Neonatal antiphospholipid syndrome (APS) is an exceptionally rare but clinically significant thrombotic disorder associated with antiphospholipid antibodies (aPL) in the neonatal period. Two principal pathogenic mechanisms have been proposed: passive transplacental transfer of maternal antiphospholipid antibodies and de novo neonatal production of aPL. Although approximately 30% of neonates born to aPL-positive mothers exhibit detectable antibodies at birth, thrombotic complications remain exceedingly uncommon. A "second-hit" model involving additional prothrombotic triggers such as infection, perinatal stress, inherited thrombophilia, or vascular catheters likely contributes to thrombogenesis. Available evidence from case reports and small series indicates that arterial thrombosis predominates, particularly neonatal arterial ischemic stroke, while venous thrombosis is less frequent. Diagnosis remains challenging because no validated neonatal-specific classification criteria exist, and interpretation of laboratory findings is confounded by transient maternal antibody transfer. Current diagnostic approaches rely on clinical suspicion, thrombosis confirmation, maternal antibody testing, serial neonatal aPL measurements, and exclusion of other prothrombotic conditions. Management strategies are extrapolated from pediatric and adult APS guidelines, with low-molecular-weight heparin representing the mainstay of anticoagulant therapy in affected neonates. Neonatal APS remains a diagnostic challenge due to its rarity and atypical presentations. Establishing age-specific criteria and long-term neurodevelopmental follow-up is critical for improving clinical outcomes and understanding the prognosis of this early-onset autoimmune condition. This narrative review aims to summarize current evidence regarding the pathophysiology, clinical manifestations, diagnostic challenges, and management of APS-associated thrombosis regarding the distinct neonatal population.

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder with variable disease course, bleeding risk, and treatment response. Artificial intelligence (AI) and machine learning (ML) approaches may address diagnostic and therapeutic challenges by identifying complex patterns across heterogeneous clinical and biological data. A systematic search of PubMed, Embase, Web of Science and Scopus from inception to 13 August 2026 was conducted for studies applying ML to patient-level prediction in primary or disease-associated secondary ITP. Twelve studies were included, eleven from China, applying a range of machine learning approaches. Reported areas under the curve ranged from 0.693 to 0.937, but only two studies reported estimates from independent cohorts. Risk of bias was assessed using PROBAST+AI and eleven of the 12 studies were at high risk of bias. Further development with external validation and prospective evaluation in real-world clinical workflows is needed before these tools can be integrated into clinical practice.

CD19 is expressed on B cells from an early stage and in most B-cell malignancies, but not in hematopoietic stem cells or other normal tissues, thereby making it an attractive therapeutic target for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphomas. While CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapies, monoclonal antibodies, and antibody-drug conjugates are effective therapies for B-cell lymphomas, outcomes in the R/R setting may depend on exposure to prior treatments with the same antigen. There are limited data on the impact of sequencing these treatment modalities. This review highlights recent trial and real-world data focusing on the efficacy and safety of the CD19-targeted agents tafasitamab-lenalidomide and loncastuximab tesirine before and after CAR-T therapy in patients with R/R B-cell lymphoma and addresses the importance of assessing pretreatment target antigen levels as well as identifying common molecular mechanisms of treatment failure. Additionally, this analysis discusses the unmet needs in patients with high-risk disease and the challenges of sequencing these therapeutic strategies, while providing expert clinical practice recommendations to optimize patient outcomes.

The introduction and refinement of tyrosine kinase inhibitors (TKIs) over the past 25 years have resulted in dramatic improvements in life expectancy in individuals with chronic myeloid leukemia (CML). There are now multiple effective and well-tolerated TKIs available, and because most patients will be receiving TKIs for their lifetime, quality-of-life (QoL) considerations are an increasing concern. Patients with CML receiving TKIs have worse QoL than the general population, but TKIs have a generally less negative impact on QoL factors than previously available treatments for CML. Commonly used TKIs (imatinib, nilotinib, dasatinib, bosutinib, ponatinib, asciminib, and olverembatinib) all have positive and negative impacts on QoL, each of which can be impacted by patient preference and priorities, as well as line of therapy. The inclusion of patient-reported QoL outcomes in clinical trials will be vital to helping physicians understand the patient experience of CML and thereby improve disease management.

Non-transfusion-dependent β-thalassemia (NTDT) was historically regarded as a relatively mild form of thalassemia because patients survive without regular transfusion therapy. However, growing evidence has challenged this perception and uncovered substantial morbidity and premature mortality driven by chronic anemia, iron overload, and hypercoagulability. This review examines three major clinical paradoxes that have reshaped the understanding of NTDT: the anemia paradox, whereby transfusion-independent patients may actually benefit from anemia correction; the iron overload paradox, characterized by clinically significant iron accumulation despite minimal or no transfusion exposure; and the hypercoagulability paradox, whereby chronic anemia coexists with a prothrombotic state. These evolving concepts have transformed NTDT from a condition traditionally managed through observation into a disease requiring proactive, risk-based intervention.

Differentiation syndrome (DS) is a life-threatening complication of all-trans retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia (APL). This review synthesizes the current understanding of DS pathogenesis, from PML::RARA degradation to cytokine storm, endothelial injury, and multi-organ damage, alongside diagnostic criteria, severity grading, and risk stratification. We describe a graded treatment framework encompassing prophylactic, therapeutic, and refractory-phase strategies, with particular emphasis on special populations, predictive models, and emerging therapies. Integrating mechanistic insights with risk-adapted, stepwise therapeutic strategies is essential to reduce DS-associated morbidity and mortality, thereby further improving outcomes in this highly curable disease.

Polycythemia vera (PV) is a clonal myeloproliferative neoplasm in which erythrocytosis, although driven by constitutive JAK2 signaling, remains dependent on iron availability. This dependency provides a rationale for therapeutic targeting of the hepcidin-ferroportin axis, whose modulation induces functional iron restriction and constrains erythropoiesis. The hepcidin mimetic rusfertide has shown durable hematocrit control and marked reduction of phlebotomy requirements across phase 2 and phase 3 studies, with predictable changes in systemic iron markers. However, current evidence is largely based on surrogate hematologic endpoints, and whether iron-directed strategies reduce thrombotic risk or modify disease trajectory remains undefined. Within this framework, iron metabolism can be viewed as a downstream, regulatable determinant of erythropoietic output, distinct from but integrated with clonal and inflammatory signaling. This review summarizes biological and clinical evidence on iron homeostasis in PV, focusing on the hepcidin-ferroportin axis and its integration with clone-directed therapies.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults and remains associated with poor overall survival. Beyond genetic factors in the bone marrow (BM) that drive clonal evolution, leukemic progression, immune evasion, and therapy resistance, far less is known about extramedullary (EM) AML, a clinically relevant manifestation characterized by leukemic infiltration of peripheral tissues and frequently associated with adverse outcomes. This review focuses on the spatial heterogeneity of AML, differentiating between BM and EM disease, elucidating how niche components shape leukemic behavior, clonal evolution, and treatment resistance. Furthermore, we review current clinical practice and evidence for the clinical approach, diagnostic management, and treatment of patients with EM AML. At last, we highlight the transformative role of spatial analysis platforms, enabling high-resolution mapping of niche cell and leukemic cell interactions and discuss their potential to improve diagnosis and personalized therapeutic strategies for EM AML.

Therapeutic advances in large B-cell lymphoma (LBCL) are rapidly emerging, but their development and availability are largely concentrated in academic centers. Most patients receive care within community health systems where more limited resources, infrastructure, and access to novel treatments may influence outcomes. This narrative review summarizes current treatment strategies and real-world outcomes for patients with relapsed or refractory (R/R) LBCL. Polatuzumab-based regimens remain standard for high-risk disease in the frontline setting and achieve durable responses; however, approximately 30-40% of patients experience R/R disease. While chimeric antigen receptor T-cell therapy offers curative potential, its use is constrained by logistical, socioeconomic, and geographic barriers. Novel therapies, including bispecific antibodies and antibody-drug conjugates, may improve treatment access in community settings. We also discuss patient- and practice-level factors affecting treatment strategies, unmet clinical needs, and the need for collaboration between community and academic centers in optimizing outcomes for patients with R/R LBCL.

The assessment of minimal residual disease (MRD) is an important prognostic factor in hematologic malignancies, including multiple myeloma (MM). Historically defined as cancer cells undetectable by conventional morphology, MRD is now more appropriately termed measurable residual disease, reflecting its quantitative and clinically actionable nature. Advances in next-generation flow cytometry and next-generation sequencing have enabled detection of disease at sensitivities as low as 10[-6] and even 10[-7], redefining the concept of complete response. Nonetheless, challenges remain regarding assay sensitivity, standardization, and interpretation of results. Achieving MRD-negativity is a strong and independent predictor of improved survival outcomes in both newly diagnosed and relapsed/refractory MM. Consequently, MRD negativity has increasingly been accepted by regulatory agencies as an intermediate endpoint supporting accelerated drug approval. This review summarizes MRD detection methodologies, clinically relevant thresholds, and therapeutic implications, highlighting the paradigm shift from "minimal" to measurable residual disease.

Repeat blood donation may progressively reduce iron stores, although the clinical relevance of biochemical iron depletion in otherwise healthy donors remains debated. This PRISMA-based systematic review and meta-analysis evaluated iron depletion among repeat whole-blood donors and explored factors associated with prevalence estimates. Sixteen studies were included in the qualitative synthesis, and 15 contributed to meta-analyses. The pooled prevalence of iron deficiency, associated with serum ferritin measurement, among regular donors was 14.26% (95% CI: 12.50-16.23). Female donors showed a higher pooled prevalence than male donors, and meta-regression identified sex and serum ferritin cut-off values as significant determinants of prevalence, whereas donation frequency was not independently associated. These findings indicate that iron depletion is common among repeat donors but highly dependent on case definitions and donor characteristics. Serum ferritin testing may support risk stratification, but universal screening should be balanced against feasibility, donor-centered outcomes, and local resources, particularly in low and middle income settings.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon but life-threatening thrombotic microangiopathy (TMA) caused by severe ADAMTS13 deficiency. Early diagnosis and prompt initiation of plasma exchange are critical; however, access to rapid ADAMTS13 testing remains variable across institutions. Clinical tools such as the PLASMIC and French scores assist risk assessment but have limited specificity. Artificial intelligence (AI) has emerged as a potential adjunctive approach to improve diagnostic and prognostic evaluation in TTP. This systematic review evaluated current evidence on AI applications in the diagnosis, risk stratification, and prognostic prediction of TTP. Following PRISMA guidelines (PROSPERO: CRD420261323545), PubMed, Scopus, Embase, and Web of Science were searched through January 9, 2026. Eight studies met inclusion criteria. Reported area under the curve (AUC) values ranged from 0.77 to 0.94. However, all studies were retrospective and relied on internal validation without external or prospective evaluation. Although several models demonstrated good discriminative performance, heterogeneity in study design and target populations limits direct comparison, evidence remains limited, and further externally validated studies are required before clinical implementation.

Infections are a leading cause of morbidity, mortality, and treatment delays in AML and APL. While international guidelines emphasize intensive chemotherapy, they often overlook less intensive regimens, rely on outdated data, and ignore rising MDR infections. A GIMEMA survey across Italian centers revealed significant heterogeneity in antimicrobial prophylaxis, and vaccination practices. An expert panel reviewed 2012-2025 English literature with focus on infections via Delphi/nominal group methods, achieving ≥70% consensus. Prophylaxis with fluoroquinolones showed low agreement (28%) for intensive chemotherapy and venetoclax-based regimens due to no survival benefit, MDR pressure and microbiota disruption; not recommended for low-intensity/palliative care. Posaconazole is advised for intensive chemotherapy with or without FLT3 inhibitors, venetoclax-based regimens, HMA with or without ivosidenib (first 4 cycles), but not APL/palliative care. Antiviral prophylaxis is recommended for APL receiving arsenic trioxide; limited evidence elsewhere. The panel supports universal pneumococcal, influenza, SARS-CoV-2 and herpes zoster vaccination. Overall, these consensus statements aim to harmonize practice and highlight key areas requiring specifically designed prospective studies.