British Journal of Haematology最新文献

Heavy periods are a common cause of anaemia in women of reproductive age. We compare the prevalence of anaemia and heavy menstrual bleeding (HMB) among women in the United Kingdom and Australia. Women aged 15-50 years were recruited through screening events conducted in the United Kingdom and Australia from 2016 to 2024. In these cross-sectional studies, self-report questionnaires screened for HMB and finger prick haemoglobin concentration (Hb) identified anaemia (Hb < 120 g/L). Of 1937 women (United Kingdom = 333, Australia = 1604), the mean age was 28.5 ± 9.2 years and 33.7% reported HMB. In the United Kingdom, the mean Hb was 129.2 ± 12.0 g/L and 19.2% were anaemic, of which 59.4% had HMB. In Australia, the mean Hb was higher (134.4 ± 12.2 g/L; p < 0.001), with fewer women being anaemic (9.7%; p < 0.001), and fewer anaemic women had HMB (30.3%; p < 0.001). Logistic regression analysis found that women in the United Kingdom were at a greater risk of being anaemic (AOR: 2.144; 95%CI:1.545, 2.946; p < 0.001). HMB was more common in the United Kingdom (45.9% vs. 31.2%; p < 0.001). In Australia, 24.7% (299/1211) reported receiving intravenous iron; while those with prior intravenous iron treatment were less likely to be anaemic (AOR: 0.616; 95%CI: 0.372, 0.982; p = 0.0496). Women in the United Kingdom are more likely to have anaemia and HMB than women in Australia, with HMB presenting a greater risk for anaemia development in the United Kingdom.

Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) link to unfavourable prognoses. We explored the mechanism of enhancer of zeste homologue 2/histone H3 of lysine 27 (EZH2/H3K27me3) downregulating C-X-C motif chemokine 10 (CXCL10) to affect CD8⁺ T-cell exhaustion, participating in MDS-to-AML transformation. NHD13 mice were treated with GSK126 (EZH2 inhibitor) and CXCL10 neutralizing antibody, with transformation time, blood cell counts and CD8⁺ T cell determined. SKM-1 cells treated with short hairpin-EZH2, overexpressing-EZH2, GSK126 and CXCL10 were co-cultured with CD8⁺ T cells. EZH2, CXCL10, H3K27me3 and EZH2 levels and EZH2 enzyme activity were assessed. CD8⁺ T-cell cytotoxicity, exhaustion, apoptosis and SKM-1 cell malignant behaviours were evaluated. In vivo, EZH2 inhibition upregulated CXCL10, decelerating MDS to AML transformation and delaying CD8⁺ T-cell exhaustion. EZH2 inhibition elevated peripheral blood cells, alleviated splenomegaly, reduced CD8⁺ T cells, elevated CD8⁺ T cytotoxicity and abated CD8⁺ T-cell exhaustion in NHD13 mice. CXCL10 neutralizing antibody accelerated AML transformation by inhibiting CD8⁺ T-cell exhaustion via EZH2. In vitro, EZH2 overexpression facilitated CD8⁺ T-cell exhaustion and SKM-1 cell malignant behaviours. EZH2-mediated H3K27me3 curbed CXCL10 transcription and secretion. Collectively, EZH2/H3K27me3 downregulates CXCL10 to facilitate CD8⁺ T-cell exhaustion, accelerating transformation from MDS to AML.

There is still no standard of care and unmet medical needs in refractory/advanced VEXAS (vacuoles in myeloid progenitors, E1 ubiquitin activating enzyme, X-linked, autoinflammatory manifestations and somatic) syndrome with or without associated haematological neoplasm. We report the clinical outcome of four multirefractory/advanced VEXAS patients treated with acute myeloid leukaemia-like therapeutic approaches. All patients responded to inflammatory/haematological VEXAS-related features, which were associated with measurable residual disease response (partial or complete). Prospective studies evaluating new and effective therapeutic strategies in order to reduce clonal burden in VEXAS patients are warranted.

B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) comprises multiple subtypes characterized by different genetic alterations. With the use of current standard-of-care tests used in clinical practice, 20%-30% of the cases may not be classified into the main genetic subtypes and additional approaches are needed. These patients are grouped in the heterogeneous category B-other ALL. Transcriptome sequencing (RNA-seq) has allowed the identification of novel fusion genes and gene expression profiles that define new molecular subtypes. We present RNA-seq results integrated, in a real-world scenario, with clinical routine diagnostic data to identify new biomarkers and reclassify a cohort of 60 B-other ALL patients in the newly described genetic subtypes. Overall, 49 rearrangements were identified, including 32 different fusion genes in 41 B-other patients (68%). Moreover, we reported six novel rearrangements (IGK::PAX5, PAX5::IL1RAPL1, ETV6::KRT78, IGH::HIC1, IGH::MIR100HG and NKAIN4::PNPLA7). The integration of RNA-seq results with standard-of-care data allowed us to classify 72% of the patients (43/60) in 11 different subtypes, being DUX4 rearranged and PAX5alt the most represented subtypes. In summary, RNA-seq is a reliable tool for the identification of new emerging genetic subtypes contributing to a better genetic risk stratification of BCP-ALL paediatric patients on the path towards a more personalized medicine.

There are scarce data in the literature focusing on newly diagnosed multiple myeloma (NDMM) patients who undergo autologous haematopoietic cell transplantation (autoHCT) after achieving suboptimal response to induction. To address this, we performed a retrospective, single-centre analysis of patients with NDMM who underwent upfront autoHCT between 2005 and 2021 with a pretransplant response of less than very good partial response (3 years and median OS of >8 years. Post-transplant maintenance further improved survival outcomes.

Globally, sickle cell disease (SCD) is the most common inherited haemoglobinopathy. The highest burden of SCD is encountered in low- and middle-income countries (LMICs), most of which lack the resources to contend with the disease. There is a marked divide between care for individuals with SCD in high-income countries (HICs) versus LMICs, whereby the few disease-modifying therapies and curative regimens are only accessible to those in HICs. As such, blood transfusion remains central to the emergent treatment and prevention of complications of SCD. However, there are a myriad of related challenges in LMICs, which have impeded efforts to treat patients with SCD effectively. In addition to blood safety and availability, examples that impact SCD specifically include capabilities to detect and/or manage red blood cell alloimmunization, capacity for automated red cell exchange, limited immunohematology, suboptimal quality oversight with a lack of safeguards to prevent transfusion of incompatible blood and limited or absent post-transfusion surveillance to detect and/or manage transfusion-associated adverse events. Consequently, clinical practices that are otherwise regarded as standard of care in HICs remain the exception in LMICs, highlighting disparities in care. A multifaceted approach that prioritizes transfusion support in LMICs is needed to improve care for patients with SCD.