Hematology, transfusion and cell therapy最新文献

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.

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.

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.

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.

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.