Expert Review of Hematology最新文献

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.

Introduction: Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma (iNHL) with mucosa-associated lymphoid tissue (MALT) lymphoma being the most common subtype. Typical of other iNHLs, a fraction of patients will experience more aggressive disease marked by early relapse despite effective front-line therapy.

Area covered: In this review, we discuss existing prognostic scoring systems for patients with MALT lymphoma undergoing first-line therapy, including the MALT-IPI, the Revised MALT-IPI, the MZL-IPI, and the EMZL-MPI. We review strengths and limitations of these systems and discuss advances in the current understanding of molecular and genomic drivers of lymphomagenesis in this disease, which are not currently reflected in prognostic scoring systems. We review evolving first-line treatment approaches and discuss how there may be opportunities to refine our ability to prognosticate outcomes because of these recent advances.

Expert opinion: Existing prognostic scoring systems for MALT lymphoma each have their own merit and are valuable for informing risk assessment in both clinical and research contexts, however, as understanding of the molecular and genetic drivers of MALT lymphomas improves and first-line treatment approaches incorporate novel targeted and immune-based therapies, there will likely be opportunities to enhance the current prognostic models.

Background: Hemoglobin (Hb) variants can cause clinical conditions like thalassemia. Understanding their molecular phenotypes and clinical profiles is essential for accurate diagnosis and genetic counseling.

Research design and methods: Blood samples from a 67-year-old Thai female and four relatives were analyzed using HPLC and capillary electrophoresis. PCR techniques and sequencing were used to identify globin gene mutations and β-globin haplotypes. Pathogenicity and transcription factor-binding sites were predicted. A rapid diagnostic method was developed and validated using 1,414 samples to assess the geographic distribution of the variants.

Results: Hb analysis revealed HbA, HbA₂, and a slower-migrating Hb fraction. Mutations identified included HBB:c.92 G > C(HbMonroe) in cis with HBB:c.-92C > G, and HBD:c.60C > A(HbA₂-Famagusta). This novel combination exhibited normal HbA₂ levels, potentially masking β-thalassemia. Combining HbMonroe with HbE leads to severe clinical symptoms. HbA₂-Famagusta was predicted to be benign, while HbMonroe was deleterious. The geographic distribution of HbMonroe was found to be 0.09% with an allele frequency of 0.00042 and 1.30% with an allele frequency of 0.00649 in β-thalassemia carriers and EF syndrome, respectively.

Conclusions: HbMonroe is a β⁰-thalassemic variant affecting splicing and structure, undetectable by standard Hb analysis. Including HbA₂ variants in total HbA₂ quantification is essential for accurate diagnosis and improved genetic counseling in thalassemia-endemic areas.

Introduction: Mucosal toxicities remain a longstanding and challenging concern in the treatment of hematopoietic malignancies (HM). In addition to the classic oral (OM) and gastrointestinal mucositis (GIM) induced by chemotherapy (CHT) and/or radiotherapy (RT), novel targeted treatments and immunotherapies may cause other forms of mucosal disorders.

Areas covered: This overview provides updated insights into the pathobiology and management strategies for mucosal toxicities induced by treatments for HMs. Additionally, it reappraises classic forms of mucositis and novel mucosal toxicities induced by new treatments for HMs.

Expert opinion: Although significant progress has been made in the pathophysiologic pathways of conventional CHT/RT-associated OM, much remains to be discovered. Indeed, OM and GIM have a multifactorial etiopathogenesis that includes direct effects, oxidative injury, upregulation of immunologic molecules, and changes in the microbiome. Preventive measures remain the cornerstone of management, mainly palliative in clinically established mucositis. However, new therapeutic insights, primarily related to mesenchymal cells and cytokine inhibitors, are emerging, and ongoing research is critical for translating these new findings into clinical practice.

Background: This study investigated the association between response to hydroxyurea (HU) treatment and fetal hemoglobin (HbF), and the prevalence of mutations that regulate HbF synthesis, drug transport and biotransformation in sickle cell disease (SCD) patients.

Research design and methods: Study included n = 390 Bahrainis with a history of sickle cell crises. Responders (n = 127; 68%) were patients achieving HbF ≥ 15% along with other improvements. Non-responders (n = 60; 32%) failed to achieve this threshold despite maximum tolerated dose treatment.

Results: Hydroxyurea treated patients had decreased frequency of painful crises and hospitalizations, increased Hb and HbF and decreased sickle cell hemoglobin (HbS), and white blood cells (WBCs). The minor allele frequency of ARG2 (rs10483801), HBS1L-MYB (rs4895441), CYP2C19 (rs4986893) CYP2C19 (rs4244285), and OATP1B3 (rs3711358) gene was significantly higher in non-responders compared to responders. A negative correlation was found between the number of pain crises and hospitalizations per year and HbF%. No significant correlation was reported between the dosage and the number of hospitalizations per year. No significant correlation was found between the duration of treatment and HbF%.

Conclusions: Findings highlight the importance of a personalized treatment approach to maximize the benefits and minimize the side effects of HU, thereby improving clinical outcomes.

Introduction: Sickle cell disease (SCD) is an inherited blood disorder affecting approximately 100,000 individuals in the United States and millions worldwide, characterized by acute vaso-occlusive pain episodes (VOEs) and other complications that frequently necessitate emergency department (ED) visits.

Areas covered: Despite therapeutic advancements, ED care remains a major concern, often cited by patients as the area of healthcare most in need of improvement. National guidelines have been established to ensure ideal emergency SCD care and management, however, these guidelines do not address barriers or facilitators that affect implementation in the complex ED setting. This review examines current diagnostic and management approaches for common SCD complications requiring ED utilization, particularly fever and pain in pediatric patients. It highlights the challenges children with SCD face in emergency care and the existing knowledge gaps. Despite guidelines recommending timely, individualized pain treatment, implementation remains inconsistent, resulting in prolonged suffering and increased hospitalizations.

Expert opinion: Future research should focus on enhancing guideline adherence, reducing disparities, and developing targeted therapies. Novel biomarkers could improve early diagnosis, while standardized severity scoring systems may optimize triage and treatment decisions. Advancing biomarker research and investigational therapies beyond traditional supportive care holds promise for improving SCD management and patient outcomes.

Introduction: The development of new lymphoma therapies in recent years has led to a significant increase in patient survival. However, in some cases, despite disease remission, the outcome of the applied therapy is diminished by the development of secondary cancers. These often have dismal outcomes and are unresponsive to standard therapies. Both therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) are well-known side effects of cytotoxic chemotherapy and/or radiation therapy.

Areas covered: This review summarizes the key factors associated with an increased risk of therapy-related neoplasms in lymphoma patients, focusing on the various elements that may contribute to this susceptibility. The major factors described in detail include the impact of different anti-lymphoma therapies, disturbances in the bone marrow microenvironment, the presence of clonal hematopoiesis, and germline predispositions. The review is based on a PubMed database search for articles published up to 1 May 2025, covering the above mentioned topics, as well as the authors' clinical and research experience.

Expert opinion: Considering the progress in lymphoma therapy and the prospect of long-term survival, efforts should be made to identify patients at higher risk of developing therapy-related myeloid neoplasms. A better understanding of germline predispositions and the role of clonal hematopoiesis should support therapy tailored to individual risk profiles.