Although programmed cell death 1 inhibitors (PD1i) are recommended in guidelines for relapsed/refractory extranodal NK/T-cell lymphoma (ENKTL), their role in frontline therapy remains unclear. In this retrospective, multi-center study of 755 newly diagnosed ENKTL patients, 17.9% received first-line PD1i. Despite harboring more adverse risk features, the PD1i group showed significantly improved progression-free survival (hazard ratio = 0.62, p = 0.007) and overall survival (hazard ratio = 0.55, p = 0.027) after a median follow-up of 32.9 months. The benefit was also observed in key subgroups (non-upper aerodigestive tract, advanced stage, intermediate/high-risk). Conventional multivariate Cox regression before propensity score matching, robust multivariate Cox analysis after matching, and the time-varying Cox model employed in landmark analysis consistently demonstrated that PD1i therapy served as an independent favorable prognostic factor for both progression-free survival and overall survival. The random forest algorithm revealed enhanced efficacy with PD1i-asparaginase combination therapy, showing about a 50% reduction in event probability, particularly in advanced-stage and intermediate/high-risk patients. Multi-state survival modeling indicated PD1i primarily delays disease progression rather than post-progression survival. Safety data showed that adding PD1i to asparaginase-based chemotherapy resulted in an expected increase in hematologic toxicities, but with a reduced risk of severe/fatal infections and rare severe immune-related adverse events, demonstrating a favorable risk-benefit profile. Overall, in this study, frontline PD1i, particularly in combination with asparaginase, yielded significantly improved outcomes and demonstrated a manageable safety profile in intermediate-/high-risk and advanced ENKTL. This evidence supports its incorporation into first-line treatment and underscores the need for prospective randomized trials.

Background:Drug resistance in diffuse large B-cell lymphoma (DLBCL) contributes to poor prognosis in 30-40% of newly diagnosed patients in the era of first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Targeting Bcl-2 has been shown to target for improve the prognosis of these patients, based on the clinical trials of its inhibitor, venetoclax. However, venetoclax resistance in DLBCL remains a challenge. Methods: The 'WGCNA' package was used to comprehensively screen for Bcl-2 inhibitor-resistant genes (Bcl-2RGs) and the Bcl-2RGs signature was established using LASSO regression analysis with ten-fold cross-validation. Results: The Bcl-2 signature is an effective prognostic prediction model using Gene Expression Omnibus data analysis. In addition, we demonstrated that the inhibition of alpha protein kinase 1 (ALPK1) decreased the proliferation of DLBCL cells and increased apoptosis. ALPK1 inhibitor treatment synergized with venetoclax to suppress the ALPK1/NFκB signaling pathway. Conclusion: Overall, we showed that the Bcl-2 signature could predict the prognosis of patients with DLBCL, and that ALPK1 could be a promising target for sensitizing patients with DLBCL to venetoclax therapy. Methods:The 'WGCNA' package was used to comprehensively screen for Bcl-2 inhibitor-resistant genes (Bcl-2RGs) and the Bcl-2RGs signature was established using LASSO regression analysis with ten-fold cross-validation. Results: The Bcl-2 signature is an effective prognostic prediction model using Gene Expression Omnibus data analysis. In addition, we demonstrated that the inhibition of alpha protein kinase 1 (ALPK1) decreased the proliferation of DLBCL cells and increased apoptosis. ALPK1 inhibitor treatment synergized with venetoclax to suppress the ALPK1/NFκB signaling pathway. Conclusion: Overall, we showed that the Bcl-2 signature could predict the prognosis of patients with DLBCL, and that ALPK1 could be a promising target for sensitizing patients with DLBCL to venetoclax therapy. Results:The Bcl-2 signature is an effective prognostic prediction model using Gene Expression Omnibus data analysis. In addition, we demonstrated that the inhibition of alpha protein kinase 1 (ALPK1) decreased the proliferation of DLBCL cells and increased apoptosis. ALPK1 inhibitor treatment synergized with venetoclax to suppress the ALPK1/NFκB signaling pathway. Conclusion: Overall, we showed that the Bcl-2 signature could predict the prognosis of patients with DLBCL, and that ALPK1 could be a promising target for sensitizing patients with DLBCL to venetoclax therapy. Conclusion:Overall, we showed that the Bcl-2 signature could predict the prognosis of patients with DLBCL, and that ALPK1 could be a promising target for sensitizing patients with DLBCL to venetoclax therapy.

The prognostic impact of exposure to PM2.5 and its components across multiple time windows in DLBCL remains unclear. A total of 1,154 newly diagnosed DLBCL patients were included across seven medical centers. Individual exposures to PM2.5 and its five chemical components, including SO42-, NO3-, NH4+, OM, and BC, were estimated across four exposure windows of 1, 3, 5, and 10 years before diagnosis. OM averaged over 1 year (HR = 1.319; 95% CI: 1.035-1.681) and 5 years (HR = 1.325; 95% CI: 1.070-1.641), as well as SO42- averaged over 3 years (HR = 1.348; 95% CI: 1.008-1.801), were associated with worse prognosis in DLBCL patients. Dose-response patterns were observed in quartile-based analyses. In multi-pollutant analysis, the combined mixture of five components averaged over 3 years was also associated with adverse prognosis. However, given the observational design, causal inference cannot be established, and further validation is warranted.

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

The efficacy of immune checkpoint inhibitors (ICI) in diffuse large B-cell lymphoma (DLBCL) is often limited by the immunosuppressive tumor microenvironment (TME), which comprises diverse cellular and non-cellular components. Among these, neutrophil extracellular traps (NETs) have emerged as potential immunomodulators that may contribute to immune suppression; however, their functional significance and regulatory mechanisms in DLBCL remain elusive. NETs levels were evaluated in DLBCL patient specimens and their effects on clinical outcomes were analyzed. Using a syngeneic murine lymphoma model, we assessed the therapeutic effect of DNase I-mediated NET degradation, both alone and in combination with anti-PD-L1 antibody. Mechanistic investigations included in vivo macrophage depletion, transcriptomic profiling, and in vitro assays under normoxic and hypoxic conditions. NETs were significantly elevated in DLBCL tissues and were correlated with advanced disease stage, elevated PD-L1 expression, and poor survival. Deoxyribonuclease I (DNase I) treatment potently inhibited tumor growth and exhibited marked synergy with PD-L1 blockade. This combination therapy robustly reduced immunosuppressive macrophages and myeloid-derived suppressor cells while enhancing CD8+ T cell infiltration and function. Mechanistically, NETs promoted T cell exhaustion primarily through macrophage-dependent pathways and affected by the oxygen tension: under normoxia, NETs drove macrophages into a dysfunctional phenotype, whereas under hypoxia, they were associated with PI3K-Akt pathway to drive macrophages toward an immunosuppressive phenotype. Furthermore, hypoxia promoted NET formation via the HIF-1α/IL-8 axis, establishing a self-reinforcing immunosuppressive circuit. Our study identifies NETs as pivotal regulators of immunosuppression in DLBCL and demonstrates that targeting NETs with DNase I effectively remodels the TME and enhances ICI efficacy, providing a compelling rationale for clinical translation of this combinatorial approach.

Previous studies have been inconsistent concerning the associations of smoking and alcohol consumption with the prognosis of diffuse large B-cell lymphoma (DLBCL). This study aimed to investigate the associations of smoking and drinking status with overall survival (OS) in male patients with DLBCL. A total of 371 male patients with newly diagnosed DLBCL were retrospectively enrolled from eight medical centers. Smoking and drinking status were assessed as binary variables (yes or no). Inverse probability of treatment weighting (IPTW) based on propensity scores was applied to adjust for potential confounders. Kaplan–Meier survival analysis and Cox proportional hazards models were used to assess associations. Overall, 17.3

OBJECTIVES:This study aimed to compare clinical, and molecular features between acute myeloid leukemia (AML) patients aged <50 and ≥50 years, while also assessing their respective treatment outcomes and prognostic factors. METHODS:We conducted a retrospective analysis of clinical data from AML patients treated at our institution between October 2015 and June 2021, supplemented by data extracted from the SEER database spanning 2000 to 2019. Survival outcomes were evaluated using Kaplan-Meier methodology. RESULTS:In patients aged ≥50 years, we observed higher prevalence of DNMT3A, IDH2, and TP53 mutations along with -5/del (5q) karyotype abnormalities. The treatment outcomes were suboptimal, with a complete response (CR) rate of 45.9%, relapse rate of 60.8%, and two-year overall survival (OS) rate of 33.3%. VEN-treated chemotherapy-intolerant patients showed significantly improved two-year OS (36.0% vs 12.1% in non-VEN group; P = 0.006). In contrast, patients aged <50 years exhibited a distinct molecular profile characterized by a predominance of NRAS, biallelic CEBPA, WT1, and C-KIT mutations, along with a higher incidence of RUNX1-RUNX1T1 and CBFB-MYH11 fusion genes. This group demonstrated more favorable clinical outcomes, with a CR rate of 73.1%, relapse rate of 36.8%, and two-year OS rate of 68.3%. CONCLUSIONS:This study revealed that patients aged ≥50 years displayed more complex genetic aberration profiles and experienced significantly poorer prognoses compared to their younger counterparts. These findings provided novel insights for optimizing treatment strategies for middle-aged and elderly AML patients in the Chinese population.

BackgroundInterleukin-6 (IL-6) and ferritin are routinely monitored during chimeric antigen receptor T-cell (CAR-T) therapy; however, their temporal dynamics and outcome-specific relevance remain inadequately characterized. This study aimed to evaluate the value of IL-6 and ferritin at multiple time points in patients with diffuse large B-cell lymphoma (DLBCL) receiving anti-CD19 CAR-T therapy.MethodsA total of 54 patients (median age 49.0 years; 64.8% male) were retrospectively analyzed. Post-infusion IL-6 and ferritin levels were measured on day 1, day 7, day 14, and the peak value was defined as the highest level within the first 14 days after infusion. Survival was evaluated using Cox proportional hazards regression, while logistic regression was used for binary outcomes, with Firth penalized regression performed as a sensitivity analysis. Spearman correlation was used to characterize relationships between IL-6, ferritin, and routine laboratory parameters.ResultsCRS occurred in 68.5% of patients, and the objective response rate was 70.4%. IL-6 levels were significantly higher in patients with CRS at day 1 (P = 0.003) and at peak levels (P = 0.005). IL-6 on day 7 was associated with mortality (OR = 1.625, 95% CI: 1.076-2.737, P = 0.038). Ferritin was associated with CRS at all time points and showed an exploratory association with mortality, but not with treatment response. Day 7 IL-6 showed the numerically highest AUC for death status, whereas Day 14 ferritin showed the numerically highest AUC for CRS. IL-6 was negatively correlated with albumin at Day +1, Day +7, and peak, whereas ferritin was negatively correlated with RBC count at Day +1, Day +7, and peak.ConclusionSerial IL-6 and ferritin measurements were associated with CRS-related inflammatory status. Day +7 IL-6 and Day +7 ferritin showed exploratory associations with mortality.

Background:Hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder characterized by uncontrolled inflammation. In adults, lymphoma is the most common underlying cause. The lipid profile is frequently dysregulated in lymphoma-associated HLH (LA-HLH), and the clinical significance remains to be determined. Objectives:This study aimed to evaluate the prognostic value of baseline lipid profiles and the dynamic changes in high-density lipoprotein cholesterol (HDL-c) in adult patients with LA-HLH. Design:A multicenter, retrospective cohort study. Methods:We analyzed 277 adult patients with LA-HLH from 27 medical centers (2015-2023). Baseline lipid levels and post-treatment HDL-c levels were measured. The optimal prognostic cutoff was determined using X-tile software. Survival analysis was performed using Kaplan-Meier and Cox regression methods. Results:Low HDL-c (<1.03 mmol/L) was observed in 93.9% (260/277) patients at diagnosis. A baseline HDL-c <0.48 mmol/L was independently associated with reduced overall survival (OS; hazard ratio, HR = 1.51, 95% confidence interval, CI: 1.10-2.09, p = 0.012) and 60-day survival (HR = 1.66, 95% CI: 1.10-2.49, p = 0.015). The post-treatment/baseline HDL-c ratio was significantly lower in patients with T/NK-cell malignancies than in those with B-cell non-Hodgkin lymphoma. A lower ratio (<1.71) was significantly associated with reduced survival. Patients with both low baseline HDL-c (<0.48 mmol/L) and low ratio (<1.71) constituted a high-risk group with the worst outcomes (60-day survival: 46.7% vs 81.8%, p = 0.004; median OS: 52 days vs not reached, p < 0.001). Conclusion:HDL-c and its dynamic changes are clinically feasible markers for predicting outcomes in patients with LA-HLH.

It is widely acknowledged that B-cell lymphoma represent a significant threat to human health, and Bruton Tyrosine Kinase inhibitors (BTKi) have been shown to exhibit superior clinical efficacy and safety in comparison to conventional chemotherapy and immunotherapy modalities. However, as patients continue to use BTKi over a time, they will inevitably encounter the drug resistance. This resistance renders the therapeutic efficacy of BTKi, thereby significantly constraining its clinical benefits. Drug resistance of tumor is a multifaceted process influenced by numerous factors, mainly including individual genetic variations, tumor stem cells, drug inactivation, reduced drug absorption, and altered metabolism of anti-tumor drugs. The tumor microenvironment (TME) has been demonstrated to exert an important influence on the process of therapy resistance. It is evident that non-cellular components (e.g. the extracellular matrix, hypoxia, an acidified microenvironment, exosome, and cytokines) modulate the drug resistance through different mechanisms. These mechanisms include physical barriers that impede drug delivery, the formation of an immunosuppressive microenvironment, metabolic reprogramming and the activation of bypass signal moueculars. Furthermore, the presence of mutations of moleculars involved in the BCR signaling pathways (e.g. BTK and PLCG2 mutations) and the aberrant activation of key pathways such as PI3K-AKT-mTOR, NF-κB, Wnt/β-catenin and MAPK/ERK signaling further weakened the efficacy of BTKi. This review focus on the mechanism of BTKi resistance, the role of the TME and its components in drug resistance. It emphasized that targeting TME remodeling and combined the inhibition of multiple pathways may provide a new strategy for overcoming drug resistance, optimizing the treatment paradigm of B-cell lymphoma.

The aim of this study was to investigate whether eprenetapopt (APR-246, PRIMA-1MET) could enhance anti-tumor effects of venetoclax (VEN) on cell proliferation and apoptosis in vitro cell lines, and to further explore the potential mechanisms underlying the enhanced effects. The cellular proliferative capacity was assessed using the CCK-8 assay, whereas apoptosis levels were evaluated through Western blot analysis and flow cytometry. Key pathways and genes were identified using the following bioinformatics tools: the Cancer Dependency Map (DepMap) and the Cancer Genome Atlas Program (TCGA) database, gene set enrichment analysis (GSEA), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Both APR-246 and VEN monotherapy demonstrated significant anti-proliferative and pro-apoptotic effects in TP53 R248Q-mutated AML cell lines. Notably, APR-246 enhanced therapeutic efficacy of VEN in TP53-mutated AML cells. From a mechanistic perspective, APR-246 may exert its anti-leukemic effects through dual pathways: (1) Associated with downregulation of PPP1CA expression, which could potentially involve the Hippo signaling pathway, coinciding with observed proliferation inhibition and apoptosis induction; (2) Attenuation of VEN-induced MCL-1 (myeloid cell leukemia-1) overexpression, potentially contributing to the augmented anti-tumor activity with VEN in TP53-mutated AML models. In TP53 R248Q-mutated AML cell lines, APR-246 augmented anti-tumor effects of VEN via proliferation inhibition and apoptosis induction. These observed enhanced effects may relate to multiple factors including: PPP1CA inhibition, Hippo pathway affecting, and MCL-1 expression suppression, warranting further investigation.

Asparaginase-based regimens and anti-PD-1 therapies have significantly improved survival in patients with extranodal natural killer/T-cell lymphoma (ENKTL) and are now increasingly incorporated into earlier treatment lines. However, clinical outcomes for patients with dual resistance to asparaginase and PD-1 inhibitors remain poorly defined. We conducted a multicenter retrospective study of 61 patients with dual resistance from a cohort of 900 ENKTL patients across 12 academic centers in China. Among 61 patients, median overall survival from initial diagnosis (OS-1) was 21.9 months (95% CI: 14.7-43.1). After the onset of dual resistance, the median post-resistance survival (OS-2) was 4.9 months (95% CI: 2.8-9.9). Rechallenge with asparaginase-based regimens or anti-PD-1 agents resulted in only limited benefit, yielding median progression-free survival (PFS) of 3.2 months (95% CI: 1.4-5.0) and 2.7 months (95% CI: 2.1-3.3), respectively. Chidamide-containing regimens were associated with a significantly longer OS-2 compared to regimens without chidamide (HR, 0.46; 95% CI: 0.24-0.88; P = 0.019). Other novel agents, including inhibitors of XPO1, PI3K, and JAK1, along with brentuximab vedotin, did not demonstrate a significant survival benefit in patients with dual-resistant ENKTL. This is the first comprehensive analysis of dual-resistant ENKTL, revealing poor prognosis and suggesting a potential signal of benefit associated with chidamide-containing regimens.

Objective:To investigate the relationship between TP53 and MYD88 mutations and treatment efficacy in patients with diffuse large B-cell lymphoma(DLBCL)who received rituximab-based standard chemoimmunotherapy.Methods:The clinical data of 92 patients with newly diagnosed DLBCL who were treated in the Department of Hematology of the Huai'an No.1 People's Hospital and Yancheng No.1 People's Hospital from January 1,2015 to December 30,2023 were retrospectively analyzed.Chi-square test,univariate and multivariate logistic regression analyses were used to identify risk factors associated with treatment efficacy,and a predictive model was further established.Survival curves were plotted using the Kaplan-Meier method,and differences in survival between groups were compared by the log-rank test.Results:Among the 92 patients,71(77.2％)achieved post-induction remission(remission group)and 21(22.8％)did not respond to treatment(non-remission group).The proportions of patients with elevated lactate dehydrogenase(LDH)(P=0.022)and those with MYD88 mutation(P=0.021)were significantly higher in the non-remission group than in the remission group.Univariate analysis showed that LDH(OR=3.482,P=0.027)and MYD88 mutation(OR=3.175,P=0.024)were factors influencing treatment efficacy in DLBCL patients receiving chemoimmunotherapy.Multivariate analysis showed that TP53 mutation(P=0.031)and MYD88 mutation(P=0.010)were independent risk factors for poor treatment efficacy in DLBCL patients.A treatment efficacy prediction model for DLBCL was established based on TP53 and MYD88 mutations,with an area under the receiver operating characteristic(ROC)curve of 0.705.According to the novel predictive model,the enrolled patients were divided into high-risk and low-risk groups.Treatment efficacy analysis showed that the objective response rate(ORR)of the low-risk group was significantly higher than that of the high-risk group(92.3％vs.66.0％,P=0.006),and the progression-free survival(PFS)and overall survival(OS)of patients in the high-risk group were significantly poorer than those in the low-risk group(PFS:P=0.024;OS:P=0.004).Conclusion:TP53 mutation and MYD88 mutation are independent risk factors for poor efficacy in DLBCL patients receiving first-line immunochemotherapy.The novel predictive model constructed based on these two mutations can identify patients with potential poor response to first-line chemoimmunotherapy,which may provide a reference for optimizing the first-line individualized treatment strategy for DLBCL.

OBJECTIVES:Numerous observational research avenues have identified a possible correlation between aplastic anemia and autoimmune diseases, rooted in analogous dysfunctional immune responses. Nevertheless, causal link between autoimmune diseases and aplastic anemia remains elusive. The study aims to investigate the causal association of autoimmune diseases and aplastic anemia. METHODS:This study leveraged summary data from genome-wide association studies pertaining to six prevalent autoimmune diseases: ulcerative colitis, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, celiac disease, and type 1 diabetes mellitus, procured from expansive, public genome-wide association studies meta-analysis databases. Aplastic anemia - related genetic information was extracted from the UK Biobank. Utilizing single nucleotide polymorphisms as genetic instruments - meeting criteria P < 5 × 10-8 and linkage disequilibrium [LD] r² < 0.001 - the study employed Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis to gauge the sensitivity concerning the impact of autoimmune diseases on aplastic anemia. RESULTS:The findings underscore a definitive causal relationship between systemic lupus erythematosus and aplastic anemia, as evidenced by the statistics (ORIVW = 1.193, 95% CI 1.013-1.404, P = 0.035). Duplicate SLE GWAS from the FinnGen database demonstrated that patients with SLE are more susceptible to AA (ORIVW = 1.193, 95% CI 1.013-1.404, P = 0.035). Additionally, the Mendelian randomization analysis reported no evidence of horizontal or directional pleiotropy. CONCLUSIONS:In summary, the study suggests that systemic lupus erythematosus could serve as a potential risk factor contributing to the onset of aplastic anemia. To substantiate this hypothesis, ensuing studies encompassing larger sample sizes are warranted.

Patients with cancer, particularly those diagnosed with hematological malignancies, exhibit thrombus incidence rates that exceed those observed in the general population by a substantial margin, and this elevated risk is associated with worse clinical outcomes. Neutrophil extracellular traps (NETs), which are web‑like structures released by neutrophils as part of their innate immune repertoire, drive coagulation and vascular occlusion by supplying a physical scaffold, recruiting procoagulant factors, and cleaving tissue factor pathway inhibitors. In hematological malignancies, emerging evidence points to NET overproduction and dysregulation as key drivers of thrombosis, representing a previously underappreciated mechanistic axis. The present review focuses on the molecular mechanisms by which NETs promote thrombosis, specifically on thrombosis associated with hematological malignancies (such as myeloproliferative neoplasm, acute myeloid leukemia, Hodgkin lymphoma, multiple myeloma and acute lymphoblastic leukemia), and also explores the clinical translation potential of NET‑related therapies. The present study offers a potential basis for refining current approaches to coagulation risk reduction in patients with hematological malignancies.

Background:The aggregate index of systemic inflammation (AISI, calculated as neutrophil count × monocyte count × platelet count/lymphocyte count) reflects systemic inflammatory status; however, its prognostic role in diffuse large B-cell lymphoma (DLBCL) remains underexplored. This study aimed to investigate the prognostic value of AISI in DLBCL. Methods:A total of 1332 DLBCL patients (median age 62 years; 52.3% male) were included in this study. Patients were stratified based on AISI quartiles, and a cut-off value was determined using restricted cubic splines (RCS) analysis. The associations between AISI and Overall survival (OS) were assessed using Kaplan-Meier analysis and Cox proportional hazards models. Results:Higher AISI levels were associated with adverse clinical features, including advanced Ann Arbor stage, poor performance status, and higher-risk categories of both the IPI and the NCCN-IPI. RCS analysis revealed a nonlinear relationship between AISI and OS, with an inflection point at 261.33. Kaplan-Meier analysis demonstrated that patients with AISI > 261.33 had significantly worse OS compared to those with AISI ≤ 261.33 (P = 0.003). Similarly, patients in the Q4 group had poorer OS than those in the lowest two quartiles (Q1-Q2) (P = 0.008). In fully adjusted Cox proportional hazards models (adjusted for age, sex, Ann Arbor stage, LDH, ECOG performance status, BMI, albumin, B symptoms, bone marrow involvement, central nervous system involvement, and liver/spleen involvement), high AISI level (> 261.33) were associated with increased mortality risk (HR = 1.28, 95% CI: 1.04-1.57, P = 0.018). Subgroup analyses indicated that the prognostic impact of AISI was particularly evident among patients classified as low risk by conventional prognostic systems. Conclusion:Elevated AISI was associated with inferior OS in DLBCL patients and may potentially serve as a prognostic biomarker.

While involved-site radiotherapy (ISRT) is the standard first-line treatment in localized non-gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the cumulative risk of distant relapse poses a persistent clinical challenge. We conducted a prospective phase II trial evaluating rituximab with 24 Gy ISRT, aiming to reduce distant relapse and enhance long-term survival. By October 2025, 60 patients with early-stage non-gastric MALT lymphoma were enrolled. Among the per-protocol efficacy-evaluable cohort (n = 55), the combined immunoradiotherapy regimen achieved a complete response rate of 100%. At a median follow-up of 30.2 months, only one distant recurrence was observed (estimated 5-year distant recurrence: 1.9%). In the full analysis set, 2- and 4-year progression-free survival rates were 98.0% and 92.9%, respectively, improving to 100% and 94.4% in the per-protocol set. Treatment-related hematologic toxicity was frequent but manageable. Infections were reported in 23.3%, including one grade 4 respiratory infection that necessitated treatment discontinuation. Immunophenotypic profiling revealed that parotid, thyroid, or mediastinal involvement correlated with higher lymphocyte proportions (39.5% ± 16.4%, P = 0.012). Post-treatment immunologic changes featured near-complete B-cell depletion and a compensatory expansion of NK cells. Overall, the combined immunoradiotherapy regimen demonstrated durable disease control in localized non-gastric MALT lymphoma, with potential synergistic benefit from NK cell-mediated immune activation. Trial registration: Chinese Clinical Trials Registry, ChiCTR2000036318; registered on Aug 22, 2020 (prospective).

OBJECTIVE:To observe the treatment response rate and safety of the combination of venetoclax and HEA (VHEA) regimen in the induction therapy of acute myeloid leukemia (AML) patients with KMT2A gene rearrangement. METHODS:Six patients with AML accompanied by KMT2A gene rearrangement were treated with the VHEA regimen ［venetoclax 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-14; Homoharringtonine 2 mg/(m2·d) on day 1-7; Etoposide 100 mg/d on day 1-5; Cytarabine 100 mg/(m2·d) on day 1-7］. The remission rate and safety of the VHEA regimen were observed. RESULTS:Among the 6 patients, 3 were relapsed or refractory AML, and 3 were newly diagnosed patients. After one course of induction chemotherapy, 5 patients achieved complete remission (CR), with 3 cases showing minimal residual disease (MRD) < 1.0×10-3 by flow cytometry and 3 cases showing 0.00% MRD by PCR, one patient who relapsed 13 months after transplantation died from pulmonary infection before evaluating the efficacy. Three patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR1, one patient relapsed 12 months after transplantation, with a total survival time of 20 months. The other 2 patients are currently in disease-free survival, with a follow-up period of 15 months and 5 months, respectively. Two patients did not undergo allo-HSCT, one patient died from relapse 4 months after survival, and the other patient is currently in CR and undergoing maintenance chemotherapy. The total CR rate of VHEA regimen in 6 patients with KMT2A gene rearrangement AML was 83.3% (5/6), with no treatment-related deaths. Chemotherapy-related adverse reactions such as myelosuppression and infection were within controllable range. CONCLUSION:The VHEA regimen can significantly improve the CR rate of AML patients with KMT2A gene rearrangement, with good safety. It may be a better choice for induction remission chemotherapy in newly diagnosed and relapsed/refractory AML patients with KMT2A gene rearrangement.