Resumo em Inglês:

Abstract Background Severe refractory alloimmune thrombocytopenia is a challenging and life-threatening complication in patients with hematologic disorders who are undergoing allogeneic hematopoietic stem cell transplantation. This study aimed to investigate the utility of continuous intravenous immunoglobulin and platelet transfusions as a therapeutic approach for alloimmune thrombocytopenia in patients undergoing allogeneic transplants. Methods A single-center retrospective analysis was conducted of ten adult allogeneic transplant patients hospitalized with transfusion-refractory alloimmune thrombocytopenia. Intravenous immunoglobulin (2 g/kg) was administered as a slow continuous infusion over 48 h along with a continuous apheresis platelet infusion (one apheresis unit over eight hours). Clinical response was defined as the resolution of bleeding or patients being able to undergo the required procedure without bleeding complications. Results The median time after the transplant was 27.5 (range: 7-299) days. Myeloablative and reduced-intensity conditioning were performed in 5 (50 %) and 5 (50 %) patients, respectively. The median platelet count at the time of infusion was 4.5 × 109/L. All patients were able to achieve clinical response with the median maximum platelet count within ten days of the infusion being 41.0 × 109/L. The median time to best response was three days with a median platelet count of 27.0 × 10⁹/L. Conclusions Continuous intravenous immunoglobulin and platelet infusions over 48 h may be able to overcome life-threatening refractory alloimmune thrombocytopenia in transplant patients and may provide a bridging measure until platelet engraftment or for life-threatening hemorrhage or invasive procedures with high bleeding risk.

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Abstract Multiple myeloma constitutes approximately 1 % of all malignancies, with a higher incidence observed in over 65-year-old individuals. New technologies have shown promising results with an increased overall survival. The objective of this cohort study was to evaluate the survival analysis of patients with multiple myeloma treated by the Brazilian Unified Health Service over 16 years and compare the effectiveness of bortezomib (Bortezomib)-based treatment with other regimens used. A retrospective national cohort study was conducted utilizing real-world evidence derived from the Brazilian Unified Health System big data. This study focused on 25,370 patients with multiple myeloma who underwent chemotherapy between 2000 and 2015. Of these patients, 50.71 % were male, and the median age was 62 years. The median overall survival was 37 months. Hematopoietic stem cell transplantation (HSCT) was the best prognostic factor with overall survival of 87 months. The bortezomib (Bortezomib)-based chemotherapy provided the best results of the different chemotherapy regimens in terms of overall survival (67 months), followed by thalidomide-based schemes with an overall survival of 54 months. Despite the significant progress made in the Brazilian health system, the National Committee for Technology Incorporation (CONITEC) needs to make quicker decisions to improve access to new oncology drugs for patients, while maintaining rigorous evaluation criteria. Earlier adoption and adequate funding for oncology services could have saved more lives compared to the treatments made available by the Unified Health Service at that time.

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Abstract Background Sickle cell disease is a hereditary blood disorder that significantly impacts morbidity and mortality, requiring comprehensive care. In Brazil, its management in the National Health Service follows the Brazilian Clinical Practice Guidelines, based on evidence and expert consensus. Periodic updates ensure alignment with new scientific findings. Objectives This study describes the methodology for updating the clinical guidelines for sickle cell disease and provides an overview of recommendations for diagnosis, treatment and monitoring, emphasizing the evidence and health technology assessments for prioritized technologies. Methods The update followed the technical guide of the Brazilian Ministry of Health, and the Gradings of Recommendation, Assessment, Development and Evaluation (GRADE) approach. All the recommendations were assessed by the National Committee for Health Technology Incorporation (Conitec). The clinical guidelines panel included health technology assessment researchers, clinical experts, and policymakers. Systematic reviews assessed new evidence with stakeholder contributions being incorporated through public consultation. Cost-effectiveness analysis was applied to support new technology coverage or changes. Results The updated clinical guidelines provide structured recommendations for screening, diagnosis, prophylaxis, vaccination, and treatment, covering pharmacological and non-pharmacological approaches. It emphasizes patient and caregiver education to promote early recognition of complications. Expected benefits include fewer pain crises, fewer hospitalizations and transfusions, and improved fetal hemoglobin level, quality of life and survival rates. Key updates include listing epoetin alfa and 100 mg hydroxyurea tablets, expanding hydroxyurea eligibility criteria and revising monitoring protocols. Conclusion The updated clinical practice guidelines standardize sickle cell disease care in the Brazilian NHS aligned with current evidence. Dissemination and integration aim to enhance healthcare delivery, while future assessments should optimize real-world implementation.

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Background and objectives Dimethyl sulfoxide has become the most common cryoprotectant used for cryopreservation of hematopoietic progenitor cells because of its efficiency, regardless of its potentially toxic side effects. Its application is considered safe, provided that the daily dose administered does not exceed 1 gram per kilogram of patient weight. Indications for its reduction after thawing are limited to patients with high risk of malignant arrhythmia and those with severely impaired renal function. However, dimethyl sulfoxide reduction can lead to the loss of viable progenitors. Methods A retrospective study of viable hematopoietic progenitor cell recovery after dimethyl sulfoxide reduction was performed with 13 patients (nine men, four women) with secondary amyloidosis in multiple myeloma (n = 9), primary amyloid light chain amyloidosis (n = 3), or severe adverse reaction at the beginning of the hematopoietic progenitor cell concentrate infusion (n = 1). The Wilcoxon signed-rank test was used. Results The results of the dimethyl sulfoxide reduction process showed a high recovery of viable nucleated cells (median: 120.85 %), and of viable mononuclear cells (median: 104.53 %). There was a significant decrease in total number of viable CD34+ cells in comparison with data obtained after original collection (median: 51.49 %). No significant decrease in colony-forming unit capacity was observed after dimethyl sulfoxide reduction (median: 93.37 %). Conclusion The dimethyl sulfoxide removal process and total process recoveries revealed considerable individual variability. To minimize the risk of prolonged engraftment or non-engraftment, it is important to apply this process only to high-risk patients.

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Abstract Introduction Allogeneic hematopoietic stem cell transplantation is potentially a curative treatment for several hematological diseases. However, post-transplant relapse remains a significant challenge. For patients who achieve a second complete remission, a second allogeneic transplantation may be a promising therapeutic option. The aim of this study was to analyze clinical outcomes including graft-versus-host disease, non-relapse mortality, and relapse rates, as well as graft sources in patients who underwent a second allogeneic transplantation in a university-based transplant program. Patients and Methods A retrospective analysis of 21 adult patients who underwent a second allogeneic transplantation between 2001 and 2023 was performed. Data on demographics, underlying disease, graft source, conditioning, graft-versus-host disease, relapse, and survival were collected. Survival estimates were calculated using the Kaplan-Meier method. Results The graft source was bone marrow in 60 % and peripheral blood in 40 % of cases. Grade III-IV acute graft-versus-host disease occurred in 5 % and extensive chronic graft-versus-host disease in 17 %. The non-relapse mortality was 69.2 %, and disease relapse occurred in 23.1 %. The one-year progression-free survival was 26.5 %, and overall survival was 42.3 %. Compared to those transplanted before 2010, patients who underwent transplantation after 2010 showed improved two-year PFS and OS, reaching 55 % and 45.4 %, respectively. Conclusion A second allogeneic transplantation may offer a survival benefit in selected patients with relapsed hematologic malignancies or bone marrow failure syndromes. Despite high non-relapse mortality, outcomes have improved in recent years with better salvage strategies.

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Abstract Introduction Haploidentical peripheral stem cell transplantation with post-transplant cyclophosphamide is the most common modality in low-and-middle-income countries. This article reports the consecutive adult patients who received this modality of transplant in a single center in Chile between 2016-2021. Methods The primary outcome was overall survival. Secondary outcomes were event-free survival, II-IV acute graft-versus-host disease at Day +100, chronic graft-versus-host disease at two years and cumulative incidence of relapse. Results The median age was 25 years (Range: 15-51), and 65 % of patients were male. Ninety-four percent had a neoplastic disease (77/82), with the most common diagnosis being acute lymphoblastic leukemia (57 %). Forty-seven percent proceeded to transplant in the first complete response. Conditioning was mostly myeloablative (96 %). Primary graft failure and poor graft function were observed in 1.2 % and 13 %, respectively with five patients (6.1 %) dying before engraftment. Grade II-III acute graft-versus-host disease was seen in 29 % and chronic graft-versus-host disease was 41 % of the patients. With a median follow-up of 33 months (Range: 1-84), the estimated three-year overall survival and event-free survival were 68.3 % (95 % CI: 59-79 %) and 64.6 % (95 % CI: 55-76 %), respectively. The three-year cumulative incidence of relapse was 23 % (95 % CI: 15-33 %). Conclusion These results demonstrate encouraging survival outcomes and acceptable rates of graft-versus-host disease following haploidentical peripheral stem cell transplantation with post-transplant cyclophosphamide, suggesting its potential as a feasible option in low-resource settings.

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Abstract Background Blood is a biological, irreplaceable, and perishable resource, provided through voluntary, altruistic, and free donation in Brazil. Although blood components are widely used in hospital settings, several challenges persist, including the limited availability of these resources, the high costs associated with their procurement, storage, and transfusion, as well as the risks inherent in the allogeneic transfusion process due to potential transfusion reactions. Therefore, there is a need to focus on Patient Blood Management (PBM) within the Brazilian transfusion system to reduce the need for transfusions, particularly of packed red blood cells, during elective cardiac surgeries. Objective To evaluate the risk factors associated with the use of packed red blood cells in elective cardiac surgeries performed at the Hospital das Clínicas, Faculty of Medicine, Botucatu. Methods This retrospective study involving 741 individuals was conducted between 2018 and 2021 with the approval of an ethics research committee. Data were analyzed using descriptive statistics, the Chi-square test, and stepwise logistic regression, with the level of significance set at 5 %. Results and conclusion Preoperative factors such as female sex (Odds ratio: 9.074; p-value <0.0001), low hematocrit levels (Odds ratio: 7.498; p-value = 0.0034), and the presence of diabetes mellitus (Odds ratio: 1.779; p-value = 0.0318), as well as intraoperative factors such as extracorporeal circulation time greater than 90 min (Odds ratio: 1.68; p-value = 0.0442), were identified as risk factors for excessive bleeding and the need for packed red blood cells during surgery.

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Abstract Background Fresh frozen plasma plays a crucial role in managing trauma and bleeding patients. The concern about a decline in labile coagulation factors limits its usage beyond 24 hours. This study aimed to analyze coagulation factor levels and microbial contamination of thawed fresh frozen plasma stored at 2-6 °C for five days. Material and methods A prospective observational study was conducted on 40 male donors with blood groups A and O selected through purposive sampling. Blood was collected in 450 mL bags and freshly prepared plasma was aliquoted and frozen at -80 °C. Aliquots were thawed at 37 °C and tested on Days 0, 1, and 5 after storage at 2-6 °C. Coagulation screening assays and activity of coagulation factors V, VIII, IX, fibrinogen, and von Willebrand factor were performed. Samples were tested for sterility on Day 5. Results One-way ANOVA revealed a significant increase in mean prothrombin time, activated partial thromboplastin time, and international normalized ratio during storage (p-value < 0.001). The activity of factors V and VIII showed a significant decrease over five days (factor V - 20.0 % and factor VIII - 42.2 %; p-value < 0.001), with factor VIII activity declining by 30.8 % within the first 24 hours and remaining relatively stable thereafter. Mean von Willebrand factor activity was lower in fresh frozen plasma from O blood group donors (p-value < 0.05) on Days 1 and 5 of storage using an unpaired t-test. Cultures were sterile on Day 5. Conclusion Key coagulation factors were well preserved in thawed plasma till five days of storage at 2-6 °C without compromising product sterility suggesting potential for extended shelf life.

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Abstract Background Aplastic anemia is a heterogeneous group of hematological disorders identified by the presence of one or more cytopenias in the bone marrow or the peripheral blood or both, affecting either one or multiple blood cell lineages. The pathophysiology of this disorder is unclear; however, the prevailing hypothesis posits that an aberrant immune response is responsible for the death of hematopoietic precursor stem cells due to autoreactive cytotoxic T lymphocytes in individuals with a genetic predisposition. Interleukin-8 acts as a pleiotropic prototype chemokine and serves as a powerful inhibitor of myelopoiesis and assumes an essential role in both the initiation and progression of acute inflammation and tissue damage. Consequently, it is postulated that the sustained elevation in interleukin-8 production could potentially lead to immune-mediated bone marrow failure in aplastic anemia. The aim of this study was to evaluate the serum interleukin-8 concentrations in individuals with aplastic anemia as well as investigate its potential connection with disease severity. Methods This study was performed at the National Center of Hematology and included 28 aplastic anemia patients and 30 healthy individuals matched by age and gender as a control group. The serum interleukin-8 levels were measured by the quantitative sandwich enzyme-linked immunosorbent assay (ELISA) method. Results Considerrable elevation in serum interleukin-8 levels were observed between the two groups (p-value = 0.405). Of the aplastic anemia patients, severe cases had significantly higher levels of interleukin-8 compared to non-severe patients (p-value = 0.0495), with a cutoff serum level of 7.71 pg/mL. Conclusion Interleukin-8 may have a role in the immune-mediated pathophysiology of aplastic anemia as well as have a significant correlation with disease severity.

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Abstract Introduction Blood transfusions are crucial for saving lives but can affect the recipient's immune system. A significant concern is the development of anti-human leukocyte antigen (HLA) antibodies, which can influence organ transplantation outcomes. The presence of these antibodies increases the risk of transplant rejection. The aim of this study was to evaluate how blood component characteristics (leukodepletion, type, number, volume) and timing from the last transfusion to anti-HLA antibody detection affect sensitization in kidney transplant candidates. Materials and Methods This retrospective study analyzed 115 candidates on the cadaveric kidney transplant list from South Bačka and Novi Sad, Serbia. Among them, 69 received blood transfusions, classified as either leukodepleted or containing leukocytes (WBCs), for sensitization control. Anti-HLA antibodies were detected using Complement-Dependent Cytotoxicity, Enzyme-Linked Immunosorbent Assay, and Luminex technology. This study evaluated demographic data, transfusion history, and sensitization. Statistical analysis focused on the relationship between sensitization and blood component variables. Results In this study, 53.7 % were sensitized. The number of blood components received (p-value = 0.437), blood unit (p-value = 0.6809), and blood volume (p-value = 0.5857) were not significantly associated with sensitization rates. The use of leukodepleted blood components (p-value = 0.0057), as well as blood components containing WBCs (p-value = 0.030) is associated with a higher sensitization. Sensitization was detected in 67.57 % of cases more than 12 months after transfusion (p-value = 0.046). A significant difference in sensitization was shown when packed red blood cells were used (89.19 % versus 68.75 %; p-value = 0.006). Conclusions Sensitization was higher with blood components containing WBCs and packed RBCs. The longer time after transfusion, the more often sensitization is detected.

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Abstract COVID-19-associated thrombotic microangiopathy has emerged as a severe complication that exacerbates morbidity and mortality in critical cases. Thrombotic microangiopathy, characterized by microvascular thrombosis and endothelial injury, includes conditions like thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome. This review investigates therapeutic plasma exchange as a potential strategy to mitigate COVID-19-induced thrombotic microangiopathy, examining its role in removing pro-inflammatory cytokines, immune complexes, and pro-thrombotic factors. Additionally, it highlights the synergistic effects when therapeutic plasma exchange is combined with treatments such as complement inhibitors and immunosuppressants. Preliminary evidence, drawn from case reports and early trials, supports the efficacy of therapeutic plasma exchange in improving outcomes for COVID-19-associated thrombotic microangiopathy. However, larger randomized controlled trials are necessary to definitively establish its place in COVID-19 management, particularly for high-risk and transplant patients with underlying immunological vulnerabilities.

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Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune disorder characterized by excessive inflammation and multiorgan involvement. Rarely, HLH can manifest with signs and symptoms isolated to the central nervous system (CNS). This case report highlights the unique clinical course of CNS-isolated HLH in a 19-year-old female who, despite a nine-year delay in diagnosis, achieved disease remission following a hematopoietic stem cell transplant (HSCT). Case The patient initially presented at 9 years old with seizures, ataxia, and progressive cognitive decline. Over the next nine years, extensive diagnostic evaluations were performed, including neuroimaging, cerebrospinal fluid analysis, and genetic testing. Genetic testing identified a compound heterozygous mutation in the PRF1 gene, confirming a diagnosis of familial HLH (FHL). The patient underwent hematopoietic stem cell transplant (HSCT) from an HLA-matched unrelated donor. Despite significant complications, including multiple infections and renal failure, she achieved remission. Six years post-transplant, the patient exhibited stabilization of neurological function, cessation of seizures, and absence of active HLH. Conclusion This case underscores the importance of considering genetic testing in patients with unexplained CNS symptoms and atypical radiological findings. Timely HSCT, even in cases with delayed diagnosis, can lead to remission and improved quality of life.