Blood Reviews最新文献

Bone marrow transplantation for non-malignant diseases such as aplastic anemia and hemoglobinopathies is a burgeoning clinical area. The goal of these transplants is to correct the hematopoietic defect with as little toxicity as possible. This requires mitigation of transplant-specific toxicities such as graft versus host disease, given this is not needed in non-malignant disorders. This review details current clinical outcomes in the field with a focus on post-transplantation cyclophosphamide and anti-thymoglobulin as intensive graft versus host disease prophylaxis to achieve that goal.

Anticoagulant drugs that are currently used to prevent and/or treat thrombosis have some limitations that hinder their ability to meet specific clinical requirements. While these drugs effectively reduce the rates of thrombotic events, they simultaneously increase the risk of bleeding. Moreover, their risk-to-benefit balance is problematic in some patients, such as those with severe chronic kidney disease or those at high bleeding risk. A novel anticoagulation method, FXI inhibition has emerged as a promising alternative. It demonstrates a strong rationale for the prevention and treatment of venous thromboembolism and the potential fulfillment of unmet clinical needs in the cardiovascular field. A number of FXI inhibitors are currently undergoing clinical investigation. The objective of this review is to provide an overview of early results of research on FXI inhibitors in the cardiovascular setting, offering valuable insights into their potential role in shaping the future of anticoagulation.

Early studies in allogeneic blood or marrow transplantation (alloBMT) demonstrated that HLA-mismatching was protective again relapse. However, benefits in relapse reduction were outweighed by a high risk of graft-versus-host disease (GVHD) when using conventional pharmacological immunosuppression. Post-transplant cyclophosphamide(PTCy)-based platforms abated the risk of GVHD thereby overcoming the negative effects of HLA-mismatching on survival. However, since its inception, PTCy has been shadowed by a reputation for a greater risk of relapse when compared with traditional GVHD prophylaxis. Specifically, whether PTCy reduces the anti-tumor efficacy of HLA-mismatched alloBMT by killing alloreactive T cells has been the subject of debate since the early 2000's. Here we review the many studies demonstrating the potent graft-versus-malignancy (GVM) properties of alloBMT with PTCy. We discuss the laboratory data from PTCy platforms supporting that T regulatory cells may be a major mechanism of prevention of GVHD and that natural killer (NK) cells may be early effectors of GVM. Finally, we propose potential paths to optimize GVM through selecting for class II mismatching and augmenting NK cell activity.

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is the most important therapeutic option for hematological disorders, although graft-versus-host disease (GVHD) remains the main cause of mortality. Post-transplantation cyclophosphamide (PTCY) induces immune tolerance and is associated with a low incidence of GVHD and non-relapse mortality. Therefore, PTCY has emerged as a safe and effective GVHD prophylaxis in haploidentical transplantation and has been expanded to matched related or unrelated donor and mismatched unrelated donor HSCT. On the basis of current understanding of the mechanisms of PTCY and antithymocyte globulin (ATG) in the prevention of GVHD, growing evidence suggests that the combination of ATG and PTCY could improve allo-HSCT clinical outcomes. Further research will focus on optimizing PTCY regimens by modifying the timing of administration or adding other immunosuppressive agents.

Waldenström macroglobulinemia (WM) is a unique CD20+, B-cell non-Hodgkin lymphoma, characterized by lymphoplasmacytic infiltration of the bone marrow and circulating monoclonal immunoglobulin M. The clinical manifestations and outcomes of patients are highly variable. High-level evidence supports integration of monoclonal anti-CD20 antibody, rituximab, to the chemotherapy backbone to treat WM. However, its contemporary management has become more nuanced, with deeper understanding of the pathophysiology and incorporation of Bruton's tyrosine kinase (BTK) inhibitors to the treatment paradigm. Prior knowledge of the patients' MYD88^L265P and CXCR4 mutation status may aid in the treatment decision-making. Currently, the two frequently utilized approaches include fixed-duration chemoimmunotherapy and BTK inhibitor-based continuous treatment until progression. Randomized trials comparing these two vastly divergent approaches are lacking. Recent studies demonstrating efficacy of B cell lymphoma-2 (BCL2) inhibitors and non-covalent BTK inhibitors in patients, previously exposed to a covalent BTK inhibitor, are a testament to the rapidly expanding options against WM.

In clinical medicine, shared decision making (SDM) is a well-recognized strategy to enhance engagement of both patients and clinicians in medical decisions. The success of liver-directed gene therapy (GT) to transform severe congenital haemophilia A (HA) from an incurable to a curable disease has launched a shift beyond current standards of treatment. However, GT acceptance remains low in the community of HA persons. We argue for both persons with haemophilia (PWH) and specialists in HA care including clinicians, as needing SDM-oriented educational programs devoted to GT. Here, we provide an ad hoc outline to implement education to SDM and tailor clinician information on GT to individual PWHs. Based on routine key components of SDM: patient priorities; recommendations based on individual risk reduction; adverse effects; drug-drug interactions; alternatives to GT; and ongoing re-assessment of the objectives as risk factors (and individual priorities) change, this approach is finalized to exploit efficacious communication.

This scoping review explores the potential of artificial intelligence (AI) in enhancing the screening, diagnosis, and monitoring of disorders related to body iron levels. A systematic search was performed to identify studies that utilize machine learning in iron-related disorders. The search revealed a wide range of machine learning algorithms used by different studies. Notably, most studies used a single data type. The studies varied in terms of sample sizes, participant ages, and geographical locations. AI's role in quantifying iron concentration is still in its early stages, yet its potential is significant. The question is whether AI-based diagnostic biomarkers can offer innovative approaches for screening, diagnosing, and monitoring of iron overload and anemia.

Haploidentical donor stem cell transplantation (haplo-SCT) has made great advances in recent decades. The granulocyte colony-stimulating factor (G-CSF)- and antithymocyte globulin (ATG)-based protocol, which is known as the Beijing Protocol, represents one of the current T-cell repletion strategies in haplo-SCT. The key elements of the Beijing Protocol for graft versus host disease (GvHD) prophylaxis include G-CSF inducing T-cell tolerance and altering graft cell components, as well as ATG administration exerting an immunoregulatory effect for intensive prophylaxis. This review will summarize the GvHD incidence, the underlying novel mechanism for GvHD prophylaxis, how to optimize GvHD prophylaxis, and the recent advances of the Beijing Protocol, mainly focusing on the issues of GvHD.

Novel developments in therapies for various hereditary hemolytic anemias reflect the pivotal role of pyruvate kinase (PK), a key enzyme of glycolysis, in red blood cell (RBC) health. Without PK catalyzing one of the final steps of the Embden-Meyerhof pathway, there is no net yield of adenosine triphosphate (ATP) during glycolysis, the sole source of energy production required for proper RBC function and survival. In hereditary hemolytic anemias, RBC health is compromised and therefore lifespan is shortened. Although our knowledge on glycolysis in general and PK function in particular is solid, recent advances in genetic, molecular, biochemical, and metabolic aspects of hereditary anemias have improved our understanding of these diseases. These advances provide a rationale for targeting PK as therapeutic option in hereditary hemolytic anemias other than PK deficiency. This review summarizes the knowledge, rationale, (pre)clinical trials, and future advances of PK activators for this important group of rare diseases.

Anemia is common in Myelodysplastic Syndromes (MDS). Different anemia treatments have been tested in clinical studies, but the full impact on patients' health-related quality of life (HRQoL) and physical function is unknown. The main aim of this review was to assess whether improvements in anemia are associated with changes in HRQoL/physical function.

Twenty-six full-text publications were identified, enrolling 2211 patients: nine randomized trials (RCTs), fourteen non-randomized studies of interventions and three cross-sectional studies. Interventions included: growth factors/erythropoiesis-stimulating agents (n = 14), red cell transfusion (n = 9), erythroid maturation agents (n = 1), or a combination (n = 2). Five RCTs reported no changes in HRQoL despite erythroid response to the intervention, raising the question of whether anemia treatment alone can effectively improve HRQoL. Many studies were considered at high risk of bias for assessing HRQoL. There is a pressing need for future clinical trials to better define the nature of the relationship between anemia and HRQoL/functional outcomes.