Expert Review of Hematology最新文献

Introduction: Waldenström's Macroglobulinemia is a rare chronic, incurable low-grade lymphoma with an increasing number of targeted agents available. Selecting efficacious treatment may reduce adverse events related to inadequate responses.

Areas covered: This review focusses on therapies in WM and management of adverse events. The role of genetic alterations (MYD88, CXCR4, TP53) and prognostic scores are discussed. Data pertaining to efficacy and adverse events are described alongside investigation for IgM-associated disorders.

Expert opinion: Apparent treatment-emergent adverse events require particular attention, as these may be a manifestation of an IgM-associated disorder particularly systemic AL amyloidosis, IgM associated neuropathy or disease progression. Treatment 'failure' may be through resistance or dose-limiting toxicities. Post Bruton's tyrosine kinase inhibitors, novel therapies and combinations are being investigated. Ongoing work on issues of quality of life and patient reported outcomes will better inform our understanding of patient experience and should be reported in clinical trials.

Introduction: Myelofibrosis is a clonal myeloproliferative neoplasm characterized by bone marrow fibrosis, extramedullary hematopoiesis, splenomegaly, progressive cytopenias, and systemic symptoms, with risk of leukemic transformation. Advances in understanding its molecular pathogenesis, particularly JAK-STAT signaling, have reshaped treatment approaches, though allogeneic transplantation remains the only potential cure.

Areas covered: We review current diagnostic frameworks, prognostic models, and treatment strategies, including approved JAK inhibitors and emerging investigational therapies. Literature was identified through PubMed searches and relevant conference proceedings, with emphasis on pivotal clinical trials, novel targeted agents, and evolving management of cytopenias and advanced disease.

Expert opinion: It is an exciting time in myelofibrosis research. Investigation into the molecular underpinnings of the disease and elucidation of many key pathways beyond JAK-STAT signaling have led to a profusion of new drug classes entering the clinic. The results of several, potentially paradigm-shifting key phase 3 trials are eagerly awaited. While JAK inhibitors remain the only approved agents, this could soon change. Equally, there is a major focus on next generation JAK inhibitors and mutant calreticulin antibodies. There is also increasing conversation around the need for novel endpoints, as the limitations of symptom assessment, in particular, become apparent and candidate biomarkers of disease modification emerge.

Introduction: Renal impairment (RI), defined as a creatinine clearance of < 40 mL/min, affects up to half of patients with multiple myeloma (MM). Patients with MM and RI historically had poorer outcomes, likely due to the limited access to novel treatments available through clinical trials. Strict eligibility criteria for MM clinical trials often exclude patients with RI, necessitating reliance on patient data acquired from real-world (RW) clinical practice to guide therapeutic decisions. Therefore, there is a need for RW data and expert recommendations to guide treatment strategies for patients with MM and RI.

Areas covered: Teclistamab treatment and pharmacokinetics in patients with mild-to-moderate RI, including the first report of a RI patient subgroup from the MajesTEC-1 study, as well as published RW experiences of teclistamab, primarily in patients with moderate-to-severe RI.

Expert opinion: Current guidelines, available data, and our clinical experience broadly support the feasibility and potential benefit of teclistamab for patients with MM and RI, including those on dialysis, providing appropriate precautions are taken. This expert opinion offers recommendations for optimizing the management of patients with MM and RI treated with teclistamab. Additional RW data will further inform the safety and efficacy profile of teclistamab in this patient population.

Background: Sickle cell disease (SCD) is a common inherited blood disorder causing high maternal and fetal morbidity during pregnancy. Hydroxyurea (HU) is a standard SCD therapy, but its safety in pregnancy remains uncertain due to concerns about congenital anomalies. This study evaluates maternal-fetal outcomes in pregnant women with SCD who received HU versus those who did not.

Research design and methods: A retrospective review was conducted at Kasturba Hospital, Gujarat, India. Pregnant women with SCD who received HU were compared with a historic control group. Maternal morbidities, fetal outcomes, and congenital anomalies were assessed. Poisson regression was done.

Results: Among a total of 235 pregnant women with SCD, 154 received HU (440.5 person-months), while 81 did not (269.6 person-months). The HU group had a lower adverse maternal event score (91.2 vs. 109.8 per 100 person-months, adjusted IRR 0.82, 95% CI 0.71-0.96, p = 0.01) and reduced maternal morbidity, blood transfusion needs, complications, and deaths. No significant increase in congenital anomalies was observed. Fetal-outcomes, including live-birth, stillbirth, low birth weight, and prematurity, were comparable between groups, with no statistically significant differences.

Conclusions: HU use in pregnancy lowered maternal morbidity without increasing congenital anomalies. Further prospective studies are needed in resource-limited settings.

Introduction: Acute myeloid leukemia (AML) is a malignant clonal hematopoietic cell disorder, characterized by impaired hematopoiesis and bone marrow failure. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an established therapy with curative potential. Post-transplant relapse does occur and has dismal prognosis, which is the main cause of death after allo-HCT. Relapses after allo-HCT in AML do cause standard treatment approaches challenging, which often necessitate individualized treatment modalities and large prospective clinical trials are needed to delineate standardized therapies. The management of AML relapse after allo-HCT remains a clinical challenge, and no standardized treatment approach currently exists.

Areas covered: This review provides an overview of the available therapeutic options for patients with relapsed AML after allo-HCT. It provides a beneficial framework on the optimal treatment approach, including factors that influence drug preferences. A search of papers published up to March 2025 was conducted on PubMed using the keywords.

Expert opinion: Combining chemotherapy, targeted agents, and immunotherapy can increase the rate of response and survival for relapsed AML after allo-HCT. Future research is needed to develop strategies that can reduce the risk of relapse after allo-HCT. Individualization of treatments and exploration of combination therapies are potential approaches for improving efficacy.

Background: Limited data exist on the association between hemoglobin levels/anemia, C-reactive protein (CRP), and hypertension in adolescents. This study aimed to examine the associations between hemoglobin levels/anemia and hypertension among adolescents in two regions of Sudan (River Nile State and Gadarif).

Research design and methods: A multicenter cross-sectional study. Sociodemographic characteristics were evaluated using a questionnaire. Standardized procedures were used to measure adolescents' weight, height, hemoglobin levels, and CRP. Multivariate binary analyses were conducted.

Results: This study included 738 adolescents; 44.0% weremales and 56.0% were females. The median age of the adolescents was 14.8 (interquartile range, IQR: 13.1-16.3) years. Of the 738 adolescents, 69 (9.4%) had hypertension, and 222 (30.1%) had anemia. In multivariate binary analysis, increasing body mass index (BMI) (adjusted odd ratio, AOR = 1.12, 95% confidenceinterval [CI]: 1.05-1.18) and male sex (AOR = 1.84, 95% CI: 1.15-3.24) were positively associated with hypertension, where as anemia (AOR = 0.36, 95% CI:0.15-0.84) demonstrated an inverse association with hypertension. No associations were found between age, CRP, location, and hypertension.

Conclusions: This study reported an inverse association between anemia and hypertension. Further research is necessary to investigate this population's complex association between hemoglobin levels/anemia and hypertension.

Background: Hodgkin lymphoma (HL), a lymphoid malignancy with bimodal age incidence, was analyzed across 204 countries (1990-2021) using data from the global burden of disease (GBD) 2021, with projections till 2050.

Research design and methods: Using GBD 2021 data, we assessed HL burden via incidence, mortality, and disability-adjusted life years (DALYs), with age-standardized rates/100,000. Trends were evaluated using frontier analysis, age-period-cohort modeling and Bayesian APC methods.

Results: From 1990-2021, global HL cases increased 19.2%, while age-standardized incidence rate (ASIR) fell 29.5%. Mortality declined 46.0%, with males showing higher ASIR (0.95 vs. 0.64) and mortality rates (0.43 vs. 0.26). High Socio-demographic Index (SDI) regions had the highest ASIR (1.42) but fastest mortality declines (estimated annual percentage change(EAPC): -3.38), whereas low SDI areas exhibited the highest age-standardized mortality rate (ASMR: 0.7) and minimal improvement. Eastern Sub-Saharan Africa recorded peak ASMR (0.85) and DALY rates (ASDR: 36.96). Bayesian Age-Period-Cohort(BAPC) projections predict sustained ASIR, ASMR, and ASDR reductions until 2050, with persistent gender/age disparities.

Conclusions: Despite rising HL cases due to demographic changes, age-standardized incidence, mortality, and DALYs declined substantially over three decades and are projected to continue declining through 2050, indicating improved treatments. Persistent disparities across SDI tiers underscore the need for region-tailored strategies.

Background: Persons with hemophilia face challenges when requiring antithrombotic therapy due to competing bleeding and thrombosis risks. The absence of robust evidence complicates clinical decision-making, relying on expert opinions and consensus.

Research design and methods: To explore the decision-making processes of physicians managing antithrombotic therapy in persons with hemophilia, identify key factors shaping clinical judgment, and develop a decision-making framework to improve patient care and research. We conducted a qualitative study grounded in constructivist methodology, recruiting seven Canadian physicians with expertise in hemophilia and/or thromboembolic disorders. Three virtual focus groups were held and analyzed using reflexive thematic analysis. Themes were developed iteratively to identify key components.

Results: Participants described five themes involving initial and continuous risk assessment of bleeding and thrombosis, selection of safe antithrombotic therapies or alternatives, and development of hemophilia-specific treatment plans. They highlighted the need for periodic reassessment of strategies and emphasized individualized, co-produced care. Each framework element encompassed multiple factors influencing decision-making toward patient-centered care.

Conclusions: This study provides a decision-making framework to guide antithrombotic therapy in persons with hemophilia. By integrating risk assessments, individualized care, and shared decision-making, the framework addresses this high-risk context. Future research should validate the framework and incorporate patient perspectives to enhance practice.