Blood Reviews最新文献

Significant advances in the field of lymphoma have resulted in two recent classification proposals, the International Consensus Classification (ICC) and the 5th edition WHO. A few entities are categorized differently in the ICC compared to the WHO. Nowhere is this more apparent than the immunodeficiency lymphoproliferative disorders. The three previous versions of the WHO classification (3rd, 4th and revised 4th editions) and the ICC focused on four clinical settings in which these lesions arise for primary categorization. In contrast the 2023 WHO 5th edition includes pathologic characteristics including morphology and viral status, in addition to clinical setting, as important information for lesion classification. In addition, the 2023 WHO recognizes a broader number of clinical scenarios in which these lesions arise, including not only traditional types of immune deficiency but also immune dysregulation. With this classification it is hoped that new treatment strategies will be developed leading to better patient outcomes.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder caused by complement-mediated hemolysis and thrombosis through the alternative pathway. The most common symptom of PNH is fatigue due to chronic anemia, which can negatively impact quality of life (QoL) and affect overall well-being. The currently approved therapies for PNH significantly limit intravascular hemolysis (IVH) and reduce the risk of thrombosis; however, they are associated with an infusion schedule that can become burdensome, and not all patients experience complete disease control. Several new complement inhibitors are in development that address the need for convenient routes of administration and aim to provide better disease control. With the variety of new treatment options on the horizon, hematologic markers as well as QoL concerns, patient opinion, and lifestyle factors should be considered to choose the optimal PNH treatment for each specific patient.

The assessment of hemostatic disorders in neonates is crucial, but remains challenging for clinicians. Although the concept of developmental hemostasis is widely accepted among hemostasis specialists globally, it is probably under-recognized by clinicians and laboratory practitioners. In parallel with age-dependent hemostatic status maturation, comprehension of the differences between normal values is crucial for the accurate diagnosis of potential hemorrhagic and thrombotic disorders of the vulnerable neonatal population. This review outlines the basics of developmental hemostasis and the features of the available coagulation testing methods, with a focus on novel tools for evaluating the neonatal hemostatic profile. Common errors, issues, and pitfalls during the assessment of neonatal hemostasis are discussed, along with their impact on patient management. Current knowledge gaps and research areas are addressed. Further studying to improve our understanding of developmental hemostasis and its reflection on everyday clinical practice is warranted.

Hemophilia A, an X-linked genetic disorder, is characterized by a deficiency or dysfunction of clotting Factor VIII. The treatment landscape has substantially changed by introducing novel extended half-life factor VIII (EHL-FVIII) replacement therapies such as efanesoctocog Alfa and non-factor replacement therapy such as emicizumab. These agents signal a shift from treatments requiring multiple weekly infusions to advanced therapies with long half-lives, offering superior protection against bleeding and improving patient adherence and quality of life. While EHL-FVIII treatment might lead to inhibitor development in some patients, non-factor replacement therapy carries thrombotic risks. Therefore, ongoing research and the generation of robust clinical evidence remain vital to guide the selection of optimal and cost-effective first-line therapies for hemophilia A patients.

E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewis^x) on acute myeloid leukemia (AML) cells leads to chemotherapy resistance in vivo. Uproleselan (GMI-1271) is a carbohydrate analog of sialyl Lewis^x that blocks E-selectin binding. A Phase 2 trial of MEC chemotherapy combined with uproleselan for relapsed/refractory AML showed a median overall survival of 8.8 months and low (2%) rates of severe oral mucositis. Clinical trials seek to confirm activity in AML and mitigation of neutrophil-mediated adverse events (mucositis and diarrhea) after intensive chemotherapy. In this review we summarize E-selectin biology and the rationale for uproleselan in combination with other therapies for hematologic malignancies. We also describe uproleselan pharmacology and ongoing clinical trials.

This systematic review and meta-analysis aimed to provide guidance on preoperative blood transfusion strategies for patients with sickle cell disease (SCD). We included all randomized controlled and observational studies exploring the clinical outcomes of preoperative blood transfusion among patients with SCD compared to the conservative transfusion strategy until 14/09/2022.

Sixteen studies involving 3486 participants were analysed. The findings revealed a significantly higher bleeding rate in patients who received preoperative transfusion than those who followed a conservative strategy (RR = 4.32, 95% CI 1.75–10.68, P = 0.002, I2 = 0%). However, the two strategies had no significant differences in other clinical outcomes, such as acute chest syndrome, painful crisis, fever, neurological complications, thrombosis, ICU admission, and mortality. It is important to note that all the included studies had a moderate risk of bias. Preoperative transfusion in SCD was associated with a higher bleeding risk but a similar risk in other outcomes compared to conservative strategies. Notably, the increased bleeding risk observed seldom had clinical significance. We recommend individualizing management strategies, considering the overall positive impact of transfusions in reducing complications. Further high-quality studies are needed to refine recommendations.

Patients with hematologic malignancies experience high rates of depression. These patients are vulnerable to depression throughout the disease trajectory, from diagnosis to survivorship, and at the end of life. In addition to the distressing nature of depression, it has substantial downstream effects including poor quality of life, increased risk of treatment complications, and worse survival. Therefore, systematic screening for depression and integration of robust psychological interventions for affected patients is crucial. Although depression has been historically studied mostly in patients with solid malignancies, research focusing on patients with hematologic malignancies is growing. In this article, we describe what is known about depression in patients with hematologic malignancies, including its assessment, prevalence, risk factors, and implications. We also describe interventions to ameliorate depression in this population. Future research is needed to test effective and scalable interventions to reduce the burden of depression among patients with blood cancers.

Advances in understanding the disease process in β-thalassemia supported development of various treatment strategies that resulted in improved survival. Improved survival, however, allowed multiple morbidities to manifest and cemented the need for frequent, lifelong treatment. This has directly impacted patients' health-related quality of life and opened the door for various psychiatric and cognitive disorders to potentially develop. In this review, we summarize available evidence on quality of life, depression and anxiety, suicidality, and cognitive impairment in adult patients with β-thalassemia while sharing our personal insights from experience in treating patients with both transfusion-dependent and non-transfusion-dependent forms.

CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 inhibitors remains to be established. Various infectious complications can be successfully prevented with appropriate risk management strategies. In this paper we reviewed the international guidelines on prevention and management of infectious complications in patients with CLL treated with BTK or BCL-2 inhibitors. Universal pharmacological anti-herpes, antibacterial or antifungal prophylaxis is not warranted. Reactivation of HBV should be prevented in HBsAg-positive subjects. For HBsAg-negative/HBcAb-positive patients recommendations differ, but in case of combination treatment should follow those for other, particularly anti-CD20, agent. Immunization should be provided preferably before the onset of treatment. Immunoglobulin therapy has favourable impact on morbidity but not mortality in patients with hypogammaglobulinemia and severe or recurrent infections. Lack of high-quality data and heterogeneity of patients or protocols included in the studies might explain differences among the main guidelines. Better data collection is warranted.

The vast spectrum of aggressive B-cell non-Hodgkin neoplasms (B-NHL) encompasses several infrequent entities occurring in association with viral infections, posing diagnostic challenges for practitioners. In the emerging era of precision oncology, the molecular characterization of malignancies has acquired paramount significance. The pathophysiological comprehension of specific entities and the identification of targeted therapeutic options have seen rapid development. However, owing to their rarity, not all entities have undergone exhaustive molecular characterization.

Considerable heterogeneity exists in the extant body of work, both in terms of employed methodologies and the scale of cases studied. Presently, therapeutic strategies are predominantly derived from observations in diffuse large B-cell lymphoma (DLBCL), the most prevalent subset of aggressive B-NHL. Ongoing investigations into the molecular profiles of these uncommon virus-associated entities are progressively facilitating a clearer distinction from DLBCL, ultimately paving the way towards individualized therapeutic approaches.

This review consolidates the current molecular insights into aggressive and virus-associated B-NHL, taking into consideration the recently updated 5th edition of the WHO classification of hematolymphoid tumors (WHO-5HAEM) and the International Consensus Classification (ICC). Additionally, potential therapeutically targetable susceptibilities are highlighted, offering a comprehensive overview of the present scientific landscape in the field.