Current Opinion in Hematology最新文献

Purpose of review: Anti-platelet factor 4 (PF4) disorders, including heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), and emerging disorders such as VITT-like monoclonal gammopathy of thrombotic significance (MGTS), are monoclonal antibody-mediated and characterized by thrombocytopenia and thrombosis. Understanding the cellular and molecular mechanisms among these anti-PF4 disorders can help explain the variability in clinical presentations.

Recent findings: Recent work demonstrated that beyond platelets, immune and vascular cells serve a critical role in driving thrombosis and the severity of clinical outcomes. Neutrophils drive thrombosis via NETosis, monocytes release tissue factor-rich microparticles, and endothelial cells provide adhesive and immunogenic surfaces that sustain thromboinflammation. Thus, our understanding of the pathogenesis of anti-PF4 disorders is defined by complex interactions and effector functions of multiple cellular contributors working in parallel to create a highly prothrombotic environment.

Summary: A deeper understanding of these intercellular pathways will shed light on the role of innate immune cells, in addition to platelets, in creating variable clinical outcomes between anti-PF4 disorders and reveal novel therapeutic targets. This expands our understanding of unifying mechanisms between these disorders and informs future strategies to improve diagnosis and treatment.

Purpose of review: Autologous stem cell transplantation (ASCT) has long been a cornerstone in the treatment of eligible patients with newly diagnosed multiple myeloma (NDMM). In this review, we analyze the evolving role of ASCT in the contemporary period.

Recent findings: With the growing integration of modern induction regimens and advanced immunotherapies such as chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies (BsAbs), the traditional paradigm of multiple myeloma treatment is being increasingly challenged. These novel treatments, which have demonstrated unique response rates and unprecedented minimal residual disease (MRD) rates, have raised the question about the role, timing, and necessity of ASCT.

Summary: ASCT has been standard of care in the treatment of NDMM for transplant-eligible patients for over three decades. With the advent of modern induction regimens and immunotherapies, treatment paradigms are evolving rapidly, challenging the current role, timing, and necessity of ASCT. This review explores the contemporary role of ASCT in NDMM. Despite the promise of immunotherapy, the current evidence continues to support ASCT as a consolidative therapy that remains highly effective, accessible, and cost-efficient, particularly when integrated with modern therapeutics and MRD-driven algorithms.

Purpose of review: Antithymocyte globulin (ATG) and posttransplant cyclophosphamide (PTCy) play essential roles in graft-vs.-host disease (GvHD) prophylaxis. ATG is considered the standard of care for matched related and unrelated donor (MRD/MUD) transplantation, while PTCy is the preferred approach for T cell-replete haploidentical transplantation. In recent years, PTCy has gained popularity in the MRD/MUD setting, prompting the publication of several large retrospective studies comparing the efficacy of ATG and PTCy, either as standalone regimens or in combination. This review aims to critically analyze the findings of these studies and provide context for the ongoing debate regarding the optimal prophylactic approach.

Recent findings: Large retrospective studies have compared ATG and PTCy in adult MRD/MUD recipients, yielding mixed results. These studies share several limitations, including their retrospective design, variability in ATG dosing and scheduling, and the inclusion of patients who underwent transplantation during different time periods. Additionally, the combination of PTCy and ATG in haploidentical transplantation has demonstrated potential in reducing GvHD incidence.

Summary: The optimal regimen for GvHD prophylaxis remains undefined. PTCy has been widely adopted for MRD/MUD transplantation, and its combination with ATG is being actively explored in the haploidentical setting. However, the current body of evidence is largely based on retrospective studies, underscoring the need for well designed prospective trials to clarify the comparative benefits of these strategies.

Purpose of review: There is an increasing recognition that mitochondria are dynamic regulators of cell fate. Mitochondria transplantation has emerged as a promising therapeutic strategy for conditions ranging from metabolic disorders to neurodegenerative diseases. Thus, there is a growing need for scalable mitochondrial sources for transplantation. We highlight megakaryocytes, best known for their role in platelet production, as a novel and versatile candidate source for mitochondria transplantation.

Recent findings: Megakaryocytes are naturally equipped to package and deliver functional mitochondria when producing platelets. Furthermore, MKs can share their mitochondria with neighboring cells in the bone marrow. Given the abundance of mitochondria in megakaryocytes, they may represent an ideal source of mitochondria for transplantation. A better understanding of the role of mitochondria in megakaryocyte heterogeneity and metabolic functions may help harness megakaryocytes for therapeutic transplantation applications.

Summary: Megakaryocyte-derived mitochondria transplantation offers a promising avenue for treating metabolic disorders, leveraging existing mechanisms. Future research should address limitations in megakaryocyte biogenesis and heterogeneity, and optimize delivery systems to maximize therapeutic efficacy.

Purpose of review: Platelet transfusion can have a significant immunological impact, exposing the recipient to alloantigens on the surface of platelets and contaminating leukocytes, a dynamic range of soluble immune mediators, and donor platelets that can directly and indirectly contribute to the inflammatory profile of the recipient. Here, we will review recent developments in our understanding of the mechanisms regulating the immune response to platelet transfusion.

Recent findings: Using animal models, much has been learned about the mechanisms regulating the alloimmune response to platelet transfusion and how this response is shaped by the underlying health of the recipient. There is also a growing appreciation of the active role platelets play in immunity and their impact on the recipient immune system and transfusion outcomes, and how these immunological profiles are shaped by product collection, processing, and storage practices.

Summary: While platelet transfusion carries significant benefit to a wide range of patients, it carries risk of alloimmunization and other immune-mediated adverse reactions. Further characterization of the mechanisms regulating these outcomes can lead to new interventions to prevent alloimmunization and help to identify which platelet products are best suited to different patient populations.

Purpose of review: Red blood cell (RBC) antigens arise from genetic variations. RBC genotyping has been increasingly used to assist serological typing, solve serological discrepancies, guide antigen matching, and tackle RBC antigens with complex genetics, such as Rh blood group. This review will discuss common applications of RBC genotyping in patient care, genotyping methods, and computational algorithms for automated and high-throughput RBC genotyping.

Recent findings: Single-nucleotide polymorphisms (SNPs) are the most common polymorphisms of genes encoding RBC antigens. High-throughput platforms focusing on identifying SNPs and small insertions and deletions (indels), such as SNP arrays and high-density SNP arrays, have been developed and/or implemented for RBC genotyping in clinical settings. Whereas SNP arrays target common variants, DNA sequencing provides more comprehensive information on RBC antigens and can identify rare and new SNPs/indels and various structural variations. Computational algorithms that address the tremendous quantities of data and bioinformatics challenges generated by DNA sequencing have been developed, enabling automated and high-throughput genotyping.

Summary: With the advances in microarray and sequencing technologies and bioinformatics, RBC genotyping may become a new gold standard for RBC antigen identification and can provide critical insights for research on RBC antigens.

Purpose of review: Acute myeloid leukemia (AML) is a biologically diverse disease that has undergone significant transformation in recent years. The rapid pace of discovery in molecular genetics, disease classification, and therapeutic development has reshaped how we approach diagnosis and treatment. This review aims to provide a timely and relevant synthesis of these advances, offering clinicians and researchers an updated perspective on AML as of 2025.

Recent findings: The 2022 WHO and ICC classifications have shifted the diagnostic focus toward genetic alterations, allowing for more precise subtyping and personalized treatment decisions. Advances in molecular profiling have improved risk stratification and highlighted the importance of measurable residual disease (MRD) in guiding therapy. Targeted agents - such as fms-like tyrosine kinase 3 (FLT3), isocitrate dehydrogenase (IDH)1/2, and menin inhibitors - have broadened options for patients who are unfit for intensive chemotherapy or have relapsed disease. Postremission strategies are evolving, with increasing use of MRD-guided transplant decisions and maintenance therapies like sorafenib and oral azacitidine. While CAR-T cell therapy remains investigational in AML, early results are promising and support continued exploration.

Summary: The integration of genomic insights with emerging therapies is transforming AML management. These developments are paving the way toward more personalized care, improved outcomes, and new opportunities for long-term disease control and cure.

Purpose of review: Chronic graft-versus-host disease (cGvHD) remains a major complication following allogeneic hematopoietic cell transplantation, frequently requiring multiple lines of immunosuppressive treatment. The increasing approval of targeted therapies demands an updated understanding of their clinical positioning, strengths, and safety considerations.

Recent findings: Several agents have been approved for cGvHD following treatment failure, including ibrutinib and ruxolitinib after first line, and belumosudil and axatilimab after at least two prior therapies. Novel compounds such as ivarmacitinib, TDI-01, rovadicitinib, and pimicotinib target distinct or combined inflammatory and fibrotic pathways and demonstrate promising efficacy across multiple organ systems. However, safety profiles and organ-specific response rates vary. Prior exposure to Janus kinase inhibitors influences therapeutic sequencing, while discrepancies between formal and patient-reported outcomes represent challenges for data interpretation.

Summary: Expanding therapeutic options in cGvHD require decision-making based on organ involvement, prior therapy, and tolerability. Emerging compounds offer the potential to modulate chronic inflammation and fibrosis more precisely, supporting a move toward personalized and combinatorial approaches in advanced-line settings.

Purpose of review: Malaria and babesiosis are important transfusion-transmitted diseases, therefore, it is important to report novel insights into the complex interactions the causative parasites share with their common host RBCs. Metabolomics is an important tool that can be used to reveal an in-depth analysis of parasite infections in the context of the host. Similarities and differences in the biochemical fingerprints between malaria and babesia infected RBCs are reviewed with potential reasons for these differences and implications for the host.

Recent findings: Recent results from Babesia-infected RBCs offer an opportunity to develop comparative models of pathogenesis for both infections. Perturbation in the levels of key biomolecules including sugars, amino-acids and lipids, along with redox homeostasis, and heme utilization, are hallmarks of both diseases. Key similarities include enhanced glycolytic rate in both infected RBCs together with lipid scavenging from RBC membranes. Differences relate to hemoglobin breakdown and the use of resultant amino acids for propagation.

Summary: Altered metabolic profiles reflect the unique lifecycles of Plasmodium and Babesia, pointing to how they carve out a niche for successful proliferation. A comprehensive understanding of the metabolic similarities and differences between the two parasites will aid in identifying new biomarkers as well as specific, effective targeted therapies.

Purpose of review: Chimeric Antigen Receptor T cell (CAR-T) has transformed B-cell malignancies treatment, with seven FDA-approved therapies to date. Despite remarkable success, a substantial fraction of patients relapse, primarily due to limited CAR-T persistence or tumor escape driven by target-antigen loss. Here, we highlight preclinical and clinical advances in programming T cells to address these challenges and are poised to drive next-generation CAR-T development.

Recent findings: Building on FDA-approved CAR designs, innovations in tailoring CAR signaling, cytokine armoring, and multiantigen targeting are paving the way toward more effective and safer treatments. Satisfyingly, these new approaches have demonstrated feasibility, safety, and promising clinical activity, including in patients relapsing after prior CAR treatment. In parallel, CARs with enhanced sensitivity to low-antigen tumors are advancing from preclinical to clinical development. These innovations aiming to enhance T cell persistence and counter tumor escape are defining the next wave of CAR therapies.

Summary: Here, we outline key advances in CAR-T programming to improve persistence, broaden antigen targeting, and enhance efficacy in B-cell malignancies. While challenges such as toxicities or identifying optimal and standardized approaches across trials remain to be addressed, these approaches provide a foundation for translating innovations into effective and potentially curative CAR immunotherapies.