Annals of Hematology最新文献

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome, among which NK-cell malignancy-associated HLH represents a clinically rare entity that has not been systematically investigated. The multicenter retrospective cohort study analyzed data from 136 adult patients diagnosed with HLH related to NK-cell malignancies between 2010 and 2024. The results demonstrated that initial treatment with etoposide-containing HLH therapy improved 60-day survival rates (P = 0.009) but did not affect overall survival (OS) (P = 0.306), whereas asparaginase-containing lymphoma regimens significantly improved both OS (P = 0.025) and 60-day survival rates (P = 0.016) in treatment-naive patients. By multivariate analysis, significant independent predictors of 60-day poor outcomes included serum albumin level < 30 g/L (HR, 2.03; 95% CI, 1.08–3.83; P = 0.029), platelet count < 20 × 10⁹/L (HR, 2.70; 95% CI, 1.46–4.99; P = 0.002), and Epstein-Barr virus DNA (whole blood) > 33,850 copies/mL (HR, 1.97; 95% CI, 1.01–3.81; P = 0.045). ECOG performance status ≥ 2 (HR, 2.00; 95% CI, 1.24–3.23; P = 0.004) and platelet count < 20 × 10⁹/L (HR, 7.61; 95% CI, 2.14–27.09; P = 0.002) were independent risk factors for poor OS. Therefore, we recommend asparaginase-based regimens as first-line therapy for treatment-naive adult patients with HLH related to NK-cell malignancies. Future multicenter prospective studies are warranted to optimize asparaginase-containing regimens, evaluate novel combination strategies, and establish precision risk-prediction models to guide clinical practice.

Whether TP53 mutation can serve as a simplified prognostic surrogate for complex genomic classifiers in diffuse large B-cell lymphoma (DLBCL) remains unclear. we comprehensively analyzed a retrospective cohort of 444 newly diagnosed DLBCL patients. TP53 mutation was an independent prognostic factor for inferior overall survival (OS) and progression-free survival (PFS) (both P < 0.001), correlating with inferior response to R-CHOP and enrichment in refractory/relapsed disease. Furthermore, multivariate analysis revealed that the adverse prognostic effect of TP53 mutation was predominantly driven by its impact within the germinal center B-cell-like (GCB) subtype, as evidenced by a significant statistical interaction. Notably, the combination of TP53 mutation and double-expression lymphoma (DEL) identified an ultra-high-risk group with synergistic poor survival. The prognostic impact was not modified by the specific protein domain, mutation burden, or gain- versus loss-of-function nature of the mutations. However, a high variant allele frequency (VAF) ≥ 53% identified a subgroup with worse survival. Finally, we adapted a p53 immunohistochemical classification from ovarian/endometrial cancer to enhance TP53 mutation prediction: overexpression (> 80%) or complete absence (< 1%) as high-risk, and heterogeneity (1%-80%) as low-risk. This approach achieved 72.5% sensitivity and 97.4% specificity, with specificity surpassed conventional ≥ 50% cutoff (P < 0.001). In conclusion, TP53 mutation is a critical, context-dependent biomarker in DLBCL, and its combination with DEL identifies a clinically actionable, ultra-high-risk group. The p53 IHC classifier shows promise as a rapid screening tool, warranting further validation.

Glanzmann Thrombasthenia (GT) is a congenital platelet disorder characterized by a life-long bleeding tendency, historically considered protective against thrombosis. This report describes a rare case of pulmonary embolism (PE) in a patient with GT, challenging this assumption and highlighting a critical management paradox. A 55-year-old woman with GT underwent elective cervical discectomy. Her perioperative hemostatic regimen included a single prophylactic dose of recombinant Factor VIIa (90 µg/kg), platelet transfusions (preoperative and daily for 3 days), and tranexamic acid. Two months postoperatively, she presented with hemoptysis. CT pulmonary angiography confirmed bilateral segmental and subsegmental PE with pulmonary infarctions. Anticoagulation with apixaban was initiated, leading to symptom resolution and thrombus regression. Therapy was discontinued after four months following a spontaneous hemarthrosis, which was managed successfully. Provoked PE can occur in GT patients following major surgery and hemostatic support. Apixaban was effective for short-term treatment, but the subsequent bleeding complication highlights the narrow therapeutic window and the need to limit anticoagulation duration in this population.

Hodgkin's lymphoma (HL), a malignant neoplasm of lymphatic system origin, poses a significant challenge to global public health. This study comprehensively analyzed global, regional, and national trends in HL burden from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) Study 2021, and projected these trends to 2035. The HL burden was assessed through age-standardized incidence (ASIR), prevalence (ASPR), disability-adjusted life years (DALYs) rates, and mortality (ASMR) from 1990 to 2021. Analytical methods included the Slope Index of Inequality (SII), concentration index, frontier analysis, decomposition analysis, joinpoint regression, and Bayesian age-period-cohort (BAPC) modeling. Between 1990 and 2021, global Hodgkin's lymphoma incidence, DALYs, and mortality rates exhibited sustained downward trends. New cases increased from 54,671 (95% UI: 45,648.6–59,832.2) to 65,182 (95% UI: 53,167.4–77,143.0), yet the incidence rate declined from 1.119 (95% UI: 0.935–1.227) to 0.794 (95% UI: 0.645–0.941). DALYs decreased from 1,324,591 (95% UI: 959,601.5–1,519,698.0) to 1,196,188 (95% UI: 847,435.8–1,528,816.4), with the rate falling from 26.055 (95% UI: 18.977–29.882) to 14.818 (95% UI: 10.434–18.955). Deaths dropped from 28,977 (95% UI: 21,389.7–33,106.9) to 28,180 (95% UI: 20,895.4–35,652.9), and the mortality rate decreased from 0.633 (95% UI: 0.474–0.722) to 0.341 (95% UI: 0.252–0.431). Males generally had higher incidence, DALYs, and mortality rates than females, with smaller sex differences in high-income regions. Children and adolescents had relatively lower rates, which increased with age, peaking in individuals aged 60 and older. Significant regional disparities existed, with high SDI regions experiencing stable or declining rates, while low SDI regions saw slight declines in incidence and mortality but increased DALYs. In 2021, sub-Saharan Africa had higher incidence and mortality rates, while high-income regions had lower rates. The study also noted increased global inequalities in DALYs and mortality rates, with low SDI regions bearing a greater burden. While there has been a global reduction in the burden of Hodgkin's Lymphoma, substantial health disparities persist in low- and middle-income regions. Future strategies should prioritize enhancing health infrastructure, improving early detection methods, and standardizing treatment protocols in resource-constrained settings. International collaboration and efficient resource allocation are essential to mitigate global health disparities.

Sensorineural hearing loss (SNHL) is an underrecognized manifestation in chronic myeloid leukemia (CML), particularly in the setting of hyperleukocytosis. Its prevalence, pathophysiology, and response to tyrosine kinase inhibitor (TKI) therapy remain poorly characterized. To assess the prevalence, severity, and reversibility of SNHL in treatment-naïve CML patients and evaluate associations with leukocyte count and disease risk. In this prospective study, 102 newly diagnosed CML patients with total leucocyte count (TLC) > 50 × 10⁹/L underwent audiological evaluation at baseline, 3 months, and 6 months post-initiation of imatinib. Age- and sex-matched healthy controls were included for comparison. SNHL was identified in 45.1% of CML patients at diagnosis, predominantly affecting mid-to-high frequencies. Elevated TLC (> 150 × 10⁹/L) and intermediate-high EUTOS long term survival (ELTS) scores were significantly associated with SNHL (p < 0.05). Following TKI therapy, 74% of patients with minimal-to-mild SNHL showed complete audiometric recovery at 6 months. No worsening was observed in patients with normal baseline hearing. SNHL is a prevalent but potentially reversible complication in newly diagnosed CML, with early TKI therapy facilitating hearing recovery. Routine audiological screening should be considered at diagnosis to detect subclinical hearing loss.

The aim of this study is to investigate the diagnostic value of long non-coding RNA PVT1 (LncRNA PVT1) in deep vein thrombosis (DVT) of the lower limbs, as well as its regulatory role in damaged endothelial cells. A total of 384 participants were enrolled, including 208 patients with DVT. 3mL venous blood were collected from each participant. Thrombosis location and severity were assessed via Doppler ultrasound or venography. An endothelial cell injury model was induced using 250 µM cobalt chloride (CoCl₂). Gene expression was evaluated using RT-qPCR, while cell function was assessed via CCK-8 assays and flow cytometry. Angiogenesis and inflammatory factor expression was measured by ELISA. Dual luciferase reporter assays validated gene-target relationships. LncRNA PVT1 was significantly upregulated in DVT patients and injured endothelial cells. LncRNA PVT1 positively correlated with D-dimer and C-reactive protein (CRP) expression, indicating risk factors for DVT induction. Treatment with CoCl₂ increased LncRNA PVT1 expression in endothelial cells, while si-PVT1 enhanced viability and reduced apoptosis in damaged endothelial cells. It also suppressed expression of angiogenesis-related factors (VEGF, FGF-2) and inflammatory cytokines (TNF-α, IL-6). miR-143-3p, a downstream target gene of LncRNA PVT1, is downregulated in DVT patients. The miR inhibitor counteracts the effects of si-PVT1 on damaged endothelial cell function and inflammatory levels. LncRNA PVT1 negatively regulates miR-143-3p, thereby suppressing endothelial cell activity and promoting apoptosis. This increases levels of angiogenesis factors and inflammatory mediators, contributing to DVT pathogenesis.

Myelodysplastic syndromes (MDS) are clonal stem cell disorders managed by risk stratification: lower-risk disease receives erythropoiesis-stimulating agents; higher-risk disease receives azacitidine. Red blood cell (RBC) transfusions manage symptomatic anaemia and improve quality of life (QoL) but carry risks of iron overload and alloimmunisation. No standardised transfusion strategy exists, requiring systematic evidence synthesis comparing liberal versus restrictive haemoglobin (Hb) thresholds for their effects on quality of life and transfusion-related complications. We performed a systematic review evaluating liberal versus restrictive RBC transfusion thresholds in adults with MDS not undergoing curative treatment such as stem cell transplantation. Primary outcome was health-related QoL measured by validated instruments. Secondary outcomes included mortality, transfusion reaction, iron overload, RBC utilisation and rise in ferritin level. Of 4,295 records screened, 212 articles underwent full-text review, with three RCTs meeting inclusion criteria. Liberal transfusion strategies were associated with improved QoL compared to restrictive approaches, with pooled standardised mean difference (Hedges g) of 0.54 (95% CI 0.06–1.02; p = 0.33; I²=9.7%). Subgroup analysis of EQ‑5D outcomes across studies revealed minimal but statistically significant difference between strategies (pooled mean difference 0.084; 95% CI: 0.033 to 0.134). Mortality (hazard ratio 0.913; 95% CI 0.167–4.98) and transfusion reactions (risk difference − 0.01; 95% CI-0.10 to 0.09) did not differ. Notably, liberal thresholds required average of 4 additional RBC units per patient (95% CI 1.43–6.79), raising concerns about iron overload (rise in ferritin; mean difference 868 µg/L; 95% CI 482–1255). Limited evidence suggests that liberal transfusion strategies in MDS may improve short-term QoL but at the cost of increased transfusion burden, with no clear impact on survival or safety. A patient-centred, multidisciplinary approach remains essential when tailoring transfusion thresholds.

The study protocol has been registered in PROSPERO (CRD420251085221). https://www.crd.york.ac.uk/PROSPERO/view/CRD420251085221.

We aimed to summarize the clinical characteristics of children diagnosed with acute leukemia (AL) and analyze the risk factors associated with early mortality occurring within 6 weeks of diagnosis. This study aimed to identify high-risk patients and to guide early intervention strategies. Data collected from 242 children diagnosed with primary AL between November 1, 2020, and April 30, 2025, were analyzed. The prognostic value of indicators in predicting early mortality was evaluated. Among the 242 children diagnosed with AL, nine died during the initial induction chemotherapy (early mortality rate: 3.72%); six deaths (66.7%) occurred within 7 days of treatment initiation. The predominant cause of early mortality was intracranial hemorrhage (5/9, 55.56%), followed by sepsis-related fatalities (3/9, 33.33%), and cerebral infarction (1/9, 11.11%). Children with acute myeloid leukemia (non-acute promyelocytic leukemia) had a significantly higher early mortality rate (13.16% vs. 1.60%, P = 0.002) and a significantly higher incidence of deaths attributed to intracranial hemorrhage or cerebral infarction (10.53% vs. 1.06%, P = 0.008) than those with acute lymphoblastic leukemia. Several risk factors for early mortality in children with AL were identified (all P < 0.01): white blood cells (WBC), fibrinogen, serum potassium, international normalized ratio (INR), serum phosphorus, prothrombin time (PT), blood urea nitrogen (BUN), activated partial thromboplastin time (aPTT), d-dimer, lactate dehydrogenase (LDH), and α-hydroxybutyrate dehydrogenase (α-HBDH). The primary causes of early mortality in children with AL include intracranial hemorrhage and sepsis. Identified risk factors for early death encompass higher tumor burden (WBC, LDH,α-HBDH), internal environment disturbances (serum potassium, serum phosphorus, BUN), and coagulopathy (fibrinogen, INR, PT, aPTT, d-dimer).

Background

Primary urinary tract lymphoma (PUTL) is a rare subtype of extranodal lymphoma, with current knowledge largely limited to case reports and small series. This study aimed to evaluate the dynamic survival patterns of PUTL using conditional survival (CS) analysis and to develop a prognostic nomogram for individualized survival prediction.

Methods

Patients diagnosed with PUTL between 2000 and 2021 were identified from the SEER database. CS estimates and annual hazard rates were calculated to assess time-dependent changes in survival probability and risk of death. A prognostic model was constructed using variables selected by Random Survival Forest (RSF) and multivariate Cox regression. A CS-nomogram was developed and validated to predict 3-, 5-, and 10-year overall survival (OS) and 10-year conditional survival.

Results

A total of 1,201 patients were included. CS analysis showed that long-term survival probabilities improved significantly with each additional year survived. The highest mortality risk occurred in the first year after diagnosis, followed by a rapid decline and stabilization after three years. Factors such as age, tumor histology, stage, and treatment modalities were identified as significant predictors of OS. The CS-nomogram demonstrated good calibration and discrimination, with AUCs of 0.740, 0.733, and 0.800 for 3-, 5-, and 10-year OS in the training set, and 0.712, 0.708, and 0.794 in the validation set, respectively. Decision curve analysis indicated favorable clinical utility.

Conclusion

This study provides the most comprehensive dynamic survival assessment of PUTL to date. CS analysis revealed a favorable shift in prognosis over time, particularly for patients who survived the high-risk early phase. The CS-nomogram enables personalized, time-updated prognostic estimates, supporting more accurate counseling, follow-up planning, and resource optimization in this rare disease.

Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms (MPNs), often associated with mutations in JAK2, CALR, and MPL. Differentiating PV from ET can be challenging in borderline cases, particularly when hemoglobin (Hb), hematocrit (Hct) and erythropoietin (EPO) values are inconclusive. Functional iron parameters and JAK2 variant allele frequency (VAF) may provide additional discriminatory value. To assess the diagnostic utility of transferrin saturation index (TSI), serum ferritin, EPO, and JAK2 VAF in distinguishing PV from ET, and to evaluate their association with mutational profiles. We conducted a retrospective, single-center study including 260 adult patients diagnosed with PV or ET between 2009 and 2024. Demographic, clinical, molecular, and laboratory parameters—including ferritin, TSI, EPO, Hb, Hct, and JAK2 VAF—were analyzed. Comparative and correlation analyses were performed using appropriate statistical tests. Compared to ET, patients with PV had significantly lower ferritin (median: 35.65 vs. 95.05 ng/mL), TSI (12.9% vs. 21.64%), and EPO (2.23 vs. 6.11 mIU/mL), but higher Hb (17.7 vs. 14.3 g/dL) and Hct (54.6% vs. 43.0%) (all p < 0.001). TSI discriminated PV from ET better than ferritin (p < 0.001 vs. p = 0.128). Among JAK2-mutated cases, VAF was higher in PV than ET (median: 48% vs. 21%, p = 0.003). VAF correlated inversely with ferritin, TSI, and EPO, and positively with Hct. TSI and JAK2 VAF outperform ferritin as diagnostic markers to differentiate PV from ET. Integrating functional iron parameters with molecular data improves diagnostic accuracy, particularly in clinically ambiguous cases, and supports their inclusion in MPN diagnostic algorithms.