Transfusion Medicine and Hemotherapy最新文献

{"title":"\"Attack!\" Cellular Therapies to Attack Pathogens and Tumors.","authors":"Britta Eiz-Vesper, Halvard Bonig","doi":"10.1159/000543415","DOIUrl":"10.1159/000543415","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"52 1","pages":"1-4"},"PeriodicalIF":1.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410896","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":"Empowering Natural Killer Cells to Combat Acute Myeloid Leukemia: Perspective on CAR-NK Cell Therapy.","authors":"Fenja Gierschek, Juliane Schlueter, Ines Kühnel, Frederik Fabian Feigl, Dominik Schmiedel, Maren Prüfer, Leon Buchinger, Adelheid Cerwenka, Claudia Cappel, Sabine Huenecke, Ulrike Köhl, Winfried S Wels, Evelyn Ullrich","doi":"10.1159/000540962","DOIUrl":"10.1159/000540962","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a high relapse rate and still limited therapeutic options. Natural killer (NK) cell-based immunotherapy has the potential to improve outcomes for patients with AML.</p><p><strong>Summary: </strong>Recent preclinical studies and early-stage clinical trials aim to enhance the intrinsic anti-leukemic properties of NK cells by selectively targeting AML cells with chimeric antigen receptors (CARs). Furthermore, NK and CAR-NK cells can be combined with other therapeutic modalities or engineered further to overcome the immunosuppressive microenvironment, and treatment resistance of AML blasts and leukemia-initiating cells (LIC).</p><p><strong>Key messages: </strong>In this review, we summarize preclinical studies with cytokine-stimulated or genetically engineered NK cells derived from different cell sources for the treatment of AML and their translation into early-phase clinical trials. We also provide an overview of promising recent developments toward innovative NK cell-based therapies that may be implemented in the near future.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"52 1","pages":"42-60"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411045","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":"Virus-Specific T-Cell Therapy for the Management of Viral Infections in the Immunocompromised.","authors":"Kiriakos Koukoulias, Penelope Georgia Papayanni, Ann Marie Leen, Spyridoula Vasileiou","doi":"10.1159/000540961","DOIUrl":"10.1159/000540961","url":null,"abstract":"<p><strong>Background: </strong>Immunocompromised individuals are at major risk for severe infectious complications. This is particularly relevant in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT) - a treatment modality that has proven curative for a range of malignant and nonmalignant hematological diseases. However, transplant-associated immune suppression leaves patients susceptible to infectious complications from viruses such as cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and BK virus (BKV). While pharmacological agents are available to prevent and/or treat some of these viruses, they can be associated with significant toxicities and are often ineffective. To circumvent these issues, several groups have explored the clinical potential of adoptively transferred virus-specific T cells (VSTs) to prevent/treat virus-associated complications after allo-HCT or solid organ transplantation (SOT) and this review will provide an overview of these endeavors.</p><p><strong>Summary: </strong>This review will focus on the progress that has been made over the past 30 years in the field of nonengineered VST manufacturing technologies and will summarize the clinical experience with VSTs, primarily in the posttransplant setting.</p><p><strong>Key messages: </strong>Over the last 3 decades, adoptively transferred VSTs - both HCT donor and third party-derived - have been tested in numerous single and multicenter clinical trials and have unequivocally proven to be safe and associated with clinical activity.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"52 1","pages":"5-26"},"PeriodicalIF":1.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411096","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":"Cytokine-Induced Killer Cells: A Unique Platform for Adoptive Cell Immunotherapy after Allogeneic Hematopoietic Stem Cell Transplantation.","authors":"Eva Rettinger","doi":"10.1159/000540964","DOIUrl":"10.1159/000540964","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapies in general, and cellular immunotherapies, in particular are becoming increasingly integrated into current personalized cancer treatment, though still facing some obstacles in the allogeneic hematopoietic stem cell transplantation (HSCT) setting.</p><p><strong>Summary: </strong>The concept of isolating immune effector cells, expanding their numbers, enhancing their anticancer capabilities by modifying them without increasing their alloreactive potential is the mainstay of adoptive cellular immunotherapy after allogeneic HSCT. In this context, cytokine-induced killer (CIK) cells, a polyfunctional heterogenous population of conventional T cells, natural killer (NK) cells, and T-NK cells capable of using T cell and NK cell-like cytotoxicity mechanisms against a various cancers, showed minimal alloreactivity in pediatric and adult patients allografted for hematological malignancies. Furthermore, CIK cells have already shown compatibility with chemotherapy, different kinds of immune checkpoint inhibitors, epigenetic drugs, antibody-targeted therapies, and recently with chimeric antigen receptor-engineering techniques.</p><p><strong>Key messages: </strong>Hence, CIK cell therapy represents a unique platform for adoptive cell immunotherapies, guiding innovative treatment approaches from preclinical research to future clinical trials for cancer patients with yet unmet medical needs. In this context, the allogeneic HSCT setting provides an alternative source for safe and efficient adoptive allogeneic CIK cell strategies against a variety of cancers.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"52 1","pages":"77-95"},"PeriodicalIF":1.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411028","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":"Erratum.","authors":"","doi":"10.1159/000541144","DOIUrl":"https://doi.org/10.1159/000541144","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000502158.].</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"51 5","pages":"361"},"PeriodicalIF":1.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508719","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":"Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy.","authors":"Wilma Barcellini, Bruno Fattizzo","doi":"10.1159/000540475","DOIUrl":"10.1159/000540475","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune hemolytic anemia (AIHA) is a rare disease due to increased destruction of erythrocytes by autoantibodies, with or without complement activation.</p><p><strong>Summary: </strong>AIHA is usually classified in warm AIHA (wAIHA) and cold agglutinin disease (CAD), based on isotype and thermal amplitude of the autoantibody. The direct antiglobulin test (DAT) or Coombs test is the cornerstone of AIHA diagnosis, as it is positive with anti-IgG in wAIHA, and with anti-C3d/IgM antisera plus high titer cold agglutinins in CAD. Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter. Splenectomy, which is still a good option for young/fit wAIHA, is contraindicated in CAD, and classic immunosuppressants are moving to further lines. Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan). Clinically, AIHAs are highly heterogeneous, from mild/compensated to life-threatening/fulminant, and may be primary or associated with infections, neoplasms, autoimmune diseases, transplants, immunodeficiencies, and drugs. Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging.</p><p><strong>Key messages: </strong>This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"51 5","pages":"321-331"},"PeriodicalIF":1.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381708","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":"Adoptive Cell Therapy from the Dish: Potentiating Induced Pluripotent Stem Cells.","authors":"Pieter L Lindenbergh, Sjoukje J C van der Stegen","doi":"10.1159/000540473","DOIUrl":"10.1159/000540473","url":null,"abstract":"<p><strong>Background: </strong>The clinical success of autologous adoptive cell therapy (ACT) is substantial but wide application is challenged by the quality and quantity of the patient's immune cells and the need for personalized manufacturing processes. Induced pluripotent stem cells (iPSCs) can be differentiated into immune effectors and thus provide an alternative, allogeneic cell source for ACT. Here, we compare iPSC-derived immune effectors to their PBMC-derived counterparts and review iPSC-derived ACT products currently under preclinical and clinical development.</p><p><strong>Summary: </strong>iPSC-derived T cells, NK cells, macrophages, and neutrophils largely mimic their PBMC-derived counterparts in terms of cell-surface marker expression and cytotoxic effector functions. iPSC-derived immune effectors can be engineered with chimeric antigen receptors and other activating receptors to redirect their cytotoxic potential specifically to tumor-associated antigens (TAAs). However, several differences between iPSC- and PBMC-derived immune effectors remain and have inspired additional engineering strategies to enhance the antitumor capacity of iPSC-derived immune effectors.</p><p><strong>Key messages: </strong>iPSCs can be engineered to facilitate the generation of immune effectors with homogenous specificity for TAAs and enhanced effector functions. TAA-specific and functionally enhanced iPSC-derived T and NK cells are currently undergoing clinical evaluation in phase 1 trials. Engineered iPSC-derived macrophages and neutrophils are in preclinical development.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"52 1","pages":"27-41"},"PeriodicalIF":1.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410898","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":"Classical Haematology: Dynamic Development at the Interface of Transfusion Medicine and Haematology.","authors":"Hubert Schrezenmeier","doi":"10.1159/000540110","DOIUrl":"10.1159/000540110","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"51 5","pages":"289-291"},"PeriodicalIF":1.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381709","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":"Paroxysmal Nocturnal Hemoglobinuria, Pathophysiology, Diagnostics, and Treatment.","authors":"Jens Peter Panse, Britta Höchsmann, Jörg Schubert","doi":"10.1159/000540474","DOIUrl":"10.1159/000540474","url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis (IVH) due to diminished or absent inhibition of the complement system because of deficient expression of cell-anchored complement regulating surface proteins. IVH leads to heterogeneous symptoms such as anemia, abdominal pain, dyspnea, fatigue and increased rates of thrombophilia. Inhibitors of the terminal Complement cascade can reverse IVH leading to a significant reduction of disease burden such as thrombembolic events and also mortality.</p><p><strong>Summary: </strong>Therapeutic inhibitors of the terminal complement cascade such as eculizumab or ravulizumab significantly improve overall survival through IVH-inhibition. However, not all patients experience complete disease control with normalization of hemoglobin levels and absolute reticulocyte counts (ARC) under terminal complement inhibition as a significant part of patients develop extravascular hemolysis (EVH). EVH can be clinically relevant causing persistent anemia and fatigue. New proximal complement inhibitors (CI) mainly targeting complement component C3 or factors of the amplification pathway such as pegcetacoplan, danicopan, and iptacopan became available and are meanwhile approved for marketing. Additional complement-inhibiting strategies are under clinical development. A switch from terminal to proximal CI in patients with significant EVH can achieve hemoglobin and ARC normalization and significant improvement in quality of life (QoL). Additional approvals of proximal CI agents for the treatment of hemolytic PNH in the first line are available for pegcetacoplan and iptacopan. So far, no evidence-based algorithm is available for decision-making in first-line treatment of which type of drug should be used for individual patients.</p><p><strong>Key messages: </strong>Terminal CIs in hemolytic PNH patients can block IVH and have led to a dramatically improved survival. Proximal CIs ameliorate anemia and improve QoL in patients with relevant EVH. However, more (real-world) data are needed to demonstrate long-term improvement in all patients with hemolytic PNH, especially those under first-line treatment with proximal CI.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"51 5","pages":"310-320"},"PeriodicalIF":1.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381711","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":"Sickle Cell Disease.","authors":"Joachim B Kunz, Laura Tagliaferri","doi":"10.1159/000540149","DOIUrl":"10.1159/000540149","url":null,"abstract":"<p><strong>Background: </strong>Sickle cell disease (SCD) is among the most frequent hereditary disorders globally and its prevalence in Europe is increasing due to migration movements.</p><p><strong>Summary: </strong>The basic pathophysiological event of SCD is polymerization of deoxygenated sickle hemoglobin, resulting in hemolysis, vasoocclusion, and multiorgan damage. While the pathophysiological cascade offers numerous targets for treatment, currently only two disease-modifying drugs have been approved in Europe and transfusion remains a mainstay of both preventing and treating severe complications of SCD. Allogeneic stem cell transplantation and gene therapy offer a curative option but are restricted to few patients due to costs and limited availability of donors.</p><p><strong>Key message: </strong>Further efforts are needed to grant patients access to approved treatments, to explore drug combinations and to establish new treatment options.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"51 5","pages":"332-344"},"PeriodicalIF":1.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383302","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}