Hematology, transfusion and cell therapy最新文献

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.

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.

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.

Background and objectives: The identification of platelet antibodies is essential for diagnosing and managing conditions such as fetal and neonatal alloimmune thrombocytopenic purpura, post-transfusion purpura, and immune platelet refractoriness. Monoclonal antibody immobilization of platelet antigens (MAIPA) is the standard method for detecting anti-human platelet antigen (HPA) antibodies, while the detection of anti-HLA antibodies once relied on the complement-dependent cytotoxicity method, however advanced technologies such as enzyme-linked immunosorbent assay and Luminex have significantly improved sensitivity and accuracy in identifying these antibodies. Flow cytometry-based techniques (platelet immunofluorescence test - PIFT) and Luminex platform-driven microsphere-based multiplex assays (Pak-Lx) are widely employed in platelet immunology laboratories owing to their remarkable flexibility and versatility. The present study compared the sensitivity, specificity, and concordance of these different serological techniques used in platelet antibody identification.

Material and methods: One hundred serum samples from patients suspected of immune-mediated platelet disorders were examined. Initially, the samples underwent testing using the MAIPA method. Subsequently, the results were compared with three alternative methods: PIFT and microsphere-based multiplex assays for both HLA and HPA antibodies.

Results: Pak-Lx demonstrated a 94 % agreement with MAIPA, while PIFT had 88 % agreement for HPA antibodies. For HLA antibody detection, Pak-Lx versus DLX had 75 % concordance, MAIPA versus DLX showed 77 %, and PIFT versus DLX displayed an 81 % concordance rate. Remarkably, there were no significant differences in concordance levels between Pak-Lx and PIFT compared to MAIPA and DLX for anti-HPA and HLA antibodies, respectively.

Conclusion: This study found no significant differences in concordance among the tested assays for detecting anti-HPA and anti-HLA antibodies. These data suggest that no single method can detect all clinically important antibodies. Therefore, it is advisable that each laboratory develops customized protocols based on their expertise and employs complementary methods for comprehensive patient assessments.

Background: As the diagnosis of Pediatric venous thromboembolism has dramatically increased in recent decades, this study aims to evaluate these patients, determining the incidence and describing their biological and clinical characteristics.

Methods: An observational, cross-sectional study was conducted at a Brazilian quaternary hospital between January 2022 and February 2023. Under 18-year-old hospitalized patients with a confirmed diagnosis of venous thromboembolism were included, while those with arterial or chronic thrombosis were excluded. Data on biological and clinical characteristics, diagnosis and treatment were evaluated. A descriptive data analysis was performed and the incidence of hospital-associated thrombosis was calculated.

Results: Thirty-nine pediatric patients were evaluated. The incidence of hospital-associated thrombosis was 19.9 cases per 10,000 pediatric hospitalizations. Median age at diagnosis was four months (range: 12 days-17 years). Most of the patients (66.7%) were asymptomatic, with venous thromboembolism being diagnosed incidentally. In all cases, at least one risk factor was identified and in 74.6% of cases four or more factors were present. The principal risk factors were the presence of a central venous catheter (89.7%) and infection (89.7%). Thrombogenic comorbidities, particularly congenital heart disease, were present in 48.7% of patients.

Conclusions: The incidence of venous thromboembolism found in the present study was lower than rates reported in developed countries. The principal characteristics of this sample were a greater frequency of central venous catheter and infection as risk factors, and the fact that the cases consisted mainly of newborns and individuals with heart disease.

Background: Neuroblastomas account for 8-10 % of all cancer diagnoses among children. Most patients present with advanced, high-risk disease and 90 % are less than five years old. The burden of morbidity and mortality is high and is quantifiable by measures of health-related quality of life (HRQL). Measuring quality of life in under five-year-old children is a particular challenge that has been met with the development of the Health Utilities Pre-School (HuPS) instrument. Quality of life studies in children with cancer are scarce in low- and middle-income countries and are usually conducted at a single center, thus limiting any conclusions drawn. This pilot study aimed to assess the health-related quality of life of children at the time of diagnosis of high-risk neuroblastomas.

Method: This prospective cross-sectional multicentric study assessed the quality of life of children with high-risk neuroblastoma. The Health Utilities Pre-School instrument was applied to under five-year-olds, and the related Health Utilities Index Mark 3 instrument to over five-year olds.

Main results: Eleven patients participated in this study. There was a high burden of morbidity at diagnosis, often equating to severe disability, indicative of states of health with scores worse than being dead in two under five-year-old children.

Conclusion: The results of the current study will help to set research priorities for subsequent investigations and provide a basis to improve supportive care for children with high-risk neuroblastoma.

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.

Background: Emergency transfusion may require the availability of O-negative red blood cell concentrates without pre-transfusion testing. At the Cliniques Universitaires Saint-Luc, the emergency department was used to having access to two decentralized O-negative red blood cell concentrates. This study aims to analyze the consumption of O-negative red blood cell concentrates in emergency situations both before and after the implementation of a novel strategy aiming at optimizing stocks. This strategy provides a combined allocation of one unit of O-positive red blood cell concentrate and one unit of O-negative red blood cell concentrate decentralized in the emergency department and reserve the transfusion of the negative unit only to under 45-year-old women and under 20-year-old men.

Materials and methods: A retrospective study was conducted of the transfusion and medical records of all patients who received immediate transfusions in the emergency department without pre-transfusion testing between 2008 and 2022.

Results: A total of 193 patients received O red blood cell concentrates without pre-transfusion testing in emergency situations between 2008 and 2022. During the first 24 h of hospitalization, 354 O-negative units were transfused. Mean ratios of number of O-negative bags between 2008 and 2020 was 1.98 unit/patient. After implementation of the new strategy, the ratio in 2021 was 1.46 unit/patient and drastically decreased in 2022 to 0.79 unit/patient.

Conclusion: In situations of emergency, allocating O-negative units only for women younger than 45 years and men younger than 20 years could have saved 85% of O-negative red blood cell concentrates transfused (303/354) yet balancing the immunological risk. Limiting the number of delocalized units of O-negative red blood cell concentrates in the emergency department seems to lower O-negative consumption. With this strategy, the units spared could have been transfused to patients with greater needs (e.g., sickle cell patients or chronically transfused patients).

Background: Anemia-associated chronic kidney disease increases in more advanced stages with a subsequent acceleration in renal impairment progressing to end-stage renal disease. Although hepcidin and erythroferrone have been described as novel biomarkers of iron metabolism, there is still an area of ambiguity regarding iron utility in anemia-associated end-stage renal disease.

Objectives: This study aims to determine the correlations between erythropoietin, erythroferrone, and hepcidin-25 in hemodialysis, and to evaluate the clinical utility of the hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness compared to reticulocyte maturation parameters.

Methods: Serum erythropoietin, erythroferrone, and hepcidin-25 levels in 35 dialysis-dependent patients on a maintenance dose of a short-acting erythropoiesis-stimulating agent were consequently assessed on Days 0, 5, and 7. The erythropoiesis activity was monitored by measuring the increment in reticulocyte maturation parameters.

Results: Though the effectiveness of erythropoiesis in these patients was not associated with the hepcidin-25/erythroferrone ratio, it was lower among those with effective erythropoiesis than those with ineffective erythropoiesis. The effective group showed a statistically significant increase in reticulocyte maturation parameters compared to the ineffective group.

Conclusions: The findings show the pathogenesis of iron homeostasis in hemodialysis, the validity of hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness, and the advantageous monitoring of reticulocyte maturation measures to improve management of anemia-associated chronic kidney disease.

Background: Providing quality supportive therapy for children with cancer is essential to reduce the high mortality rates in low- and middle-income countries. Febrile neutropenia is the most common life-threatening complication of cancer in children. The objective of this study was to evaluate the long-term effectiveness of the 'Golden Hour' intervention in reducing the time to administer antibiotics and its impact on clinical outcomes in a Mexican hospital.

Methods: A comparative study of children with febrile neutropenia who attended the emergency department at the Hospital Universitario "Dr. José Eleuterio González" was performed between January 2017 and December 2022. In May 2019, this center joined the collaborative 'Mexico in Alliance with St. Jude' project. An adapted improvement program was developed based on the implementation of an algorithm comprising institutional guidance, supplies kit, standardization of sample processing, training of healthcare providers, and patient education. The time to antibiotic administration was compared with clinical outcomes between the historical control and post-intervention groups.

Results: A total of 291 patients were included, 122 in the pre-intervention period and 169 in the intervention period. Only 5.7 % of the pre-intervention group received the first dose of antibiotics within 60 min of presenting to the emergency department compared to 84.6 % in the intervention group (p-value <0.000). The median times to antibiotic administration in the pre-intervention and post-intervention periods were 269.4 and 50.54 min, respectively (p-value <0.000). Clinical deterioration and admission to the pediatric intensive care unit decreased significantly from 6.6 % to 2.3 % (p-value = 0.03).

Conclusions: Sustainability of the quality improvement project 'Golden Hour' in low- to mid-income countries demonstrated high effectiveness in reducing time to antibiotic administration among children with febrile neutropenia and improved clinical outcomes over three years of implementation.