Expert Review of Hematology最新文献

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.

Introduction: Cytopenia is one of the most common adverse events after BCMA chimeric antigen receptor (CAR) T cell therapy in the treatment of relapsed multiple myeloma (MM). The term Immune Effector Cell Associated Hematotoxicity (ICAHT) was coined to describe the unique hematological toxicities following novel CAR T cell therapies. The management of prolonged ICAHT ( > 30 days) is quite challenging, and patients have high incidences of infections, require prolonged transfusion support and have an increased non-relapse mortality. Stem cell boost (SCB) leads to prompt and durable count recovery and can minimize long-term complications while enabling therapeutic options in the post CAR T-cell therapy relapse setting.

Areas covered: Herein we review current data on ICAHT, determine how SCB can lead to improved outcomes, and offer a view on future applications of SCB. The database 'pubmed' was searched for the terms 'CAR-T,' 'ICAHT', and 'Stem Cell', and results as well as selected citations were used for the present study.

Expert opinion: SCB for prolonged ICAHT improves morbidity and potentially mortality. Future use of SCB will depend on the long-term outcomes of CAR-T cell therapy in earlier treatment lines. For patients with high likelihood of ICAHT, prophylactive stem cell collection should be considered.

Background: Artificial Intelligence (AI) is increasingly vital in transfusion medicine for enhancing service quality and efficiency. However, bibliometric studies in this area are scarce. This analysis maps current and emerging research trends.

Research design and methods: Publications from 1 January 2000 to 31 August 2025, were retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, and Excel were used to visualize contributions and trends across authors, institutions, journals, and countries.

Results: Among 159 publications, the U.S.A. China, and India led in output. The University of Colorado was the top institution, while Transfusion had the highest citations. Axel Hofmann was the most cited author. Keywords such as 'machine learning' and 'deep learning' highlight the rapid adoption of advanced AI technologies.

Conclusions: This study outlines current trends and emerging frontiers, offering valuable insights and guidance for future AI applications in transfusion medicine.

Background: Hemophilia A is an inherited bleeding disorder caused by a deficiency of clotting factor VIII (FVIII), leading to joint bleeding and arthropathy. While prophylactic FVIII therapy reduces bleeding, evidence suggests maintaining higher FVIII levels (FL) may better protect joint health, particularly in physically active individuals and those with joint damage. However, data on optimal FLs required to prevent joint deterioration and complications remains limited.

Research design and methods: This study utilized the Sheffield Elicitation Framework (SHELF) methodology to elicit expert opinions on optimal FLs for patient-centric and clinical outcomes. Five European hemophilia experts participated in virtual workshops, providing probability-based estimates of FLs required to prevent bleed-related hospitalizations, orthopedic procedures, target joint incidence, and support physical activity without additional infusions or joint damage.

Results: Experts consistently recommended higher FLs for individuals with joint damage than for those without. Optimal average FLs ranged from 24% to 51%, exceeding traditionally recommended prophylactic trough levels (3-5%). Considerable uncertainty was noted around FLs for physical activity, reflecting the complexity of individualized care.

Conclusions: Standard prophylaxis regimens may not provide sufficient protection for all patients, particularly those with joint damage. A personalized treatment approach, targeting higher FLs when necessary, may be critical for optimizing outcomes.

Background: This systematic review and network meta-analysis(NMA) comprehensively evaluated the efficacy and safety of non-first-line drugs in the treatment of adult patients with immune thrombocytopenia (ITP).

Researchdesign and methods: PubMed, Web of Science, Embase, and the Cochrane Library were systematically searched. Randomized controlled trials (RCTs) investigating Count data were extracted in the form of event occurrences/non-occurrences. NMA was carried out via R.

Results: 29 RCTs were encompassed. In contrast to placebo, the avatrombopag 20 mg group demonstrated the highest PR (RR = 12.23, 95% CrI: 5.48-33.72). The combination of eltrombopag and danazol exhibited the lowest incidence of bleeding events (RR = 0.31, 95% CrI: 0.16-0.57), while the avatrombopag 5 mg group had the lowest incidence of SAEs (RR = 0.44, 95% CrI: 0.22-0.84). The comprehensive evaluation suggested that romiplostim, initiated at a dose of 1 μg/kg within a dose-adjustment regimen, may confer one of the most favorable benefit - risk profiles, with a relatively high PR (SUCRA = 75.1%) and a low incidence of bleeding events (SUCRA = 54.8%).

Conclusions: When initiating therapy with romiplostim at a dose of 1 μg/kg and subsequently titrating the dosage according to the patient's platelet response, romiplostim may represent one of the most effective therapeutic options.

Registration: The study protocol for this systematic review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) database (http://www.crd.york.ac.uk/prospero/), and it was allocated the PROSPERO identification number.