Blood Reviews最新文献

Children with Down syndrome (DS) have a 10- to 20-fold greater predisposition to develop acute leukemia compared to the general population, with a skew towards myeloid leukemia (ML-DS). While ML-DS is known to be a subtype with good outcome, patients who relapse face a dismal prognosis. Acute lymphocytic leukemia in DS (DS-ALL) is considered to have poor prognosis. The relapse rate is high in DS-ALL compared to their non-DS counterparts. We have a better understanding about the mutational spectrum of DS leukemia. Studies using animal, embryonic stem cell- and induced pluripotent stem cell-based models have shed light on the mechanism by which these mutations contribute to disease initiation and progression. In this review, we list the currently available treatment strategies for DS-leukemias along with their outcome with emphasis on challenges with chemotherapy-related toxicities in children with DS. We focus on the mechanisms of initiation and progression of leukemia in children with DS and highlight the novel molecular targets with greater success in preclinical trials that have the potential to progress to the clinic.

Multiple myeloma is a plasma cell neoplasm driven by primary (e.g. hyperdiploidy; IGH translocations) and secondary (e.g. 1q21 gains/amplifications; del(17p); MYC translocations) chromosomal events. These are important to detect as they influence prognosis, therapeutic response and disease survival. Currently, cytogenetic testing is most commonly performed by interphase fluorescence in situ hybridisation (FISH) on aspirated bone marrow samples. A number of variations to FISH methodology are available, including prior plasma cell enrichment and incorporation of immunophenotypic plasma cell identification. Other molecular methods are increasingly being utilised to provide a genome-wide view at high resolution (e.g. single nucleotide polymorphism (SNP) microarray analysis) and these can detect abnormalities in most cases. Despite their wide application at diagnostic assessment, both FISH and SNP-array have relatively low sensitivity, limiting their use for identification of prognostically significant low-level sub-clones or for disease monitoring. Next-generation sequencing is increasingly being used to detect mutations and new FISH techniques such as by flow cytometry are in development and may address some of the current test limitations. Here we review the primary and secondary cytogenetic aberrations in myeloma and discuss the range of techniques available for their assessment.

Melphalan, has been a major component of myeloma therapy since the 1950s. In the context of hematopoietic cell transplantation (HCT), high dose melphalan (HDM) is the most common conditioning regimen used due to its potent anti-myeloma effects and manageable toxicities. Common toxicities associated with HDM include myelosuppression, gastrointestinal issues, and mucositis. Established approaches to reduce these toxicities encompass dose modification, nausea prophylaxis with 5HT3 receptor antagonists, cryotherapy, amifostine use, and growth factors. Optimization of melphalan exposure through personalized dosing and its combination with other agents like busulfan, or bendamustine show promise. Propylene glycol-free melphalan (Evomela) represents a novel formulation aiming to enhance drug stability and reduce adverse effects. This review explores strategies to enhance the efficacy and mitigate the toxicity of HDM in multiple myeloma. Future directions involve exploring these strategies in clinical trials to improve the safety and efficacy of HDM, thereby enhancing outcomes for multiple myeloma patients undergoing autologous HCT.

Artificial intelligence (AI) and its application in classification of blood cells in the peripheral blood film is an evolving field in haematology. We performed a rapid review of the literature on AI and peripheral blood films, evaluating the condition studied, image datasets, machine learning models, training set size, testing set size and accuracy. A total of 283 studies were identified, encompassing 6 broad domains: malaria (n = 95), leukemia (n = 81), leukocytes (n = 72), mixed (n = 25), erythrocytes (n = 15) or Myelodysplastic syndrome (MDS) (n = 1). These publications have demonstrated high self-reported mean accuracy rates across various studies (95.5% for malaria, 96.0% for leukemia, 94.4% for leukocytes, 95.2% for mixed studies and 91.2% for erythrocytes), with an overall mean accuracy of 95.1%. Despite the high accuracy, the challenges toward real world translational usage of these AI trained models include the need for well-validated multicentre data, data standardisation, and studies on less common cell types and non-malarial blood-borne parasites.

Genomic advancements have yielded pivotal insights into hematological neoplasms, particularly concerning germline predisposition mutations. Following the WHO 2016 revisions, dedicated segments were proposed to address these aspects. Current WHO 2022, ICC 2022, and ELN 2022 classifications recognize their significance, introducing more mutations and prompting integration into clinical practice.

Approximately 5–10% of hematological neoplasm patients show germline predisposition gene mutations, rising with risk factors such as personal cancer history and familial antecedents, even in older adults.

Nevertheless, technical challenges persist. Optimal DNA samples are skin fibroblast-extracted, although not universally applicable. Alternatives such as hair follicle use are explored. Moreover, the scrutiny of germline genomics mandates judicious test selection to ensure precise and accurate interpretation.

Given the significant influence of genetic counseling on patient care and post-assessment procedures, there arises a demand for dedicated centers offering specialized services.

α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and β globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload). Several novel therapies are also in development, including curative gene manipulation techniques and disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia. This review of α-thalassemia and its various manifestations provides practical information for clinicians who practice beyond those regions where it is found with high frequency.

Iron deficiency is the most common and widespread nutritional deficiency in the world. For women, the risk of iron deficiency and iron deficiency anemia increases due to iron demands during pregnancy and regular iron losses due to menstruation during reproductive years. These interrelated conditions are of public health concern as they are highly prevalent, and the negative consequences such as chronic fatigue, cognitive impairment and poor quality of life are broad and multifaceted. People of low socioeconomic status are at higher risk of iron deficiency due to low intake of expensive iron-rich foods, and decreased access to healthcare. In this review, we applied a health equity lens to describe the current state of care for women with iron deficiency with or without anemia. We have highlighted several structural challenges that span from the laboratory diagnosis, inconsistent screening guidelines, and stigma associated with heavy menstrual bleeding, to treatment barriers.

Idiopathic multicentric Castleman disease (iMCD) is a rare disease, and it is likely underdiagnosed because of the heterogeneity of clinical manifestations and laboratory findings. While the disease leads to significant morbidity and mortality, its causes are not yet fully elucidated. There have been significant advances in diagnosis and treatment of iMCD in the past decade, including the approval of the anti-IL-6 antibody siltuximab. In this review, we provide an update of the many new developments and publications surrounding iMCD.

Richter transformation (RT) represents an aggressive histological transformation from chronic lymphocytic leukaemia, most often to a large B cell lymphoma. It is characterised by chemo-resistance and subsequent short survival. Drug development has struggled over recent years in light of the aggressive kinetics of the disease, lack of pivotal registrational trials and relative rarity of the phenomenon. In this review we will highlight the diagnostic and therapeutic challenges of managing patients with RT as well as taking a look to the future therapeutic landscape. Highly active therapies developed across B cell malignancies are starting to impact this field, with T-cell activation therapies (CAR-T, bispecific antibodies), antibody-drug conjugates, and novel small molecule inhibitor combinations (e.g. BTKi-BCL2i) being actively studied. We will highlight the data supporting these developments and look to the studies to come to provide hope for patients suffering from this devastating disease.