Current Opinion in Hematology最新文献

{"title":"Challenges and opportunities in shared care for international patients treated with cellular therapy for nonmalignant disease.","authors":"Syeda A Mina,&nbsp;Ibrahim N Muhsen,&nbsp;Shahrukh K Hashmi","doi":"10.1097/MOH.0000000000000742","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000742","url":null,"abstract":"<p><p>As cellular therapies gradually become the mainstay of treatment for several nonmalignant diseases, there appears to be varied accessibility to these therapies globally. Despite considerable burden of nonmalignant conditions, such as sickle cell disease, thalassemia, and aplastic anemia in populations of low-middle-income countries, the utilization of cellular therapies remain sparse because of lack of resources. Globally, the frequency of hematopoietic stem cell transplant (HSCT) has increased disproportionately in countries with higher gross national income (GNI) per capita, governmental healthcare expenditures, and a high human development index. This leads to a large subset of international patients seeking care in the United States. This review summarizes the unique set of challenges that often arise when offering sophisticated therapies such as HSCT to international patients constituting of cross-cultural, logistical, financial, and medical challenges and the opportunities that are available to bridge the gap.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10777131","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":"Editorial introduction.","authors":"","doi":"10.1097/MOH.0000000000000744","DOIUrl":"10.1097/MOH.0000000000000744","url":null,"abstract":"","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10763168","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":"Haematopoietic stem cell quiescence exposed using mitochondrial membrane potential.","authors":"Saghi Ghaffari","doi":"10.1097/MOH.0000000000000746","DOIUrl":"10.1097/MOH.0000000000000746","url":null,"abstract":"<p><strong>Purpose of review: </strong>Quiescence is a fundamental property of haematopoietic stem cells (HSCs). Despite the importance of quiescence in predicting the potency of HSCs, tools that measure routinely the degree of quiescence or select for quiescent HSCs have been lacking. This Commentary discusses recent findings that address this fundamental gap in the HSC toolbox.</p><p><strong>Recent findings: </strong>Highly purified, phenotypically-defined HSCs are heterogeneous in their mitochondrial membrane potential (MMP). The lowest MMP subsets are enriched in greatly quiescent HSCs with the highest potency within the purified HSC population. MMP provides an intrinsic probe to select HSC subsets with unique cell cycle properties and distinct stem cell potential. Using this approach, new and unanticipated metabolic properties of quiescent HSCs' exit have been discovered. This methodology may improve the mechanistic understanding, of HSCs' exit from and entry to, quiescence.</p><p><strong>Summary: </strong>Selecting HSCs using MMP is likely to lead to discoveries of new HSC properties, may improve the ex vivo maintenance of HSCs and has implications for the clinic, including for improving HSC transplantations.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9331411","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":"Global perspectives on cellular therapy for children with sickle cell disease.","authors":"Tami D John,&nbsp;Ruth Namazzi,&nbsp;Lulu Chirande,&nbsp;Venée N Tubman","doi":"10.1097/MOH.0000000000000738","DOIUrl":"10.1097/MOH.0000000000000738","url":null,"abstract":"<p><strong>Purpose of review: </strong>Low-income and middle-income countries (LMICs), primarily in sub-Saharan Africa (SSA), predominantly experience the burden of sickle cell disease (SCD). High frequency of acute and chronic complications leads to increased utilization of healthcare, which burdens fragile health systems. Mortality for children with limited healthcare access remains alarmingly high. Cellular based therapies such as allogeneic hematopoietic stem cell transplant (HSCT) are increasingly used in resource-rich settings as curative therapy for SCD. Broad access to curative therapies for SCD in SSA would dramatically alter the global impact of the disease.</p><p><strong>Recent findings: </strong>Currently, application of cellular based therapies in LMICs is limited by cost, personnel, and availability of HSCT-specific technologies and supportive care. Despite the challenges, HSCT for SCD is moving forward in LMICs. Highly anticipated gene modification therapies have recently proven well tolerated and feasible in clinical trials in resource-rich countries, but access remains extremely limited.</p><p><strong>Summary: </strong>Translation of curative cellular based therapies for SCD should be prioritized to LMICs where the disease burden and cost of noncurative treatments is high, and long-term quality of life is poor. Focus on thoughtful modifications of current and future therapies to meet the need in LMICs, especially in SSA, will be especially impactful.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10269338","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":"Immunomodulatory roles of red blood cells.","authors":"Jane Dobkin,&nbsp;Nilam S Mangalmurti","doi":"10.1097/MOH.0000000000000734","DOIUrl":"10.1097/MOH.0000000000000734","url":null,"abstract":"<p><strong>Purpose of the review: </strong>To discuss recent advances supporting the role of red blood cells (RBCs) in the host immune response.</p><p><strong>Recent findings: </strong>Over the last century, research has demonstrated that red blood cells exhibit functions beyond oxygen transport, including immune function. Recent work indicates that the nucleic acid sensing receptor, toll-like receptor 9 (TLR9), is expressed on the RBC surface and implicated in innate immune activation and red cell clearance during inflammatory states. In addition to this DNA-sensing role of RBCs, there is growing evidence that RBCs may influence immune function by inducing vascular dysfunction. RBC proteomics and metabolomics have provided additional insight into RBC immune function, with several studies indicating changes to RBC membrane structure and metabolism in response to severe acute respiratory syndrome coronavirus 2 infection. These structural RBC changes may even provide insight into the pathophysiology of the 'long-coronavirus disease 2019' phenomenon. Finally, evidence suggests that RBCs may influence host immune responses via complement regulation. Taken together, these recent findings indicate RBCs possess immune function. Further studies will be required to elucidate better how RBC immune function contributes to the heterogeneous host response during inflammatory states.</p><p><strong>Summary: </strong>The appreciation for nongas exchanging, red blood cell immune functions is rapidly growing. A better understanding of these RBC functions may provide insight into the heterogeneity observed in the host immune response to infection and inflammation.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10258465","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":"Emerging functional microfluidic assays for the study of thromboinflammation in sickle cell disease.","authors":"Ran An,&nbsp;Umut A Gurkan","doi":"10.1097/MOH.0000000000000731","DOIUrl":"10.1097/MOH.0000000000000731","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review briefly summarizes the significant impact of thromboinflammation in sickle cell disease in relation to recent advances in biomarkers that are used in functional microfluidic assays.</p><p><strong>Recent findings: </strong>Sickle cell disease (SCD) is an inherited hemoglobinopathy that affects 100 000 Americans and millions worldwide. Patients with SCD exhibit chronic haemolysis, chronic inflammation and thrombosis, and vaso-occlusion, triggering various clinical complications, including organ damage and increased mortality and morbidity. Recent advances in functional microfluidic assays provide direct biomarkers of disease, including abnormal white blood cell and red blood cell adhesion, cell aggregation, endothelial degradation and contraction, and thrombus formation.</p><p><strong>Summary: </strong>Novel and emerging functional microfluidic assays are a promising and feasible strategy to comprehensively characterize thromboinflammatory reactions in SCD, which can be used for personalized risk assessment and tailored therapeutic decisions.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10258468","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":"Iron status of blood donors.","authors":"Bryan R Spencer,&nbsp;Alan E Mast","doi":"10.1097/MOH.0000000000000733","DOIUrl":"10.1097/MOH.0000000000000733","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review examines recent research on the prevalence and importance of iron deficiency in blood donors, and on efforts to mitigate it.</p><p><strong>Recent findings: </strong>Premenopausal females, teenagers, and high-frequency donors are at the highest risk for donation-induced iron deficiency, in both high-resource and low-resource settings. The physiology relating iron stores to hemoglobin levels and low hemoglobin deferral is well elucidated in blood donor populations, yet the clinical effects attributable to iron loss in the absence of anemia are challenging to identify. Expanded adoption of ferritin testing is improving donor management but may cause decreases in the blood supply from temporary donor loss. The potential for personalized donor management is emerging with development of computational models that predict individual interdonation intervals that aim to optimize blood collected from each donor while minimizing low hemoglobin deferrals.</p><p><strong>Summary: </strong>Measures to reduce iron deficiency are available that can be deployed on a standardized or, increasingly, personalized basis. Blood centers, regulators, and donors should continue to evaluate different tactics for addressing this problem, to obtain a balanced approach that is optimal for maintaining adequate collections while safeguarding donor health.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10258464","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":"Hyperviscosity syndromes; hemorheology for physicians and the use of microfluidic devices.","authors":"Jamie O Musick, Kirby S Fibben, Wilbur A Lam","doi":"10.1097/MOH.0000000000000735","DOIUrl":"10.1097/MOH.0000000000000735","url":null,"abstract":"<p><strong>Purpose of review: </strong>Hyperviscosity syndromes can lead to significant morbidity and mortality. Existing methods to measure microcirculatory rheology are not readily available and limited in relevance and accuracy at this level. In this review, we review selected hyperviscosity syndromes and the advancement of their knowledge using microfluidic platforms.</p><p><strong>Recent findings: </strong>Viscosity changes drastically at the microvascular level as the physical properties of the cells themselves become the major determinants of resistance to blood flow. Current, outdated viscosity measurements only quantify whole blood or serum. Changes in blood composition, cell number, or the physical properties themselves lead to increased blood viscosity. Given the significant morbidity and mortality from hyperviscosity syndromes, new biophysical tools are needed and being developed to study microvascular biophysical and hemodynamic conditions at this microvascular level to help predict those at risk and guide therapeutic treatment.</p><p><strong>Summary: </strong>The use of 'lab-on-a-chip' technology continues to rise to relevance with point of care, personalized testing and medicine as customizable microfluidic platforms enable independent control of many in vivo factors and are a powerful tool to study microcirculatory hemorheology.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10258463","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":"Immunologic effects of red blood cell and platelet transfusions in neonates.","authors":"Patricia Davenport, Martha Sola-Visner","doi":"10.1097/MOH.0000000000000736","DOIUrl":"10.1097/MOH.0000000000000736","url":null,"abstract":"<p><strong>Purpose of review: </strong>Premature neonates are frequently transfused red blood cells (RBCs) or platelets to raise hemoglobin or platelet counts. However, these transfusions may have unintended effects on the immune system. This review will summarize the newest discoveries on the immunologic effects of RBC and platelet transfusions in neonates, and their potential impact on neonatal outcomes.</p><p><strong>Recent findings: </strong>Neonatal RBC transfusions are associated with increases in plasma pro-inflammatory cytokines, but recent findings suggest sex-specific differential responses. At least one cytokine (monocyte chemoattractant protein-1) rises in females receiving RBC transfusions, but not in males. These inflammatory responses correlate with poorer neurodevelopmental outcomes in heavily transfused female infants, while preterm male infants seem to be more sensitive to severe anemia. Platelet transfusions in preterm neonates are associated with increased neonatal mortality and morbidity. The underlying mechanisms are unknown, but likely related to the immune/inflammatory effects of transfused platelets. Adult platelets are different from neonatal platelets, with the potential to be more pro-inflammatory. Early preclinical data suggest that platelet transfusions alter the neonatal systemic inflammatory response and enhance immune cell migration.</p><p><strong>Summary: </strong>RBC and platelet transfusions alter neonatal immune and inflammatory responses. Their pro-inflammatory effects might worsen neonatal disease or affect neurodevelopmental outcomes.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10616017","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":"Umbilical cord blood: an undervalued and underutilized resource in allogeneic hematopoietic stem cell transplant and novel cell therapy applications.","authors":"Patricia A Shi, Larry L Luchsinger, John M Greally, Colleen S Delaney","doi":"10.1097/MOH.0000000000000732","DOIUrl":"10.1097/MOH.0000000000000732","url":null,"abstract":"<p><strong>Purpose of review: </strong>The purpose of this review is to primarily discuss the unwarranted decline in the use of umbilical cord blood (UCB) as a source of donor hematopoietic stem cells (HSC) for hematopoietic cell transplantation (HCT) and the resulting important implications in addressing healthcare inequities, and secondly to highlight the incredible potential of UCB and related birthing tissues for the development of a broad range of therapies to treat human disease including but not limited to oncology, neurologic, cardiac, orthopedic and immunologic conditions.</p><p><strong>Recent findings: </strong>When current best practices are followed, unrelated donor umbilical cord blood transplant (CBT) can provide superior quality of life-related survival compared to other allogeneic HSC donor sources (sibling, matched or mismatched unrelated, and haploidentical) through decreased risks of relapse and chronic graft vs. host disease. Current best practices include improved UCB donor selection criteria with consideration of higher resolution human leukocyte antigen (HLA) typing and CD34+ cell dose, availability of newer myeloablative but reduced toxicity conditioning regimens, and rigorous supportive care in the early posttransplant period with monitoring for known complications, especially related to viral and other infections that may require intervention. Emerging best practice may include the use of ex vivo expanded single-unit CBT rather than double-unit CBT (dCBT) or 'haplo-cord' transplant, and the incorporation of posttransplant cyclophosphamide as with haploidentical transplant and/or incorporation of novel posttransplant therapies to reduce the risk of relapse, such as NK cell adoptive transfer. Novel, non-HCT uses of UCB and birthing tissue include the production of UCB-derived immune effector cell therapies such as unmodified NK cells, chimeric antigen receptor-natural killer cells and immune T-cell populations, the isolation of mesenchymal stem cells for immune modulatory treatments and derivation of induced pluripotent stem cells haplobanks for regenerative medicine development and population studies to facilitate exploration of drug development through functional genomics.</p><p><strong>Summary: </strong>The potential of allogeneic UCB for HCT and novel cell-based therapies is undervalued and underutilized. The inventory of high-quality UCB units available from public cord blood banks (CBB) should be expanding rather than contracting in order to address ongoing healthcare inequities and to maintain a valuable source of cellular starting material for cell and gene therapies and regenerative medicine approaches. The expertise in Good Manufacturing Practice-grade manufacturing provided by CBB should be supported to effectively partner with groups developing UCB for novel cell-based therapies.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10266040","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}