Current Opinion in Hematology最新文献

{"title":"Mixed donor chimerism following stem cell transplantation for sickle cell disease.","authors":"Niketa C Shah,&nbsp;Hemalatha G Rangarajan,&nbsp;Alexander Ngwube,&nbsp;Shalini Shenoy","doi":"10.1097/MOH.0000000000000786","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000786","url":null,"abstract":"<p><p>Sickle cell disease is a debilitating hemoglobinopathy with high morbidity and mortality. Hematopoietic stem cell transplantation (HCT) is curative, but the presence of mixed donor/recipient chimerism post-HCT raises concerns about disease control long-term. Mixed donor/recipient chimerism is reported in significant numbers even after aggressive HCT conditioning regimens. Post-HCT, adequacy of donor erythropoiesis is crucial for disease control. This review explores the relationship between mixed donor/recipient chimerism and outcomes post-HCT. Serial chimerism analysis in lineage specific manner in erythroid or myeloid cells post-HCT predicts for disease control and HCT success. Adequate and stable donor-derived erythropoiesis is essential for reversing SCD manifestations. Myeloid lineage chimerism mirrors erythropoiesis is commercially available, and a reliable indicator of adequacy. Using this tool, the minimum threshold of donor chimerism is required to prevent SCD-related complications and maintain sickle hemoglobin less than 50% is approximately 20-25% even when a donor has Hb S trait. Curative interventions should, at a minimum, meet this goal long-term. Achieving a balance between successful engraftment while minimizing toxicity is important in patients vulnerable because of age or preexisting morbidity and is the objective of recent clinical trials. As HCT and gene therapies evolve, efficient long-term follow-up that includes durability assessment of mixed donor/recipient chimerism will be crucial.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 6","pages":"187-193"},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immunology of PF4 polyanion interactions.","authors":"Anh T P Ngo, Veronica Bochenek, Kandace Gollomp","doi":"10.1097/MOH.0000000000000782","DOIUrl":"10.1097/MOH.0000000000000782","url":null,"abstract":"<p><strong>Purpose of review: </strong>Platelet factor 4 (PF4, CXCL4), the most abundant α-granule platelet-specific chemokine, forms tetramers with an equatorial ring of high positive charge that bind to a wide range of polyanions, after which it changes conformation to expose antigenic epitopes. Antibodies directed against PF4 not only help to clear infection but can also lead to the development of thrombotic disorders such as heparin-induced thrombocytopenia (HIT) and vaccine-induced thrombocytopenia and thrombosis (VITT). This review will outline the different mechanisms through which PF4 engagement with polyanions combats infection but also contributes to the pathogenesis of inflammatory and thrombotic disease states.</p><p><strong>Recent findings: </strong>Recent work has shown that PF4 binding to microbial polyanions may improve outcomes in infection by enhancing leukocyte-bacterial binding, tethering pathogens to neutrophil extracellular traps (NETs), decreasing the thrombotic potential of NET DNA, and modulating viral infectivity. However, PF4 binding to nucleic acids may enhance their recognition by innate immune receptors, leading to autoinflammation. Lastly, while HIT is induced by platelet activating antibodies that bind to PF4/polyanion complexes, VITT, which occurs in a small subset of patients treated with COVID-19 adenovirus vector vaccines, is characterized by prothrombotic antibodies that bind to PF4 alone.</p><p><strong>Summary: </strong>Investigating the complex interplay of PF4 and polyanions may provide insights relevant to the treatment of infectious disease while also improving our understanding of the pathogenesis of thrombotic disorders driven by anti-PF4/polyanion and anti-PF4 antibodies.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 6","pages":"219-229"},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Warm autoimmune hemolytic anemia: new insights and hypotheses.","authors":"Donald R Branch","doi":"10.1097/MOH.0000000000000779","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000779","url":null,"abstract":"<p><strong>Purpose of review: </strong>Warm autoimmune hemolytic anemia (wAIHA) is the most common of the immune hemolytic anemias. Although there are numerous case reports and reviews regarding this condition, some of the unusual and more recent findings have not been fully defined and may be contentious. This review will provide insight into the common specificity of the warm autoantibodies and hypothesize a novel mechanism of wAIHA, that is proposed to be linked to the controversial subject of red blood cell senescence.</p><p><strong>Recent findings and hypotheses: </strong>It is now well established that band 3 on the red blood cell is the main target of autoantibodies in wAIHA. wAIHA targets the older red blood cells (RBCs) in about 80% of cases and, recently, it has been shown that the RBCs in these patients are aging faster than normal. It has been proposed that in these 80% of patients, that the autoantibody recognizes the senescent red blood cell antigen on band 3. It is further hypothesized that this autoantibody's production and potency has been exacerbated by hypersensitization to the RBC senescent antigen, which is processed through the adaptive immune system to create the pathogenic autoantibody. Recent publications have supported previous data that the senescent RBC antigen is exposed via a dynamic process, wherein oscillation of a band 3 internal loop flipping to the cell surface, creates a conformational neoantigen that is the RBC senescent antigen. It has also recently been shown that the cytokine profile in patients with wAIHA favors production of inflammatory cytokines/chemokines that includes interleukin-8 which can activate neutrophils to increase the oxidative stress on circulating RBCs to induce novel antigens, as has been postulated to favour exposure of the senescent RBC antigen.</p><p><strong>Summary: </strong>This manuscript reviews new findings and hypotheses regarding wAIHA and proposes a novel mechanism active in most wAIHA patients that is due to an exacerbation of normal RBC senescence.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 6","pages":"203-209"},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/60/cohem-30-203.PMC10552839.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the glycobiology of immune thrombocytopenia.","authors":"Katherine H Tiemeyer, David J Kuter, Christopher W Cairo, Marie A Hollenhorst","doi":"10.1097/MOH.0000000000000781","DOIUrl":"10.1097/MOH.0000000000000781","url":null,"abstract":"<p><strong>Purpose of review: </strong>The platelet surface harbors a lush forest of glycans (carbohydrate polymers) attached to membrane proteins and lipids. Accumulating evidence suggests that these glycans may be relevant to the pathophysiology of immune thrombocytopenia (ITP). Here, we critically evaluate data that point to a possible role for loss of sialic acid in driving platelet clearance in ITP, comment on the potential use of neuraminidase inhibitors for treatment of ITP, and highlight open questions in this area.</p><p><strong>Recent findings: </strong>Multiple lines of evidence suggest a role for loss of platelet sialic acid in the pathophysiology of thrombocytopenia. Recent work has tested the hypothesis that neuraminidase-mediated cleavage of platelet sialic acid may trigger clearance of platelets in ITP. Some clinical evidence supports efficacy of the viral neuraminidase inhibitor oseltamivir in ITP, which is surprising given its lack of activity against human neuraminidases.</p><p><strong>Summary: </strong>Further study of platelet glycobiology in ITP is necessary to fill key knowledge gaps. A deeper understanding of the roles of platelet glycans in ITP pathophysiology will help to guide development of novel therapies.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"210-218"},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red cell extracellular vesicles and coagulation activation pathways.","authors":"Denis F Noubouossie, Nigel S Key","doi":"10.1097/MOH.0000000000000780","DOIUrl":"10.1097/MOH.0000000000000780","url":null,"abstract":"<p><strong>Purpose of review: </strong>Packed red blood cells (PRBCs) are the most commonly transfused blood products. Preparation of PRBCs requires blood collection from donors, processing, and storage prior to transfusion to recipients. Stored red blood cells (RBCs) undergo structural and metabolic changes collectively known as the storage lesion. RBC extracellular vesicles (sREVs) are released in PRBC units during storage, and are transfused along with intact RBCs into recipients. For several decades, extracellular vesicles have been the focus of intense research, leading to the discovery of a wide variety of endogenous biological properties that may impact numerous physiologic and/or pathologic pathways.</p><p><strong>Recent findings: </strong>This study reviews the characteristics of extracellular vesicles present in PRBC units and the impact of prestorage and pretransfusion processing, as well as storage conditions, on their generation. Importantly, we discuss recently described interactions of sREVs with coagulation pathways and related interplay with inflammatory pathways in vitro and in vivo using animal models.</p><p><strong>Summary: </strong>Extracellular vesicles present in stored PRBC units are capable of activating coagulation pathways. However, it remains unclear whether this affects clinical outcomes in recipients of PRBC units. Further understanding of these pathways and their relationship to any adverse outcomes may yield novel strategies to mitigate complications of blood transfusion.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 6","pages":"194-202"},"PeriodicalIF":3.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation and bone marrow fibrosis: novel immunotherapeutic targets.","authors":"Francesca Rossella Calledda,&nbsp;Alessandro Malara,&nbsp;Alessandra Balduini","doi":"10.1097/MOH.0000000000000778","DOIUrl":"10.1097/MOH.0000000000000778","url":null,"abstract":"<p><strong>Purpose of review: </strong>Myelofibrosis (MF) is primarily driven by constitutive activation of the Janus kinase/signal transducer of activators of transcription (JAK/STAT) pathway. While JAK inhibitors have shown to alleviate disease symptoms, their disease-modifying effects in MF are limited. The only curative treatment remains allogeneic stem cell transplantation, which can be applied to a minority of patients. As a result, there is a need to explore novel targets in MF to facilitate appropriate drug development and therapeutic pathways.</p><p><strong>Recent findings: </strong>Recent research has focused on identifying novel signals that contribute to the abnormal cross-talk between hematopoietic and stromal cells, which promotes MF and disease progression. Inflammation and immune dysregulation have emerged as key drivers of both the initiation and progression of MF. A growing number of actionable targets has been identified, including cytokines, transcription factors, signalling networks and cell surface-associated molecules. These targets exhibit dysfunctions in malignant and nonmalignant hematopoietic cells, but also in nonhematopoietic cells of the bone marrow. The study of these inflammation-related molecules, in preclinical models and MF patient's samples, is providing novel therapeutic targets.</p><p><strong>Summary: </strong>The identification of immunotherapeutic targets is expanding the therapeutic landscape of MF. This review provides a summary of the most recent advancements in the study of immunotherapeutic targets in MF.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"237-244"},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel approaches to measure transfusion effectiveness.","authors":"Marianne Elaine McPherson Yee, Ross M Fasano","doi":"10.1097/MOH.0000000000000783","DOIUrl":"10.1097/MOH.0000000000000783","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review encompasses different considerations of transfusion effectiveness based upon clinical scenario and transfusion indication. Tissue oxygenation, cerebral metabolic oxygen use, and red blood cell (RBC) survival are important elements of transfusion effectiveness in individuals with acute and chronic transfusion requirements.</p><p><strong>Recent findings: </strong>Noninvasive measures of tissue and cerebral oxygen extraction include near-infrared spectroscopy (NIRS) and specialized MRI sequences. RBC survival timepoints including 24 h posttransfusion recovery, 50% recovery timepoint, and mean potential lifespan may be accurately measured with biotin-labeling of RBC prior to transfusion. Labeling at different cell surface densities allows survival of multiple RBC populations to be determined.</p><p><strong>Summary: </strong>Although past trials of optimal transfusion thresholds have focused on Hb as a singular marker for transfusion needs, measures of oxygenation (via NIRS or specialized MRI) and RBC survival (via biotin labeling) provide the opportunity to personalize transfusion decisions to individual patient's acute health needs or chronic transfusion goals.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"230-236"},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial introductions","authors":"","doi":"10.1097/moh.0000000000000784","DOIUrl":"https://doi.org/10.1097/moh.0000000000000784","url":null,"abstract":"Current Opinion in Hematology was launched in 1994. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of hematology is divided into nine sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Editor and the Section Editors for this issue. SECTION EDITORS Christine Duncan, MDChristine Duncan, MDChristine Duncan is a physician-researcher whose work focuses on the cellular therapy of children and young adults with rare inherited diseases. She is a Principal Investigator, Staff Physician, and Medical Director of Clinical Research and Clinical Development of the Gene Therapy Program at Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Assistant Professor of Pediatrics at Harvard Medical School, and Associate Clinical Director of Inpatient Pediatric Hematopoietic Stem Cell Transplant Service at Boston Children's Hospital. In addition to her work on allogeneic and gene therapy for rare pediatric diseases, Dr. Duncan investigates the long-term complications of cellular therapies. Karina YazdanbakhshKarina YazdanbakhshDr Karina Yazdanbakhsh is the Head of the Laboratory of Complement Biology of the Lindsley F. Kimball Research Institute (LFKRI) of the New York Blood Center (NYBC). She received her Ph.D. in molecular biology from the National Institute for Medical Research (MRC) at Mill Hill London and did her postdoctoral training in molecular and cellular immunology at Columbia and Rockefeller Universities. She joined NYBC in 1996 and served as the Executive Director of LFKRI from 2016-2019. She has extensive experience in transfusion immunology and her current research is on patient-orientated translational studies focusing on immune regulatory networks in thrombocytopenia and hemolytic anemia and understanding sickle cell immune-pathophysiology. Dr Yazdanbakhsh has served on numerous National Institutes of Health (NIH) review panels and has been a member of several committees for the American Association of Blood Banks (AABB) and the American Society of Hematology. She was the Chair of the Abstract Selection Committee of AABB from 2016-2020 and the Chair of the Scientific Committee of ASH and currently serves on the Editorial Board of Transfusion. She has spoken as an invited speaker and chair at many national and international meetings, including AABB, American Society of Hematology Meeting, European Hematology Association, and International Society of Blood Transfusion. She was inducted into the Hall of Fame of the National Blood Foundation of AABB in 2016 for her contributions to transfusion medicine.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135342859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet mitochondria: the mighty few.","authors":"Abigail Ajanel, Robert A Campbell, Frederik Denorme","doi":"10.1097/MOH.0000000000000772","DOIUrl":"10.1097/MOH.0000000000000772","url":null,"abstract":"<p><strong>Purpose of review: </strong>Platelet mitochondrial dysfunction is both caused by, as well as a source of oxidative stress. Oxidative stress is a key hallmark of metabolic disorders such as dyslipidemia and diabetes, which are known to have higher risks for thrombotic complications.</p><p><strong>Recent findings: </strong>Increasing evidence supports a critical role for platelet mitochondria beyond energy production and apoptosis. Mitochondria are key regulators of reactive oxygen species and procoagulant platelets, which both contribute to pathological thrombosis. Studies targeting platelet mitochondrial pathways have reported promising results suggesting antithrombotic effects with limited impact on hemostasis in animal models.</p><p><strong>Summary: </strong>Targeting platelet mitochondria holds promise for the reduction of thrombotic complications in patients with metabolic disorders. Future studies should aim at validating these preclinical findings and translate them to the clinic.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 5","pages":"167-174"},"PeriodicalIF":3.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10269507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial introduction.","authors":"","doi":"10.1097/MOH.0000000000000776","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000776","url":null,"abstract":"","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 5","pages":"v"},"PeriodicalIF":3.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9898316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}