Autoimmune diseases (ADs) are strongly associated with a significantly increased risk of lymphoma, with the standardised incidence ratio (SIR) markedly elevated in certain conditions, most notably in Sjögren’s disease (SjD) where an SIR as high as 18.8 has been reported. The risk is particularly prominent for diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma. This review systematically elucidates the epidemiological features, pathological mechanisms, risk factors, and therapeutic strategies of ADs-associated lymphomas. Epidemiological studies have confirmed strong associations between ADs such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and SjD with specific lymphoma subtypes, and these associations appear to be bidirectional. Core pathogenic mechanisms involve malignant transformation driven by the immune–inflammatory continuum: chronic antigenic stimulation and the inflammatory microenvironment result in regulatory cell (Treg/Breg) dysfunction, tertiary lymphoid structure (TLS) formation, and clonal evolution. Specific autoantibodies directly contribute to oncogenesis by interfering with intracellular signalling pathways, mimicking antigenic stimulation, and forming immune complexes, while infectious agents such as Epstein–Barr virus synergistically promote malignant transformation within immunosuppressive microenvironments. Risk factors encompass intrinsic disease features, treatment-related risks and gene–environment interactions. Clinical management must balance the dual imperatives of “controlling inflammation” and “minimising treatment-related risks”. Targeted therapies, such as rituximab and BTK inhibitors, as well as haematopoietic stem cell transplantation (HSCT), have offered hope, but prognosis remains profoundly influenced by baseline immune status. Future research should focus on risk stratification guided by multi-omics, the application of novel immunotherapies in the autoimmune setting, and the optimisation of multidisciplinary care models.

Relapsed or refractory CNS lymphoma (R/R CNSL) has limited treatment options. This multicenter retrospective study enrolled 84 consecutive R/R CNSL patients (median age 59 years; 53 PCNSL, 31 SCNSL) to evaluate efficacy and safety profiles of glofitamab therapy. With a median of 2.5 prior lines of therapy, the objective response rates (ORR) and complete response rates (CRR) for PCNSL were 88% (CRR 59%) with glofitamab monotherapy (n=32) and 100% (CRR 81%) with combination therapy (n=21), respectively; for SCNSL, ORR and CRR were 88% (CRR 75%) with glofitamab monotherapy (n=8) and 91% (CRR 65%) with combination therapy (n=23). At 14.7 months follow-up, median progression-free survival was 19.5 months for PCNSL and 13.5 months for SCNSL. Cytokine release syndrome occurred in 40% (all grade 1-2) of patients, and ICANS in 8%. Glofitamab-based therapy demonstrated substantial activity with manageable toxicity in this study, offering a promising treatment paradigm for R/R CNSL patients.

BackgroundPatients with previously untreated follicular lymphoma (FL) or marginal zone lymphoma (MZL) with high-tumor burden represent a subset with unfavorable prognosis. However, the efficacy of obinutuzumab in this specific high-risk population remains incompletely characterized. This study aimed to compare the efficacy and safety of obinutuzumab-based versus rituximab-based chemotherapy in patients with high-risk features of FL and MZL. MethodsA retrospective analysis was conducted on 186 patients with histologically confirmed FL or MZL who received either obinutuzumab-based (n=92) or rituximab-based (n=94) chemotherapy at the First Hospital of Jilin University from February 2016 to February 2025. A propensity score overlap weight (PSOW) analysis was performed to adjust statistical influences between the two groups. Efficacy evaluation included complete response rate (CRR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and progression of disease within 24 months (POD24).ResultsAfter induction therapy, the CRR was significantly higher in the obinutuzumab group compared to the rituximab group (82.6% vs. 54.3%, p=0.014). With a median follow-up of 31.5 months, the obinutuzumab group demonstrated superior 3-year PFS (81.4% vs. 62.1%, p=0.0026) and 3-year OS (99.0% vs. 87.3%, p=0.004). The incidence of POD24 was lower in the obinutuzumab group (13.0% vs. 24.5%, p=0.046). Multivariable analysis identified rituximab-based treatment as an independent risk factor for inferior OS (HR 9.6, p=0.026). Safety profiles were similar between the two groups, with no significant differences in adverse event rates. ConclusionObinutuzumab-based chemotherapy was associated with significantly higher CRR, improved survival outcomes, and a lower POD24 rate compared to rituximab-based chemotherapy in patients with high-tumor burden of FL and MZL. These findings support the preferential use of obinutuzumab in this high-risk population.

Outcomes in older patients with Hodgkin lymphoma (HL) are compromised by the interplay of patient frailty and disease aggressiveness; however, current stratification tools, including the International Prognostic Score (IPS) and Comprehensive Geriatric Assessment (CGA), lack sufficient prognostic discrimination in the older HL population. We developed and validated a prognostic model integrating metabolic tumor burden and geriatric assessment. In this retrospective study across 14 centers in China between 2006 and 2024, we enrolled 306 patients aged ≥ 60 years with histologically confirmed HL. Patients were randomly partitioned into training (n = 250) and validation (n = 56) cohorts. Among the 306 patients, 98 deaths and 130 progression events were recorded during follow-up. We analyzed 21 candidate variables. The least absolute shrinkage and selection operator (LASSO) analysis and multivariable Cox regression identified five independent predictors for 5-year overall survival (OS): age > 73 years, baseline 18F-FDG PET/CT-derived total lesion glycolysis (TLG) > 200, hemoglobin ≤ 101 g/L, activities of daily living (ADL) dependence, and lymphocyte-depleted classical Hodgkin lymphoma (LDCHL). A weighted Geriatric Risk Score stratified patients into low-, intermediate-, and high-risk groups. In the validation cohort, the Geriatric Risk Score showed higher discriminatory accuracy than the CGA for both OS (C-index, 0.770 [95% CI, 0.674-0.867] vs. 0.671 [0.581-0.762]) and PFS (0.761 [0.668-0.853] vs. 0.635 [0.535-0.735]). Among advanced-stage (Ann Arbor stage III-IV) patients, it also outperformed the IPS-7 and IPS-3. By integrating metabolic tumor burden and geriatric assessment, the Geriatric Risk Score improves risk stratification over existing tools in older patients with HL.

Hodgkin lymphoma (HL) is a B-cell–derived hematologic malignancy originating from germinal centre B cells. Owing to its remarkable sensitivity to chemotherapy and radiotherapy, HL has become one of the most curable adult malignancies. Over the past decades, treatment regimens such as ABVD and escalated BEACOPP, combined with radiotherapy, have achieved 5-year survival rates exceeding 90% in early-stage patients and long-term remission rates above 75% in advanced-stage disease. However, long-term toxicities associated with conventional therapies—including secondary malignancies, cardiovascular disease, pulmonary fibrosis, and infertility—have increasingly compromised survivors’ quality of life. Meanwhile, approximately 5%–10% of patients exhibit primary refractory disease, and 10%–30% eventually relapse.In recent years, the emergence of targeted and immunotherapeutic agents, particularly the anti-CD30 antibody–drug conjugate (brentuximab vedotin) and immune checkpoint inhibitors (e.g., PD-1 inhibitors), has profoundly reshaped the therapeutic landscape of HL. This review systematically summarises the epidemiological characteristics and biological foundations of HL, as well as the achievements and limitations of conventional therapies. We place particular emphasis on key clinical trial evidence in recent years and discuss paradigm shifts in four major areas: treatment de-escalation and toxicity reduction in frontline therapy, precision salvage strategies for relapsed/refractory HL, the evolving role of transplantation, and the application of precision medicine tools such as circulating tumour DNA (ctDNA) and molecular subtyping. We further explore how HL treatment is transitioning from a “cure-oriented” model focused solely on survival to a novel paradigm of “functional cure” that balances efficacy with long-term quality of life. We define “functional cure” as durable remission with minimal long−term toxicity, preserving organ function and quality of life—a unifying principle of modern HL management. Special attention is given to clinical decision-making in PD-1–exposed patients, emerging therapeutic targets, cellular therapies, and the growing role of real-world evidence. These insights aim to inform future individualised treatment strategies in HL.

Background:Neutropenia is one of the most common complications of chemotherapy in lymphoma patients. To treat and prevent this condition, polyethylene glycol-conjugated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; mecapegfilgrastim) has been developed. This study compared the efficacy of PEG-rhG-CSF with that of recombinant human granulocyte colony-stimulating factor (G-CSF) in preventing neutropenia after chemotherapy for lymphoma. Methods:A prospective randomized study of 154 patients with lymphoma admitted to The First Hospital of Jilin University from September 2020 to September 2022 was conducted. The predetermined sample size is established with a power analysis-driven approach, followed by rigorous non-inferiority testing to evaluate therapeutic equivalence. The patients were randomized at a 1:1 ratio to receive PEG-rhG-CSF or G-CSF. The duration and incidence of grade 3 or higher neutropenia (≥ G3 neutropenia), and the occurrence rates of febrile neutropenia (FN) and ≥ G3 neutropenia were compared between the two groups. A subgroup analysis was performed based on the chemotherapy regimen and tumor origin. Results:The duration of ≥ G3 neutropenia in the first cycle of chemotherapy was 1.56±2.23 days in the PEG-rhG-CSF group and 2.34±2.82 days in the G-CSF group (P=0.059). The incidence of ≥ G3 neutropenia in the first cycle of chemotherapy was 44.16% in the PEG-rhG-CSF group and 53.25% in the G-CSF group (P=0.26). The incidence of ≥ G3 neutropenia in cycles 2-4 of chemotherapy was 22.08% in the PEG-rhG-CSF group and 38.96% in the G-CSF group (P=0.02). After four cycles, the complete response rate of the PEG-rhG-CSF group was 73.58%, while that of the G-CSF group was 63.64%. Conclusions:PEG-rhG-CSF was more effective than G-CSF in preventing neutropenia induced by chemotherapy regimens with a moderate- to-high-risk of FN in patients with lymphoma and contributes to better chemotherapy efficacy. Trial Registration:ClinicalTrials.gov NCT05834751.

Hepatitis B virus (HBV) infection worsens the prognosis of patients with diffuse large B-cell lymphoma (DLBCL), possibly through epigenetic mechanisms. We conducted a prospective, single-arm, open-label clinical trial (NCT04661943) to evaluate the efficacy and safety of chidamide maintenance therapy in patients with HBV+ DLBCL who achieved complete or partial response after first-line treatment. Seventy patients with HBV+ were enrolled, including 30 receiving chidamide (20 mg twice weekly for two years) and 40 controls who declined treatment, with a propensity score-matched HBV- cohort for comparison. Chidamide maintenance significantly improved progression-free survival (p = 0.035) and overall survival (p = 0.041) in patients with HBV+ and was well tolerated without unexpected adverse events. These findings indicate that chidamide maintenance therapy can overcome HBV-associated poor prognosis in DLBCL and may serve as an effective maintenance strategy for this high-risk group.

Introduction Indolent non-Hodgkin lymphomas, such as marginal zone lymphoma (MZL), typically follow an indolent course and are associated with favorable long-term survival. Therefore, balancing efficacy and toxicity is critical when selecting front-line therapies. According to the 2023 CSCO lymphoma guidelines, there is no universally accepted standard first-line regimen for newly diagnosed MZL. For patients with indications for systemic therapy, CD20 monoclonal antibody–based regimens (± other agents) are recommended. Phosphatidylinositide 3-kinases (PI3Ks) are intracellular enzymes that regulate multiple signaling pathways, and several PI3K inhibitors have been approved for the treatment of MZL. Linperlisib, a highly selective oral PI3Kδ inhibitor, has shown promising anti-tumor activity and manageable safety in relapsed/refractory (R/R) MZL.This study aims to evaluate the efficacy and safety of first-line Linperlisib in combination with Obinutuzumab in previously untreated MZL patients, providing new evidence for a potentially more effective front-line option.Methods We conducted a prospective, single-arm, phase Ib/II clinical trial (NCT06592170) in treatment-naïve MZL patients meeting treatment criteria per NCCN B-cell lymphoma guidelines (Version 2.2025).In the phase Ib dose-finding stage (Linperlisib 80 mg), the recommended phase II dose (RP2D) was determined to be Linperlisib 60 mg daily.The induction regimen consisted of three 28-day cycles of Linperlisib (60 mg orally, once daily) combined with Obinutuzumab (1000 mg intravenously). Subsequent therapy was response-directed: per Lugano 2014 criteria, patients achieving complete response (CR) or partial response (PR) proceeded to Linperlisib maintenance until disease progression or other discontinuation criteria, for a maximum of 24 months. Patients with stable disease (SD) or progressive disease (PD) discontinued study treatment.If patients failed to achieve CR or PR after two cycles of induction, investigators could decide whether to extend induction up to a maximum of six cycles.The primary endpoint was CR rate; secondary endpoints included overall response rate (ORR), duration of overall response (DOR), progression-free survival (PFS), overall survival (OS), and safety.Results Between November and December 2024, five patients were enrolled in the phase Ib stage. The median age was 64 years (range, 62–68); 80% had advanced-stage disease, and 40% had high tumor burden (per GELF criteria for Follicular Lymphoma). Among four efficacy-evaluable patients, the ORR was 100%: CR in 75% and PR in 25%. A total of 21 adverse events (AEs) were reported. Two patients experienced three grade ≥3 non-hematologic AEs (rash, interstitial pneumonia, and invasive pulmonary aspergillosis) that led to treatment discontinuation. In the ongoing phase II study (October 2024–present), eight patients have been enrolled. The median age was 68 years (range, 39–74); 87.5% had advanced-stage disease, and 37.5% had high tumor burden. Ki-67 positivity ≥10% was observed in 75% of patients; one patient had 70% p53 protein expression. Among three efficacy-evaluable patients so far, the ORR was 100%, all achieving CR. Fifteen AEs were reported, all were laboratory abnormalities. Only one patient experienced grade ≥3 hematologic toxicity (neutropenia); no grade ≥3 non-hematologic AEs or treatment discontinuations occurred. Conclusion Front-line treatment with Linperlisib and Obinutuzumab in MZL demonstrated encouraging early efficacy with a manageable safety profile. Further enrollment and follow-up are ongoing to confirm these preliminary findings and better define the role of this response-adapted strategy in the first-line setting for MZL.

Background Elderly patients (≥60 years) with classical Hodgkin lymphoma (cHL) experience disproportionately poor outcomes, with historical 5-year overall survival (OS) rates of 50% globally due to treatment-related toxicity, comorbidities, and disease biology. In China, this population faces additional challenges including delayed diagnoses and limited access to novel therapies-brentuximab vedotin (BV) and PD-1 inhibitors were only approved in 2020 and 2019, respectively. Real-world data on treatment evolution and survival impacts in elderly Chinese cHL patients, particularly those with high comorbidity burdens (CIRS-G ≥10 prevalence >30% in prior studies), remain critically scarce. This 15-year multicenter analysis aims to define the survival benefit of novel agents and identify key prognostic factors in this vulnerable cohort. Methods We conducted a retrospective study of 493 consecutive newly diagnosed cHL patients ≥60 years treated at 13 tertiary centers across China (2008-2023). Inclusion required pathological confirmation and ≥6-month follow-up. Collected variables: 1) Baseline characteristics: age, Ann Arbor stage, B-symptoms, ECOG PS; 2) Geriatric metrics: CIRS-G comorbidity index (severe: ≥10), Activities of Daily Living (ADL) scale (impairment: score <6); 3) Treatment details: frontline/salvage regimens (chemotherapy/radiotherapy/novel agents), BV/PD-1 utilization timelines; 4) Response and toxicity: PET-CT parameters (Deauville, total metabolic tumor volume [TMTV] available in 336 patients [68%]), grade 3-5 adverse events (CTCAE v5.0); 5) Molecular profiling: 475-gene next-generation sequencing panel in 158 patients (32%). Survival endpoints (OS/PFS) were compared between novel-agent-containing (BV±PD-1±chemo) and chemo-only groups using Kaplan-Meier/log-rank tests. Multivariable Cox regression identified OS predictors adjusting for age, stage, CIRS-G, and ADL. Biomarker correlations used logistic regression. Results The cohort (median age 72 years, 58% male) exhibited high-risk features: 64% stage III/IV, 48% with ≥3 comorbidities (CIRS-G≥10: 31%), and 22% ADL impairment. Treatment patterns shifted dramatically post-2020: BV utilization increased from 0 (pre-2020) to 21% (2020-2023), while PD-1 inhibitor use rose from 1% to 27% (P<0.001). Frontline regimens included ABVD (43%), AVD (20%), BV-AVD (8%), and PD-1±chemo (7%). Landmark survival analysis demonstrated transformative benefits with novel agents: 3-year OS was 78% (95%CI 72-84) for novel-agent recipients (n=142) versus 53% (95%CI 47-59) for chemo-only patients (n=351) (HR=0.45, P<0.001); 3-year PFS was 65% (59-71) vs 38% (32-44) (HR=0.49, P<0.001). This OS advantage persisted in high-risk subgroups: age >75 years (HR=0.52, P=0.008) and CIRS-G≥10 (HR=0.57, P=0.01). Overall cohort median OS was 58 months (5-year OS 46%), with multivariable analysis confirming independent OS predictors: age >75 years (HR=2.1, P=0.001), ADL impairment (HR=2.8, P<0.001), and ≥3 comorbidities (HR=1.9, P=0.01). Grade ≥3 toxicity was lower with novel agents (38% vs 52% for chemo-only, P=0.03), though BV-related neuropathy was more frequent (18% vs 6%, P<0.001). Exploratory biomarker analysis revealed high TMTV (>80 cm³) predicted inferior PFS (HR=1.8, P=0.02), and TP53 mutations (21%) associated with primary refractoriness (OR=3.1, P=0.004). Conclusion This largest real-world study of elderly Chinese cHL establishes that BV and PD-1 inhibitors confer unprecedented survival improvements (25% absolute 3-year OS gain), fundamentally altering treatment paradigms for this high-risk population. The survival benefit extends to traditionally excluded subgroups (>75 years, high comorbidity burden), supporting frontline integration of novel agents in fit patients. Geriatric assessments (ADL/CIRS-G) outperform conventional staging in predicting mortality risk, underscoring their essential role in treatment stratification. While toxicity profiles differ from chemotherapy, novel regimens demonstrate overall better tolerability. Emerging biomarkers (TMTV, TP53) offer pathways for personalized therapy-a critical need given the 46% 5-year OS rate with conventional approaches. Prospective trials optimizing novel-agent combinations guided by geriatric and molecular metrics are urgently warranted.

Abstract Background : Lymphoplasmacytic Lymphoma/Waldenström macroglobulinemia (LPL/WM) is a rare B-cell lymphoma consist of lymphocytes,lymphoplasmacytic cells, and plasma cells. Although there is a general consensus on the diagnosis and treatment of LPL/WM, there is no standard first-line therapy due to the lack of prospective randomized clinical trials. Aims This study evaluated the efficacy and safety of different regimen in treatment-naïve (TN) LPL/WM patients through the real-world retrospective analysis. Methods:We retrospectively analysied LPL/WM patients were diagnosed during October, 2014 and October, 2024 in our hospital. These patients recived CHOP or CHOP like, FC chemotherapy. BR (Bendamustine, 70-90mg/m2, d1-2, Rituximab, 375mg/m2, d0), or VD (Bortezomib 1.3mg/m2,d1,8,15, Dexamethasone, 20mg, d1,2,8,9,15,16,22,23) or BTKi (Bruton Tyrosine kinase inhibitor, Ibrutinib 140mg QD, or Zanubrutinib 160mg BID), as the first line treatment. Then we evaluated the efficacy and survial of different treatments, analyzed PFS and OS of treatment-naïve LPL/WM patients Results There were 118 patients were diagnosed with LPL/WM from October, 2014 to October, 2024. 101 eligible patients were enrolled. The median age was 64 (range, 44-85) years,72.9% patients were over 60 years old. 58.5% patients were intermediate-high risk according to IPSSWM evaluation system. Hemoglobin decreased (median,78g/L, range 23-159), and Immunoglobulin M increased (median 35.6g/L,range 19-101) significantly. 35.0% patients with increased lymphocytes (more than 50%), 43.0% patients with increased plasma cell (more than 10%), 78% patients with MYD88 L265P mutation, only 12.82% patients with CXCR4 mutation from bone marrow detection. All the patients received median 4 cycles (range 2-6) treatment. The ORR and CRR were 85% and 5%, respectively. The VGPR, PR and MRR were 20%,30% and 30%, respectively. At a median follow-up of 38 months（range 4-108), the median PFS was 50 months. The median OS not reached. 5-year PFS and OS were 37.7% and 83.7%, respectively. The subgroup analysis results indicated that target therapy, BR, VD or BTKi with prolonged PFS （P=0.01）and OS （P=0.012）compared with traditional chemotherapy. BTKi, BR with increased MRR or VGPR than VD gruop (P＜0.05), and improved 5-years PFS, 100%, 58.3% and 30.9%, respectively (P＜0.05). The patients with increased lymphocytes or splenomegaly, BR group with better MRR or VGPR than VD regimen (P＜0.05). The patients with much more plasma cells or increased IgM, VD with increased MRR than BR regimen，and transformed to OS and PFS improvement (P＜0.05). Several independent prognostic factors affecting PFS, including high risk/very high risk (R-IPSS), non-targeted therapy, elevated LDH level, bone marrow plasma cells >10%. Non-targeted therapy is an independent prognostic factor affecting OS. Conclusions Targeted therapy has a significant effect, and individualized selection is recommended for LPL/WM patients. BR is mainly recommended for patients with increased lymphocyte and splenomegaly. VD is more suitable for patients with increased plasma cell, which can reduce IgM and relieve related symptoms.

Background: Both PEG-rhG-CSF and rhG-CSF are widely used in autologous hematopoietic stem cell mobilization for lymphoma. There is still a lack of prospective studies comparing the two mobilizing agents in autologous stem cell mobilization for lymphoma. Aims: To evaluate the efficacy and safety of PEG-rhG-CSF in autologous stem cell mobilization for lymphoma patients. Methods: In this single-arm, multicenter, bidirectional cohort clinical study (NCT04460508), 140 patients were planned to be enrolled. This is the result of the interim analysis, and all the patient data are from the Department of Hematology, the First Hospital of Jilin University. All patients underwent chemotherapy combined with mobilization. The chemotherapy regimen was selected according to the patients' previous chemotherapy regimens and the researchers' experience. In the experimental group, 48 - 72 hours after the end of chemotherapy, a fixed dose of 9mg of PEG-rhG-CSF was subcutaneously injected. In the control group, when the platelets and white blood cells began to rise after reaching the lowest point after chemotherapy, rhG-CSF (Filgrastim) at a dose of 10 μg/kg/d was given. In both groups, routine blood tests and peripheral blood CD34+ cell counts were monitored daily. Collection was started when WBC≥2.0×109 /L and CD34+ cells≥20/ul. The collection endpoint was to collect ≥2×106 /kg CD34+ cells. If the collection failed to reach the endpoint after more than 3 times, it was regarded as a collection failure. The primary endpoint was the mobilization success rate. The secondary endpoints were the lowest and peak values of white blood cells, the time to the highest point of D34+ cells (the number of days from the first day of chemotherapy to the peak of CD34+ count), the single collection volume, the number of collection. In this study, patients with bone marrow involvement and massive splenomegaly were excluded, and the use of plerixafor for rescue was not allowed. Results: 1. From January 1, 2021, to May 16, 2024, 76 eligible patients were enrolled. Six patients withdrew from the study due to personal reasons. A total of 70 patients were included in this analysis, with 26 in the experimental group (PEG-rhG-CSF) and 44 in the control group (rhG-CSF). 2. There were no significant differences in baseline comparisons between the two groups in terms of age, gender, body weight, liver and kidney function, white blood cells, hemoglobin, platelets, and absolute neutrophil count. 2. The primary study endpoint was the mobilization success rate. In the experimental group, it was 90.5% (19/21), and in the control group, it was 88.4% (38/44), with P > 0.999. 3. The secondary study endpoints, the nadir and peak values of white blood cells: in the experimental group, the median was 0.8 (0.1 - 3.3)×109 /L and 18.2 (10.6 - 45.8)×109 /L; in the control group, they were 0.6 (0.1 - 5.5)×109 /L and 23.9 (4.5 - 92.5)×109 /L, with P = 0.981 and P = 0.334. The number of days to reach the peak of CD34+ count: the median in the experimental group was 9.0 (5 - 17) days, and in the control group, it was 14 (4 - 42) days, P < 0.001. The optimal single collection volume: the median in the experimental group was 4.3 (0.6 - 31.5)×106 /kg, and in the control group, it was 3.8 (0.6 - 20.4)×106 /kg, with P = 0.699. The number of collections: the median in the experimental group was 1 time (52.4% had successful single collection, 28.6% had successful collection in 2 times, and 19% had collection in 3 times), and in the control group needed 2 collections (46.5% had successful single collection, 53.5% had successful collection in 2 times, and 0% had collection in 3 times), P = 0.006. 4. Among the grade ≥ 3 adverse reactions, the highest incidence was thrombocytopenia, with 65.4% in the experimental group and 27.3% in the control group, P = 0.002; followed by decreased lymphocyte count (73.1%, 70.5%, P = 0.814) and anemia (26.9%, 13.6%, P = 0.288). Conclusions: For lymphoma patients undergoing chemotherapy combined with PEG-rhG-CSF for mobilizing peripheral blood stem cells, compared with the combination of rhG-CSF, the mobilization success rate is the same, while the peak of CD34+ is reached earlier, and the number of collections to reach the standard is significantly reduced, with 52.4% of patients only needing 1 collection. Among the adverse reactions, the degree and proportion of thrombocytopenia during the PEG-rhG-CSF process are more severe, which requires clinical attention.

Background: Burkitt lymphoma (BL) is a highly aggressive B-cell malignancy requiring intensive immunochemotherapy. While rituximab(R)combined with regimens like DA-EPOCH has improved outcomes, resistance and toxicity remain challenges. Obinutuzumab(G), a glycoengineered type II anti-CD20 monoclonal antibody, demonstrates enhanced antibody-dependent cellular cytotoxicity (ADCC) and direct cell death induction compared to rituximab in other B-cell malignancies, but its efficacy in BL is underexplored. Methods: This single-center retrospective study compared outcomes of BL patients treated with G-based intensive immunochemotherapy (from July 2022 to December 2024) versus a historical cohort treated with R-based regimens (from May 2018 to June 2022). Endpoints included complete response (CR) rate, partial response (PR) rate, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. To minimize follow-up bias, the maximum follow-up period was capped at 33 months. Results: A total of 23 BL patients were included in this retrospective cohort study. Nine received R-based immunochemotherapy (2018.05–2022.06), and 14 received G-based therapy (2022.07–2024.12). To reduce follow-up bias, the maximum follow-up duration was limited to 33 months. The 2-year OS and PFS were 38.9% and 40.0%(R-based) vs. 69.2% and 71.2%(G-based), respectively (P>0.05). A favorable trend toward improved OS and PFS was observed in the G-based group. Multivariate analysis identified older age as an independent predictor of worse OS and PFS (OS: HR=11.81, P=0.0257; PFS: HR=11.91, P=0.0224). G-based therapy was not significantly associated with long-term survival but showed a trend toward benefit (OS: HR=0.43, P=0.3214; PFS: HR=0.33, P=0.1932). Adverse event rates were comparable between groups, though non-hematologic AEs appeared more favorable in the G-based group. Conclusion: G-based immunochemotherapy demonstrated comparable short-term efficacy to R-based therapy, with a consistent trend toward improved long-term survival and a more favorable non-hematologic toxicity profile. While these findings did not reach statistical significance, they suggest a potential clinical advantage of G-based regimens in BL. Prospective studies are warranted to confirm these observations.

Hepatitis B virus X protein (HBx) is implicated in the pathogenesis of diffuse large B cell lymphoma (DLBCL). In this study, HBx-stably overexpressing DLBCL cell lines and mouse xenograft models were established to investigate HBx-driven transcriptional changes and functional effects. HBx enhanced cell proliferation, migration, and invasion in vitro and altered cell cycle progression. Transcriptomic analysis of tumor tissues revealed distinct gene expression profiles. Integrative analyses, including differential expression, WGCNA, and LASSO regression, identified five HBx-associated hub genes. Among these, NTN1 was consistently upregulated in a large DLBCL patient cohort and associated with poorer overall survival. Elevated NTN1 expression was confirmed in HBx-overexpressing cells. These findings highlight NTN1 as a potential biomarker or therapeutic target in HBV-related DLBCL. This study provides a multi-omics framework integrating in vivo and in vitro models to elucidate the viral contribution to lymphoma progression.

Liver involvement of lymphomas is not rare in clinical patients. Metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) is well accepted as a potential precursor for liver cancer, but it is unknown whether MASH could promote extranodal infiltration of lymphoma. In this study, the subpopulation of tumor-initiating cells and Wnt signaling pathway activation were studied in T-lymphoblastic lymphoma cells. Tumor growth, Wnt/β-catenin signaling, and fenofibrate therapy were investigated in an MASH-lymphoma mouse model. We found that up-regulated Wnt/β-catenin and epithelial cell adhesion molecule signaling contributed to aggressive growth of T-lymphoblastic lymphoma in vitro and in vivo. Lack of fibroblast growth factor 21 (FGF21) worsened lipid metabolic disorder in the hepatic microenvironment which further promoted lymphoma growth in the MASH liver. Fenofibrate therapy upregulated the peroxisome proliferator-activated receptor alpha (PPAR-α)-FGF21 axis, thereby alleviated not only MASH but also liver infiltration of T-lymphoblastic lymphoma. In addition, down-regulated FGF21 but up-regulated Wnt signaling was found in T-cell lymphoma patient samples. In conclusion, aberrant lipid metabolism contributed to the aggressive growth of T-lymphoblastic lymphoma cells in MASH liver. Wnt/β-catenin signaling could be a potential lymphomagenetic mechanism for extranodal infiltration of T-lymphoblastic lymphoma. Fenofibrate has the potential to be an effective therapeutic strategy against liver infiltration of T-lymphoblastic lymphoma in MASH liver.

Background: Treatment of non-Hodgkin lymphoma (NHL) with high tumor burden remains challenging, and treatment with R-CHOP in this population require further optimization. Pegylated liposomal doxorubicin (PLD) offers a promising alternative to conventional doxorubicin, leveraging enhanced permeability and retention effects for longer circulation and less cardiotoxicity. Aims: This study evaluated the efficacy and safety of PLD combined with R-COP (R-CDOP) in treatment-naïve (TN) NHL patients with high tumor burden. Methods: In this single-arm, multicenter, prospective trial (NCT05040555). TN patients with CD20+ diffuse large B-cell lymphoma or grade 3b follicular lymphoma with high tumor burden were recruited. Patients are considered to have high tumor burden if they meet at least one of the following criteria: (1) presence of at least three lymph nodes with a diameter of 3 cm or more; (2) presence of any lymph nodes or extranodal masses with a diameter of 7 cm or more; (3) presence of hepatomegaly and splenomegaly confirmed by PET-CT; Spleen: female > 15cm, male > 16cm); (4) presence of pleural and peritoneal effusions determined through cytological examination, flow cytometry, or diagnosed by PET-CT, (5) LDH levels exceeding 3 times the upper limit of normal value, and (6) PET-CT TMTV exceeding 220cm3. The patients received R-CDOP: Rituximab (375mg/m2, d0), PLD (30-35mg/ m2, d1), Cyclophosphamide (750mg/ m2, d1), Vindesine (3mg/ m2, d1) / Vincristine (1.4mg/m2, d1) and Prednisone (60mg/ m2, d1-5) every 21 days for 4 (Limited-stage lymphoma) or 6 (Advanced lymphoma) cycles with an additional 2 cycles of Rituximab therapy. The primary endpoint was objective response rate (ORR). The secondary endpoints were complete response rate (CRR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: From November 13, 2021 to December 14, 2024, 64 eligible patients were enrolled. The median age was 64.5 (range, 34-77) years, with 63 cases of diffuse large B-cell lymphoma (DLBCL), and 1 case of follicular lymphoma (FL) 3b or DLBCL. Forty-nine patients (76.6%) with stage III-IV. Among 59 efficacy-evaluable patients, the ORR and CRR were 86.4% (51/59) [95%CI, 75.0%-94.0%] and 52.5% (31/59) [95%CI, 39.1%-65.7%], respectively. The DCR was 93.2% (55/59) [95%CI, 83.5%-98.1%]. The subgroup analysis results indicated that for high-risk, advanced-stage, patients with abnormal LDH levels, and those with dual expression, promising therapeutic effects were observed. At a median follow-up of 11.6 months, the median PFS and the median OS were not reached, with a 1-year PFS rate of 75.8% and a 1 -year OS rate of 81.7%. The most common grade 3/4 treatment-related adverse events (TRAEs) were neutropenia (17.2%), leucopenia (12.5%) and anemia (14.1%). One patient (1.6%) experienced mild atrial premature contractions and no congestive heart failure occurred. Conclusions: The preliminary results of the study demonstrated promising efficacy and a manageable safety profile for the R-CDOP regimen in treatment-naïve NHL patients with high tumor burden, supporting further investigation.

Diffuse large B-cell lymphoma and follicular lymphoma exhibit complex metabolic and immune microenvironments that influence disease progression and treatment response. Metabolic reprogramming, including glycolysis, amino acid, and lipid metabolism, supports tumor growth while suppressing anti-tumor immunity. Immune components such as tumor-infiltrating lymphocytes and checkpoint molecules (PD-L1, LAG-3, TIM-3) further modulate prognosis. Elevated tumor metabolic volume and glycolytic activity correlate with aggressive disease and poor outcomes. Conversely, high TIL density often predicts better responses. Integrating metabolic and immune biomarkers enhances risk stratification and therapeutic strategies, highlighting the potential for combined metabolic inhibitors and immunotherapies to improve precision medicine in lymphoma.

BACKGROUND:The high mobilization failure rate with the mobilization strategy of combining chemotherapy and filgrastim (rhG-CSF) in autologous hematopoietic stem cell transplantation (auto-HSCT) in lymphomas is one of the unresolved issues. Whether the combination of polyethylene glycol filgrastim [pegfilgrastim (PEG-FIL), PEG-rhG-CSF] and filgrastim (FIL) improves the mobilization success rate and the timing of combination therapy has not been studied. METHODS:107 lymphoma patients who received auto-HSCT were retrospectively enrolled and divided into groups of PEG+FIL and FIL. The group of PEG+FIL received pegfilgrastim (9 mg) on the third day of the chemotherapy, followed by filgrastim (10 μg/kg/day) based on the counts of peripheral blood stem cells (PBSC). The group of FIL received filgrastim 10 μg /kg/day depending on the number of PBSCs. RESULTS:The incidence of neutropenic fever in the group of PEG+FIL was significantly lower than in the group of FIL. The mean recovery time of leukocytes at autologous stem cell transplantation was significantly shorter in the group of PEG+FIL than in the group of FIL. Compared to the groups of FIL, the group of PEG+FIL had lower hospitalization costs. We found that the combination therapy is more recommended for patients with a bone marrow hematopoietic area of less than 30 %. Filgrastim is best administered 5-6 days after pegfilgrastim administration. CONCLUSIONS:Compared to conventional filgrastim mobilization, the combination of pegfilgrastim and filgrastim schedule has high efficacy, non-inferior safety, and superior health economic benefits during auto-HSCT.

Diffuse large B cell lymphoma (DLBCL) is the predominant subtype of malignant lymphoma in adults with high heterogeneity. Hepatitis B virus (HBV) has been shown to infect B lymphocytes and has been associated with a higher risk of developing DLBCL, most clearly in countries where HBV is endemic. Accumulating evidence suggests that the standard chemotherapy regimens for DLBCL patients with HBV infection exhibit limited efficacy and unfavorable outcomes. The HBx antigen, encoded by the X gene in the four open reading frames of HBV, may be a key molecule promoting the heightened malignant biological characteristics of DLBCL, but whether it affects the chemotherapy response and the mechanism in DLBCL remains unclear. Through the implementation of in vitro and in vivo experiments, our study demonstrates that the HBx antigen triggers excessive activation of the NF-κB pathway, resulting in increased expression of the X-linked inhibitor of apoptosis protein (XIAP). This upregulation inhibits caspase-3-mediated intrinsic apoptosis and enhances resistance to first-line chemotherapeutic agents like epirubicin and vincristine in DLBCL. These findings offer insights into the development of innovative combination therapies for DLBCL patients with HBV infection.