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.
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.
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.
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.
Patient blood management (PBM) is a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient’s own blood, while promoting patient safety and empowerment. Globally, PBM guidelines have been developed locally in several countries and societies based on the expertise and resources of each. In Lebanon, the presence of prevalent iron deficiency anemia and hemoglobinopathies, together with scarce resources and economic constraints, necessitate generating local PBM guidelines to improve outcomes, cost-effectiveness, and safety. The following guidelines were established based on the recommendations of a multidisciplinary taskforce committee of Lebanese experts from different medical specialties including hematology, obstetrics, gynecology, surgery, anesthesiology, critical care, and pediatrics. The recommendations provide key practice points for the optimization of red blood mass, minimization of blood loss, and optimization of tolerance to anemia in different settings, supported by evidence from international guidelines in the field of PBM.
Immune thrombocytopenia (ITP) remains therapeutically challenging in patients with refractory or relapsed disease despite expanding second-line options. Increasing evidence implicates autoreactive plasma cells in treatment resistance, providing a rationale for anti-CD38 therapy. In this review, we place anti-CD38 therapy in ITP within its broader biological and emerging clinical context, while formally synthesizing the published daratumumab literature through a scoping review. The available evidence suggests that anti-CD38 therapy, particularly daratumumab, may induce rapid platelet responses and durable remissions in a subset of heavily pretreated patients. However, the current evidence base is heterogeneous and largely uncontrolled, spanning different patient populations, treatment settings, response definitions, and concomitant therapies. Safety reporting is inconsistent, although infusion-related reactions, infections, and hypogammaglobulinemia are recurring concerns. Anti-CD38 therapy represents a promising investigational approach for refractory ITP, with daratumumab currently supported by most robust clinical data; however further prospective studies are needed to better define its optimal use, safety profile, and durability of response.
Platelets are small anucleate blood cells derived from megakaryocytes, essential for hemostasis and involved in thrombosis, inflammation, immunity, and tissue repair. Their production depends on tightly regulated processes of megakaryopoiesis and thrombopoiesis. Inherited platelet disorders (IPDs) are a heterogeneous group of rare diseases caused by germline variants affecting megakaryocyte development and maturation, platelet production, structure, or function. These include inherited thrombocytopenias, characterized by reduced platelet counts, and inherited platelet function disorders, caused by qualitative platelet defects. Depending on the underlying genetic alteration, patients may present with bleeding, syndromic manifestations, or predisposition to hematologic malignancies. Recent advances in platelet biology and molecular genetics have improved diagnosis, personalized management, and genetic counseling. In parallel, IPDs have emerged as valuable human models for understanding the molecular mechanisms regulating platelet biogenesis and function in health and disease.
Artificial intelligence (AI) is transforming morphological assessment in hematologic malignancies by enabling automated cell classification, detection of disease-specific features, and prediction of genetic alterations from blood and bone marrow smear images. Deep learning models have achieved expert-level performance in identifying malignant patterns, uncovering morphologic-molecular associations, and providing patient-level diagnoses through multiple instance learning approaches. This review summarizes recent advances in AI-driven morphological analysis across myeloid and lymphoid neoplasms, emphasizing their impact on diagnosis and disease classification. We further examine emerging evidence linking image-derived features, such as nuclear texture, cytoplasmic granularity, and spatial cell organization, to molecular and prognostic variables. In addition, we discuss enabling technologies, including virtual staining and interpretability methods, that support clinical integration. Finally, we address key challenges, including data heterogeneity, the need for prospective validation, and interdisciplinary collaboration. AI-powered, explainable morphological analysis has the potential to advance precision hematology and personalized patient management.
Advancements in the treatment of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) (AYA-ALL) have resulted in significant survival improvements over the last decade, however AYA patients continue to face worse outcomes compared to the pediatric population. Tailoring treatments to address these differences, alongside refining supportive care and psychosocial interventions, is essential to improving the prognosis and quality of life for this unique patient population. Here we review the multiple challenges faced when treating AYA-ALL including disease biology, treatment optimization, psychosocial issues and behavioral and life stressors.
Classic Hodgkin lymphoma (cHL) is highly curable, yet its diagnosis, risk stratification, and response assessment remain susceptible to significant uncertainty. Hodgkin Reed–Sternberg (HRS) cells are rare and embedded within a heterogeneous inflammatory tumor microenvironment (TME), creating diagnostic ambiguity in small biopsies. Moreover, FDG PET/CT shows notable inter-reader and inter-institutional variability. At the same time, key biologic determinants of outcome, including TME architecture and immune evasion mechanisms, have proven challenging to standardize as clinically actionable biomarkers. This narrative review synthesizes emerging evidence on the use of artificial intelligence (AI) to address these limitations across three domains: (i) histopathologic diagnosis and refinement of gray-zone entities, (ii) PET/CT-based prognostication and response assessment, and (iii) computational interrogation of the TME. We summarize retrospective and proof-of-concept studies leveraging digital pathology, radiomics, and multimodal modeling, with attention to dataset characteristics, validation strategies, and clinical endpoints. Across applications, most AI models are trained on single-center retrospective cohorts, lack external validation, and exhibit substantial risk of bias, limiting conclusions about generalizability and clinical utility. Current evidence indicates that AI is most advanced as a decision-support and standardization tool—facilitating HRS cell quantification, harmonizing PET-derived features, and enabling reproducible spatial immune profiling—rather than as an autonomous diagnostic or prognostic system. Real-world translation will require large multicenter datasets, clearly defined clinical use-cases, rigorous bias and performance assessment, external validation, and adherence to emerging reporting frameworks (TRIPOD-AI, QUADAS-AI, PROBAST-AI). We outline practical steps needed to progress AI in cHL from technical feasibility toward clinically reliable implementation.
Autoimmune cytopenias (AICs) arise from pathogenic autoantibody-mediated destruction of blood cells. Current treatments often fail to achieve durable remission, necessitating long-term treatment including immunosuppression and exposure to treatment-related toxicities. Insights into B cell biology demonstrate the central role of autoreactive B cells and plasma cells in sustaining disease activity and relapse, providing a rationale to achieve sustained, treatment-free remissions through "immune reset". This review summarizes the current understanding of immune reset in AICs and examines clinical data for depletion strategies targeting distinct stages of B cell maturation. We compare therapeutic modalities across monoclonal antibodies, bispecific T cell engagers (TCE), and chimeric antigen receptor (CAR) T cells. The depth and breadth of depletion, kinetics of immune reconstitution, and treatment-related risks are critical determinants of long-term outcome potential and individualized risk-benefit assessment. Collectively, these advances support a potential paradigm shift from chronic immunosuppression towards durable remissions off therapy with time-limited therapeutic interventions.
This systematic review aimed to identify clinical practice guidelines (CPGs) for platelet transfusion in non-surgical and non-traumatic care settings, and appraise their methodological quality. We searched three databases and eight grey literature sources for CPGs published between 2015 and 2025. Methodological characteristics of the literature review and guideline development process were charted. Data on the targeted population, transfusion indication, and the direction and strength of the recommendations were extracted. CPG methodological quality was assessed using the AGREE II Rigour of Development domain. We identified 30 CPGs, including 89 recommendations. Platelet transfusion recommendations were summarized in interactive evidence maps. These tools can aid clinicians seeking evidence-based guidance to support clinical decision making, and highlight priorities for future research. AGREE II assessment indicated good to poor methodological quality of the included CPGs. This work underscores the importance of applying a rigorous and transparent methodology to ensure the development of reliable CPGs.
Autoimmune hemolytic anemias comprise warm AIHA (wAIHA), due to IgG autoantibodies reacting at body temperatures, and cold agglutinin disease (CAD), due to IgM reacting in cold and strongly activating complement. The diagnosis, based on the direct antiglobulin test (DAT), is sometimes difficult since the DAT is performed with various methods with different sensitivity and specificity. Novel investigation includes DAT by flow-cytometry that helps the diagnosis of DAT-negative forms and in-deep bone marrow examination that aims to understand AIHA pathogenesis. Therapy is different in wAIHA and CAD: in the former, steroids represent the first-line, followed by rituximab, splenectomy and immunosuppressors, while in the latter rituximab is recommended frontline, followed by rituximab plus chemotherapy or the complement inhibitor sutimlimab. Plasmacell-directed therapies (bortezomib and daratumumab) may be administered in refractory patients. Several new therapies are under investigation, including inhibitors of Bruton's and spleen tyrosine kinases, neonatal Fc receptor, and cytokines, and bi-specific monoclonal antibodies.
