American Journal of Hematology最新文献

Non-severe aplastic anemia (NSAA) is a heterogeneous bone marrow failure syndrome with limited standardized treatment options. Cyclosporine A (CsA) monotherapy often yields suboptimal responses, highlighting an unmet clinical need for more effective therapies. Thrombopoietin receptor agonists (TPO-RAs) have shown satisfying outcomes in severe aplastic anemia (SAA), but data on their frontline use in NSAA remain scarce. We enrolled 54 adults with newly diagnosed NSAA, including 25 with transfusion-dependent NSAA (TD-NSAA) in the prospective, single-arm Phase 2 trial (NCT05660785) to evaluate the efficacy and safety of hetrombopag, an oral TPO-RA, in combination with CsA. At 24 weeks, the overall response rate (ORR) was 81.5% (44/54), comprising 72.2% partial responses and 9.3% complete responses (CRs). Notably, CR and robust partial response (robust PR) were achieved in 46.3% (25/54) of patients. In the TD-NSAA subgroup, the ORR was even higher at 88.0% (22/25) with substantial improvements in hematologic parameters and quality of life. Extending treatment from 16 to 24 weeks increased the CR and robust PR rate from 24.0% to 44.0%. The median time to achieve an initial response was 6, and 14 weeks for robust PR. Adverse events occurred in 35% of patients, predominantly Grade 1 or 2 and were manageable. Importantly, no clonal progression to myelodysplastic syndrome or leukemia was observed. These findings support hetrombopag plus CsA as a potential first-line therapeutic intervention for NSAA, especially in TD-NSAA patients.

Iron deficiency anemia (IDA) is prevalent in pregnancy, yet oral iron therapies are associated with poor adherence and many intravenous (IV) iron formulations require multiple doses for treatment. Ferric derisomaltose (FDI) is a newer IV iron formulation that is safe and efficacious in non-pregnant individuals, yet pregnancy data is lacking. We evaluated the safety, efficacy, and maternal and neonatal outcomes associated with a single 1000 mg IV dose of FDI in pregnant individuals with IDA. We conducted a prospective, single-arm interventional trial of FDI administered in the second or third trimester of pregnancy from January 2024 to July 2025. The primary outcome was efficacy (hemoglobin increase of ≥ 1 g/dL). Secondary outcomes included safety, other hematologic parameters, patient-reported quality of life, and maternal and neonatal outcomes. Among 78 participants enrolled, 75 received FDI. From baseline to delivery, mean hemoglobin increased by 1.3 g/dL, with significant improvements (p < 0.001) in ferritin and transferrin saturation through 6 weeks postpartum. Patient-reported fatigue scores improved (p < 0.001), as did Edinburgh Postnatal Depression Scale scores (p = 0.003). The mean FDI infusion time was 24 min. Cord blood ferritin and hemoglobin values suggested enhanced neonatal iron status. No major infusion reactions or hospitalizations occurred. Minor infusion-related symptoms were uncommon and self-limited: chest tightness (6.7%), flushing (5.3%), mild shortness of breath (4%), urticaria (2.7%), rash (1.3%). Two patients (2.6%) did not complete the infusion due to reaction. These findings support single-dose IV FDI as a safe and effective option for late-pregnancy IDA, meriting further evaluation in larger controlled trials.

Postpartum hemorrhage (PPH) remains the leading cause of preventable maternal mortality despite standard interventions. Recent fibrinogen trials failed to improve outcomes, prompting interest in coagulation factor XIII (FXIII). FXIII functions as "molecular cement," cross-linking fibrin and stabilizing clots. During pregnancy, FXIII activity decreases 20%-30%, with further depletion during PPH. Observational studies show low antepartum FXIII predicts bleeding risk, while ex vivo supplementation restores clot firmness. The SWIFT trial (NCT06481995) represents the first randomized controlled trial evaluating early FXIII supplementation in PPH. Although implementation challenges are significant (diagnostic accessibility, thrombotic monitoring, supply constraints), even modest hemostatic improvements could substantially reduce maternal mortality.

Acute chest syndrome (ACS) is one of the most common severe complications of sickle cell disease (SCD). In recent years, a major role of inflammation and innate immunity has been evidenced, but ACS pathophysiology remains incompletely understood, and therapeutic options are limited. We performed proteomic analysis of induced sputum and tracheal aspirates in eight SCD children during ACS (four intubated and four non-intubated) and in three during vaso-occlusive crisis (VOC) without ACS. Proteomic analysis revealed that one of the main canonical pathways involved during ACS was the complement system. To further investigate its implication, we measured the main components of the complement alternative and terminal pathways in sputum and plasma from SCD children during 27 ACS episodes compared with 16 VOC episodes without ACS. A dramatic increase in the median level of C3a, C5a, sC5b-9, factor B, factor D, properdin, and factor H was observed in the sputum from SCD children during ACS. In the plasma, no significant increase was observed during ACS compared to VOC, except for sC5b-9, whose median level was twofold higher than during VOC but 16-fold lower than the sC5b-9 median level in the sputum during ACS. Also, the C3a/C3 and C5a/C5 ratios were significantly increased in sputum compared to plasma during ACS, reflecting a predominant local pulmonary activation of the complement system compared to systemic activation. Our results reveal the potentially crucial role of complement activation in the lungs during ACS and open new therapeutic perspectives with anti-complement agents for this severe complication of SCD.

Despite advances in therapy, extramedullary disease (EMD) remains an aggressive form of multiple myeloma associated with poor outcomes. Patients with true EMD, in which plasmacytomas have become completely independent of bone, have a particularly poor prognosis. The pathogenesis of EMD is driven by complex mechanisms involving loss of adhesion molecules, heterogeneous genetic and epigenetic changes, and a solid tumor-like architecture within the microenvironment. Although the introduction of advanced imaging techniques and immunotherapy has led to improved detection and more promising outcomes and regimens, respectively, more prospective studies dedicated to true EMD are needed.