Blood advances最新文献

The best frontline treatment for acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs) is unclear. To support a clinical practice guideline, we systematically reviewed and meta-analyzed evidence on (1) asparaginase-based ("pediatric") versus non-asparaginase-based ("adult") regimens, and (2) allogeneic hematopoietic stem cell transplantation (HSCT) versus no HSCT for AYAs (15-39 years old) with ALL in first complete remission (CR). Data Sources: PubMed, CINAHL, and PsycINFO from inception through November 29, 2023. Eligible studies compared regimens or use of HSCT and reported survival, remission, toxicity, or quality of life in AYAs. We included 19 studies (14 comparative, 5 single-group; N=3,607) comparing regimens and 7 studies (N=7,492) comparing HSCT and no HSCT. Studies were mostly of poor quality, with sparse randomized controlled trials [RCTs]), yielding low certainty findings. Pediatric regimens were associated with higher 5-year overall survival (OS) (relative risk [RR] 1.40, 1.18-1.65), event-free survival (RR 1.80, 1.13-2.85), disease-free survival (DFS) (RR 1.55, 1.32-1.82), and lower treatment-related mortality (TRM) (RR 0.29, 0.09-0.90).. HSCT was associated with lower 5-year OS (RR 0.72, 0.61-0.84) and DFS (RR 0.78, 0.68-0.90), and higher non-relapse mortality (RR 2.70, 1.18 - 6.18) and TRM (HR 6.88, 3.02-15.70). Relapse risk varied by time point. In AYA with Ph-negative ALL, pediatric regimens may improve survival; toxicity-related evidence remains limited. HSCT may lead to inferior overall survival and DFS. With a dearth of RCTs, low-certainty evidence highlights the need for high quality studies and sub-analyses of AYAs.

Our knowledge of which bone marrow cells affect red cell production is still incomplete. To explore the role of osteocytes in the process we performed bulk RNAseq of osteocytes isolated from control and phlebotomized mice. The second top-upregulated gene following phlebotomy was Erfe - erythroferrone. Erfe expression in osteocytes was also upregulated after erythropoietin (EPO) treatment and hypoxia in vitro. To explore if osteocytes contribute to systemic ERFE levels, we generated two mouse models. We first transplanted wild-type bone marrow (BM) in Erfe-/- mice creating a model where ERFE is produced in the BM but not by osteocytes. After phlebotomy, liver hepcidin suppression was significantly lower in mice where the osteocytes could not produce ERFE. To confirm that osteocytes are responsible for this difference, we generated mice lacking EPO receptors in osteocytes by crossing Eporflox/flox and Dmp1-Cre mice. After phlebotomy, these mice showed reduced hepcidin suppression in the liver and higher circulating serum hepcidin levels compared with controls. Our work identified a novel function of osteocytes in suppressing systemic hepcidin levels during stress erythropoiesis.

Hemoglobinopathies comprise the commonest monogenic diseases worldwide. In Europe, formerly low-prevalence regions have seen increasing numbers of carriers and patients, with important public health implications. Implementation of policies and laboratory methodologies varies across countries, affecting equitable care. This study aimed to provide a snapshot of current screening and diagnostic practices and to identify gaps and priorities. A cross-sectional online survey was conducted from May to October 2024 across the COST Action HELIOS network participants. The survey, including 21 questions, covered hematological methods, molecular diagnostics, and laboratory practices and policies. Responses were provided directly by centers and summarized descriptively in tables and maps. Responses were received from 38 centers in 20 countries. Hematology remains the diagnostic backbone for hemoglobinopathies, DNA-based testing is widely adopted though advanced genomics are limited, NBS is implemented widely for SCD and thalassemia, carrier reporting practices vary, and genetic modifier testing is emerging. The findings highlight opportunities for cross-country collaboration and targeted capacity-building, identifying centers that could benefit from shared expertise and resources. They can guide strategies to harmonize protocols, strengthen diagnostic capabilities, and support broader implementation of best practices across Europe.

Von Willebrand factor (VWF) is a key coagulation protein, tethering platelets to sites of injury through binding sites for platelet GPIbα and for exposed subendothelial collagen. VWF synthesis occurs in endothelial cells and megakaryocytes, a complex process involving the VWF propeptide, dimerization and multimerization, and glycosylation. Von Willebrand disease (VWD) results from defects or dysfunction in VWF and includes both quantitative and qualitative issues with the VWF protein. VWF is cleaved by ADAMTS13 and ultimately cleared from circulation. While it is clear that VWF plays an important role in clot formation, it may also be important in a number of other areas including angiogenesis. Our knowledge of VWF has come a long way in the 100 years since the first publication by Erik von Willebrand in 1926 thanks to a large number of researchers in the VWF biology field.

Abstract: Outside of pregnancy, placental growth factor (PlGF), is produced by erythroid cells in typically undetectable levels. In pregnancy, PlGF is strongly expressed by the trophoblast layer covering the placental villi. PlGF levels rise progressively due to placental growth, peak at 28 to 30 weeks gestation, and then slowly decline toward term. Low PlGF has emerged as a powerful diagnostic test for preterm preeclampsia. However, its interpretation in context of sickle cell disease (SCD) is potentially confounded by upregulation of cellular PlGF expression in nonpregnant individuals with SCD, and higher third trimester circulating PlGF levels documented in healthy Black compared with White individuals. Primary objectives were to determine the distribution of PlGF at midtrimester in pregnant individuals with SCD compared with unaffected Black controls and to explore the diagnostic accuracy of PlGF in the context of suspected preeclampsia in pregnancies of individuals with SCD. Secondary objective was to examine the relationship between low PlGF and placental disease in pregnancies of individuals with SCD. Pregnant individuals with SCD at Mount Sinai Hospital in Canada (January 2017 to September 2021) with at least 1 PlGF measurement 20+0 to 35+6 weeks gestation, and pregnant Black controls without SCD with suspected preeclampsia or growth restriction, were included in this retrospective study. Maternal and neonatal outcomes were extracted from medical records. For early-onset, but not late-onset, preeclampsia, a PlGF cutoff of <100 pg/mL demonstrated 100% sensitivity and specificity at 20 to 24 weeks gestation. This study is, to our knowledge, the first to demonstrate the utility of PlGF in predicting early-onset preeclampsia in pregnancies of individuals with SCD, allowing clinicians to anticipate and mitigate adverse pregnancy outcomes.

Plasma cell dyscrasias (PCD) are a group of hematological disorders associated with immune dysfunction from underlying disease and/or treatment. With continued circulation of SARS-CoV-2, optimizing and maintaining durable protection in this vulnerable population through vaccination remains important. A prospective cohort study was conducted between August 2021 and January 2023 across 12 sites in Canada to evaluate humoral immunity to COVID-19 vaccination in participants with hematological malignancies. Participants were monitored longitudinally, and finger-prick dried blood spot (DBS) cards were obtained at specific intervals based on vaccination. Serum antibodies against SARS-CoV-2 proteins after the 3rd, 4th and 5th dose were measured by high-throughput ELISA. Differences in anti-spike seropositivity by vaccine dose number and clinical risk factors were analyzed by logistic regression. A total of 262 unique participants with 983 samples were included for analysis, among which 66% were diagnosed with PCD. Analysis of the predicted probability of immunity showed consistently higher proportions of PCD participants with vaccine (anti-S) immunity compared to those with infection-derived (anti-N) immunity throughout the study. While vaccine responses appeared to wane 6 months after dose 3 and, to a lesser extent, dose 4, subsequent doses cumulatively increased anti-S immunity. Seropositivity decreased with anti-CD38 therapy and older age, although receipt of additional vaccine doses significantly improved anti-S immunity. Overall, this study demonstrated that the third and subsequent COVID-19 vaccine doses could safely improve humoral immunity in PCD participants. While anti-CD38 therapy and age reduced seropositivity, antibody responses could still be enhanced with vaccine doses beyond the primary three-dose series.

Abstract: Although obesity is an established modifiable risk factor for multiple myeloma (MM), the influence of obesity on survival among Black patients, among whom obesity and MM are more common, is less clear. We evaluated the association of body mass index (BMI) with progression free survival and overall survival among 834 histologically confirmed patients with newly diagnosed MM (NDMM) enrolled in the Integrative Molecular And Genetic Epidemiology study between 2009 and 2020. We estimated the association of BMI with the risk for progressed disease and all-cause and MM-specific mortality using hazard ratios (HR) and corresponding 95% confidence intervals (CI), calculated from multivariable Cox proportional hazard models adjusted for prognostic factors. When compared with NDMM patients with a normal BMI at diagnosis (18.5-24.9 kg/m2) positive associations with all-cause mortality were observed at the extremes with a 52% and 147% increased risk for death in patients with underweight (BMI, <18.5 kg/m2, HR, 1.52; 95% CI 0.48-4.84) and those with obesity (BMI, ≥30.0 kg/m2, HR, 2.47; 95% CI, 1.26-4.85), respectively. Patients with severe obesity (BMI, ≥35kg/m2) had the highest risk when compared with those with a normal BMI (HR, 3.14; 95% CI, 1.50-6.55), particularly among White (HR, 3.22; 95% CI, 1.30-7.94) and female (HR, 4.17; 95% CI, 1.20-14.47) patients with NDMM; however, the differences by race and sex were not statistically significant (Pinteraction ≥.60). Severe obesity was also associated with an 83% elevated risk for progressed disease among patients with NDMM (HR, 1.83; 95% CI, 1.04-3.24). These findings were similar for MM-specific mortality and highlight weight management as a potential strategy to improve the prognosis of all patients with NDMM.