Current Opinion in Hematology最新文献

{"title":"Augmenting immune reconstitution after adult allo-haematopoietic stem cell transplantation: current developments and modifiable determinants.","authors":"Sebastian J Grocott, Igor Novitzky-Basso","doi":"10.1097/MOH.0000000000000944","DOIUrl":"10.1097/MOH.0000000000000944","url":null,"abstract":"<p><strong>Purpose of review: </strong>Immune reconstitution after adult allogeneic haematopoietic stem cell transplantation (allo-HSCT) shapes infection risk, vaccine responsiveness, relapse and nonrelapse mortality. Advances in graft-vs.-host disease (GvHD) prophylaxis, serotherapy exposure management, cytomegalovirus (CMV) control, functional immune monitoring and adoptive cellular therapy have changed which aspects of recovery can be modified and which augmentors are realistic in current practice. This review sets out what has evolved in adult practice and where intervention can now improve it.</p><p><strong>Recent findings: </strong>GvHD prophylaxis, serotherapy dosing and CMV prophylaxis can increasingly be tuned to individual risk rather than applied uniformly, and exposure-guided and function-based measures are beginning to supplement simple subset counts. Adoptive approaches such as virus-specific T-cells offer targeted immune replacement in refractory viral disease, while thymic regeneration and cytokine-based strategies remain investigational. Updated vaccination guidance and recent immunogenicity data are sharpening humoral monitoring.</p><p><strong>Summary: </strong>Taken together, these developments point towards a move from numerical subset counts to function- and exposure-guided assessment of immune reconstitution. Several determinants, including serotherapy exposure, GvHD prophylaxis, CMV control, microbiome preservation and selective adoptive immune replacement, now support individualised decisions, although prospectively validated intervention thresholds remain few.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"243-252"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655059","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":"Nutrition as a regulator of hematopoietic stem cell biology and transplantation.","authors":"Sophia Shi, Ying Liang","doi":"10.1097/MOH.0000000000000940","DOIUrl":"10.1097/MOH.0000000000000940","url":null,"abstract":"<p><strong>Purpose of review: </strong>Nutrition is increasingly recognized as a biologically active regulator of hematopoietic stem cell (HSC) function and transplant recovery. This review summarizes recent advances linking nutrient availability, metabolic signaling, and the gut-marrow axis to HSC maintenance and hematopoietic stem cell transplantation (HSCT) outcomes.</p><p><strong>Recent findings: </strong>Recent work supports a model in which nutrient sensing, glucose, amino acid and lipid metabolism, mitochondrial redox control, and microbiome-derived metabolites collectively shape HSC quiescence, regenerative capacity, immune recovery, and susceptibility to transplant-related complications. Dietary states such as caloric restriction, fasting, obesity, and high-fat diet exposure alter HSC behavior through metabolic, inflammatory, and niche-mediated pathways. In HSCT, nutritional status before and after transplantation appears to interact with mucosal injury, microbial disruption, graft-versus-host disease (GVHD), infection, and overall outcomes, although causal evidence remains limited.</p><p><strong>Summary: </strong>Nutrition should be viewed as more than a background component of supportive care in hematology. A better mechanistic understanding of how diet and metabolism influence HSC biology may help define biomarker-informed and clinically actionable nutritional strategies to improve transplant recovery.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"315-321"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280120","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":"Factor XIa inhibition for the prevention of thrombosis: mechanism, clinical trial signals, and indication-specific positioning.","authors":"Evan Kidder, Nirav Dhanesha","doi":"10.1097/MOH.0000000000000941","DOIUrl":"10.1097/MOH.0000000000000941","url":null,"abstract":"<p><strong>Purpose of review: </strong>Factor XI (FXI) and its activated form, factor XIa (FXIa), have emerged as a leading novel anticoagulant target of the past decade. This review summarizes mechanistic and clinical data from 2023 through 2026 and proposes an indication-specific framework for FXIa inhibitor positioning.</p><p><strong>Recent findings: </strong>Three large randomized studies diverged by indication. Abelacimab reduced major and clinically relevant nonmajor bleeding by 62% versus rivaroxaban in atrial fibrillation (AZALEA-TIMI 71). Asundexian was inferior to apixaban for stroke prevention in atrial fibrillation (OCEANIC-AF) yet reduced recurrent stroke after noncardioembolic events (OCEANIC-STROKE). Milvexian entered a three-trial phase 3 program. FXIa has been found to drive platelet and endothelial activation in inflammation-associated thrombosis, whereas the FXI zymogen has noncoagulation roles that include activation of bone morphogenetic protein 7-SMAD1/5 cardioprotection. A fifth drug class of allosteric FXI activation inhibitors was further characterized.</p><p><strong>Summary: </strong>FXIa contribution to thrombus formation varies by anatomic site, flow conditions, and inflammatory phenotype. The clinical data support indication-specific positioning for cancer-associated thrombosis, secondary stroke prevention, and patients at high bleeding risk, but provide weaker support for broad substitution for direct oral anticoagulants.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"322-329"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334531","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":"Dynamic myeloid suppressor states in cancer and inflammation and their therapeutic potential.","authors":"Alexandra Pommier, Jose A Cancelas","doi":"10.1097/MOH.0000000000000939","DOIUrl":"10.1097/MOH.0000000000000939","url":null,"abstract":"<p><strong>Purpose of review: </strong>Myeloid-derived suppressor cells (MDSCs) are central mediators of immune dysregulation in cancer, infection, and inflammatory diseases. This review highlights recent advances redefining MDSCs' biology, with a focus on their developmental origin, functional plasticity, and the signaling and metabolic networks that regulate their expansion and activity within the bone marrow and peripheral tissues.</p><p><strong>Recent findings: </strong>Single-cell and lineage-tracing studies demonstrate that MDSCs do not represent a discrete lineage but instead arise as dynamic functional states across the myeloid continuum during emergency myelopoiesis. These states encompass polymorphonuclear and monocytic subsets derived from both immature progenitors and reprogrammed mature myeloid cells under inflammatory conditions. Transcriptional regulators, including STAT3, C/EBPβ, and IRF8, coordinate their differentiation, while cytokine signaling, chemokine-mediated trafficking, and metabolic reprogramming sustain suppressive function within diseased tissues. Emerging evidence further implicates bone marrow niche-derived signals and microbial cues as critical modulators of MDSC expansion and recruitment.</p><p><strong>Summary: </strong>MDSCs are best understood as context-dependent myeloid states shaped by inflammatory and metabolic cues. Defining the regulatory checkpoints governing these transitions has important implications in hematological malignancies and inflammatory disorders. Emerging therapeutic strategies aimed at limiting MDSC recruitment, reprogramming suppressive myeloid states, or targeting their metabolic and signaling dependencies hold significant potential to enhance immunotherapy efficacy and restore immune homeostasis across cancer and inflammatory diseases.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"304-314"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334550","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":"Complement targeting in autoimmune diseases.","authors":"Vasil Vasilev, Mariana Petkova, Maria Radanova, Lubka T Roumenina","doi":"10.1097/MOH.0000000000000945","DOIUrl":"10.1097/MOH.0000000000000945","url":null,"abstract":"<p><strong>Purpose of review: </strong>Complement is a central effector of cell and tissue injury in hematological and autoimmune diseases, and recent intensive research brought new inhibitors to the clinic. This review summarizes complement-mediated mechanisms across hematological, systemic, and kidney-specific autoimmune diseases, appraises emerging biomarker strategies, and evaluates these therapies.</p><p><strong>Recent findings: </strong>For years, clinical complement inhibition was possible only at C5, first in paroxysmal nocturnal hemoglobinuria. The arsenal has now expanded to the initiation pathways: sutimlimab (anti-C1s) is effective in the hematological autoimmune condition cold agglutinin disease, pegcetacoplan (C3-inhibitor) in C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis, and oral iptacopan (Factor B-inhibitor) reduces proteinuria in immunoglobulin A nephropathy and C3 glomerulopathy. Nevertheless, challenges remain. Avacopan (C5aR1-inhibitor) faces proposed withdrawal after trial manipulation and hepatotoxicity, and although complement is central to systemic lupus erythematosus and contributes to membranous nephropathy, no effective strategy has yet emerged.</p><p><strong>Summary: </strong>Recognizing complement's role in the pathophysiology of hematological and autoimmune diseases has driven effective new therapies. Comprehensive profiling complement biomarkers, now feasible through complementomics in fluids and tissues, may reveal responsive endotypes and optimal cascade steps to target in diseases where complement is implicated but trials have not yet matched the right drug to the right patients.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"278-286"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914486","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":"Maintenance therapy after allogeneic stem cell transplantation for relapse prevention in myeloid malignancies.","authors":"Nihar Desai, Ivan Pasic","doi":"10.1097/MOH.0000000000000948","DOIUrl":"10.1097/MOH.0000000000000948","url":null,"abstract":"<p><strong>Purpose of review: </strong>Relapse remains the leading cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and outcomes after relapse are poor. This review summarizes and critically appraises current evidence for post-HCT maintenance therapy aimed at relapse prevention.</p><p><strong>Recent findings: </strong>Patient selection increasingly rests on disease risk and the presence of a targetable mutation. FLT3 inhibitors carry the strongest evidence: randomized trials support sorafenib and gilteritinib in FLT3 internal tandem duplication ( FLT3-ITD ) AML, and the MORPHO trial showed that measurable residual disease (MRD) status identifies patients most likely to benefit. Isocitrate dehydrogenase ( IDH ) inhibitors and menin inhibitors are promising but lack randomized data. For patients without actionable mutations, hypomethylating agent maintenance has produced inconsistent results, and the evidence more strongly supports MRD-triggered preemptive therapy.</p><p><strong>Summary: </strong>Post-HCT maintenance has shifted from broadly applied, poorly tolerated regimens toward targeted, MRD-guided strategies. Important uncertainties remain regarding optimal patient selection, agent choice, timing, and duration. Adequately powered, HCT-specific randomized trials with standardized MRD endpoints are the principal unmet need.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"229-235"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723213","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":"Sickle cell disease and hematopoietic stem cell transplantation: donor expansion, gene-modified grafts and prenatal horizons.","authors":"Giula Mackina, Panicos Shangaris","doi":"10.1097/MOH.0000000000000955","DOIUrl":"10.1097/MOH.0000000000000955","url":null,"abstract":"<p><strong>Purpose of review: </strong>To review advances from the past 18 months in allogeneic hematopoietic stem cell transplantation (HSCT) and autologous gene-modified stem cell transplantation for sickle cell disease (SCD), and to relate these developments to stem cell biology, conditioning and emerging prenatal strategies.</p><p><strong>Recent findings: </strong>Matched sibling HSCT remains the clinical benchmark, but recent studies show age- and regimen-dependent trade-offs between durable engraftment, graft-versus-host disease and toxicity. Haploidentical platforms using posttransplant cyclophosphamide, thiotepa or intensified low-dose irradiation have widened donor access, although infection, graft failure and chronic graft-versus-host disease remain important. Autologous CRISPR-edited and lentiviral grafts can nearly eliminate severe vaso-occlusive events, but still require stem cell collection, individualized manufacture and myeloablative conditioning. New work identifies inflammation, lineage skewing, reduced GATA1 and premature senescence as determinants of sickle stem cell fitness, while culture-sparing editing and antibody-directed conditioning offer routes to safer transplantation.</p><p><strong>Summary: </strong>Curative SCD therapies are converging on the same challenge: establishing durable healthy hematopoiesis with acceptable toxicity. Progress will depend on graft quality, safer niche creation, patient-centred outcomes and equitable delivery. In vivo and prenatal approaches remain preclinical and require a substantially higher maternal-foetal safety threshold.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"271-277"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914495","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":"Prekallikrein: the catalytic crossroads of inflammation and thrombosis.","authors":"Aditya K Malhotra, Arjun Tomer, Ocean Punsalan, Nidhi Patel, Samantha A Moellmer-Gomez, Cristina Puy, Aleksandr Shamanaev, Lukas Seifer, Owen J T McCarty, Joseph J Shatzel","doi":"10.1097/MOH.0000000000000946","DOIUrl":"10.1097/MOH.0000000000000946","url":null,"abstract":"<p><strong>Purpose of review: </strong>The contact activation pathway, historically considered dispensable for hemostasis, has re-emerged as a critical mediator of thromboinflammation. Plasma prekallikrein, through its activation to kallikrein, links coagulation, inflammation, and vascular biology. This review is timely given increasing interest in targeting the contact system to develop safer antithrombotic therapies that minimize bleeding risk.</p><p><strong>Recent findings: </strong>Emerging preclinical and translational studies demonstrate that prekallikrein contributes to thrombosis, inflammation, and endothelial dysfunction, despite minimal involvement in baseline hemostasis. Animal models reveal context-dependent roles of prekallikrein in arterial and venous thrombosis, while human data confirm that prekallikrein deficiency is not associated with bleeding. Clinical success of prekallikrein inhibition in hereditary angioedema validates the therapeutic relevance of the kallikrein-kinin system. Early-phase studies and related work targeting contact pathway components, particularly factor XI, further support this pathway as a viable antithrombotic target.</p><p><strong>Summary: </strong>Collectively, current evidence positions prekallikrein as a promising therapeutic target that may allow selective inhibition of thromboinflammatory processes without impairing hemostasis. Further clinical investigation is needed to define the efficacy and safety of prekallikrein-directed therapies in thrombosis and other inflammatory conditions.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"296-303"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992644","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":"Allogeneic haematopoietic stem cell transplantation: when will better measures lead to better survival?","authors":"Igor Novitzky-Basso","doi":"10.1097/MOH.0000000000000950","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000950","url":null,"abstract":"","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"33 6","pages":"227-228"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149118907","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":"Inflammation as a pleiotropic regulator of megakaryocyte and platelet hemostatic, immune, and metabolic function.","authors":"Guadalupe Rojas-Sanchez, Pavel Davizon-Castillo","doi":"10.1097/MOH.0000000000000943","DOIUrl":"10.1097/MOH.0000000000000943","url":null,"abstract":"<p><strong>Purpose of review: </strong>During infectious and noninfectious inflammatory diseases, disruption of the immune-hemostatic balance increases both thrombotic and hemorrhagic risk. We propose that this bidirectional dysregulation reflects the integrated contribution of megakaryocyte reprogramming during thrombopoiesis and direct remodeling of circulating platelets by inflammatory mediators, two interconnected regulatory levels that together shape the prothrombotic and hemorrhagic platelet phenotypes observed across inflammatory conditions.</p><p><strong>Recent findings: </strong>Current evidence supports a two-level framework through which inflammation remodels platelet responses. Upstream, recent studies demonstrate that inflammation remodels thrombopoiesis, megakaryocyte transcriptional programs, and immunometabolism, generating platelets with altered immunothrombotic, thromboinflammatory, and prothrombotic properties. Converging evidence from aging, sepsis, myeloproliferative neoplasms, and rheumatoid arthritis identifies autophagy as a central target of inflammatory signaling linking megakaryocyte and platelet reprogramming to mitochondrial dysfunction and impaired clot contraction. Downstream, inflammatory mediators directly remodel platelet receptor signaling and promote receptor transfer, generating context-dependent platelet functional states that contribute to both thrombotic and hemorrhagic complications.</p><p><strong>Summary: </strong>The platelet phenotype observed across inflammatory diseases reflects the integrated contribution of megakaryocyte reprogramming during thrombopoiesis and direct remodeling of circulating platelets by inflammatory mediators. These two levels of regulation likely operate simultaneously and may amplify each other, yet how they interact to determine platelet functional outcomes in specific inflammatory contexts remains to be determined. Defining these interactions will inform the development of mechanism-based therapeutic strategies that target inflammation-driven platelet dysfunction to reduce thrombotic and hemorrhagic complications across inflammatory diseases.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"287-295"},"PeriodicalIF":2.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655102","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}