European Journal of Haematology最新文献

Objective: To examine global practices for identifying and managing central venous access device (CVAD) complications-catheter-associated bloodstream infection (CABSI), thrombosis, and occlusion-in paediatric cancer care, comparing patterns between high- and other-income countries.

Methods: A cross-sectional international survey was conducted from 2022 to 2023 and analysed 2024 to 2025. Clinicians involved in paediatric CVAD cancer care were recruited through global networks.

Results: A total of 161 respondents from 38 countries completed the complication section, including 102 (63.4%) from high-income and 59 (36.6%) from other-income countries (lower- and upper-middle income). For CABSI, blood culture was the main diagnostic method (122 [75.8%]; high-income: 87 [85.3%], other-income: 35 [59.3%]). Differential time to positivity was more often reported in other-income settings (33 [55.9%] vs. 35 [34.3%]), who also more frequently initiated antibiotics based on nonspecific or immediate criteria. CABSI treatment varied, with intravenous antibiotics (68 [60.7%]) and catheter removal (47 [42.0%]) most reported. For thrombosis, anticoagulation before line removal was common (88 [54.7%]), and alteplase use was higher in high-income countries (76 [74.5%] vs. 19 [32.2%]). Thrombolytic agents were the most reported treatment for occlusion (103 [64.0%]), especially in high-income countries (77 [75.5%] vs. 26 [44.1%]).

Conclusions: CVAD complication management varies by country income level, highlighting the need for context-adapted guidelines, training, and equitable access to key resources.

Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a dNTPase that regulates intracellular nucleotide pools, preserves genomic stability, and mediates intrinsic antiviral immunity. While its role in adult hematologic malignancies is established, its implications for pediatric leukemia-particularly acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)-remain underexplored. This review integrates transcriptomic, protein interaction, and immune correlation analyses to examine the dual role of SAMHD1 in pediatric hematological malignancies: as an antiviral restriction factor that impairs lentiviral gene therapy and as a therapeutic barrier that limits the efficacy of nucleoside analog-based chemotherapy. We compare emerging transduction-enhancing strategies, including Vpx delivery, SAMHD1 inhibition, and lipid nanoparticles, and evaluate their pediatric applicability. A conceptual schematic highlights the translational challenges unique to the developing immune and hematopoietic systems. Limitations of commonly used cellular models, such as THP-1 cells, are discussed alongside the need for pediatric-specific preclinical tools. We conclude by outlining a clinical translation roadmap and emphasizing the urgency of validating SAMHD1-targeted strategies in pediatric trials to ensure their safety, efficacy, and integration into future treatment paradigms.

Momelotinib, a novel JAK1/2 inhibitor with inhibitory activities on activin A receptor type I, has shown breakthrough clinical efficacy in patients with myelofibrosis (MF) and anemia, a disease-related manifestation of challenging management. In this retrospective real-life multicenter Italian study, we investigated the safety and efficacy of momelotinib in a cohort of 39 consecutive MF patients, regardless of prior therapy. The median duration of treatment was 7 months, and the overall response rate was 56% in transfusion-dependent patients and 46% in the transfusion-independent group. At 24 weeks of treatment, a hemoglobin increase > 1.5 g/dL was observed in 26% of patients, and constitutional symptom improvement was reported in 51% of cases, with a spleen volume reduction > 35% in 28%. Therapy discontinuation occurred in 18% of patients, with only one leukemia progression and three deaths during follow-up. The safety profile was similar to that reported in clinical trials, with most toxicities of grade I-II. In conclusion, our real-life results support the use of momelotinib as an effective and safe therapeutic option for heavily pre-treated, cytopenic MF patients in real-world clinical practice.

Mantle Cell Lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma characterized by the hallmark t(11;14)(q13;q32) translocation, resulting in cyclin D1 overexpression. Predominantly affecting elderly males, MCL exhibits marked clinical and biological heterogeneity, ranging from indolent SOX11-negative variants to highly proliferative blastoid variants. Despite initial responsiveness to chemoimmunotherapy, relapse is frequent, and median overall survival remains limited. Aberrant B-cell receptor (BCR) signaling—mediated by kinases including Bruton's tyrosine kinase (BTK)—plays a central role in MCL pathogenesis. BTK inhibitors (BTKis) such as ibrutinib (as monotherapy or combined with R-CHOP/R-DHAP), acalabrutinib (with rituximab and bendamustine), and pirtobrutinib have significantly improved outcomes of relapsed/refractory disease. However, their efficacy is challenged by resistance mutations (e.g., BTK C481S) and off-target toxicities. Next-generation reversible BTKis represent an important advance, offering activity in the setting of resistance and improved tolerability. Resistance is further sustained by the tumor microenvironment through stromal support and immunosuppressive cellular interactions. Consequently, combination strategies incorporating BTKis with BCL-2 inhibitors, monoclonal antibodies, and cellular therapies are being investigated to enhance response depth and durability. In parallel, biomarker-driven approaches and precision-medicine strategies are emerging to personalize disease monitoring and treatment selection. Collectively, these developments underscore the evolving role of BTK inhibition within broader immune-based and targeted treatment paradigms in MCL.