Annals of Hematology最新文献

Nodal T-follicular helper (TFH) cell lymphomas (nTFHLs) are the most common mature nodal T-cell lymphomas (nTCL) in Europe, characterized by an aggressive course, poor prognosis, and recurrent expression of TFH markers. Their mutational landscape and the impact of these mutations on survival outcomes remain underexplored. In this study, we characterized nTCL features in a Slovenian cohort, comprising 91 nTFHL, 9 peripheral TCL, not otherwise specified (PTCL-NOS), and 8 composite lymphomas [co-occurrence of nTFHL, angioimmunoblastic type (nTFHL-AI) with monoclonal B-cell proliferation], with a median follow up of 23 months. Using immunohistochemistry, clonality testing, and high-throughput sequencing with a lymphoma panel targeting 172 genes, we analyzed their mutational landscape and examined the mutational impact on survival outcomes. The mutational analysis uncovered TET2 (43%), RHOA (26%), IDH2 (9%), PLCG1 (8%), and DNMT3A (6%) as the most commonly mutated genes. RHOA mutations correlated with TET2, IDH2, and DNMT3A mutations, and CD10 expression was linked to TET2 mutations. Multiple mutations, high International Prognostic Index, progressive disease after first-line treatment, and the absence of autologous stem cell transplantation (ASCT) were independent predictors for shorter survival. To date, this study is one of the largest nTCL series, confirming that nTFHLs outnumber PTCL-NOS (92% vs. 8%). Our findings underscore the complex role of genetic factors in nTCL’s clinical behaviour and emphasize the importance of ASCT. We also highlight the need for prospective clinical trials, which explore tailored therapeutic interventions, such as hypomethylating agents or IDH inhibitors, for improving survival in specific genetic contexts.

Epstein-Barr virus-encoded small RNA (EBER), a hallmark of EBV infection, is a poor prognostic factor in peripheral T-cell lymphoma (PTCL). Current clinical-based prognostic scores inadequately identify high-risk EBER-positive patients or guide therapy, underscoring the need for improved risk-stratification and treatment strategies. This multicenter cohort study, encompassing 167 PTCL patients, systematically analyzed the impact of EBER status on patient survival and treatment response. Utilizing LASSO-penalized Cox regression, a novel prognostic risk scoring system was developed incorporating EBER status and clinical indicators. With a median follow-up of 22.1 months, 63 patients (38%) died. The objective response rate was 57%. EBER-positive status was associated with older age, hypoalbuminemia, high IPI scores, shorter median overall survival (mOS), higher positivity rates for CD30, CD4, BCL6, PD-1, and poorer response to first-line chemotherapy. Multivariate analysis identified independent adverse prognostic factors (p < 0.05): Albumin < 40, Platelet-to-Monocyte Ratio ≤ 300, Lactate Dehydrogenase > 250, Age > 70, and EBER-positivity. A prognostic model incorporating these factors stratified patients into three significantly distinct risk groups (p < 0.001): Low-risk (n = 45; 3-year OS 87.6%, mOS not reached), Intermediate-risk (n = 60; 3-year OS 49.7%, mOS 32.8 months), High-risk (n = 62; 3-year OS 25.1%, mOS 14.3 months). The model outperformed existing models and demonstrated excellent discrimination, stability, clinical utility across PTCL subgroups. This novel prognostic score, integrating subtype-specific marker and clinical features, provides a refined framework for precise PTCL risk stratification and treatment guidance.

We aimed to evaluate the clinical value of splenectomy as a treatment for Chronic active Epstein-Barr virus disease (CAEBVD). We retrospectively reviewed the clinical data from clinical records of patients received splenectomy in our institution from October 1, 2014, to October 1, 2024. The splenectomy cohort (n = 16) was matched to non-splenectomy controls (n = 32) at a 1:2 ratio using propensity scores derived from gender, age, baseline EBV-DNA copies, whether with HLH, and whether received Allo-HSCT. A total of 48 CAEBVD patients were enrolled in this study. Splenectomy cannot minimize the EBV-DNA copies in peripheral blood. The median OS of patients who received splenectomy was 86 months, while that of patients without splenectomy was 23 months. There was no statistically significant difference between the two groups (P = 0.189). When patients experienced recurrence-related death, no significant difference in survival time was observed between the two groups (P = 0.607). In the CAEBVD with HLH subgroup, there was no significant difference in survival times between patients with and without splenectomy (P = 0.423). A total of 18 patients received Allo-HSCT. The time to WBC and PLT engraftment between the non-splenectomy group and splenectomy group showed no significant difference (P = 0.788, P = 0.407). Splenectomy demonstrated no significant benefit in reducing EBV copies and symptom relief, and suggests splenectomy fails to prolong patient survival supporting its limited role in CAEBVD management.

Limited studies investigated the low dose emicizumab prophylaxis, especially in patients switched from pharmacokinetic (PK)-guided FVIII prophylaxis. A retrospective study was conducted among inhibitor-free boys with severe hemophilia A (SHA). They received PK-guided FVIII prophylaxis for six months and then switched to low dose emicizumab regimen for one year. The patients’ demographic data, PK profiles and clinical outcomes (annualized bleeding rates and zero bleeding proportions) were collected from six-month pre-switch to one-year post-switch. The target joints and direct cost of treatment were also calculated. Twenty boys with SHA were enrolled and the median age was 4.3 years (IQR 3.1–5.8). With a median dose and infusion frequency of 25.3 IU/kg and 3.5 infusions per week, their trough FVIII level is 3.5 IU/dL with range of 2.0-5.8 IU/dL. After their switch to emicizumab, the median dose was 3.5 mg/kg/month with range of 3.0–4.0 mg/kg/month. Significantly improved annualized bleeding rate [0(0, 0.75) vs. 2(2,4), P < 0.0001], annualized treated bleeding rate [0(0, 0.75) vs. 1.0 (0, 3.5), P < 0.01], annualized joint bleeding rate [0(0,0) vs. 0(0, 3.5), P < 0.05] and zero bleeding proportion [75% vs. 20%, P < 0.01] were observed. Compared with FVIII, low dose emicizumab showed a much lower direct cost [median, 26676 vs. 35568 dollars yearly, P < 0.01]. Participants received well improved clinical outcomes of reduced annualized bleeding rates and increased zero bleeding proportions. The emicizumab prophylaxis demonstrated a significant decrease in direct cost of 25% compared with FVIII infusions. PK-guided individualized emicizumab prophylaxis could be expected to enhance cost-effectiveness further.

Primary diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a rare lymphoma with a poor prognosis. An accurate predictive model for the prognosis of these patients is lacking. Here, we retrospectively analyzed the clinical data of 968 adult patients who were diagnosed with PCDLBCL, LT between 2000 and 2020 obtained from the Surveillance, Epidemiology and End Results (SEER) database. Multivariate Cox regression analysis revealed that age, marital status and radiation were independent prognostic factors for overall survival (OS), while age, Ann Arbor stage and radiation were independent prognostic factors for disease-specific survival (DSS). Nomograms were constructed to predict 1-, 3- and 5-year OS and DSS. The concordance indices, receiver operating characteristic curves and calibration curves revealed that the established nomograms had good accuracy in predicting the outcomes of patients with PCDLBCL, LT. The web-based calculators were subsequently developed to provide individualized predictions for OS and DSS in patients with PCDLBCL, LT. Moreover, according to the risk scores of the nomograms, patients were divided into low-, median-, and high-risk groups. In conclusion, the nomograms and accompanying web-based survival calculators offer practical tools for individualized prediction of OS and DSS in patients with PCDLBCL, LT. Risk stratification based on these tools may assist clinicians in identifying high-risk patients and guiding optimal treatment decisions.

In this report, a panel of multiple myeloma experts assesses the role of melflufen (melphalan flufenamide) in the treatment of patients with relapsed or refractory multiple myeloma (RRMM). Based on available data, recommendations for administration of melflufen, management of adverse events and optimal patient selection are given. Melflufen, a first-in-class peptide-drug conjugate, is approved in the European Union and the United Kingdom in combination with dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least three prior lines of therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy. For patients with a prior autologous stem cell transplantation, the time to progression should be at least three years from transplantation. Melflufen has demonstrated sustained and durable responses in single-arm and randomized trials. The recommended starting is 40 mg intravenously every 28 days in combination with dexamethasone. Adverse events are mainly dose-related haematological toxicities and infections, which are manageable according to standard guidelines. Melflufen is recommended in patients with no prior high-dose melphalan therapy or in those with a long treatment-free interval after such treatment (> 36 months). In high-risk patients, including patients with del(17p) and TP53 gene mutations, melflufen may be considered as a treatment option, especially if patients have not previously been treated with high-dose melphalan.

This retrospective cohort study investigated the diagnostic performance of cerebrospinal fluid (CSF) β2-microglobulin (β2-M) in patients with central nervous system lymphoma (CNSL). Between January 2018 and August 2024, 1,349 hospitalized patients with CSF β2-M in our center were categorized into lymphoma, leukemia, solid tumor, and other disease cohorts, with additional stratification by central nervous system involvement. CSF β2-M concentrations were markedly elevated in CNSL relative to all other comparator groups (p < 0.001). A cut-off value of 1.85 mg/L discriminated CNSL from non-CNS-involved lymphoma with high diagnostic accuracy, yielding 85.7% sensitivity and 89.7% specificity. Longitudinal assessment further demonstrated that dynamic CSF β2-M trajectories correlated with therapeutic response and relapse risk. Collectively, these findings establish CSF β2-microglobulin as a reliable, accessible, and cost-effective diagnostic biomarker for CNSL.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal disease with a low survival rate. It is important to identify the patients at risk of poor prognosis among HLH patients. In this multicenter and retrospective study, we reviewed 90 newly diagnosed HLH patients treated at the Second Affiliated Hospital of Nanjing Medical University and the First Affiliated Hospital of Anhui Medical University from April 2014 to February 2025. Four pre-treatment clinical characteristics of HLH patients were confirmed to be the independent risk factors: age (hazard ratio (HR) 1.041, 95% confidence interval (CI)1.023–1.059, p < 0.001); splenomegaly (HR 2.112, 95% CI 1.178–3.787, p = 0.012); platelet (PLT) count (HR 0.992, 95% CI 0.984–0.999, p = 0.035); aspartate aminotransferase (AST) (HR 1.002, 95% CI 1.001–1.003, p < 0.001). Subsequently, the patients’ prognostic risk scores were calculated based on these four risk factors to stratify patients to high-risk and low-risk groups. Besides, these four factors were included in the final clinical prediction model. Receiver operating characteristic (ROC) curves revealed that this model had a good discrimination with optimism-corrected area under the curve (AUC) values of 0.78 (95% CI: 0.68–0.88) for 30-day mortality and 0.82 (95% CI: 0.74–0.92) for 90-day mortality. The calibration curves aligned with the model predictions and actual observations. The decision curve analysis also confirmed our model’s robust predictive power. These results point out that age, splenomegaly, PLT, and AST levels are independent indicators of overall survival in patients with HLH and that the proposed model has a good prognostic value.