Expert Review of Hematology最新文献

Introduction: Mantle cell lymphoma (MCL) represents a distinct subtype of mature B-cell lymphoma, considered incurable with a pattern of recurrent relapses and suboptimal responses to subsequent therapies that portends poorer prognosis with each recrudescent disease.

Areas covered: Covalent and non-covalent Bruton tyrosine kinase inhibitors (BTKi) have transformed the relapsed/refractory (R/R) MCL landscape as monotherapy but may emerge to be more effective as combinations with B-cell lymphoma-2 (BCL-2) inhibitors and immunotherapy. Immune-leveraging therapies, including chimeric antigen receptor (CAR) T-cell therapy and T-cell engaging antibodies are gaining momentum, with the former demonstrating durable responses in a subset of patients while the latter being evaluated in various combination regimens. Allogeneic hematopoietic stem cell transplants remain a potentially curative option for selected patients.

Expert opinion: This review seeks to navigate this increasingly complex therapeutic landscape while providing a suggested treatment and sequencing algorithm that may be tailored to individual patients.

Introduction: Chronic myeloid leukemia (CML) has been transformed by ATP-competitive BCR:ABL1 tyrosine kinase inhibitors (TKIs); however, resistance, intolerance, and long-term toxicity remain clinically relevant challenges, particularly in patients requiring prolonged therapy or multiple treatment lines. Asciminib, the first-in-class Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor, represents a paradigm shift by restoring physiologic ABL1 autoinhibition through allosteric binding.

Areas covered: This Special Report reviews the mechanistic basis, preclinical development, and clinical evidence supporting asciminib in CML. We summarize key data from pivotal trials, including ASCEMBL and ASC4FIRST, as well as emerging real-world studies, focusing on molecular response depth, safety, resistance mechanisms, and patient selection. Particular attention is paid to how STAMP inhibition differs from ATP-competitive TKIs in terms of selectivity, toxicity profile, and resistance patterns, and how asciminib can be positioned relative to ponatinib in later-line settings.

Expert opinion: Asciminib has established itself as an effective and generally well-tolerated option for patients with TKI-resistant or -intolerant CML and is poised to expand into earlier lines of therapy. Its ability to induce rapid and deep molecular responses with reduced off-target toxicity may have important implications for long-term disease control and future treatment-free remission (TFR) strategies. Ongoing studies will clarify its optimal sequencing, combination potential, and role in facilitating durable TFR.

Background: Faced with a shortage of blood sources, clinicians have been striving to utilize blood judiciously for critically ill patients. Although some researchers have attempted to explore this issue, there is still no consensus on its applicability in different situations. Therefore, we first conducted a systematic review and meta-analysis by category, providing a more scientific and reasonable basis for clinical treatment decisions.

Research design and methods: We searched databases up to 11 June 2025, including PubMed, EmBase, Cochrane, and Web of Science. The participants were adult critically ill patients. We collected and grouped different hemoglobin (Hb) thresholds during restricted and liberal blood transfusions. The primary outcomes encompassed mortality rate, length of hospital stay, and adverse reactions.

Results: 30,943 critically ill patients were included in 33 studies. Patients with closed head injuries in the restricted group had a higher risk of mortality (RR = 1.78, 95% CI: 1.48-2.15), particularly those with concomitant subarachnoid hemorrhage; Mortality rates were also higher among cardiovascular patients over the age of 60 (RR = 1.54, 95% CI = 1.05-2.24); Tertiary hospitals were found to facilitate patient recovery.

Conclusions: Critical patients with closed brain injuries and comorbidities, as well as those over 60 years old with cardiovascular diseases, may benefit from high-threshold liberal strategies.

Background: Lymphoma poses a significant public health challenge with complex subtypes. While obesity and adipokines have been linked to lymphoma, causal relationships remain unclear. This study uses Mendelian randomization (MR) to systematically assess these associations.

Research design and methods: Two-sample MR analyzed genetic data from genome-wide association studies to evaluate causal links between obesity, adipokines (adiponectin, leptin, and resistin), and lymphoma subtypes (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Hodgkin lymphoma, and other unspecified types of non-Hodgkin lymphoma). Primary analysis used inverse variance weighted (IVW), supported by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses (MR-Egger regression, Cochran's Q test, MR-PRESSO, leave-one-out) and linkage disequilibrium score regression (LDSC) ensured robustness.

Results: IVW revealed obesity positively associated with follicular lymphoma (OR = 1.352, 95% CI: 1.095-1.670, p = 0.005) and other unspecified types of non-Hodgkin lymphoma (OR = 1.297, 95% CI: 1.050-1.603, p = 0.016). No significant links were found between adipokines and lymphoma. Sensitivity analyses confirmed no heterogeneity or pleiotropy.

Conclusions: Obesity may independently increase lymphoma risk, unrelated to adipokines. These findings highlight new risk factors, urging further research into pathological mechanisms and biomarkers.

Introduction: Immune thrombocytopenia (ITP) is an autoimmune-bleeding disorder; its management is shifting from empiricimmunosuppression and splenectomy to targeted, pathway-specific drugs that raise platelet counts with fewer long-term toxicities.

Areas covered: This review critically appraises evidence behind six mechanistic drug classes poised to reshape ITP care: thrombopoietin receptor agonists, spleen tyrosine kinase inhibitors, reversible Brutontyrosine kinase inhibitors, neonatal Fc-receptor antagonists, proximal complementblockers, and plasma-cell or BAFF-directed therapies. We interrogated PubMed, ClinicalTrials.gov, and hematology-conference abstracts (January 2010-May2025), retrieving synthesizing phase 2-3 trials and key observational studies. Throughout, we contrast these agents with steroids, intravenous immunoglobulin, and rituximab, highlighting shared immunomodulatory nodes and unique points of divergence that may inform rational sequencing or combination.

Expert opinion: Mechanism-focused agents already enable steroid-sparing outpatient regimens and personalized care, yet durable remission and predictive biomarkers remain elusive. FcRn and reversible BTK inhibitors are closest to regulatory approval; complement blockade delivers24-hour platelet rescue, while plasma-cell or BAFF inhibition may consolidate sustained disease control. Research priorities include biomarker-guided pathway selection, optimal positioning with thrombopoietin receptor agonists, long-termpharmacovigilance, and cost-effectiveness analyses to ensure equitable global access.

Background: Genetic factors associated with familial multiple myeloma (MM) have been studied, yet the somatic engagement of germline predisposition genes remains underexplored. This study aims to systematically analyze somatic variants in previously reported germline familial myeloma predisposition genes.

Research design and methods: A systematic literature search identified 179 genes associated with familial MM. Somatic variants and associated demographic data from the Multiple Myeloma Research Foundation (MMRF) CoMMpass Study, which includes non-selected myeloma patients (5.3% with a first-degree family history of hematological malignancy) were analyzed.

Results: 1863 somatic variants across the 179 predisposition genes were detected, with substitutions being the most common variant type (95.7%) and missense variants the most frequent consequence (40.6%). Notably mutated genes with pathogenic potential included DIS3, LRP1B, EP300, SAMHD1, ARID1A, DNAH2, MUC17, BIRC6, MYH14, DSP, and DCHS1. Pathogenic variants did not show significant demographic associations. Moreover, variant types, consequences, and associated demographics revealed similar rates in young myeloma patients (≤50 years) and patients with a first-degree family history of hematological malignancy.

Conclusions: This study highlights a significant rate of pathogenic somatic variants in germline predisposition genes of familial myeloma, suggesting candidate genes to be investigated in myelomagenesis.

Background: Adherence to iron chelation therapy (ICT) is essential for preventing iron overload complications and optimizing health outcomes in transfusion-dependent thalassemia (TDT) patients. This study evaluates the cost-effectiveness of ICT adherence in Malaysia.

Research design and methods: A cross-sectional analysis was conducted at a tertiary hospital. Adherence was measured using the Malaysia Medication Adherence Assessment Tool, and health utility values were assessed with SF-6D. Based on the societal perspective, costs and quality-adjusted life years (QALYs) were compared between adherent and non-adherent patients, with incremental cost-effectiveness ratio (ICER) calculations and sensitivity analyses.

Results: One hundred and sixty-two adult TDT patients were recruited. Adherent patients (n = 76) achieved higher QALYs (0.783 vs. 0.733) but incurred slightly higher annual costs ($7,773.26 vs. $7,643.33). The ICER of $2,598.90 per QALY remained below Malaysia's willingness-to-pay threshold ($5,441.16), confirming cost-effectiveness. Sensitivity analyses indicated that cost variations significantly influenced the ICER, while utility values had minimal impact.

Conclusions: The findings underscore the economic and clinical benefits of ICT adherence, advocating for targeted strategies to enhance compliance. Future research should explore long-term cost implications and intervention strategies to improve adherence, ensuring sustainable thalassemia management.

Background: Studies showed that lncRNA HCP5 was associated with a variety of autoimmune diseases. This study evaluated the diagnostic potential of lncRNA HCP5 for immune thrombocytopenia (ITP) and its prognostic value in predicting disease progression, offering clinical application insights.

Research design and methods: This study analyzed 40 ITP patients and 40 controls. qRT-PCR measured lncRNA HCP5 expression, while flow cytometry quantified Th17/Treg percentages. Pearson correlation assessed HCP5-clinical feature relationships. ROC analysis determined diagnostic potential, and Kaplan-Meier/Cox regression evaluated prognostic significance.

Results: ITP patients showed decreased platelet counts, Treg percentages, and lncRNA HCP5 levels, but increased Th17%s versus controls. LncRNA HCP5 showed positive correlation with platelets/Tregs but negative with Th17 cells, and was associated with ITP bleeding severity. With a cutoff of 0.825, lncRNA HCP5 had an AUC of 0.979 for ITP diagnosis, sensitivity of 0.900, and specificity of 0.925. Kaplan-Meier analysis showed increased 1-year recurrence with low HCP5 expression, and Cox regression confirmed it as a poor prognostic factor.

Conclusions: LncRNA HCP5 expression correlated significantly with Treg cell percentage, Th17 cell percentage, and the degree of bleeding in ITP patients. LncRNA HCP5 has high diagnostic and prognostic value for ITP.