American Journal of Hematology最新文献

Anthracyclines are an essential component of induction therapy for acute myeloid leukemia (AML), but their optimal dosing and the associated risk for cardiotoxicity remain under debate. The DaunoDouble trial compared daunorubicin at 60 (Dauno60) versus 90 mg/m² (Dauno90) in combination with cytarabine (100 mg/m² for 7 days) in newly diagnosed AML patients aged 18–65 years. Cardiac function was assessed by left ventricular ejection fraction (LVEF) and cardiac biomarkers (high-sensitivity troponin T [hsTnT], NT-proBNP) before treatment and on Day 15 in 317 randomized patients. Median LVEF declined significantly from 65% [IQR 60%–68.5%] to 61% [IQR 58%–67.8%] across all patients (p < 0.01), without significant differences between treatment arms. NT-proBNP levels measured after induction therapy correlated negatively with LVEF at the same time point (ρ = −0.24, p = 0.02), but did not change significantly during induction—neither between Day 1 and 15 nor between treatment arms. HsTnT levels increased significantly from 5 [IQR 4–8] to 8 ng/L [IQR 6–14] across all patients (p < 0.01), with higher post-induction values in the Dauno90 group (9.5 ng/L [IQR 7–14]) compared to Dauno60 (7 ng/L [IQR 5–14]; p < 0.01). In exploratory subgroup analyses, post-induction hsTnT levels were also significantly higher in patients with obesity and arterial hypertension. These findings provide evidence of a dose-dependent cardiotoxic effect of daunorubicin, already apparent at standard induction doses, and underscore the importance of early cardiac monitoring. Long-term follow-up will be essential to determine the clinical significance of these early changes.

Trial Registration: ClinicalTrials.gov identifier: NCT02140242

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.