Best Practice & Research Clinical Haematology最新文献

{"title":"Anti-GM-CSF autoantibodies in myeloid leukemias","authors":"Anna Sergeeva,&nbsp;Wingchi K. Leung,&nbsp;Lisa St John,&nbsp;Jeffrey J. Molldrem","doi":"10.1016/j.beha.2025.101611","DOIUrl":"10.1016/j.beha.2025.101611","url":null,"abstract":"<div><div>Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional cytokine integral to the differentiation, proliferation, and activation of various immune cells, especially those of myeloid lineage. Recombinant human GM-CSF (rhGM-CSF) plays a critical role after high-dose chemotherapy, hematopoietic cell transplantation, and high-dose irradiation by accelerating myeloid recovery and reducing the risk of severe infections. As an adjuvant in anti-tumor vaccines, rhGM-CSF stimulates the differentiation and activation of dendritic cells and promotes their recruitment to tumor sites.</div><div>Despite the therapeutic benefits, rhGM-CSF can induce the production of anti-GM-CSF-autoantibodies (GM-CSF-Ab) that have been implicated in rare diseases, such as autoimmune pulmonary alveolar proteinosis. These antibodies can neutralize GM-CSF activity, impairing macrophages and neutrophils. Furthermore, anti-GM-CSF-Ab have been linked to myeloid leukemias, where they are associated with active disease. The mechanisms behind anti-GM-CSF-Ab production and their role in disease progression remain poorly understood. This review article provides an overview of GM-CSF and anti-GM-CSF-Ab.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101611"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629545","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":"Human mesenchymal stem cell therapy: Potential advances for reducing cystic fibrosis infection and organ inflammation","authors":"Tracey L. Bonfield ,&nbsp;Hillard M. Lazarus","doi":"10.1016/j.beha.2025.101602","DOIUrl":"10.1016/j.beha.2025.101602","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Innovation in cystic fibrosis (CF) supportive care, including implementing new antimicrobial agents, improved physiotherapy, and highly effective modulators therapy, has advanced patient survival into the 4th and 5th decades of life. However, even with these remarkable improvements in therapy, CF patients continue to suffer from pulmonary infection and other visceral organ complications associated with long-term deficient cystic fibrosis transmembrane conductance regulator (CFTR) expression. Human mesenchymal stem cells (MSCs) have been utilized in tissue engineering based upon their capacity to provide structural components of mesenchymal tissues. An alternative role of MSCs, however is their versatile utilization as cell-based infusion powerhouses due to the unique capacity to deliver milieu specific soluble biologic factors, promoting immune supportive antimicrobial and anti-inflammatory potency. MSCs derived from umbilical cord blood, bone marrow, adipose and other tissues can be expanded in &lt;em&gt;ex vivo&lt;/em&gt; using good manufacturing procedure facilities for a safe, unique therapeutic to reduce and limit CF infection and facilitate the resolution of multi-organ inflammation. In our efforts, we conducted extensive preclinical development and validation of an allogeneic derived bone marrow derived MSC product in preparation for a clinical trial in CF. In this process, potency models were developed to ensure the functional capacity of the MSC product to provide clinical benefit. &lt;em&gt;In vitro&lt;/em&gt;, murine &lt;em&gt;in vivo&lt;/em&gt; and patient tissue &lt;em&gt;ex vivo&lt;/em&gt; potency models were utilized to follow MSC anti-infective and anti-inflammatory potency associated with the CFTR deficient environment. We showed in our “First in CF” clinical trial that the allogeneic MSCs obtained from healthy volunteer bone marrow samples were safe. The advent of improved CF care measures and exciting new small molecules has changed the survival and morbidity phenotype of patients with CF, however, there are CF patients who cannot tolerate or have genotypes that are non-responsive to modulators. Additionally, even with the small molecule therapy, CF patients are living longer, but without genetic correction, with the CF disease manifestation aggravated by the continuance of pre-existing CFTR-associated clinical issues such as ongoing inflammation. MSCs secrete bio-active factors that enhance and protect tissue function and can promote “self-immune” regulation. These properties can provide therapeutic support for the traditional and changing face of CF disease clinical complications. Further, MSC-derived bio-active factors can directly mitigate colonizing pathogens' survival by producing antimicrobial peptides (AMPs) which change the pathogen surface and increase host recognition, elimination, and sensitivity to antibiotics. Herein, we review the potential of MSC therapeutics for treating many facets of CF, emphasizing the potential for providing great additive ther","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101602"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642649","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":"Cytokines in hematopoietic cell transplantation and related cellular therapies","authors":"Abdul-Hamid Bazarbachi ,&nbsp;Markus Y. Mapara","doi":"10.1016/j.beha.2025.101600","DOIUrl":"10.1016/j.beha.2025.101600","url":null,"abstract":"<div><div>Cytokines are pleiotropic molecules involved in hematopoiesis, immune responses, infections, and inflammation. They play critical roles in hematopoietic cell transplantation (HCT) and immune effector cell (IEC) therapies, mediating both therapeutic and adverse effects. Thus, cytokines contribute to the immunopathology of graft-<em>versus</em>-host disease (GVHD), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). This review examines cytokine functions in these contexts, their influence on engraftment and immune recovery post-transplantation, and their role in mediating toxicities. We focus on current and potential uses of cytokines to enhance engraftment and potentiate IEC therapies, as well as strategies to mitigate cytokine-mediated complications using cytokine blockers (<em>e.g</em>., tocilizumab, anakinra) and JAK inhibitors (<em>e.g</em>., ruxolitinib). We discuss new insights into GVHD physiology that have led to novel treatments, such as CSF1R blockade, which is effective in refractory chronic GVHD.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101600"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551936","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":"CAR assembly line: Taking CAR T-cell manufacturing to the next level","authors":"Jiasheng Wang ,&nbsp;Paolo F. Caimi","doi":"10.1016/j.beha.2024.101595","DOIUrl":"10.1016/j.beha.2024.101595","url":null,"abstract":"<div><div>The widespread adoption of chimeric antigen receptor (CAR) T-cell therapy has been limited by complex, resource-intensive manufacturing processes. This review discusses the latest innovations aiming to improve and streamline CAR T-cell production across key steps like T-cell activation, genetic modification, expansion, and scaling. Promising techniques highlighted include generating CAR T cells from non-activated lymphocytes to retain a stem-like phenotype and function, non-viral gene transfer leveraging platforms like transposon and CRISPR, all-in-one fully automated bioreactors like the CliniMACS Prodigy and the Lonza Cocoon, rapid CAR T-cell manufacturing via abbreviating or eliminating <em>ex vivo</em> T-cell culture, implementing decentralized point-of-care automated manufacturing platforms, and optimizing centralized bioreactor infrastructure integrating end-to-end automation. Adoption of these emerging technologies can reduce production costs and timelines while enhancing product quality and accessibility. However, significant knowledge gaps persist regarding the feasibility, superiority, and optimal protocols for effectively incorporating many emerging techniques into widespread clinical practice. Further validation through clinical studies is still needed for many of these novel approaches.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101595"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146264","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":"Analyte heterogeneity analysis as a possible potency parameter for MSC","authors":"David Kaplan ,&nbsp;Eric Christian ,&nbsp;Sarah Planchon Pope ,&nbsp;Hillard M. Lazarus ,&nbsp;Jeffrey A. Cohen","doi":"10.1016/j.beha.2025.101596","DOIUrl":"10.1016/j.beha.2025.101596","url":null,"abstract":"<div><div>Mesenchymal stem/stromal cells (MSC) have been transplanted for therapeutic purposes with inconsistent results. MSC preparations are heterogeneous, and this person-to-person heterogeneity may account for the variable clinical outcomes. Additionally, the mechanisms of therapeutic action for MSC are unclear which confounds attempts to understand and identify factors that may account for variable clinical results. Here, we report our analysis of MSC preparations for the expression levels of molecules that have been hypothesized to mediate MSC function. Although most of the analytes assessed demonstrated little divergent expression, several molecules were found with enhanced heterogeneity both within individual MSC preparations and among MSC preparations from the sample of multiple sclerosis patients. The variable expression of these molecules may relate to the therapeutic heterogeneity of MSC. Additionally, we found a novel set of molecules that were highly intercorrelated in MSC. The tight association of this group of molecules may represent an invariant molecular organization that is integral to MSC activity. The precise analysis of molecular expression levels in MSC has the potential to answer concerns about variable therapeutic effects of MSC transplantation as well as to understand the mechanism of clinical effects.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101596"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372935","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":"A reflection on Arnold Caplan, the father of MSC","authors":"James M. Anderson","doi":"10.1016/j.beha.2025.101597","DOIUrl":"10.1016/j.beha.2025.101597","url":null,"abstract":"<div><div>Arnold Caplan was the father of MSC, mesenchymal stem cells. His pioneering efforts have led to significant advances in the utilization of mesenchymal stem cells for the treatment of a wide variety of clinical diseases. This reflection provides some insight into Arnold's commitment to education and research regarding mesenchymal stem cells. Moreover, he was a good friend. Arnold will be missed.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101597"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551471","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":"Cytokine therapy of acute radiation syndrome","authors":"Hillard M. Lazarus ,&nbsp;Robert Peter Gale","doi":"10.1016/j.beha.2025.101599","DOIUrl":"10.1016/j.beha.2025.101599","url":null,"abstract":"<div><div>Radiological accidents/incidents are common with nearly 400 reported since 1944 exposing about 3000 people to substantial doses of ionizing radiations with 127 deaths. Damage to hematopoietic stem and progenitor cells with resulting bone marrow failure is a common consequence of exposure to whole body acute high-dose and -dose-rate ionizing radiations and is termed hematopoietic-acute radiation syndrome, or H-ARS. Therapy of H-ARS includes transfusions, anti-bacterial and -viral drugs, molecularly-cloned hematopoietic growth factors and hematopoietic cell transplants. We considered the role of recombinant human granulocyte-colony-stimulating factor (rhu G-CSF; filgrastim) and recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF; sargramostim) in the setting of H-ARS. The favorable <em>benefit-to-risk</em> ratio of these drugs over hematopoietic cell transplants suggests giving them soon after exposure to acute high-dose and-dose-rate whole body ionizing radiations.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101599"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551937","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":"Bispecific antibody therapy for lymphoma","authors":"Genevieve M. Gerhard,&nbsp;Gottfried von Keudell","doi":"10.1016/j.beha.2025.101598","DOIUrl":"10.1016/j.beha.2025.101598","url":null,"abstract":"<div><div>The rapid development of novel therapeutics in B-cell Non-Hodgkin's lymphoma (B-NHL) over the past decade has presented a critical inflection point for the field. Bispecific antibodies are one such therapeutic class emerging as an effective, off-the-shelf option for B-NHL. In this review, we focus primarily on Diffuse Large B-cell Lymphoma (DLBCL), highlighting the evolution, comparison, tolerability, ongoing challenges, and future potential of bispecific antibodies that are currently approved or in clinical trials for B-NHL. With the number of anti-lymphoma drugs increasing every year, it is important to optimize clinical trial analysis and design so that outcomes, toxicities, and predictors thereof can be understood and compared amongst therapeutic classes to ensure that patients get the safest and most effective treatments for them at the most appropriate line of therapy.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101598"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509201","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":"CARs for lymphoma","authors":"Ishan J. Tatake,&nbsp;Jon E. Arnason","doi":"10.1016/j.beha.2025.101601","DOIUrl":"10.1016/j.beha.2025.101601","url":null,"abstract":"<div><div>Chimeric Antigen Receptor (CAR)-T cell therapy has revolutionized treatment options for B-cell Non-Hodgkin Lymphoma (NHL). CD19-targeting CAR-T cell therapy is approved for treatment in Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. CAR-T cells demonstrate robust and durable responses even in heavily pretreated patients. Clinicians should monitor for Cytokine Release Syndrome (CRS) and Immune Effector Cell Neurotoxicity Syndrome (ICANS), as well as cytopenias, infection, and secondary malignancies. Ongoing questions remain in improving manufacturing efficacy, sequencing CAR-T cells amongst other therapies including bi-specific antibodies (BiTEs), and predicting optimal responders. In addition, novel CARs are being developed with alternative targets or that secrete activating cytokines (i.e. “armored CARs”). CAR-T cells represent an effective lymphoma therapy and should be considered for eligible patients.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101601"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551472","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 to “Special issue 37.2 and 37.3 Genetics and Function of HLA and immune-related genes in transplantation and cellular immunotherapy” [Best Pract Res Clin Haematol (2024) 101588]","authors":"Katharina Fleischhauer","doi":"10.1016/j.beha.2024.101594","DOIUrl":"10.1016/j.beha.2024.101594","url":null,"abstract":"","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101594"},"PeriodicalIF":2.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650880","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}