Transfusion Medicine and Hemotherapy最新文献

{"title":"Effectors of the Future: Universal Chimeric Antigen Receptor","authors":"Lara Sophie Schlegel, Patrick Schlegel","doi":"10.1159/000539609","DOIUrl":"https://doi.org/10.1159/000539609","url":null,"abstract":"Background: Cellular therapies leveraging genetically engineered immune effector cells have witnessed a remarkable surge in success, particularly evident in the notable high rates of remission induction and durable remissions observed in a substantial proportion of heavily pretreated patients with refractory B-lineage malignancies. A diverse array of effector cells and therapeutic strategies are now at our disposal, representing the culmination of advancements made over the past 3 decades. The swift pace of development in modern genetic diagnostics, the emergence of spatial proteomics, and the expanding capabilities and precision of computational sciences have profoundly enriched our comprehension of tumor biology and the intricate workings of our immune system. Empowered by advancements in synthetic biology and genome editing, we can expedite the development of next-generation immune effector cells tailored for clinical applications, balancing safety with efficacy. Summary: Universal adapter chimeric antigen receptor (CAR) technologies present the most straightforward solution to tackle antigen heterogeneity and antigen evasion mechanisms employed by tumors. Moreover, due to the decoupling of antigen recognition and signaling in adapter CAR technologies, additional effector functions can safely enhance anticancer activity and most importantly, synergistic combination of patient-specific cellular products with off-the-shelf manufactured antibodies promise increased cost-efficiency. The pivotal collaboration between clinical trial units and regulatory institutions holds the key to surmounting contemporary challenges in trial design, potentially paving the way for the exploration of patient-individualized therapies. Key Messages: In this review, we elaborate on the concept of antibody-dependent cellular cytotoxicity mediated by universal adapter CARs and delineate how recent strides in CAR engineering have the potential to furnish a versatile cellular platform, ushering in an era of cancer-adapted, multitargeted immunotherapies employing universal CAR effector cells.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141833526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Blood Group Expression: Another Layer of Complexity to Consider.","authors":"Christoph Gassner, Martin L Olsson","doi":"10.1159/000539611","DOIUrl":"10.1159/000539611","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of the Lewis Blood Group Antigen Expression: A Literature Review Supplemented with Computational Analysis.","authors":"Martin Wipplinger, Sylvia Mink, Maike Bublitz, Christoph Gassner","doi":"10.1159/000538863","DOIUrl":"10.1159/000538863","url":null,"abstract":"<p><strong>Background: </strong>The Lewis (Le) blood group system, unlike most other blood groups, is not defined by antigens produced internally to the erythrocytes and their precursors but rather by glycan antigens adsorbed on to the erythrocyte membrane from the plasma. These oligosaccharides are synthesized by the two fucosyltransferases <i>FUT2</i> and <i>FUT3</i> mainly in epithelial cells of the digestive tract and transferred to the plasma. At their place of synthesis, some Lewis blood group carbohydrate antigen variants also seem to be involved in various gastrointestinal malignancies. However, relatively little is known about the transcriptional regulation of <i>FUT2</i> and <i>FUT3</i>.</p><p><strong>Summary: </strong>To address this question, we screened existing literature and additionally used in silico prediction tools to identify novel candidate regulators for <i>FUT2</i> and <i>FUT3</i> and combine these findings with already known data on their regulation. With this approach, we were able to describe a variety of transcription factors, RNA binding proteins and microRNAs, which increase <i>FUT2</i> and <i>FUT3</i> transcription and translation upon interaction.</p><p><strong>Key messages: </strong>Understanding the regulation of <i>FUT2</i> and <i>FUT3</i> is crucial to fully understand the blood group system Lewis (ISBT 007 LE) phenotypes, to shed light on the role of the different Lewis antigens in various pathologies, and to identify potential new diagnostic targets for these diseases.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HLA in Transplantation: Challenges and Perspectives.","authors":"Nils Lachmann, Axel Pruß","doi":"10.1159/000538982","DOIUrl":"10.1159/000538982","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Bioinformatically Initiated Approach to Evaluate GATA1 Regulatory Regions in Samples with Weak D, Del, or D– Phenotypes Despite Normal RHD Exons","authors":"Eunike C. McGowan, Ping Chun Wu, Å. Hellberg, G. Lopez, Catherine A. Hyland, Martin L Olsson","doi":"10.1159/000538469","DOIUrl":"https://doi.org/10.1159/000538469","url":null,"abstract":"Introduction: With over 360 blood group antigens in systems recognized, there are antigens, such as RhD, which demonstrate a quantitative reduction in antigen expression due to nucleotide variants in the non-coding region of the gene that result in aberrant splicing or a regulatory mechanism. This study aimed to evaluate bioinformatically predicted GATA1-binding regulatory motifs in the RHD gene for samples presenting with weak or apparently negative RhD antigen expression but showing normal RHD exons. Methods: Publicly available open chromatin region data were overlayed with GATA1 motif candidates in RHD. Genomic DNA from weak D, Del or D– samples with normal RHD exons (n = 13) was used to confirm RHD zygosity by quantitative PCR. Then, RHD promoter, intron 1, and intron 2 regions were amplified for Sanger sequencing to detect potential disruptions in the GATA1 motif candidates. Electrophoretic mobility shift assay (EMSA) was performed to assess GATA1-binding. Luciferase assays were used to assess transcriptional activity. Results: Bioinformatic analysis identified five of six GATA1 motif candidates in the promoter, intron 1 and intron 2 for investigation in the samples. Luciferase assays showed an enhancement in transcription for GATA1 motifs in intron 1 and for intron 2 only when the R2 haplotype variant (rs675072G>A) was present. GATA1 motifs were intact in 12 of 13 samples. For one sample with a Del phenotype, a novel RHD c.1–110A>C variant disrupted the GATA1 motif in the promoter which was supported by a lack of a GATA1 supershift in the EMSA and 73% transcriptional activity in the luciferase assay. Two samples were D+/D– chimeras. Conclusion: The bioinformatic predictions enabled the identification of a novel DEL allele, RHD c.1–110A>C, which disrupted the GATA1 motif in the proximal promoter. Although the majority of the samples investigated here remain unexplained, we provide GATA1 targets which may benefit future RHD regulatory investigations.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140992402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet Additive Solutions SSP+ and T-PAS+ Are Interchangeable for Platelet Concentrate Storage despite Differences in Composition and Plasticizer","authors":"Britt Van Aelst, Karen Bens, B. Sabot, Sarah Vertongen, H. Feys, V. Compernolle, Katrijn R. Six","doi":"10.1159/000538003","DOIUrl":"https://doi.org/10.1159/000538003","url":null,"abstract":"Introduction: Platelet additive solutions support ex vivo storage of platelet concentrates used for transfusion. The composition of platelet additive solutions within one generation (i.e., PAS-E) is similar but not identical. Additionally, the platelet additive solution storage bag may contain different plasticizers. This study compares the effect of two PAS-E solutions (SSP+ vs. T-PAS+, stored in a DEHP-containing and DEHP-free bag, respectively) to investigate if both additive solutions are interchangeable for platelet concentrate storage. Methods: Platelet concentrates stored in plasma supplemented with SSP+ or T-PAS+ were compared by using a pool-and-split design. Platelet metabolism was investigated using a blood gas analyzer. The degree of platelet storage lesion was determined by flow cytometry to measure granule release and phosphatidylserine scrambling. Results: The quality of platelet concentrates stored in either SSP+ or T-PAS+ is acceptable as pH decreased only slightly as a function of time. PH remained above 7.2 on exiration day +1 (day 6), which is far above the minimal criterion of 6.4. Platelet storage lesion was comparable between the two study groups with only limited α-granule release and phosphatidylserine surface expression in both groups after storage for 5 days, p = 0.547 and p = 0.825, respectively. Conclusion: This study supports a safe switch between SSP+ and T-PAS+ storage solutions for platelet concentrates despite slight differences in storage solution composition and DEHP content.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140380625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000534302","DOIUrl":"https://doi.org/10.1159/000534302","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000533624.].</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive Long-Term Outcome of Kidney Allocation via Acceptable Mismatch Program in Highly Sensitized Patients","authors":"Yara Strehler, N. Lachmann, M. Niemann, F. Halleck, K. Budde, Axel Pruß","doi":"10.1159/000536533","DOIUrl":"https://doi.org/10.1159/000536533","url":null,"abstract":"Introduction: Eurotransplant established the acceptable mismatch (AM) program to facilitate timely kidney transplantations of highly sensitized patients, but long-term granular clinical and immunological outcomes regarding overall graft survival and de novo DSA (dnDSA) formation are still intensively researched. The right choice of induction therapy in patients with differing immunological risk is not conclusively determined, as well as the impact of human leukocyte antigen (HLA) epitope matching on dnDSA formation. Methods: This monocentric, retrospective study analyzed 94 patients transplanted within the AM program between 2000 and 2019 compared to case-control matched cohorts of non- (PRA 0–5%; PRA-0) and intermediately sensitized (PRA 6–84%; PRA-6/84) patients transplanted through Eurotransplant Kidney Allocation System. Results: Estimated 10-year overall graft survival between the PRA-0 and AM cohorts was similar, whereas PRA-6/84 was significantly disadvantageous compared to PRA-0. Estimated 10-year incidence of antibody-mediated rejection rates was significantly lower in the PRA-0 group compared to AM and PRA-6/84 groups. Compared to the AM group, estimated incidence of de novo donor-specific antibody (dnDSA) was significantly lower in PRA-0 patients, with no differences between the AM and PRA-6/84 cohorts. The PRA-6/84 cohort was the only subgroup in which interleukin-2 receptor antagonist (IL2RA) induction was associated with longer overall graft survival, patient survival, and graft survival compared to depleting induction (ATG or OKT3). Broad HLA-A, -B, -DR mismatches (mmABDR) and HLA epitope mismatches determined by Eplets and PIRCHE-II were predictive for dnDSA formation in the total cohort, and the AM subgroup. Discussion: The high efforts expended on AM patients are justified to allow timely organ transplantation with acceptable risk profile and non-inferior outcomes. IL2RA induction in intermediately sensitized patients is associated with superior overall graft survival, patient survival, and graft survival compared to ATG/OKT3 induction, without negative effects on rejection episodes or dnDSA formation. In silico epitope matching might further help reduce dnDSA formation, particularly in high-risk AM patients.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140417515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth and Distribution of Bacteria in Contaminated Whole Blood and Derived Blood Components","authors":"U. Gravemann, W. Handke, Torsten J. Schulze, Axel Seltsam","doi":"10.1159/000536242","DOIUrl":"https://doi.org/10.1159/000536242","url":null,"abstract":"Introduction: Bacterial contamination of blood products presumably occurs mainly during blood collection, starting from low initial concentrations of 10–100 colony-forming units (CFUs) per bag. As little is known about bacterial growth behavior and distribution in stored whole blood (WB) and WB-derived blood products, this study aims to provide data on this subject. Methods: WB units were inoculated with transfusion-relevant bacterial species (Acinetobacter baumannii, Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Pseudomonas fluorescens, Serratia marcescens, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus dysgalactiae, Streptococcus pyogenes, Yersinia enterocolitica; n = 12 for each species), stored for 22–24 h at room temperature, and then centrifuged for separation into plasma, red blood cells (RBCs), and buffy coats (BCs). The latter were pooled with 3 random donor BCs and one unit of PAS-E each to yield plasma-reduced platelet concentrates (PCs). Samples for bacterial colony counting were collected after WB storage and immediately after blood component production. Sterility testing in PCs (n = 12 for each species) was performed by bacterial culture after 7 days of storage. Results: Bacterial growth in WB varied remarkably between donations and species. Streptococcus species produced the highest titers in WB, whereas Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas fluorescens did not multiply. Centrifugation resulted in preferential accumulation of bacteria in BCs, with titers of up to 3.5 × 103 CFU/mL in BCs and up to ≤0.9 × 103 CFU/mL in BC-derived PCs. Overall, 72/144 PCs (50%) tested positive for bacteria after storage. Sterility test results were species-dependent, ranging from 12 of 12 PCs tested positive for Streptococcus pyogenes to 1 of 12 PCs positive for Escherichia coli. Bacterial contamination of RBC and plasma units was much less common and was associated with higher initial bacterial counts in the parent WB units. Conclusions: Bacterial growth in WB is species-dependent and varies greatly between donations. Preferential accumulation of bacteria in BCs during manufacturing is a critical determinant of the contamination risk of BC-derived pooled PCs.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140444257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged Thrombocytopenia and Severe Transfusion Reaction after ABO-Incompatible Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with Chronic Myelomonocytic Leukemia","authors":"Lina S. Silva-Bermúdez, D. Heidenreich, Stefan A. Klein, Patrick Wuchter, Harald Klüter, Sabine Kayser","doi":"10.1159/000534272","DOIUrl":"https://doi.org/10.1159/000534272","url":null,"abstract":"Introduction: Major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HCT) is a common practice and represents a challenging transfusion scenario. Prolonged thrombocytopenia with increased platelet transfusion needs is one of its reported adverse effects, and this has been linked to the persistence of recipient anti-donor isoagglutinins. Case Presentation: A 55-year-old male patient, O Rh(D)-positive, with chronic myelomonocytic leukemia underwent major incompatible allo-HCT from a A Rh(D)-negative donor. He presented with prolonged thrombocytopenia and multiple transfusion reactions after A Rh(D)-negative platelet transfusions. Considering the outcomes of numerous examinations, we tested the anti-A1 titers, finding a significant persistence of anti-donor isoagglutinins. We limited platelet transfusions to blood group O Rh(D)-negative donors, which significantly decreased the requirement for platelet transfusions. In addition, the transfusion reactions ceased. Conclusion: In case of transfusion reactions against platelet products in major ABO-incompatible allo-HCT patients, isoagglutinin monitoring should be considered and a change in the platelet transfusion protocol may be beneficial in patients presenting high isotiters against recipient’s blood type.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139442847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}