Blood Reviews最新文献

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.

Anticoagulation therapy (AT) is fundamental in atrial fibrillation (AF) treatment but poses challenges in implementation, especially in AF populations with elevated thromboembolic and bleeding risks. Current guidelines emphasize the need to estimate and balance thrombosis and bleeding risks for all potential candidates of antithrombotic therapy. However, administering oral AT raises concerns in specific populations, such as those with chronic kidney disease (CKD), coagulation disorders, and cancer due to lack of robust data. These groups, excluded from large direct oral anticoagulants trials, rely on observational studies, prompting physicians to adopt individualized management strategies based on case-specific evaluations. The scarcity of evidence and specific guidelines underline the need for a tailored approach, emphasizing regular reassessment of risk factors and anticoagulation drug doses. This narrative review aims to summarize evidence and recommendations for challenging AF clinical scenarios, particularly in the long-term management of AT for patients with CKD, coagulation disorders, and cancer.

Hodgkin lymphoma is a rare, but highly curative form of cancer, primarily afflicting adolescents and young adults. Despite multiple seminal trials over the past twenty years, there is no single consensus-based treatment approach beyond use of multi-agency chemotherapy with curative intent. The use of radiation continues to be debated in early-stage disease, as part of combined modality treatment, as well as in salvage, as an important form of consolidation. While short-term disease outcomes have varied little across these different approaches across both early and advanced stage disease, the potential risk of severe, longer-term risk has varied considerably.

Over the past decade novel therapeutics have been employed in the retrieval setting in preparation to and as consolidation after autologous stem cell transplant. More recently, these novel therapeutics have moved to the frontline setting, initially compared to standard-of-care treatment and later in a direct head-to-head comparison combined with multi-agent chemotherapy.

In 2018, we established the HoLISTIC Consortium, bringing together disease and methods experts to develop clinical decision models based on individual patient data to guide providers, patients, and caregivers in decision-making. In this review, we detail the steps we followed to create the master database of individual patient data from patients treated over the past 20 years, using principles of data science. We then describe different methodological approaches we are taking to clinical decision making, beginning with clinical prediction tools at the time of diagnosis, to multi-state models, incorporating treatments and their response. Finally, we describe how simulation modeling can be used to estimate risks of late effects, based on cumulative exposure from frontline and salvage treatment.

The resultant database and tools employed are dynamic with the expectation that they will be updated as better and more complete information becomes available.