Siltuximab is the only approved treatment for idiopathic multicentric Castleman Disease but in many countries the only available treatment is rituximab based. We are performing an indirect comparison of rituximab-based regimens (RBR) and siltuximab by using single arm meta-analysis and the generalized linear mixed model methods comparing outcome in five significant clinical end-points (CR, PR, ORR, 2ysPFS and 2ysOS). Patient's data were extracted from 14 cohort or phase I and II trials conducted with siltuximab (n = 387 pts) and six cohort studies treating iMCD patients with rituximab (n = 138 pts). Response rates and depth of response is similar between the two arms of the study but 2ys PFS is significantly better with siltuximab monotherapy. Using the generalized linear mixed model in order to provide an indirect comparison of odds to achieve the 2yPFS end-point, the reported OR is 0,358, 95% CI (0,147-0,873) and p = 0,027 favoring siltuximab over rituximab-based regimens (RBR). This is the major finding of our study and to our knowledge is the first time that in a big cohort of patients siltuximab is proved more effective compared to RBR.

The prognosis of patients with AML, who fail to achieve complete remission after induction therapy (= primary refractory disease) has been dismal for many years. Allo-HSCT is the only curative approach and standard of care for eligible patients in this group. The need for inducing a remission before transplantation in primary refractory patients has not been finally clarified. The objective of this retrospective single-center evaluation is to analyze the outcomes of primary refractory patients who underwent immediate allogeneic HSCT after chemotherapy induced aplasia in the context of the conditioning regimen in a real-life setting. We started a program of immediate transplantation policy for eligible patients with refractory AML after induction chemotherapy in our center in 2010. All patients with a diagnosis of primary refractory AML who underwent their first allogeneic hematopoietic stem cell transplantation in active disease between 03/2010 and 07/2023 at the department of Hematology at Klinikum Nuremberg, Germany, were included and analyzed. 50 patients were included in this analysis. Mean time from start of induction treatment to transplantation was 3 months (range 1.4-7.8 months). Melphalan (100-140 mg/m) for induction of aplasia was used in 45/50 pts (90%) prior to conditioning. After a median follow-up of 9.97 (range: 0.03-143.8) months 18/50 (36%) patients were alive without relapse. Median and mean relapse free survival were 9.97 (range: 0.03-143.8) and 28.13 (range: 0.03-143.8) months respectively. The median and mean OS were 9.97 (range: 0.03-143.8) and 28.64 (range: 0.03-143.8) months. The 100-day, 1-year and 2-year survival rates were 66%, 48% and 42% respectively. Cumulative incidence of relapse at 2-years after transplantation was 18.5% (95% C.I., 10.3% - 33.1%) with a median time from HSCT to relapse of 4.85 (Range: 0.67-18,3) months. Cumulative incidence of non-relapse mortality at 100 days, 1- year and 2-years was 26% (95% C.I., 16.3% - 41.5%), 36.3% (C.I., 25.1% - 52.5%) and 38.4% (95% C.I., 26.9% - 54.7%) respectively. Main cause of overall mortality was TRM (58.1%) with Sepsis (41.9%) being the biggest single contributor. The only significant independent factor associated with decreased overall and 100-day survival was a positive patient CMV-status (independent of donor CMV-serostatus). The observed survival-rates in our study compare favorably to those published for established salvage-therapy regimens as well as other retrospective studies analyzing HSCT in active disease. We demonstrate that allogeneic hematopoietic stem cell transplantation in active disease is a reasonable approach for patients with primary refractory AML offering the chance for long-term survival for about one third of patients. The effect is compromised by the high incidence of non-relapse mortality.

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by increased red blood cell production, with high risk of venous and arterial thrombosis. Mutations in the JAK2 gene, particularly JAK2 V617F, play a central role in its pathogenesis. Ropeginterferon alfa-2b is a novel long-acting interferon showing promise in managing PV through hematologic and molecular control.This study aimed to evaluate the efficacy and safety of Ropeginterferon alfa-2b in patients with PV based on a systematic review and meta-analysis of available clinical trials.A systematic search was conducted across PubMed, Cochrane Library, Web of Science, Google Scholar, and Scopus on May 8, 2025. Randomized controlled trials (RCTs) assessing Ropeginterferon alfa-2b in PV were included. The PRISMA guidelines were followed, and the protocol was registered in PROSPERO (CRD420251051466). Quality assessment was performed using RoB 2.0 and ROBINS-I tools. A random-effects model was applied using R software.Eight studies involving 761 patients were included and only six studies included in single arm meta-analysis with 328 patients. The pooled proportion of complete hematological response at 12 months was 0.63 (95% CI [0.51-0.73]), with high heterogeneity. Reductions in JAK2 V617F allele burden were significant (MD: 26.57, 95% CI [13.49-39.65]). Molecular response was achieved in 25% (95% CI [0.04-0.70]) of patients. The most common adverse events were elevated liver enzymes (AST: 0.28; ALT: 0.32), influenza-like illness (0.11), and anemia (0.09), with unresolved heterogeneity in all outcomes.Ropeginterferon alfa-2b shows promising efficacy in achieving hematological and molecular responses in patients with PV. However, notable heterogeneity and safety concerns, particularly liver-related adverse effects, warrant further investigation in large-scale trials.

Despite remarkable advancements in the last decade for individuals with chronic lymphocytic leukemia (CLL), the prognosis for those with Richter transformation (RT) remains poor, unfavorable and still challenging. Multiagent chemoimmunotherapy agents which are usually anthracycline based have been frequently employed; however, the outcomes are significantly inferior compared to those seen with identical regimens in de novo diffuse large B-cell lymphoma. Despite the emergence of numerous novel therapeutic agents in the last few years and yet still more to come, almost all studies outcomes are still not satisfactory to control this aggressively transformed CLL state.

Extranodal NK/T-cell lymphoma (ENKTL), an aggressive non-Hodgkin lymphoma subtype, exhibits understudied links between lipid metabolism and clinical outcomes. We analyzed 1,017 patients newly diagnosed with ENKTL and matched controls, with longitudinal LC-MS-based metabolomic profiling (n = 29) and pretreatment tumor transcriptomic analysis (n = 65). Multivariable Cox models evaluated lipid biomarkers. Patients with ENKTL showed significantly elevated triglycerides (TG) and reduced apolipoprotein A1 (ApoA1) vs. controls (both p < 0.001). Elevated TG (progression-free survival [PFS] HR = 1.33, 95% CI 1.04-1.69; overall survival [OS] HR = 1.37, 95% CI 1.04-1.80) and reduced ApoA1 (PFS HR = 1.47, 95% CI 1.07-2.03; OS HR = 1.65, 95% CI 1.15-2.38) independently predicted inferior survival (all p < 0.05). Patients with an objective response demonstrated metabolic profile normalization: patients with high-TG levels (≥ median) experienced TG reduction and patients with low-ApoA1 levels (< median) experienced ApoA1 elevation (both p < 0.001), whereas patients with stable or progressive disease retained baseline profiles. These metabolic shifts predicted survival benefit (all p < 0.001). In the prospective cohort, patients with complete response (CR) had significantly higher baseline levels of 22 serum TG species compared with non-CR patients (fold change > 2.0, p < 0.05). Longitudinal analyses revealed divergent TG trajectories: patients without CR exhibited sustained high-level fluctuations, whereas patients with CR demonstrated stabilization at low levels. Transcriptome analysis suggested tumor-intrinsic lipid dysregulation in patients with high-TG/low-ApoA1 levels. Serum TG and ApoA1 serve as dynamic biomarkers in ENKTL.

Light-chain (AL) amyloidosis is a rare disease and its early diagnosis remains challenging. This study aimed to develop an artificial intelligence (AI)-based diagnostic assistance system to improve the early diagnosis of AL amyloidosis and facilitate earlier and more precise disease management. Through cooperation with 18 hospitals in the Chinese Registration Network for Light-chain Amyloidosis (CRNLA), 1,355 patients with AL amyloidosis were registered and followed up from January 2010 to January 2022. Ten variables that are easily monitored in clinics, including age, cardiac troponin I (cTnl), N-terminal prohormone B-type natriuretic peptide (NT-ProBNP), creatinine (Crea), albumin (ALB), total bilirubin (Tbil), alkaline phosphatase (ALP), interventricular septum (IVS), left ventricular posterior wall (LVPW), and ejection fraction (EF), were selected. An early assistant diagnostic model of AL amyloidosis was established using gradient boosting decision tree (GBDT), support vector machine (SVM), random forest (RF), and ensemble learning models. A validation subset of challenging cases from the external validation set was used to compare the performance of the AI-based early diagnostic assistance system to that of physicians. All of the typical machine learning algorithms, namely the GBDT, SVM, RF, and ensemble learning models, performed well. The ensemble learning model was considered to have the best performance in the external validation set based on its highest F1 value (0.94) and an area under the receiver operating characteristic (ROC) curve of 0.9784 (95% confidence interval [CI]:0.963-0.987). Performance comparisons between the AI-based early diagnostic assistance model and physicians suggested that the diagnostic accuracy of the AI model (0.95,95%CI:0.92-0.98;P < 0.05) substantially exceeded that of the hematologists (0.73,95%CI:0.7-0.82) and other physicians (0.65,95%CI: 0.61-0.71). The model established by AI, which uses routine laboratory and echocardiography results, can predict the possibility of AL amyloidosis in various scenarios, which may support the early diagnosis of this rare disease.

Molecular diagnostic methods largely rely on expensive equipment and complex operations, which makes it difficult to achieve rapid and low-cost detection. In recent years, the increasing demand for point-of-care testing has driven the rapid development of isothermal amplification techniques, due to their simplicity and low equipment requirements. However, complex nucleic acid extraction steps are still required before most isothermal amplification. In this study, we propose a nucleic acid extraction-free gene detection method: direct multiplex Recombinase Aided Amplification combined with reverse dot blot hybridization (dmRAA-RDB). This method can detect multiple targets simultaneously and offers advantages such as high sensitivity, high specificity, low cost, no need for expensive instruments, and visual detection. By pre-treating whole blood samples with sodium hydroxide solution, the samples can be directly used for isothermal amplification and combined with commercial reverse dot blot (RDB) technology to rapidly detect 17 types of β-thalassemia mutations. The experimental results demonstrated that the pre-treated whole blood samples allowed for the simultaneous, stable, and efficient enrichment of all three target fragments via direct multiplex isothermal amplification. This single-tube triple amplification strategy demonstrates significant innovation in the field of isothermal amplification. Moreover, the workflow is shortened by nearly half, and a side-by-side comparison of 60 clinical samples showed 100 % agreement with the commercial PCR-RDB kit. The dmRAA-RDB method offers a highly promising, innovative solution for large-scale, rapid, and low-cost β -thalassemia screening in primary-care and resource-limited settings, and opens a new avenue for detecting other mutant genes.

Chronic graft-versus-host disease (cGVHD) is a major complication for long-term survivors after hematopoietic cell transplantation (HCT). Bronchiolitis obliterans syndrome (BOS) is the crucial manifestation of lung cGVHD. Ruxolitinib has been approved by the Food and Drug Administration (FDA) for cGVHD treatment, but the response for BOS has not been sufficiently evaluated. We conducted a multicenter study involving 125 patients diagnosed with BOS post-HCT who received second-line therapies, including 77 patients treated with ruxolitinib (ruxolitinib group) and 48 patients with non-ruxolitinib therapies (control group). The primary endpoint was progression of BOS. By the third month, 18.2% of patients in the ruxolitinib group progressed, versus 43.8% in the control group (p = 0.001). The 2-year overall survival (OS) was 73.2% (95%CI 63.5%-84.5%) for the ruxolitinib group versus 60.2% (95%CI 47.4%-76.6%) for the control group (p = 0.012). The BOS-progression-free survival (BOS-PFS) was 69.0% (95%CI 59.1%-80.5%) versus 51.2% (95%CI 38.7%-67.7%, p = 0.011). Early switch to second-line therapy for BOS independently favored lower progression incidence (OR = 0.203, [95%CI 0.070-0.585], p = 0.003). Additionally, we observed that ruxolitinib was well-tolerated during the treatment of BOS. In conclusion, our findings indicated that ruxolitinib is an effective and safe second-line option for BOS.

Given the adverse impact of deep vein thrombosis (DVT) on the prognosis of multiple myeloma (MM) patients, identifying biomarkers for DVT is crucial for improving MM patient clinical outcomes. Therefore, this study aimed to evaluate the predictive value of miR-503-5p for DVT in MM, and explored the underlying mechanisms. Serum samples were collected from MM patients with and without DVT to measure miR-503-5p expression levels. ROC and Kaplan-Meier curves were employed to examine the predictive potential of miR-503-5p in MM-related DVT. MM serum-cultured human umbilical vein endothelial cells (HUVECs) were used to investigate the mechanisms of miR-503-5p in influencing the disease. Cell viability, oxidative stress status, and IL-6, TNF-α, TF, and TM levels were evaluated by CCK-8, antioxidant activity assay, and qRT-PCR. MiR-503-5p was upregulated in MM patients with DVT. The upregulation of miR-503-5p was a risk factor that demonstrated a high predictive value for DVT in MM patients. MiR-503-5p upregulation mediated the promotive effect of MM serum on HUVEC viability reduction, IL-6, TNF-α, and TF expression, and oxidative stress, and the inhibitory effect of MM serum on HUVEC TM expression. Moreover, WNT3A was a potential target of miR-503-5p in MM-related DVT. WNT3A downregulation mediated the effect of miR-503-5p on HUVECs. MiR-503-5p might be a promising biomarker for predicting DVT development in MM patients. MiR-503-5p might promote thrombosis in MM by affecting vein endothelial cells (VECs) through targeting WNT3A.

Hemoglobin Suresnes (Hb Suresnes) is a rare hemoglobin variant caused by a substitution of arginine to histidine at position 141 (p.Arg142His) in the COOH terminus of the α-globin chain. This structural change alters the oxygen affinity of hemoglobin and leads to erythrocytosis. We report the first genetically confirmed case of Hb Suresnes co-inherited with α-thalassemia (--/αα) in an East Asian patient, diagnosed via trio whole exome sequencing (WES). A 33-year-old male presented with asymptomatic erythrocytosis, microcytosis, and a family history of elevated red cell indices. Under genetic analysis with WES, we identified a heterozygous Hb Suresnes variant [NM_000558.3(HBA1): c.425G > A (p.Arg142His)] inherited from his father, alongside α-thalassemia (--/αα) inherited from his mother. The overlapping hematologic phenotype initially mimicked polycythemia vera, prompting empirical therapeutic phlebotomy. This case highlights the diagnostic pitfall of misclassifying hereditary erythrocytosis as polycythemia vera and emphasizes the role of WES in resolving the complexity of coexisting hemoglobinopathies, ensuring accurate diagnosis and appropriate management.

Multiple myeloma (MM) is a refractory hematologic malignancy driven by clonal plasma cell proliferation and a complex bone marrow microenvironment. CD81, a tetraspanin protein, has been implicated in immune regulation and cancer progression, but its role in MM remains unclear. This study investigated the prognostic significance of CD81 expression and its relationship with immune cells in 178 newly diagnosed MM patients. CD81 positivity (60.67%) was associated with reduced overall survival (OS) but not progression-free survival (PFS). High CD81 expression correlated with decreased peripheral CD8 + T cell counts and increased M2 macrophage infiltration (CD206+), both linked to poorer outcomes. Conversely, high CD68 expression (pan-macrophage marker) was associated with improved prognosis, potentially reflecting favorable M1 macrophage activity. These findings highlight CD81 as a prognostic marker in MM, influencing immune cell dynamics and clinical outcomes. The interplay between CD81, M2 macrophages, and CD8 + T cells underscores the complexity of the MM immune microenvironment, suggesting novel therapeutic targets. Further studies are needed to elucidate CD81's mechanistic role in immune modulation.

Primary central nervous system lymphoma (PCNSL) is a rare form of lymphoma with a poor prognosis. We used the LOC network database, including 365 patients from 14 voluntary centers. Inclusion criteria were age ≥ 60 years, immunocompetence, confirmed PCNSL diagnosis and treatment with curative intent with MPV-based regimen (Methotrexate, Procarbazine, Vincristine) between 2011 and 2021. We analyzed LOS from first day of chemotherapy to dismissal from hospital. Using the MAXStat method we found the LOS threshold of 15 days, to be one of most statistically significant and most convenient to separate two groups with different OS. The median age of the whole population was 71 years, median Karnofsky performance score (KPS) was 70%. The main differences between short and long LOS groups were median KPS at diagnosis (70% vs 50%) and deep structure involvement status (51% vs 67%). With a median follow up of 22.8 months, the median OS was respectively 62.2 and 20 months for short and long LOS. Median PFS was respectively 18 and 9.3 months. Multivariate analysis found in our cohort that age was associated with OS (P = 0.01) and LOS with OS (P = 0.005) and PFS (P = 0.014). KPS at diagnosis is a cofounder to LOS in the analysis. LOS remains associated with OS (P = 0.016) in a subgroup analysis of patients with baseline KPS < 70%. Altogether, the LOS > 15 days identifies a population of patients with poorer outcome in elderly PCNSL patients. Its underlying drivers require further investigation in larger and prospective cohorts.

As life expectancy in patients with chronic myeloid leukemia (CML) approaches that of the general population, fertility preservation has become a critical quality-of-life consideration, especially for younger patients. Although third-generation (3G) tyrosine kinase inhibitors (TKIs), such as olverembatinib, demonstrate potent efficacy against TKI-resistant disease, their reproductive safety profiles remain largely undefined. We report two TKI-resistant male patients who achieved sustained deep molecular responses with olverembatinib and who subsequently conceived healthy offspring with their partners. These cases provide clinical evidence that olverembatinib exposure does not preclude normal male fertility or healthy offspring, emphasizing the need for systematic reproductive safety data on 3G TKIs.

Chimeric antigen receptor T-cell (CAR-T) therapy has transformed diffuse large B-cell lymphoma (DLBCL) treatment, but data in diverse urban populations remain limited. We report outcomes from a comprehensive cancer center in the Bronx. Montefiore Health System treated 79 DLBCL patients with CAR-T from March 2018 to July 2024. Demographics, comorbidities, socioeconomic factors, and acute complications, including immune effector cell neurotoxicity syndrome (ICANS), cytokine release syndrome (CRS), cardiotoxicity, and pulmonary events, were tabulated. Kaplan-Meier survival analysis was performed up to five years. Multivariate adjusted hazard ratios (aHR) were calculated for remission and 3-year mortality. CAR-T achieved complete remissions in 50.6%, partial remission in 16.5%, and progression in 22.8%. Cumulative mortality was 10.1% during treatment and 34.2% by five years. Complete remission reduced 3-year mortality (aHR 0.13; 95% CI 0.04-0.43). Complications included CRS (76.0%), ICANS (49.4%), neutropenic fever (58.2%), and sepsis (19.0%). ICANS correlated with CRS, ICU stay, and sepsis. Socioeconomic status was not linked to mortality, but comorbidities increased risk. CAR-T complete remission is an independent predictor of reduced mortality. High rates of complications, particularly CRS and ICAN, reinforce the need for vigilant monitoring and management strategies to enhance long-term outcomes.

Pediatric acute lymphoblastic leukemia (ALL) is the most prevalent hematologic malignancy in children. This study aimed to investigate the diagnostic value and functional role of serum microRNA-493-3p (miR-493-3p) in pediatric ALL. Serum miR-493-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in103 ALL patients and 85 healthy controls. Bioinformatic tools were used to screen potential target genes of miR-493-3p, and dual-luciferase reporter assays were performed for validation. Functional experiments were conducted by regulating miR-493-3p and its target gene expression to assess changes in leukemic cell malignant phenotypes. Serum miR-493-3p expression was notably downregulated in ALL patients compared with healthy controls (P < 0.001), demonstrating good diagnostic accuracy with an area under the curve (AUC) of 0.881. Low miR-493-3p expression was associated with advanced risk stratification (P = 0.001) and poor survival (P < 0.05). Mechanistically, we identified Dpy-30 histone methyltransferase complex regulatory subunit (DPY30) as a direct target of miR-493-3p, showing an inverse correlation in clinical samples (r=-0.755, P < 0.001). Functional experiments revealed that miR-493-3p overexpression suppressed leukemic cell proliferation and invasion (P < 0.001) while promoting apoptosis through targeting DPY30, effects that were partially reversed by DPY30 restoration. Serum miR-493-3p serves as a promising noninvasive biomarker for pediatric ALL diagnosis and prognosis Our findings demonstrate that miR-493-3p functions as a tumor suppressor in ALL by targeting DPY30, suggesting the miR-493-3p/DPY30 axis as a potential therapeutic target for ALL treatment.

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.

Lymphoblastic lymphoma (LBL) is a rare, aggressive malignancy comprising T-cell (T-LBL) and B-cell (B-LBL) subtypes. While outcomes for LBL have improved, comprehensive national data on clinical and biological features remain limited. We conducted a retrospective review of children and adolescents with LBL in Ireland over 20 years (2004-2023). Data on demographics, clinical presentation, tumour characterization, treatment protocols, and outcomes were analysed. The cohort included 52 patients: 79% with T-LBL and 21% with B-LBL. T-LBL cases predominantly affected males (2.2:1) and presented with advanced disease, including mediastinal masses (98%) and high lactate dehydrogenase levels. B-LBL cases had a female predominance (0.4:1) and localized disease (82%). Survival outcomes were excellent for B-LBL, with 5-year event-free survival (EFS) and overall survival (OS) of 100%. For T-LBL, 5-year EFS and OS were 85%. Relapsed/refractory disease occurred in 4% (T-LBL only). Genetic, Minimal Disseminated Disease and Minimal Residual Disease analyses were limited. LBL outcomes in Ireland align with international reports, highlighting favourable survival but underscoring the need for improved risk stratification and genetic profiling, particularly for T-LBL.

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.