INTRODUCTION:Nilotinib has been shown to be highly effective for the treatment of chronic myeloid leukemia (CML) and advancing patients to treatment-free remission (TFR). However, its efficacy and safety may be compromised by nonadherence due to its twice-daily fasting requirement. A reduced-dose nilotinib tablet may address these limitations. AREAS COVERED:PubMed search (1966 to July 2026) for papers related to the pathology, etiology, and treatment of CML, pivotal clinical trials and real-world studies for tyrosine kinase inhibitors (TKI) focusing on nilotinib, and recent pharmacokinetic and adherence research, including data on the nilotinib tablet. Nilotinib achieves more rapid deep molecular responses and TFR rates vs imatinib. Nilotinib also offers efficacy comparable to dasatinib, bosutinib, and asciminib. Twice-daily administration with fasting requirements for nilotinib contribute to real-world nonadherence, which often remains undetected by healthcare professionals, undermines TFR goals, and may increase the risk of cardiovascular adverse events. EXPERT OPINION:The nilotinib tablet provides bioequivalent exposure to nilotinib capsules under overnight fasted conditions at a reduced dose without a food effect on absorption. It offers a solution to the complex dosing regimen for nilotinib capsules, potentially supporting better adherence and outcomes with reduced concern about food-related inconvenience.
BACKGROUND:Accelerating research advancing health equity for the entire inheritable bleeding disorders community requires a new approach. It must be firmly rooted in health equity, diversity, and inclusion (HEDI) and center the knowledge of people living with inheritable bleeding disorders, the Lived Experience Experts (LEEs). The National Bleeding Disorders Foundation charged seven multidisciplinary working groups (WGs) with developing a National Research Blueprint (NRB) for this Bleeding Disorders Research Collaborative (BDRC). RESEARCH DESIGN AND METHODS:The Infrastructure and Workforce WGs, in collaboration with the HEDI and LEE WGs, met virtually to develop recommendations for BDRC operationalization. RESULTS:A progressive network of elements and processes capacitating diverse community-prioritized research ideas into successfully completed BDRC projects is proposed. Essential components for launch, iterative evolution, effective conduct, and accountability are described. Sharing resources and expertise and embedding research in inheritable bleeding disorders care will create synergistic efficiencies. Education and training to grow and empower interdisciplinary research teams, including LEEs and HEDI champions as valued members, are detailed. Shared leadership integrating LEE and HEDI expertise throughout will provide dynamic governance. CONCLUSIONS:BDRC infrastructure and workforce development must start small and grow iteratively in partnership with the many organizations that share its vision of health justice.
BACKGROUND:The U.S. National Bleeding Disorders Foundation charged seven multidisciplinary working groups (WGs) with developing a National Research Blueprint (NRB) for a novel Bleeding Disorders Research Collaborative (BDRC) firmly rooted in health equity, diversity, and inclusion (HEDI) and centering the knowledge of people living with inheritable bleeding disorders, the Lived Experience Experts (LEEs). RESEARCH DESIGN AND METHODS:The HEDI, LEE, Community Engagement, and Policy WGs met virtually to develop recommendations for BDRC design and operationalization. RESULTS:Engaging, empowering, and elevating guidance and practices to ground BDRC research and operations in HEDI principles are detailed. The full potential of integrating LEE knowledge throughout research conduct and BDRC governance is explored, potential barriers identified, and solutions proposed. Investing in relationships, trust, and transparency are elaborated as keys to meeting community members wherever they are on a research engagement continuum and facilitating desired progression. Expert advocacy and partnerships will be essential to securing policies and funding supporting the BDRC. CONCLUSIONS:The proposed community-inspired BDRC has the potential to catalyze a paradigm shift in U.S. inheritable bleeding disorders research and ultimately advance health equity for all.
BACKGROUND:Inheritable bleeding disorders (BDs) research has not historically reflected the diversity or needs of the entire community. The National Bleeding Disorders Foundation charged seven multidisciplinary working groups (WGs) with developing a U.S. National Research Blueprint (NRB) for a Bleeding Disorders Research Collaborative (BDRC) inspired by Lived Experience Experts (LEE) and grounded in health equity, diversity, and inclusion (HEDI). RESEARCH DESIGN AND METHODS:The Research and Development and Workforce WGs, in collaboration with the HEDI and LEE WGs, met virtually and in-person to develop recommendations for BDRC operationalization. RESULTS:An agenda of 327 feasible research priorities spanning nine main topics, each with four to six scientific areas of interest is proposed. It captures the hope that new diagnostic and therapeutic technologies and innovative research approaches enriched by LEE and HEDI expertise may advance health equity for all. Key constraints of time, expertise, funding, resources, and diversity were identified as important barriers to the capacitation of the interdisciplinary research workforce required to successfully achieve this research. Mentorship, partnership, training and education, collaboration, and advocacy solutions to these barriers are proposed. CONCLUSIONS:The BDRC seeks to capacitate a diverse, inclusive, collaborative workforce, and effectively accelerate research that advances health equity for all.
INTRODUCTION:The National Research Blueprint proposes a Bleeding Disorders Research Collaborative (BDRC) centering people, priorities, and principles. Driven by community-identified unmet needs, the National Bleeding Disorders Foundation (NBDF) coordinated a five-year co-creation endeavor engaging a multitude of diverse stakeholders. AREAS COVERE:Seven multidisciplinary working groups built upon previous NBDF State of the Science Summit conclusions to draft a blueprint of the research and development, workforce, infrastructure, community engagement, policy, Lived Experience Expert, and health equity, diversity, and inclusion elements of the novel research collaborative. Implementing their proposal will engage the entire inheritable bleeding disorders community mobilizing all its expertise, resources, champions, and partners. Education, training, and mentorship will be key in empowering diverse research teams working together in respectful partnership. EXPERT OPINION:The proposed BDRC has the potential to transform inheritable bleeding disorders research through its collaborative infrastructure centering lived experience expertise and health equity, diversity, and inclusion to efficiently advance health justice for the entire community.
INTRODUCTION:Mantle cell lymphoma is a biologically heterogeneous B-cell lymphoma characterized by highly variable clinical outcomes. This review discusses the evolution of risk stratification and emerging treatment approaches, highlighting the need for personalized and risk-adapted treatment strategies. AREAS COVERED:This review examines the evolution of risk stratification in mantle cell lymphoma, from clinical prognostic models to molecular and dynamic biomarkers, such as TP53 mutation, genomic profiling, minimal residual disease, and circulating tumor DNA. Emerging therapeutic approaches, including targeted combinations, chemotherapy-free regimens, cellular immunotherapy, and minimal residual disease-driven strategies, are critically reviewed. The literature search was conducted using PubMed (MEDLINE) and updated through June 2026. EXPERT OPINION:Risk stratification is increasingly shifting from traditional clinical models toward integrated biological and genomic models that better capture disease heterogeneity and support personalized and risk‑adapted treatment. Emerging evidence supports novel chemo-free targeted combinations, particularly for high-risk patients while further research is needed to refine treatment selection and identify additional determinants of prognosis and treatment resistance in lower‑risk disease.
INTRODUCTION:Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder with heterogeneous risk of progression to active multiple myeloma. Most patients are managed with observation, but selected high-risk patients may benefit from early intervention. Daratumumab, an anti-CD38 monoclonal antibody, has recently emerged as a promising therapeutic option in this setting. AREAS COVERED:This review summarizes the biological rationale for targeting CD38 in SMM, including the immune-mediated and direct antimyeloma effects of daratumumab. It discusses current approaches to SMM risk stratification, with an emphasis on the Mayo 20/2/20 and IMWG 2020 models. The review also covers clinical evidence supporting daratumumab, particularly the phase III AQUILA trial, which showed that fixed-duration subcutaneous daratumumab delayed progression to active multiple myeloma compared with active monitoring. Ongoing studies of daratumumab-based combinations and other anti-CD38 strategies are also discussed. EXPERT OPINION:Daratumumab marks an important step toward early, disease-modifying therapy for high-risk SMM. Future strategies may include triplets, quadruplets, and immune-based combinations to achieve deeper responses and a possible functional cure. However, these approaches must be balanced against the risks of toxicity, infection, immunosuppression, and overtreatment. Precise patient selection remains the key challenge.
BACKGROUND:Liver stiffness measurement (LSM) assessed by transient elastography (TE) is a validated noninvasive tool for staging liver fibrosis. This cross-sectional study investigated the determinants of LSM in a well-managed cohort of patients with transfusion-dependent β-thalassemia (TDT). RESEARCH DESIGN AND METHODS:We included 163 TDT patients (42.06 ± 9.07 years; 46% females) enrolled in the Extension-Myocardial Iron Overload Network. All participants underwent magnetic resonance imaging (MRI) for iron quantification within three months of TE. Endocrine complications were defined according to established clinical criteria. RESULTS:Mean LSM was 6.78 ± 3.49kPa, and advanced fibrosis (LSM ≥8kPa) was identified in 23.3% of patients. LSMs were significantly higher in patients with chronic hepatitis C virus (HCV) infection compared with those who were never infected or had cleared HCV, and in patients with at least one endocrinopathy compared with those without. LSMs correlated positively with body mass index and with mean serum levels of ferritin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT). No association was observed between LSM and MRI-derived liver iron concentration. Multivariate regression analysis identified chronic HCV infection, AST, and GGT as independent predictors of LSM. CONCLUSIONS:Chronic HCV infection and markers of hepatocellular injury were the main determinants of liver stiffness, underscoring the multifactorial nature of liver fibrosis in TDT.
BACKGROUND:Sepsis-induced coagulopathy (SIC) is a severe complication of sepsis with high mortality. The lactate dehydrogenase-to-albumin ratio (LAR), a composite marker of cell injury and inflammation, is associated with sepsis prognosis, but its role in SIC remains unclear. RESEARCH DESIGN AND METHODS:Data from 1,500 SIC patients in the Medical Information Mart for Intensive Care database were used. The primary outcome was 30-day all-cause mortality and the secondary outcome was 90-day mortality. Kaplan-Meier curves, Cox regression, restricted cubic splines, and subgroup analyses were used. RESULTS:Compared with the low-LAR group, medium- and high-LAR groups had higher 30- and 90-day mortality rates (p < 0.001). The fully adjusted Cox model showed positive correlations of ln(LAR) with 30-day (HR = 1.17, 95% CI: 1.03-1.31, p = 0.013) and 90-day mortality rates (HR = 1.17, 95% CI: 1.04-1.30, p = 0.007). The relationship between ln(LAR) and 30-day mortality rate was nonlinear (P-non-linear = 0.007), with an inflection point at 4.57. An interaction was observed for dobutamine therapy (P-interaction = 0.03). CONCLUSIONS:LAR is associated with poor prognosis in patients with SIC, especially once ln(LAR) surpasses 4.57.
INTRODUCTION:The approval of (GT) for sickle cell disease (SCD) marks a major milestone in hematology, offering curative potential without the need for a matched sibling donor. Yet early real-world uptake has been slow. This delay in integration is likely due to complex intertwined barriers that require further elucidation. AREAS COVERED:We conducted a structured review of the literature, searching PubMed/MEDLINE, Embase, and ClinicalTrials.gov through April 2026 for evidence on the economic, institutional, clinician-level, and patient-level barriers limiting adoption of GT for SCD, as well as global disparities in access. EXPERT OPINION:Slow uptake of GT reflects the expected challenge of introducing a complex, resource-intensive intervention into a fragmented care system. Addressing these barriers requires coordinated efforts from payers, institutions, clinicians, and patient communities. Without deliberate structural reform, GT risks widening existing health disparities rather than alleviating them.
INTRODUCTION:Osteolytic bone disease is the hallmark of multiple myeloma (MM) patients caused by an excessive osteoclast activation and impaired osteoblast function. It occurs in up to 80-90% of patients at the diagnosis or during the disease. Osteolytic lesions lead to skeletal-related events (SREs) such as pathological fractures, severe bone pain or spinal cord compression. Consequently, SREs are associated with reduced quality of life and potentially decreased survival. AREAS COVERED:Bone-targeted therapy with bisphosphonates (BPs) including zoledronic acid or pamidronate has long been the standard of care, showing a significant effect on the prevention of the SREs; however, renal toxicity may limit their use. Denosumab, a monoclonal antibody anti-RANKL has been approved for the treatment of bone disease also in patients with renal insufficiency. The efficacy and the possible toxic effects of these drugs are discussed in this review balancing effective treatment with preventing SREs development in MM patients. EXPERT OPINION:Bone modifying agents (BMAs) including BPs and denosumab are effective in the prevention of SREs in MM patients. Overall, these drugs are manageable with a low incidence of side effects. The effect of BMAs on MM patient survival in the era of the new drugs is still debated.
INTRODUCTION:ADAMTS13, a crucial enzyme in hemostasis, that specifically cleaves von Willebrand factor (VWF), plays a pivotal role in the pathogenesis and diagnosis of thrombotic thrombocytopenic purpura (TTP), a microcirculatory form of thrombotic microangiopathy (TMA). Its deficiency leads to the accumulation of ultra-large VWF multimers, causing microvascular thrombosis. Understanding and measuring ADAMTS13 activity are essential for diagnosis and management of TTP and other thrombotic diseases associated with ADAMTS13 deficiency. AREAS COVERED:This review explores the evolution of ADAMTS13 assays from labor-intensive methods to rapid, automated platforms. It examines congenital and acquired ADAMTS13 deficiencies, highlighting diagnostic strategies and therapeutic interventions. A comprehensive literature search was conducted between September 2025 and June 2026 using PubMed and GoogleScholar, focusing on recent advancements and extending to foundational studies when necessary. EXPERT OPINION:The integration of rapid ADAMTS13 testing has the potential to improve clinical decision-making by shortening diagnostic uncertainty and supporting earlier differentiation of TTP from other TMAs. Despite progress, challenges remain in assay standardization, sensitivity, and interpretation. Future developments may include point-of-care technologies and conformation-sensitive assays to enhance relapse prediction and monitoring. Collaboration between clinicians and laboratories is crucial to optimize patient outcomes and advance the field of ADAMTS13 diagnostics.
INTRODUCTION:Acute chest syndrome (ACS) is the leading cause of death and a major cause of hospitalization in sickle cell disease (SCD). Despite advances in care, ACS remains a life-threatening complication with no FDA-approved targeted therapy for established disease. This review examines the current evidence base for supportive care, preventive strategies, and emerging therapies. AREAS COVERED:We conducted a comprehensive literature search of PubMed, clinical trial registries, and major hematology conferences through December 2025. This review synthesizes data on supportive measures (fluid management, analgesia, antibiotics, oxygen/respiratory support, and transfusion), preventive interventions (incentive spirometry and nocturnal bilevel positive airway pressure), disease-modifying therapies (hydroxyurea, L-glutamine), investigational agents (therapeutic anticoagulation, inhaled nitric oxide, and pyruvate kinase activators), and recently approved gene therapies (exagamglogene autotemcel, lovotibeglogene autotemcel). Pathophysiology, biomarkers, and barriers to implementation in resource-limited settings are also addressed. EXPERT OPINION:Supportive care has reduced ACS mortality but remains reactive and non-curative. Hydroxyurea remains first-line prevention, while L-glutamine offers a complementary option. Gene therapies represent a paradigm shift toward durable or potentially curative prevention of ACS. With expanding access to these therapies, ACS may become a rare complication of SCD, although significant barriers related to cost, infrastructure, and global equity must be overcome.
INTRODUCTION:Myelofibrosis (MF) is a heterogeneous myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, cytopenias, and risk of leukemic transformation. As therapeutic options expand, treatment discontinuation and sequencing are increasingly recognized as clinically relevant determinants of patient outcomes. AREAS COVERED:A literature search was performed using PubMed/MEDLINE and major hematology conference proceedings (ASH and EHA), covering publications from January 2010 through February 2026. This review discusses mutation-informed risk stratification, current and emerging JAK inhibitor treatment sequencing strategies, and practical approaches to treatment discontinuation and therapeutic transition in MF. EXPERT OPINION:Optimizing outcomes in MF increasingly requires proactive transition management rather than reactive treatment interruption. Early identification of treatment failure, phenotype-guided therapeutic sequencing, and integration of molecular risk assessment may improve long-term disease management and could contribute to better clinical outcomes, although prospective confirmation remains necessary.
