leukemia is a subtype of acute myeloid leukemia, characterized by the presence of neoplastic promyelocytes, due to the reciprocal balanced translocation between chromosomes 15 and 17. Currently, with the use of agents that act directly on this molecular change, such as all-trans retinoic acid and arsenic trioxide, APL has shifted from a highly mortal to a curable disease. However, some cases are still at high risk of death, especially early death, and acquiring a better understanding of the clinical and biological factors involving APL is needed to correctly identify and treat such cases. The early suspected diagnosis and prompt initiation of the target therapy are important for better response rates. The follow-up and outcomes, using real-life data from 44 consecutive APL patients, were studied between 2001 and 2013. The overall survival rate was 82.7% and early death was 16%. Almost all patient deaths were due to severe bleeding, which was confirmed by multivariate analysis, as the most important prognostic factor leading to death. A better understanding the pathogenesis of the hemorrhagic complications in APL is needed, as well as the risk factors associated with early death in APL patients, as this has become synonymous with overall mortality.

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ABSTRACT Aberrant expression of long non-coding RNAs (lncRNAs) has been detected in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped on transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated by quantitative real-time PCR in bone marrow samples from children with T-ALL (n = 32) and common-ALL/pre-B ALL (n = 30). In pediatric ALL, higher expression levels of uc.112 were found in patients with T-ALL, compared to patients with B-ALL. T-cells did not differ significantly from B-cells regarding uc.112 expression in non-tumor precursors from public data. Additionally, among B-ALL patients, uc.112 was also found to be increased in patients with hyperdiploidy, compared to other karyotype results. The uc.122, uc.160, and uc.262 were not associated with biological or clinical features. These findings suggest a potential role of uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

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ABSTRACT Introduction: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological diseases. In addition to defects in hematologic progenitor and stem cells, dysfunctions in the bone marrow microenvironment (BMM) participate in the MDS pathogenesis. Furthermore, the immune response is deregulated by the pro-inflammatory response prevailing in low-risk MDS, while immunosuppression predominates in high-risk MDS. Mesenchymal stromal cells (MSC), part of the BMM, are characterized by plastic adherent growth and multipotentiality. They exhibit immunomodulatory properties and sustain hematopoiesis. There is conflicting evidence regarding their status in MDS. The aim of this study was to characterize MDS-MSC and evaluate the effect of 5-Azacytidine. Methods: The MSC from MDS patients and controls were cultured and characterized according to the International Society of Cell Therapy recommendations. Immunomodulatory properties were assessed by studying the MSD cytokine production, using the cytometric bead array. We evaluated the effect of 5-Azacytidine on the MSC cytokine production. Results: We included 35 MDS patients and 22 controls. The MSC from patients and controls were cultured and characterized. The MSC from patients showed morphological differences, but there were no differences in immunophenotype or multipotentiality. The interleukin 6 (IL-6) was the main MSC secreted cytokine. The MDS-MSC produced higher levels of IL-6, IL-17, interferon gamma, or interferon γ (INF-γ), and tumor necrosis factor alpha (TNF-α). The in vitro 5-Azacytidine treatment induced a significant decrease in the IL-6 production by MDS-MSC. Conclusions: The MDS-MSC show an increased production of pro-inflammatory cytokines. The in vitro treatment with 5-Azacytidine lead to a significant reduction in the IL-6 production by the MDS-MSC, restoring the IL-6 levels to those found in controls. The MSC produced inflammatory cytokines involved in the MDS pathogenesis, representing a potential future therapeutic target. Moreover, 5-Azacytidine may have a stromal effect, modulating the immune response in MDS.

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ABSTRACT Introduction: von Willebrand's disease (VWD) is the most common inherited bleeding disorder. The 1-desamino-8-d-arginine vasopressin (DDAVP) is the treatment of choice for most responsive patients with VWD. The aim of this study was to evaluate DDAVP use in the management of VWD. Method: We implemented a survey targeting medical doctors involved in the management of VWD in Brazil. Data was collected during a national congress on Hematology in November 2017. Main results: A total of 51/80 (63.8%) questionnaires were collected. Most participants (76.2%) were hematologists who assisted adult patients and approximately 60% worked at hemophilia treatment centers (HTCs). Approximately half of participants who reported treating patients with VWD, assisted on average, less than 5 patients per month, and approximately 60% declared not having used any DDAVP for treating VWD in the previous year. However, most participants (70%) prescribed FVIII-containing VWF concentrate (VWF/FVIII) for 1-10 patients in the previous year. More than 80% of the participants recognized the main indications for DDAVP. Physicians who recognized indication for DDAVP for type 1 VWD more often had prescribed DDAVP in previous year (p = 0.03). Barriers for prescribing DDAVP varied and included unavailability of laboratory facilities and consumables for DDAVP testing and lack of skills on its prescription. Conclusion: The DDAVP is currently underused in Brazil, as opposed to the excessive use of VWF/FVIII in VWD patients. We suggest the adoption of measures targeting educational and auditing programs. Furthermore, availability of laboratory reagents is needed to evaluate response and increment the correct use of DDAVP.

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ABSTRACT Introduction: Chronic Myeloid Leukemia (CML) is a myeloproliferative disease that affects mainly adults between 50 and 55 years. In Brazil, information from the Sistema Único de Saúde (SUS) Outpatient Information System indicates that 12,531 patients had the Autorização de Procedimento Ambulatorial (APAC) approved for the CML treatment in 2017. Disease monitoring through molecular response evaluation is critical to the care of CML patients. The quantitative PCR test (real-time polymerase chain reaction) provides adequate evaluation parameters that allow the health professional to intervene at the right moments in order to reduce the chance of progression of the disease, providing the best outcome to the patient, including the possibility of treatment discontinuation for eligible patients. Although the test is included in the Clinical Protocol and Therapeutic Guidelines (PCDT) of CML, it is not possible to monitor the molecular response within SUS since there is no reimbursement for this test. Objective: Obtain expert recommendations on the importance, financing, and reimbursement of molecular monitoring in SUS. Methods: Six CML experts with different perspectives participated in the panel. The discussion was based in the main publications about the quantitative PCR test in CML monitoring. Results: Experts' recommendations: Molecular monitoring should be part of the integral treatment of patients with CML to reduce the chances of disease progression and costs to the health system; The government should put into practice what is provided in the PCDT of Chronic Myeloid Leukemia in Brazil: performing the monitoring of the molecular response via quantitative PCR; The government should create a code with adequate nomenclature and reimbursement value in SIGTAP, so that the test is carried out and covered by the public health network, as it is contained in the PCDT of the disease and the existing APAC does not cover the operational costs for its performance; Patients with chronic phase CML should perform a quantitative PCR every 3 months and, after reaching the MMR, should perform the examination every 6 months, as recommended by international guidelines; Patients should be monitored in reference laboratories that are standardized according to the international scale; The laboratories that are within the reference public centers could absorb all the test demand in Brazil, and other centers could be qualified through an ABHH accreditation; Adequate molecular monitoring may allow some patients to stop taking drugs and selffinancing the molecular test for all SUS patients Conclusion: A solution for the molecular test (BCR-ABL1) funding is urgent to ensure the monitoring of CML patients in SUS. The savings that might be generated with patients that stop taking the medication when adequately monitored may finance the test.

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ABSTRACT Background: The allogeneic transfusion-related immunomodulation (TRIM) may be responsible for an increase in survival of renal transplants but in contrast it could increase the rate of bacterial infections or the recurrence rate of tumors post-operatively. Objective: This review focuses in the implications of perioperative allogeneic transfusions on the immune-inflammatory response of surgical transfused patients. Results: ABTs modify immune functions in recipients including decrease of the number of lymphocytes; decrease the CD4 cells; decrease the CD4/CD8 T-cell ratio; decrease NK cells; and decrease the lymphocyte response to mitogens. TRIM effects may be mediated by allogeneic white cells present in blood products; soluble peptides present in transfused plasma; and/or biologic mediators released into the supernatant of blood units. A recent systematic review and meta-analysis including 36 clinical observational studies (n = 174,036) concluded that perioperative ABTs not only decreased overall survival and reduced colorectal cancer-specific survival. Furthermore ABTs increased the rate of infectious, cardiac, pulmonary and anastomotic complications in colorectal cancer patients undergoing surgery. Conclusions: It has been demonstrated by laboratory tests that TRIM is associated with transfusion recipient immune alterations but its influence in colorectal cancer recurrence after resection remains controversial though may exist. Surgical techniques reducing intraoperative blood loss have limited the number of ABTs perioperatively, however increase in mortality continues to be reported in literature after ABT in colorectal cancer surgery. Poor survival associated to TRIM in colorectal cancer might be due to higher number of allogeneic transfused units and/or prolonged length of blood storage.

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ABSTRACT Autoimmune diseases are an important field for the development of bone marrow transplantation, or hematopoietic stem cell transplantation. In Europe alone, almost 3000 procedures have been registered so far. The Brazilian Society for Bone Marrow Transplantation (Sociedade Brasileira de Transplantes de Medula Óssea) organized consensus meetings for the Autoimmune Diseases Group, to review the available literature on hematopoietic stem cell transplantation for autoimmune diseases, aiming to gather data that support the procedure for these patients. Three autoimmune diseases for which there are evidence-based indications for hematopoietic stem cell transplantation are multiple sclerosis, systemic sclerosis and Crohn's disease. The professional stem cell transplant societies in America, Europe and Brazil (Sociedade Brasileira de Transplantes de Medula Óssea) currently consider hematopoietic stem cell transplantation as a therapeutic modality for these three autoimmune diseases. This article reviews the evidence available.

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ABSTRACT Introduction: It is important to know if patients with hemoglobinopathy could be more susceptible to COVID-19. Objective: Analyze SARS-CoV-2 infection in pediatric patients with hemoglobinopathy. Methods: Using the online platforms LILACS, PUBMED and EMBASE, on 17- JUL-2020 a search was made for the terms COVID-19 and SARS-CoV-2 associated with "sickle cell", "thalassemia" and "hemoglobinopathy". Results: There were 623 pediatric and adult patients with sickle cell disease (SCD) or beta thalassemia (BT) and COVID-19. Total mortality rate was 6.42%. No pediatric patient with BT has been described. So, our analysis focused on children and adolescents with SCD: there were 121 pediatric patients, one adolescent died, prophylactic anticoagulation was prescribed to six patients, 11.76% needed intensive care unit, blood transfusion was prescribed in 29.70%. Vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) were the main clinical manifestations in SCD. Discussion: Pediatric patients with SCD and COVID-19 have a low mortality rate when compared to adults, although is higher than the global pediatric population with COVID-19 (0−0.67%). The comorbidities associated with age and the long-term complications inherent to hemoglobinopathies may contribute to the increased mortality outside the pediatric age group. In SCD the clinical manifestations, both in children and adults, are VOC and ACS, and there was increase in blood requirement. Pediatric SCD patients with COVID-19 need more intensive care unit than the global pediatric population (3.30%). Conclusion: Despite pediatric population with SCD needs more intensive care, the outcome after infection by COVID-19 is favorable.