PURPOSE OF REVIEW: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. RECENT FINDINGS: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. SUMMARY: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.
ABSTRACT:Platelets, the smallest blood cells, weave through health and disease, their history profound, some of their functions yet to be revealed. Terminology often drifts, but by naming with precision, we illuminate understanding, guide newcomers and set a clear path for research and collaboration.
Purpose of review 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. Recent findings 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. Summary 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.
PURPOSE OF REVIEW:Acute graft-versus-host disease (aGVHD) remains a principal driver of nonrelapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fifty percent of patients fail to achieve durable responses to first-line corticosteroids, defining steroid-refractory aGVHD (SR-aGVHD) and limited long-term survival. The Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib became the standard second-line therapy. Nevertheless, primary resistance and secondary loss of response continue to leave a substantial proportion of patients without effective treatment. RECENT FINDINGS:This review synthesizes evidence available up to June 2026 on second-line and salvage options that complement or follow ruxolitinib, including mesenchymal stromal cells, extracorporeal photopheresis administered alone or in combination with ruxolitinib, mammalian target of rapamycin (mTOR) inhibitors with or without interleukin-2 receptor antagonists (IL-2RAs), the humanized anti-CD25 monoclonal antibody xenopax, antithymocyte globulin as salvage, and investigational agents. We examine 2025 four-RCT meta-analysis supporting mesencymal stem cells (MSCs), the 2025 conditional approval by the Chinese NMPA of umbilical cord-derived MSC product for SR-aGVHD, the REACH2 long-term data, and biomarker-guided risk stratification using suppression of tumorigenicity 2 and regenerating islet-derived 3-alpha (REG3α). SUMMARY:We propose an evidence-based clinical sequencing algorithm that integrates ruxolitinib, MSCs, extracorporeal photopheresis (ECP), mTOR-targeted salvage, ATG, and clinical trial enrollment and supportive-care priorities, including infectious prophylaxis and organ-specific management.
PURPOSE OF REVIEW:Allogeneic hematopoietic cell transplantation (allo-HCT) is complicated by life-threatening conditions whose prompt diagnosis is essential yet frequently delayed. This review examines proteomic approaches to biomarker discovery for the most common posttransplant complications, emphasizing methodological reliability and translational status. RECENT FINDINGS:Proximity extension assay (PEA) and aptamer-based platforms now permit simultaneous quantification of thousands of proteins from microliter plasma volumes. For acute graft-versus-host disease (GVHD), validated plasma panels incorporating ST2 and REG3α have been established as prognostic tools, and a PEA discovery study in patients with acute myeloid leukemia identified a four-marker panel (SLAMF7, IL-1ra, BTN3A2, and DAB2) with an area under the curve of 0.90. For sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), a PEA study of very severe cases identified multiple candidate proteins at diagnosis and four proteins whose serum levels declined during defibrotide treatment. Proteomic evidence for other complications remains sparse and early in development. SUMMARY:Most proteomic biomarker studies in allo-HCT derive from small single-center discovery cohorts. Multicenter validation, harmonized biobanking, and integration with clinical risk models are required before these biomarkers can enter transplant practice.
