American Journal of Hematology最新文献

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.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL in the Western Hemisphere. It comprises a heterogenous group of lymphomas, with different biology and clinical prognoses. R-CHP remains the backbone of therapy, and frontline therapeutic options in fit patients are pola-R-CHP and R-CHOP, whereas elderly or frail/unfit patients may be treated with R-mini-CHOP or palliation. Frontline trials aim to improve outcomes for patients with high-risk disease utilizing R-CHOP + novel agents, CAR-T, and bispecific antibodies. Trials in the elderly/unfit population are minimizing and omitting chemotherapy. Risk-adapted approaches targeting cell of origin (COO) and utilizing interim PET imaging or ctDNA to guide therapy escalation or deescalation remain under investigation. Second line therapy curative-intent approaches include CAR-T or autologous stem cell transplantation, depending upon timing of disease progression after first-line therapy. In the relapsed/refractory setting, there has been a rapid growth in the therapeutic armamentarium, including bispecific antibody combinations with chemotherapy, bispecific antibodies with antibody-drug conjugates, and brentuximab vedotin + lenalidomide + rituximab. Multiple novel trials are further advancing the field away from chemotherapy including targeted therapy-antibody combinations, new bispecific antibodies and bispecific antibody combinations, immunomodulatory agents, and cellular therapy. In this review, we summarize recent data and discuss ongoing efforts to improve the management of DLBCL.

It is an exciting era in leukemia owing to the development of novel targeted therapies and advances in genomics, pathophysiology, prognostication, and monitoring (e.g., highly sensitive measurable residual disease assays). Currently, most leukemias are effectively treated with immunotherapies (highly effective monoclonal antibodies targeting CD19 [blinatumomab], or CD22 [inotuzumab ozogamicin]), BCR::ABL1 tyrosine kinase inhibitors (TKIs; e.g., dasatinib, ponatinib), Bruton TKIs (e.g., ibrutinib, acalabrutinib), BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, olutasidenib, and enasidenib), FLT3 inhibitors (e.g., midostaurin, quizartinib, and gilteritinib), menin inhibitors (revumenib, ziftomenib), and chimeric antigen receptor T-cell therapies. These novel agents and their judicious use in combination strategies have transformed the treatment landscape across all leukemias, significantly increased survival and quality of life for patients, and attenuated the need for intensive chemotherapy and hematopoietic stem cell transplantation. Leukemia subtypes, such as Philadelphia-positive acute lymphoblastic leukemia (incurable before 2000) and chronic lymphocytic leukemia (previously considered incurable) with historically dire prognoses were recently transformed to favorable leukemias with 5- and 10-year survival rates of 80+% and 90+%, respectively. The BCR::ABL1 TKIs resulted in normal life expectancy in chronic myeloid leukemia. Notable advances have also been made in AML with targeted therapies, although some subsets (older/unfit patients for intensive chemotherapy, complex karyotype, TP53-mutated, KMT2A-rearranged, and treated secondary AML) still have unfavorable outcomes. Herein, we provide a high-level overview of prominent clinical developments across all leukemias. In contemporary times, harnessing the benefits of novel targeted therapies and the evolving treatment landscape bolster the optimistic view that most, if not all, leukemias are curable.

Disease overview: Marginal zone lymphoma (MZL) is a heterogeneous group of indolent mature B-cell neoplasms with classically three major subtypes: nodal, splenic, and extranodal MZL of mucosa-associated lymphoid tissue (MALT).

Diagnosis: Diagnosis and disease evaluation of MZL is further advanced by the use of genomic testing and PET/CT with emerging evidence for the use of circulating tumor DNA. The RECLASS classification system proposed a hierarchical approach to classifying MZL while the FIL-NF10 investigators introduced a fourth MZL subtype, disseminated MZL. Though the prognosis of MZL varies between subtypes and stages, the MZL IPI and FLIPI24 indices can be used for prognostication.

Treatment: Frontline treatment of MZL varies between localized disease and advanced-stage diseases. The former favor the use of local therapies such as radiotherapy and anti-microbial in certain subtypes with a selective role of rituximab monotherapy. The latter requires systemic immunotherapy ± chemotherapy with emerging data for cytotoxic-free and covalent Bruton tyrosine kinase inhibitor (cBTKi)-based regimens. cBTKi and immunomodulators are established in relapsed/refractory MZL, while data for antibody-drug conjugates, T-cell engagers, and potentially CAR T-cell therapies are maturing.