Search

ObjectiveTo explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. MethodsClinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. ResultsThe frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2DmutBTG2mut had poorer OS than those with KMT2Dwt BTG2mut (P=0.07) and KMT2Dwt BTG2wt (P=0.05). On the contrary, patients with KMT2Dmut CD79Bmut had better OS than those with KMT2Dmut CD79Bwt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2DmutBTG2mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P

Abstract Monitoring quality of healthcare is vital to ensure that changes made to clinical practice achieve the intended goals. Assessing temporal trends due to the accumulated effect of all changes in clinical practice in a given period is essential in quality monitoring. However, this assesment is compplicated by the fact that numerous of changes might occour over time unrelated to the clinical practice. Furthermore, the methods used to assess temporal trends in patient outcomes in the medical literature are heterogeneous, making it difficult to compare results between studies. In this paper, we describe methods that enable researchers to investigate temporal trends in survival data and we discuss their pros and cons. Numerous unrelated changes may occur over time which must be taken into account and disentangled when assessing the improvement in clinical management. The methods and interpretation thereof are exemplified on patients with diffuse large B-cell lymphoma from the Danish lymphoma registry.

Abstract Chimeric antigen receptor T-cell (CAR-T)-mediated therapies have shown promising clinical benefit in patients with refractory or relapsing (R/R) diffuse large B-cell lymphoma (DLBCL). However, CAR-T treatment presents challenges such as lack of drug accessibility, financial barriers, variable physician preference or experience, and risk assessment based on patient-specific characteristics. This article thus aims to provide an overview of the CAR-T landscape for R/R DLBCL in Asia, with a focus on identifying barriers to access, from the perspective of Asian and international lymphoma experts. Presently, existing clinical data indicate that CAR-T therapy is a potentially curative strategy for R/R DLBCL in addition to stem cell transplantation, provided the patient’s disease profile and treatment history have been thoroughly considered. However, longer-term follow-up data from large-scale studies are needed to confirm curative potential and define optimal sequencing of CAR-T in the context of novel emerging treatments, such as bi-specific antibodies, in the management of R/R DLBCL. Consequently, further research into CAR-T would benefit from collaboration between institutions. Furthermore, there is a wide disparity in CAR-T accessibility across regions due to complicated logistics and cost, which represent a significant barrier to patients in Asia. Hence, there is a need to increase representation and engagement across different stakeholders such as policymakers, payers, and the industry to arrive at a consensus on patient selection, establish clear guidelines, and develop strategies to lower CAR-T costs. Ultimately, data can support a multi-stakeholder approach when devising strategies to make CAR-T feasible and sustainable for patients.

Abstract Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematopoietic neoplasm that affects humans as well as dogs. While previous studies on canine DLBCL (cDLBCL) have significantly advanced our understanding of the disease, the majority of this research has relied on whole-exome sequencing, which is limited in its ability to detect copy number aberrations and other genomic changes beyond coding regions. Furthermore, many of these studies lack sufficient clinical follow-up data, making it difficult to draw meaningful associations between genetic variants and patient outcomes. Our study aimed to characterize the mutational landscape of cDLBCL using whole-genome sequencing of matched tumor-normal samples obtained from a cohort of 43 dogs previously enrolled in a clinical trial for which longitudinal follow-up was available. We focused on identifying genes that were significantly or recurrently mutated with coding point mutations, copy number aberrations, and their associations with patient outcomes. We identified 26 recurrently mutated genes, 18 copy number gains, and 8 copy number losses. Consistent with prior studies, the most commonly mutated genes included TRAF3, FBXW7, POT1, TP53, SETD2, DDX3X and TBL1XR1. The most prominent copy number gain occurred on chromosome 13, overlapping key oncogenes such as MYC and KIT, while the most frequent deletion was a focal loss on chromosome 26, encompassing IGL, PRAME, GNAZ, RAB36, RSPH14, and ZNF280B. Notably, our set of recurrently mutated genes was significantly enriched with genes involved in epigenetic regulation. In particular, we identified hotspot mutations in two histone genes, H3C8, and LOC119877878, resulting in H3K27M alterations predicted to dysregulate gene expression. Finally, a survival analysis revealed that H3K27M mutations in H3C8 were associated with increased hazard ratios for progression-free survival. No copy number aberrations were associated with survival. These findings underscore the critical role of epigenetic dysregulation in cDLBCL and affirm the dog as a relevant large animal model for interrogating the biological activity of novel histone-modifying treatment strategies.

Abstract Background This investigation assessed the therapeutic potential of combining linperlisib, a targeted inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), with gemcitabine and oxaliplatin (GEMOX) for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Methods This was a multicenter, phase Ib/II clinical study conducted across six sites in China, enrolling 39 individuals with histologically confirmed R/R DLBCL. The treatment protocol included oral linperlisib alongside GEMOX administered intravenously every three weeks for up to six cycles. The primary efficacy endpoint was the objective response rate (ORR). Results The ORR observed in the full study population was 53.8% (95% confidence interval [CI]: 37.2–69.9). The median duration of response was 5.7 months (95% CI: 4.3–9.1), and the median progression-free survival was 5.4 months (95% CI: 1.8–6.7). The 1-year OS rate was 65.5% (95% CI: 48.1–78.3). Frequently observed adverse events included decreases in neutrophil counts (74.4%), white blood cell counts (64.1%) and platelet counts (64.1%). Conclusions This study highlights the potential of linperlisib plus GEMOX as a treatment for R/R DLBCL, demonstrating a tolerable safety profile and encouraging efficacy results. Trial registration NCT04500561.

Introduction: Condensin, a family of structural maintenance of chromosome complexes, has been shown to regulate chromosome compaction and segregation during mitosis. NCAPD3, a HEAT-repeat subunit of condensin II, plays a dominant role in condensin-mediated chromosome dynamics but remains unexplored in lymphoma. Objectives: The study aims to unravel the molecular function and mechanism of NCAPD3 in diffuse large B-cell lymphoma (DLBCL). Methods: The expression and clinical significance of NCAPD3 were assessed in public database and clinical specimens. Chromosome spreads, co-immunoprecipitation (co-IP), mass spectrometry (MS), and chromatin immunoprecipitation (ChIP) assays were conducted to untangle the role and mechanism of NCAPD3 in DLBCL. Results: NCAPD3 was highly expressed in DLBCL, correlated with poor prognosis. NCAPD3 deficiency impeded cell proliferation, induced apoptosis and increased the chemosensitivity. Instead, NCAPD3 overexpression facilitated cell proliferation. In vivo experiments further indicated targeting NCAPD3 suppressed tumor growth. Noteworthily, NCAPD3 deficiency disturbed the mitosis, triggering the formation of aneuploids. To reveal the function of NCAPD3 in DLBCL, chromosome spreads were conducted, presenting that chromosomes became compact upon NCAPD3 overexpression, instead, loose, twisted and lacking axial rigidity upon NCAPD3 absence. Meanwhile, the classical transcription-activated marker, H3K4 trimethylation, was found globally upregulated after NCAPD3 knockout, suggesting that NCAPD3 might participate in chromatin remodeling and transcription regulation. MS revealed NCAPD3 could interact with transcription factor, TFII I. Further co-IP and ChIP assays verified NCAPD3 could be anchored at the promoter of SIRT1 by TFII I and then supported the transcription of SIRT1 via recognizing H3K9 monomethylation (H3K9me1) on SIRT1 promoter. Function reversion assay verified the oncogenic role of NCAPD3 in DLBCL was partially mediated by SIRT1. Conclusion: This study demonstrated that dysregulation of NCAPD3 could disturb chromosome compaction and segregation and regulate the transcription activity of SIRT1 in an H3K9me1-dependent manner, which provided novel insights into targeted strategy for DLBCL.

Various types of lymphoma can involve the lumbosacral plexus, mainly diffuse large B-cell lymphoma, in which cancer-related persistent fatigue and fatigability (a new concept that assesses fatigue to specific activities) can occur. We report a rare case of acute right L2-S1 lumbosacral plexopathy secondary to diffuse large B-cell lymphoma, presenting with persistent lower back pain and pronounced fatigability. A 49-year-old male with controlled primary hypothyroidism experienced progressive lower back pain extending to the right lower limb, accompanied by dysesthesias and significant fatigue exacerbated by physical activities. Clinical examination revealed asymmetrical lower limb weakness, an absent right ankle reflex, and a positive straight leg raise test indicative of lumbosacral plexopathy. Comprehensive serological and imaging evaluations, including MRI and 18F-FDG PET-CT, identified lumbosacral spine lesions and widespread lymphomatous involvement. Immunohistochemical analysis confirmed the presence of CD20+, CD10+, bcl2+, bcl6+, and MUM1+ cells, establishing a diagnosis of diffuse large B-cell lymphoma. This case underscores the importance of considering lymphomatous lumbosacral plexopathy in the differential diagnosis of fatigability and lower back pain to prevent misdiagnosis and ensure timely, appropriate treatment. Further studies are suggested to explore the implications of lymphoma on neuropathy and chronic fatigability among survivors.

Lymphomas encompass a group of malignancies involving the lymphoreticular system, while extranodal non-Hodgkin’s lymphomas affect any organ or tissue excluding lymph nodes and the spleen. Extranodal lymphomas (ENLs) have different characteristics and often have distinct pathogenic mechanisms and clinical behavior, which has a significant impact in their diagnosis and treatment. This unique case series highlights the difficulty in diagnosing ENL cases from different sites because they clinicoradiologically mimic inflammatory pathology. Although clinical diagnosis, imaging studies, and histopathological diagnosis help arrive at a final diagnosis, this diagnostic dilemma should be kept in mind and additional workup for biopsy should be considered. Here, we present five cases which had ENLs in the gastrointestinal tract, tonsils, thyroid gland, and testis for which histopathology needs ancillary studies like immunohistochemistry to confirm the tissue diagnosis. It is important to note that any delay in diagnosis will have an impact in the appropriate treatment of the patients in such instances.

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adult, characterized by uncontrolled cell proliferation and strong aggressiveness. Previous studies have found that cyclin-dependent kinase 1(CDK1) are related to tumor growth and metastasis. However, the role of CDK1 in DLBCL is exclusive. This study investigated the clinical implications and expression of CDK1 in DLBCL. Methods Gene expression data for healthy subjects were sourced from the Genotype-Tissue Expression repository. Clinical details and survival statistics of patients with DLBCL were obtained from the Gene Expression Omnibus archive (GSE10846). Patients were categorized based on CDK1 expression levels, and differences in clinical outcomes between the groups were examined. Univariate and multivariate Cox regression analyses were used to ascertain whether CDK1 expression independently predicted DLBCL prognosis. The protein expression of CDK1 was gauged by immunohistochemistry. Additionally, we investigated the effect of CDK1 inhibition on DLBCL cell growth and death using the Cell Counting Kit-8 and flow cytometry. Results In the control group, CDK1 expression was predominantly observed in the hematopoietic and reproductive systems. CDK1 levels in patients with DLBCL were notably elevated compared with those in controls. Significant differences were noted in the lactate dehydrogenase ratio and overall survival based on CDK1 expression. Statistical analyses confirmed that CDK1 was an independent predictor of DLBCL outcomes. Elevated CDK1 protein levels were observed in a significant number of DLBCL samples, in contrast to normal lymph node samples from individuals without lymphoma. The inhibitor Ro-3306 curtails DLBCL cell growth and enhances cell death in vitro. Conclusions Elevated CDK1 levels are correlated with poor prognosis in patients with DLBCL.

Abstract Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma rarely presents with circulating lymphoma cells (CL) at diagnosis. Previous studies were limited by small sample size precluding robust analysis. Hence, we evaluated the prognostic relevance of CL cells in newly diagnosed DLBCL patients. Based on peripheral blood (PB) immunophenotyping, patients were grouped into CL + and CL−. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of DLBCL. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and diagnosis-to-treatment interval (DTI). Among the 1266 patients with DLBCL, 621 had PB flow at diagnosis, and after excluding patients not meeting eligibility criteria, 588 cases remained. Among these, 85 (15%) were CL + and 503 were CL- (85%). Patients in CL + group were younger (67 vs. 70 years, p = 0.03) with a higher proportion of non-bulky disease (85% vs. 56%, p

Abstract Introduction Primary bone marrow diffuse large B-cell lymphoma is a rare clinical entity, and the “bone marrow–liver–spleen” type of diffuse large B-cell lymphoma is rarer, with only a few published cases in literature. Though bone marrow–liver–spleen-type diffuse large B-cell lymphoma has unique presentations such as fever, cytopenias, and hemophagocytic lymphohistiocytosis, no cases with cold autoimmune hemolytic anemia have been reported. Case presentation A 39-year-old Sri Lankan woman, previously healthy, presented with shortness of breath, productive cough, and fever for 4 days. Examination revealed pallor, icterus, and massive hepatosplenomegaly with no peripheral lymphadenopathy. Further investigation revealed pancytopenia (hemoglobin 58 g/L, white blood cell count 1.73 × 109/L, platelets 23 × 109/L, a reticulocyte index of 4.43%, and lactate dehydrogenase levels of 1690 U/L). Blood picture analysis was suggestive of hemolytic anemia, which was confirmed by a positive direct antiglobulin test with anti-C3d. The bone marrow biopsy revealed markedly hypercellular marrow with polymorphic infiltrate of mononuclear cells accounting for about 80–85% of nucleated cells. These cells were predominantly medium to large cells in size with scanty cytoplasm, irregular nuclear margins, prominent nucleoli, and many mitotic figures. These mononuclear cells were positive for immunohistochemical markers of CD20, BCL2, and CD10. The Ki-67 index was 24%. In addition, this patient had cold autoimmune hemolytic anemia. Contrast-enhanced computed tomography of the chest, abdomen, and pelvis revealed homogeneously enlarged liver and spleen with no significant lymphadenopathy. These findings were compatible with the diagnosis of bone marrow–liver–spleen-type diffuse large B-cell lymphoma. The patient was referred for specialized oncological management. Conclusion Though there are reported cases of primary bone marrow diffuse large B-cell lymphoma presenting with cold autoimmune hemolytic anemia, no such cases of bone marrow–liver–spleen-type diffuse large B-cell lymphoma have been reported. As this unique entity has a rather grim prognosis, it is of utmost importance to identify it early and treat aggressively. Owing to the limited availability of published accounts of this uncommon disease, we believe it is important to document our case to add to the understanding of this rare condition and its various presentations, which can easily be misinterpreted.

Abstract Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous hematological malignancy resulting in a range of outcomes, and the early prediction of these outcomes has important implications for patient management. Clinical scoring systems provide the most commonly used prognostic evaluation criteria, and the value of genetic testing has also been confirmed by in-depth research on molecular typing. [18F]-fluorodeoxyglucose positron emission tomography / computed tomography ([18F]FDG PET/CT) is an invaluable tool for predicting DLBCL progression. Conventional baseline image-based parameters and machine learning models have been used in prognostic FDG PET/CT studies of DLBCL; however, numerous studies have shown that combinations of baseline clinical scoring systems, molecular subtypes, and parameters and models based on baseline FDG PET/CT image may provide better predictions of patient outcomes and aid clinical decision-making in patients with DLBCL.

Abstract Background Infections are common complications and causes of death during immunochemotherapy in diffuse large B-cell lymphoma (DLBCL). The gut microbiota plays a significant role in bacterial infection, but its relationship and predictive capacity with infectious complications in DLBCL are unknown. Methods We performed 16S rRNA gene sequencing of fecal samples collected from 41 patients with newly diagnosed DLBCL at baseline, after every two cycles of standard immunochemotherapy, during infection, and after infection recovery. Analysis of the diversity and species composition of these samples was used to evaluate the relationship between gut microbiota and bacterial infection. Results Our findings demonstrate the dynamic changes of Enterobacteriaceae in patients with DLBCL during immunochemotherapy. The abundance of Enterobacteriaceae was markedly higher at baseline in patients who subsequently developed bacterial infection during immunochemotherapy than in those who did not (P 4.5% was independently associated with post-immunochemotherapy bacterial infection. Conclusions Our findings suggest that the gut microbiota signatures differ between patients with DLBCL who do and do not develop bacterial infection. The baseline abundance of Enterobacteriaceae is associated with the post-immunochemotherapy bacterial infection, and it has certain predictive value. Detecting the changes of gut microbiota can help predict the risk of bacterial infection after immunochemotherapy.

Abstract The relationship between D-AA metabolic enzymes and cancer development remains unclear. We aimed to investigate this relationship using mice deficient in D-AA-related metabolic enzymes. We examined mice lacking these enzymes for approximately 900 days and the effects of altered D-AA metabolism on cancer development based on lifespan, pathological findings, and gene expression. The lifespan of female DASPO -knockout (DASPO −/− ) mice was shorter than that of the other group mice; furthermore, these mice showed tumor-like masses in the liver, spleen, and small intestine. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) was made. RNA sequencing of the liver samples showed specific alterations in the expression of 71 genes in DASPO −/− mice compared with that in wild-type B6 mice; RGS 1, MTSS1, and SMARCD 1 were identified as DLBCL-related genes. Patients with DLBCL exhibiting low DASPO expression demonstrated a shorter survival period than those showing high expression. However, the role of DASPO in DLBCL development is unclear. Therefore, future research should focus on B cells. DASPO may serve as novel biomarkers and therapeutic targets in cancer. Graphical abstract

Abstract This study aimed to develop a PANoptosis-related gene prognostic index (PANGPI) to explore its potential value in predicting the prognosis and immunotherapy response of diffuse large B-cell lymphoma (DLBCL). Differentially expressed genes of DLBCL from GEO databases were analyzed and mapped to the PANoptosis gene set. The independent prognostic value of the PANGPI signature was evaluated using LASSO Cox regression and multivariate Cox regression. Additionally, the tumor infiltrating lymphocyte (TIL) characteristics and mutation landscape of both subgroups were evaluated, and drug sensitivity was predicted using the GDSC database. Furthermore, in silico docking and molecular dynamic simulation studies were presented to elucidate the mode of interaction of these predicted drugs. The PANGPI risk score was an independent risk factor for the prognosis of patients with DLBCL and exhibited good prognostic predictive performance. Furthermore, the cytolytic activity of the TILs was positively correlated with the PANGPI scores. Additionally, the PANGPI enabled the identification of 3 chemotherapeutic agents, including BMS-536924, Gefitinib, Navitoclax for DLBCL patients in the high-risk group. We established a novel PANoptosis-related gene subtyping system in DLBCL, which could shed a novel light on the development of new biomarkers for DLBCL.

Abstract Background and objective Positron emission tomography/computed tomography (PET/CT) is recommended as the standard imaging modality for diffuse large B-cell lymphoma (DLBCL) staging. However, many studies have neglected the role of patients' prognostic factors with respect to imaging PET/CT of quantitative features. In this paper, a multi-view learning (MVL) model is established to make full use of both clinical and imaging data to predict the prognosis of DLBCL patients and thereby assist doctors in decision-making. Methods Feature engineering, including feature extraction, feature screening by recursive feature elimination, and dimensionality reduction by principal component analysis, are successively performed on the clinical data and imaging data of the research subjects to obtain the study data. After dividing the data into training and test sets, an instance weighting method is applied to the training data. Subsequently, kernel mapping is performed on the imaging features and clinical features separately, and this kernel mapping is processed in the new kernel feature space using kernel canonical correlation analysis (KCCA). Lastly, model training is performed on the obtained common kernel subspace using a support vector machine (SVM). The final overall model, named SVM-2view-KCCA (SVM-2 K), was compared with three other multi-view models (Ensemble-SVM, Multi-view maximum entropy discrimination, and canonical correlation analysis). The performance of the model was evaluated on the test data with respect to several dichotomous metrics: accuracy, sensitivity, F1 score, the area under the curve (AUC), and G-mean. Results The SVM model improved AUC by 10.5%, sensitivity by 11.9%, accuracy by 9.8%, F1 score by 9.2%, and G-mean by 7.8% for the DLBCL test data after feature engineering based on dimensionality reduction and instance weighting. In the performance comparison of single-view learning models, the SVM-based integration of clinical and imaging features achieved the best overall performance (AUC = 86.3%, accuracy = 91.6%, sensitivity = 83.2%, F1 = 85.7%, and G-mean = 86.1%). In the comparison of MVL models, SVM-2 K achieved the best overall performance (AUC = 92.1%, accuracy = 96.9%, sensitivity = 90.9%, F1 = 92.8%, and G-mean = 91.4%), and the performance of each MVL model was better than that of the best single-view learning model. Conclusions MVL models outperformed single-view learning models. Of the MVL models, the proposed SVM-2 K achieved the best overall performance and could accurately predict patient prognosis.

Abstract The clinical phenomenon whereby diffuse large B-cell lymphoma (DLBCL) occurs in patients with a history of autoimmune disease (AD) has been noted, but it remains controversial. This study aimed to evaluate the causal associations between nine ADs and DLBCL via a Mendelian randomization (MR) study. Single-nucleotide polymorphism (SNP) obtained from published genome-wide association studies (GWAS) was chosen as instrumental variable (IV). A total of nine ADs of European ancestry including asthma (56,167 cases and 352,255 controls), psoriasis (4,510 cases and 212,242 controls), autoimmune hyperthyroidism (962 cases and 172,976 controls), inflammatory bowel disease (31,665 cases and 33,977 controls), type 1 diabetes (6,683 cases and 12,173 controls), multiple sclerosis (14,498 cases and 24,091 controls), sarcoidosis (2,046 cases and 215,712 controls), ankylosing spondylitis (9,069 cases and 1,550 controls), and celiac disease (12,041 cases and 12,228 controls), were set as the exposure and DLBCL (209 cases and 218,583 controls) of European ancestry as the outcome. Inverse-variance weighted (IVW) was used as the primary analysis method, and the weighted median and MR-Egger method were used as supplementary methods. The sensitivity analyses employed in this study include the MR-Egger intercept, MR-PRESSO global test, Cochran’s Q test, leave-one-out analysis, and funnel plot. IVW showed that inflammatory bowel disease (OR = 1.241, 95% CI 1.009–1.526, P = 0.040) and autoimmune hyperthyroidism (OR = 1.464, 95% CI 1.103–1.942, P = 0.008) increased the risk of DLBCL without significant heterogeneity or horizontal pleiotropy, and the results remained stable according to the leave-one-out analysis. The IVW results revealed no associations between the other seven ADs and DLBCL: asthma (OR = 0.782, 95% CI 0.395–1.546, P = 0.159), psoriasis (OR = 0.842, 95% CI 0.669–1.060, P = 0.143), type 1 diabetes (OR = 1.071, 95% CI 0.860–1.334, P = 0.537), multiple sclerosis (OR = 1.331, 95% CI 0.941–1.883, P = 0.105), sarcoidosis (OR = 1.324, 95% CI 0.861–2.038, P = 0.200), ankylosing spondylitis (OR = 1.884, 95% CI 0.776–4.573, P = 0.161), and celiac disease (OR = 1.003, 95% CI 0.854–1.178, P = 0.969). Although no significant heterogeneity or horizontal pleiotropy was detected in these seven ADs and DLBCL, these results did not pass the leave-one-out analysis; therefore, the results need to be interpreted with caution. Inflammatory bowel disease and autoimmune hyperthyroidism may increase the onset of DLBCL. The risk of DLBCL should be considered in specific types of ADs.

Abstract Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) are at increased risk of developing atrial fibrillation (AF). Abnormal P-wave parameters (PWPs) have been identified as independent predictors of AF, however, their prognostic significance in DLBCL patients remains unknown. Newly diagnosed DLBCL patients from January 2015 to August 2022 were retrospectively included in this study. Patients were devided as with abnormal PWPs or without it. Primary outcome was the all-cause mortality. The median duration of follow-up was 16.3 months. The Kaplan‒Meier method and multivariable COX proportional hazards regression models were used to analyze the relationship between PWPs and all-cause mortality. Logistic regression analyses were performed to identify risk factors associated with PWPs. A total of 374 newly diagnosed DLBCL patients were included, of whom 137 patients exhibited abnormalities in PWPs. Compared to the group with normal PWPs, patients with PWPs abnormalities had a higher proportion of males (p = 0.001), elevated levels of blood urea nitrogen (p = 0.038) and blood creatinine (p = 0.005), and a higher rate of all-cause mortality (p = 0.001). PWPs, particularly P-wave duration (p = 0.017) and P-wave terminal force in lead V1 (PTFV1) (p = 0.001), were independently correlated with all-cause mortality in DLBCL patients. Furthermore, male patients exhibited a higher susceptibility to abnormal PWPs (p = 0.001). PWPs, particularly P-wave duration and PTFV1, serve as simple yet effective prognostic indicators for all-cause mortality in DLBCL patients. Consequently, vigilant monitoring of PWPs, particularly in male patients, is warranted to accurately evaluate the prognosis of DLBCL.

Abstract The phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway is critically active in many cell types, both normal and neoplastic. Many small-molecule inhibitors targeting different levels of the PI3K/AKT pathway have been developed for cancer therapy, but their efficacy is reduced by compensatory pathway re-activation mechanisms, and their tolerability by toxic side effects. We studied this problem using cell lines representing diffuse large B-cell lymphoma (SUDHL-4 and OCI-Ly7), a genetically-encoded live-cell reporter of AKT activity, and 3 small-molecule inhibitors targeting different levels of the pathway: idelalisib (PI3Kδ), GSK2334470 (PDPK1), and ipatasertib (AKT). Half-maximal (IC50) concentrations of these inhibitors for AKT activity inhibition at 1 h, when used individually, were much lower than their IC50 values for reduction of viable cell number after 4 days. Time-course studies explained this discrepancy: AKT activity in the continuous presence of the inhibitors returned to normal after 24 h, and was supranormal after inhibitor removal. Combining all 3 inhibitors produced sustained inhibition of AKT activity, was broadly synergistic at reducing viable cell number, enabled substantially lower doses of each inhibitor to be used, and was enhanced further by the mTOR inhibitor rapamycin. Moreover, combined PDPK1 and AKT inhibition showed synergy with multiple different PI3K inhibitors. In a syngeneic mouse cell line model of lymphoma (A20), the triple combination showed antitumor activity and no evidence of toxicity. Our findings provide proof of concept suggesting further study of the safety and efficacy of low-dose multilevel PI3K/AKT pathway inhibition, for lymphoma and perhaps other cancers.

Diffuse large B‐cell lymphoma (DLBCL) is the most prevalent subtype of non‐Hodgkin lymphoma (NHL) in domestic dogs, with many similarities to its human counterpart. The progression of the disease is rapid, and treatment must be initiated early to achieve cancer remission and extend life. This study examined the relationship between progression‐free survival (PFS) and microRNA (miRNA) expression in dogs with DLBCL. miRNAs are small non‐coding RNA molecules that typically regulate gene expression post‐transcriptionally. They are involved in several pathophysiological processes, including the growth and progression of cancer. Based on the analysis of small RNA sequencing (sRNA‐seq) data, we validated a group of miRNAs in lymph nodes from 44 DLBCL‐affected dogs with known outcomes. We used quantitative PCR to quantify their expression and report a specific subset of miRNAs is associated with decreased PFS in dogs with DLBCL. The miR‐192‐5p and miR‐16‐5p expression were significantly downregulated in dogs with increased PFS. These results indicate that miRNA profiling may potentially identify dogs with DLBCL that will experience poor outcomes following treatment. Identifying specific miRNAs that correlate with the progression of canine DLBCL could aid the development of individualized treatment regimens for dogs.

Non-Hodgkin's lymphoma are neoplasms derived from T cells and B cells and their precursors in the lymphoid system with higher susceptibility in involvement of extra-nodal sites. Predominant ureteric involvement is an unusual presentation. We present a case of diffuse large B-cell lymphoma with secondary involvement of ureter who had symptoms of urinary tract infection in absence of positive urine culture, non-responsive to broad spectrum antibiotics and masquerading pyogenic infection leading to pyelonephritis with ureteritis. Radiological examination revealed mass like soft tissue thickening of ureter extending from renal pelvis throughout the length of ureter. FNAC as well as biopsy from the periureteric thickening revealed lymphomatous involvement of ureter. The following case report provides insight on differentials and varied symptoms of lymphomatous involvement of ureter.

The article presents a detailed analysis of clinical observation of primary diffuse large B-cell lymphoma of the adrenal glands, a rare disease affecting less than 1% of patients with non-Hodgkin’s lymphomas. It describes the case of a 46-year-old man hospitalized with progressive limb paralysis, later diagnosed as paraneoplastic polyradiculoneuropathy associated with bilateral adrenal lymphoma. The diagnostic challenges of this pathology, including ambiguous imaging results and the need for histological verification to confirm the diagnosis are discussed. Special attention is paid to the uniqueness of clinical manifestations and the importance of early symptom recognition to improve prognostic outcomes in highly aggressive forms of the disease. The necessity of multidisciplinary approach in managing such patients with the participation of oncologists, endocrinologists, and neurologists to optimize diagnostic and therapeutic processes is also emphasized.

Background: Diffuse large B-cell lymphoma (DLBCL) is globally recognized as the most prevalent and aggressive subtype of non-Hodgkin lymphoma. While conventional treatments are effective initially, the disease can become resistant or relapse over time. The study aimed to examine the differentially expressed genes at the transcriptome level and molecular pathways in DLBCL patients. Methods: This investigation utilized RNA sequencing analysis to compare differentially expressed gene samples from five diffuse large B-cell lymphoma patients with two healthy volunteers. These participants were admitted to UKM Medical Center, Kuala Lumpur between 2019 and 2020. The differentially expressed genes were conducted using the DESeq2 R package (version 1.10.1) using a negative binomial distribution model. The obtained P values were corrected with the Benjamin and Hochberg method and identified using a False Discovery Rate threshold of

Introduction: Neurolymphomatosis (NL) is a rare condition characterized by the infiltration of malignant lymphoma cells into the peripheral nervous system. The optimal treatment for NL remains unclear, and patients with secondary NL have a poor prognosis. Although early recognition of NL may contribute to successful treatment, the predictive factors for secondary NL are yet to be established. Case Presentation: Here, we present our investigation on the predictive factors for secondary NL, and report two cases of secondary NL with a literature review. We analyzed chromosomal abnormalities in patients with secondary NL and found a common deletion of chromosome 10 and add(11)(p11). The chromosomal abnormalities might be a predictive factor for secondary NL; therefore, confirmation of chromosomal abnormalities can possibly give a hint for early detect of secondary NL. Prompt histopathological examination or imaging techniques can lead to early diagnosis of secondary NL in patients with diffuse large B-cell lymphoma (DLBCL). Conclusion: When neurological symptoms manifest in patients with DLBCL and there are chromosomal abnormalities, the possible development of secondary NL should be considered.

BackgroundCarbohydrate antigen 125 (CA125) is one of the most commonly used tumor biomarker for evaluating the prognosis of solid neoplasms. It has been reported that serum CA125 is correlated with the prognosis of non-Hodgkin’s lymphoma. The objective of this study is to explore the clinical value of CA125 in diffuse large B-cell lymphoma (DLBCL).MethodsWe retrospectively analyzed the clinical and pathological data in a cohort of 315 newly diagnosed patients with DLBCL. In our case, the correlations between serum CA125 and clinicopathological parameters were analyzed. Kaplan-Meier survival curve and cox proportional hazards model were applied to evaluate the prognosis. The expression of CA125 in DLBCL paraffin tissues was detected by immunohistochemistry.Results82 patients (26%) with DLBCL had elevated serum CA125 levels at diagnosis. Elevated serum CA125 levels were associated with poor performances status, greater than or equal to 2 Extra-nodal sites, advanced Ann Arbor stage (III-IV), presence of B symptoms, presence of bulky mass, presence of effusion, intermediate/high-risk International Prognostic Index (IPI), elevated lactate dehydrogenase levels and reduced albumin levels. Patients with elevated serum CA125 levels at diagnosis had shorter progression free survival (PFS) and overall survival (OS). Multivariate analysis revealed that serum CA125, cell of origin, IPI score and albumin were independent prognostic factors for OS and PFS. In addition, the results of the immunohistochemistry indicated that none of the 82 DLBCL paraffin tissues expressed CA125 in lymphoma cells and the surrounding microenvironment cells.ConclusionsSerum CA125 detected at the initial diagnosis is a strong predictor of prognosis in patients with DLBCL.

IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in humans, and it is a highly heterogeneous malignancy with a 40% to 50% risk of relapsed or refractory (R/R), leading to a poor prognosis. So early prediction of R/R risk is of great significance for adjusting treatments and improving the prognosis of patients.MethodsWe collected clinical information and H&E images of 227 patients diagnosed with DLBCL in Xuzhou Medical University Affiliated Hospital from 2015 to 2018. Patients were then divided into R/R group and non-relapsed & non-refractory group based on clinical diagnosis, and the two groups were randomly assigned to the training set, validation set and test set in a ratio of 7:1:2. We developed a model to predict the R/R risk of patients based on clinical features utilizing the random forest algorithm. Additionally, a prediction model based on histopathological images was constructed using CLAM, a weakly supervised learning method after extracting image features with convolutional networks. To improve the prediction performance, we further integrated image features and clinical information for fusion modeling.ResultsThe average area under the ROC curve value of the fusion model was 0.71±0.07 in the validation dataset and 0.70±0.04 in the test dataset. This study proposed a novel method for predicting the R/R risk of DLBCL based on H&E images and clinical features.DiscussionFor patients predicted to have high risk, follow-up monitoring can be intensified, and treatment plans can be adjusted promptly.

ABSTRACT Introduction Lymphoma is a common malignancy among adolescents and young adults (AYAs) which is generally defined as 15–39 years. Relative to other age groups, lymphoma in AYAs remains understudied with heterogeneous treatment options. Methods We performed a retrospective review of patients aged 18–60 years in the Australasian Lymphoma and Related Diseases Registry (LaRDR) with new diagnoses of the common subtypes of lymphoma in AYAs between January 2016 and April 2023. The subtypes are classic Hodgkin lymphoma (cHL), diffuse large B‐cell lymphoma (DLBCL), primary mediastinal B‐cell lymphoma (PMBCL) and Burkitt lymphoma (BL). Patient demographics, disease characteristics, treatment and outcome data were collected, and comparisons were made between AYAs (18–39 years) and older adults (OAs) (aged 40–60). Results AYAs had higher rates of cHL and PMBCL whereas OAs presented more frequently with DLBCL. AYAs with cHL and PMBCL had higher rates of early‐stage and low‐risk disease than OAs. In contrast, both AYAs and OAs were more likely to present with advanced‐stage DLBCL and BL. AYAs with cHL were more likely to be treated with BEACOPP as compared to OAs who were more commonly treated with ABVD. There was no significant difference in treatment regimens for DLBCL, PMBCL or BL between AYAs and OAs. AYAs with cHL had better overall survival (OS) compared to OAs; specifically, cHL AYAs had better OS and DLBCL AYAs had better progression‐free survival (PFS) and OS compared to OAs. Conclusion The study provides valuable data on patient and disease characteristics, treatments used and outcomes in AYA compared to OA aged 40–60 years. Registry data such as from LaRDR can help improve treatment standardisation and AYA patient outcomes. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission

Abstract Background There is limited knowledge of the long‐term effects on the immune system after treatment for diffuse large B‐cell lymphoma (DLBCL). Methods This study included DLBCL patients from the Danish Lymphoma Registry who obtained complete remission (CR) after (R)‐CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)‐like immunochemotherapy. Each R+ CHOP‐like treated patient was matched to five comparators from the Danish background population and furthermore compared to R− CHOP‐like treated patients. Incidence rate ratios (IRRs) and risk differences (RDs) were calculated for a wide range of infections, autoimmune conditions, and immune deficiencies (AC‐IDs) combined and by subtypes. Results R+ CHOP‐like treated patients had a higher risk of infections overall (IRR 1.5, 95% confidence interval [CI] 1.4–1.7: 10‐year RD 5.0%, 95% CI 2.2%–7.8%) and for a majority of the subtypes than matched comparators. Likewise, they had a higher risk of AC‐IDs overall (IRR 1.4, 95% CI 1.1–1.7; RD 0.8%, 95% CI 0.7%–2.2%) than matched comparators, however only of clinical relevance for three subtypes; autoimmune diseases of the endocrine system, sarcoidosis and immune deficiencies. The addition of rituximab to CHOP‐like therapy did not alter the incidence rates (IR) of infections overall (IRR 1.1, 95% CI 0.9–1.3) or AC‐IDs overall (IRR 0.8, 95% CI 0.5–1.3) compared to CHOP‐like therapy alone, although the IR for respiratory infections was significantly elevated (IRR 1.5, 95% CI 1.1–2.1). However, an increased use of IVIG treatment was observed among R+ CHOP survivors. Conclusion R‐CHOP‐like treated patients face an increased risk of infections and AC‐IDs overall compared with the background population. The risk of infections and AC‐IDs did not change overall after the addition of rituximab to CHOP, however, an increased risk of respiratory infections is notable. These findings could highlight the need for expanded vigilance and prophylaxis strategies.

ABSTRACT Choledochoduodenal fistula secondary to pancreatic lymphoma is a rare phenomenon, reflecting the complex relationship between lymphoproliferative disorders and gastrointestinal complications. Fistula formation should be suspected in patients with persistent liver function abnormalities and a history of treated hematological malignancies.

Luteolin, a flavonoid present in botanical drugs, plants, and dietary sources, has demonstrated anticancer properties against various tumors, yet its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to uncover the molecular mechanism of luteolin in DLBCL treatment using a combination of in vitro and in vivo experiments and computational analysis. Human DLBCL cell lines U2932 and OCI-LY10 were utilized to assess luteolin’s impact on cell growth, apoptosis, cell cycle progression, and the modulation of JAK2/STAT3 pathway proteins. In vivo, a U2932 tumor-bearing nude mice model was employed to evaluate luteolin’s antitumor efficacy and its effects on JAK2/STAT3 pathway protein expression. Additionally, molecular dynamics simulations were conducted to explore the interaction between luteolin and JAK2. The findings revealed that luteolin significantly suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase in both cell lines. In the mouse model, luteolin effectively inhibited tumor growth and downregulated the expression of phosphorylated JAK2 and STAT3 without altering the total protein levels of JAK2 and STAT3. Computational analysis indicated stable binding of luteolin to JAK2. Collectively, these results suggest that luteolin’s anti-DLBCL activity may be mediated through the regulation of the JAK2/STAT3 signaling pathway, positioning it as a potential therapeutic agent for DLBCL.

ABSTRACT Background Recently, microRNAs (miRNAs) have been applied as biomarkers for diffuse large B‐cell lymphoma (DLBCL) patients. Early diagnosis and management of DLBCL can improve patient survival and prognosis. Aims This systematic review and meta‐analysis aimed to evaluate the diagnostic and prognostic accuracy of miRNA biomarkers in DLBCL patients. Methods We used the keywords “diffuse large B‐cell lymphoma” and “microRNA” to search databases for original publications until June 14, 2023. Specificity, sensitivity, and AUC were used to assess diagnostic accuracy, and the prognostic value was assessed using the overall survival (OS) and progression‐free survival (PFS) hazard ratio (HR). A subgroup analysis was performed based on the sample type acquired to investigate the heterogeneity. Results Thirteen diagnostic and 33 prognostic studies were included from 839 articles. The Reitsma bivariate model estimated a sensitivity of 0.788 (95% CI: 0.733–0.834, p < 0.001), a specificity of 0.727 (95% CI: 0.654–0.790, p < 0.001), and an AUC of 0.824 in. The pooled AUC was 0.7385 (95% CI: 0.6847–0.7923, p 1) were 2.2847 (95% CI: 1.7248–3.0263, p 0.1) and a specificity of 0.725 (p

ABSTRACT Background Distinctive heterogeneity characterizes diffuse large B‐cell lymphoma (DLBCL), one of the most frequent types of non‐Hodgkin's lymphoma. Mitochondria have been demonstrated to be closely involved in tumorigenesis and progression, particularly in DLBCL. Objective The purposes of this study were to identify the prognostic mitochondria‐related genes (MRGs) in DLBCL, and to develop a risk model based on MRGs and machine learning algorithms. Methods Transcriptome profiles and clinical information were obtained from the Gene Expression Omnibus (GEO) database. The risk model was defined using Least Absolute Shrinkage and Selection Operator (Lasso) regression algorithm, and its prognostic value was further examined in independent datasets. Patients were stratified into two clusters based on the risk scores, additionally a nomogram was generated based on the risk score and clinical characteristics. Gene pathway level, microenvironment, expression of targeted therapy‐associated genes, response to immunotherapy, drug sensitivity, and somatic mutation status were compared between clusters. Results Eighteen prognostic MRGs (DNM1L, PUSL1, CHCHD4, COX7A1, CPT1A, CYP27A1, POLDIP2, PCK2, MRPL2, PDK3, PDK4, MARC2, ACSM3, COA7, THNSL1, ATAD3B, C15orf48, TOMM70A) were identified to construct the risk model. Remarkable discrepancies were observed between groups. The high‐risk group had shorter overall survival, less immune infiltration, lower CD20 and higher PD‐L1 expression than the low‐risk group. Distinct immune microenvironment, responses to immunotherapy and predictive drug IC50 values were found between groups. Conclusions We established a novel prognostic mitochondria‐related signature by machine learning algorithm, which also demonstrated outstanding predictive value in tumor microenvironment and responses to therapies.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous metastatic lymphoma that can be treated by targeting angiogenesis. Apolipoprotein C1 (APOC1) plays a significant role in the proliferation and metastasis of various malignant tumors; however, its role in DLBCL—particularly its effects on angiogenesis—remains largely unexplored. This study investigates the correlation between APOC1 expression and patient prognosis in DLBCL. Using APOC1 gene knockdown, apoptosis, migration, and invasion were assessed through flow cytometry, the EDU assay, wound healing, and Transwell assays. Additionally, human umbilical vein endothelial cells (HUVEC) angiogenesis was evaluated. Advanced techniques, such as immunofluorescence, TUNEL assay, and immunohistochemical labeling were employed to analyze the effects of APOC1 knockdown on the PI3K/AKT/mTOR signaling pathway and tumor formation in nude mice. Results showed that APOC1 is overexpressed in DLBCL tissues and cells, with high APOC1 levels associated with poor patient prognosis. In vitro experiments revealed that APOC1 knockdown increased apoptosis and inhibited cell proliferation, migration, invasion, HUVEC angiogenesis, and PI3K/AKT/mTOR signaling pathway protein expression in DLBCL cells. Similarly, in vivo studies demonstrated that APOC1 knockdown significantly reduced tumor growth, angiogenesis-related proteins, and phosphorylated PI3K/AKT/mTOR pathway proteins in nude mice. APOC1 knockdown promotes apoptosis and suppresses angiogenesis in DLBCL cells by inhibiting the PI3K/AKT/mTOR pathway.

Background: Few trials have been conducted regarding using PET/CT metabolic parameters as a predictor for the long-term survival of patients with lymphoma. The present study aimed to determine the prognostic value of quantitative metabolic parameters based on FDG-PET/CT in predicting 2-year mortality and disease recurrence in patients with diffuse large B-cell lymphoma (DLBCL). Materials and Methods: This cross-sectional study was performed on patients who suffered DLBCL and assessed by FDG-PET/CT. All patients have been scheduled for first-line therapy, including the R-CHOP regimen (Rituximab, Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone). The records of patients eligible for the study were extracted from the hospital archive. All subjects were followed up for 2 years to assess progression-free survival (PFS) and overall survival (OS). Results: Complete response to treatment was revealed in 80.0%, while the disease was progressive in 5.7% and stable in 2.9%. At the end of 2 years of follow-up, in all groups, five people (14.2%) experienced disease relapse, and one person (2.9%) died. Comparing metabolic parameters of PET/CT between survived and non-survived groups showed no difference between the two groups. Similarly, the median value of pointed metabolic parameters was insignificant between groups with and without disease relapse. The comparison of the treatment metabolic response state between non-survived and survived subgroups showed no difference. However, regarding the metabolic response status according to the presence or lack of recurrence, those with disease recurrence experienced a higher rate of progressive metabolic disease condition. Treatment metabolic non-response status and higher Deauville 5-point score (D5PS) score could effectively differentiate the groups with and without disease recurrence. Conclusion: FDG-PET/CT complete metabolic response can predict longer PFS in patients with DLBCL, but its related metabolic parameters may not predict disease outcome.

BackgroundPrimary cardiac lymphoma (PCL) is an exceedingly uncommon type of lymphoma that primarily affects the heart and/or pericardium, or manifests through cardiac symptoms due to myocardial infiltration. The infrequency of PCL, coupled with its non-specific clinical presentations, often complicates early diagnosis. This study aims to fill the existing gap in clinical knowledge regarding PCL by detailing a case of PCL and examining its clinical features, auxiliary examinations, treatment approaches, and prognostic outcomes, thereby facilitating early detection and enhancing patient care.MethodsA thorough search of the PubMed and Chinese National Knowledge Infrastructure (CNKI) database was performed using keywords “heart” and “lymphoma” or “primary cardiac lymphoma”. This search encompassed publications from January 1, 2014, to November 1, 2024.ResultsThe review included 121 cases. These cases usually present with atypical symptoms, mainly circulatory and respiratory, including chest tightness, dyspnea, and edema, along with occasional neurological and gastrointestinal symptoms. Echocardiography served as the primary diagnostic method in 92.6% of cases, while a definitive diagnosis was achieved through pathological examination in all cases (100%). Treatment strategies predominantly included surgical intervention (44.6%) and chemotherapy (76.0%). Although surgery did not have a significant effect on survival rates, chemotherapy proved to be critical in improving patient survival.ConclusionsPCL, which arises in the cardiac or pericardial areas, is generally associated with a poor prognosis. It is essential for clinicians to develop a greater awareness and understanding of the characteristics of PCL to enhance early diagnosis. The timely initiation of chemotherapy is vital for improving survival rates and the overall quality of life for patients with PCL.

ABSTRACT Background The prognostic significance of extranodal sites in stage IV diffuse large B‐cell lymphoma (DLBCL) remains uncertain, making it challenging to select appropriate treatment strategies for individual patients. In this study, we aimed to evaluate the influence of different extranodal sites on prognosis in young patients with stage IV DLBCL who achieved complete remission (CR) following initial chemo‐immunotherapy and to explore the potential of autologous hematopoietic stem cell transplantation (ASCT) as a consolidation treatment for specific patient subgroups. Methods We retrospectively reviewed data from 119 patients with DLBCL aged

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639–0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882–0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60–80%, >40–60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51–0.97) to 0.48 (95% CI, 0.36–0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

Jing Wang,1,&ast; Lei Tian,2,&ast; Weilong Zhang,1,&ast; Shuhan Tang,1 Wei Zhao,1 Yu Guo,1 Chaoling Wu,1 Yuansheng Lin,1 Xiaoyan Ke,1 Hongmei Jing1 1Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Health Management Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Ke; Hongmei Jing, Email xykbysy@163.com; hongmeijing@bjmu.edu.cnBackground: The application of rituximab has significantly enhanced the overall survival rates in patients with diffuse large B-cell lymphoma (DLBCL). Regrettably, a significant number of patients still progress to relapse/refractory DLBCL (rrDLBCL).Methods: Herein, we employed targeted sequencing of 55 genes to investigate if gene mutations could predict the progression to rrDLBCL. Additionally, we compared the mutation profiles at the time of DLBCL diagnosis with those found in rrDLBCL cases.Results: Our findings highlighted significantly elevated mutation frequencies of TP53, MEF2B and CD58 in diagnostic biopsies from patients who progressed to relapse or refractory disease, with CD58 mutations exclusively observed in the rrDLBCL group. In assessing the predictive power of mutation profiles for treatment responses in primary DLBCL patients, we found that the frequency of CARD11 mutations was substantially higher in non-response group as compared with those who responded to immunochemotherapy. In addition, we revealed mutations in HIST2H2AB, BCL2, NRXN3, FOXO1, HIST1H1C, LYN and TBL1XR1 genes were only detected in initial diagnostic biopsies, mutations in the EBF1 gene were solely detected in the rrDLBCL patients.Conclusion: Collectively, this study elucidates some of the genetic mechanisms contributing to the progression of rrDLBCL and suggests that the presence of CD58 mutations might serve as a powerful predictive marker for relapse/refractory outcomes in primary DLBCL patients.Keywords: targeted sequencing, mutation profile, relapse/refractory disease, diffuse large B-cell lymphoma

Abstract Background This study evaluates the health-related quality of life (HRQoL) of persons with diffuse large B-cell lymphoma (DLBCL) by using EQ-5D-5L and SF-6Dv2 and compares the measurement properties of the two instruments. Method DLBCL patients were identified via a patient group and were surveyed using web-based questionnaires. Demographic information, socioeconomic status (SES), clinical characteristics, and EQ-5D-5L and SF-6Dv2 responses were collected and statistically described. The association between the EQ-5D-5L and SF-6Dv2 dimensions were analyzed using the Spearman's correlation coefficient, whereas the correlation of the utility scores was evaluated using Pearson's correlation coefficient. The agreement between the responses of the two instruments were examined using a Bland–Altman (B-A) plot. A one-way analysis of variance (ANOVA) was performed to compare the utility scores across subgroups in different clinical states (a t-test was used if there were two subgroups). In addition, the graded response model (GRM) was used to describe the discrimination ability and difficulty characteristics of the dimensions in the two instruments. Results In total, 582 valid responses were collected, among which 477 respondents were associated with initial-treatment and 105 respondents were relapsed/refractory (RR) patients. The mean (standard deviation [SD]) EQ-5D-5L and SF-6Dv2 utility scores of the DLBCL patients were 0.828 (0.222) and 0.641 (0.220), respectively. The correlation between the EQ-5D-5L and SF-6Dv2 dimensions ranged from 0.299 to 0.680, and the correlation between their utility scores was 0.787. The B-A plot demonstrated an acceptable but not strong agreement between EQ-5D-5L and SF-6Dv2 utility scores. The GRM model results indicated that all dimensions of each instrument were highly discriminating overall, but EQ-5D-5L had suboptimal discriminative power among patients with good health. Conclusion Both the EQ-5D-5L and SF-6Dv2 showed valid properties to assess the HRQoL of DLBCL patients. However, utility scores derived from the two instruments had substantial difference, thereby prohibiting the interchangeable use of utilities from the two instruments.

Background. Assessing nutritional status at the start of treatment for patients with diffuse large B-cell lymphoma allows us to plan adequate accompanying treatment for patients in whom early nutritional support can improve the results of antitumor treatment.Aim. To assess the prevalence of nutritional deficiency, features of usual diet energy and protein composition in patients with diffuse large B-cell lymphoma who are starting antitumor treatment.Materials and methods. The study included 96 adult patients (m = 61), average age 38.9 ± 16.8 years, with newly diagnosed diffuse large B-cell lymphoma of various localization and prevalence. Additional laboratory screening (total protein, albumin, C-reactive protein (CRP), total cholesterol, triglycerides, daily urea excretion), anthropometric measurements (height, body weight (BW), weight loss over 6 months, body mass index), questionnaire (considering the intake of nutrients during the previous 3 days, calculating the intake of protein and energy, nitrogen balance) were performed in all patients before the first course of antitumor treatment. GLIM (Global Leadership Initiative on Malnutrition) criteria were used to diagnose protein-energy malnutrition (PEM).Results. In studied patients, energy intake was 27.92 ± 6.47 kcal/kg BW per day, protein 0.91 ± 0.18 g/kg BW per day, and nitrogen balance was –3.57 ± 2.94 g/day. Moderate PEM was diagnosed in 37 (38.5 %) patients. Differences in some laboratory parameters were revealed in patients with PEM and without nutritional disorders: CRP level (20.38 ± 14.69 mg/L versus 12.52 ± 5.66 mg/L; p = 0.0004), glucose (5.07 ± 1.09 mmol/L versus 4.57 ± 0.62 mmol/L; p = 0.005), total cholesterol (4.35 ± 1.27 mmol/L versus 5.36 ± 1.45 mmol/L), triglycerides (1.22 ± 0.51 mmol/L versus 2.02 ± 0.78 mmol/L; p = 0.001).Conclusion. Moderate PEM is detected in more than a third of patients with diffuse large B-cell lymphoma who begin antitumor treatment. The leading symptom in this case is unintentional weight loss over the past 6 months. An increased CRP level, moderate hyperglycemia, and lower concentrations of total cholesterol and blood triglycerides also characterize PEM in this cohort of patients. With sufficient energy supply, the amount of protein in the natural diet of patients with PEM turned out to be low, and the nitrogen balance was negative, which in the future can lead to the development of sarcopenia and requires nutritional support.

Graft failure (GF) is an extremely rare complication of autologous hematopoietic stem cell transplantation (auto-HSCT) with a frequency not exceeding 3–5 % of all cases of this technology. Primary graft failure is distinguished when restoration of hematopoiesis has not occurred by day +28 after hematopoietic stem cell transfusion, and secondary GF, implying the occurrence of neutropenia

Abstract Somatic hypermutations (SHMs) in the variable region (VH) of the immunoglobulin heavy chain (IgH) gene are common in diffuse large B‐cell lymphoma (DLBCL). Recently, IgH VH SHMs have become known as immunogenic neoantigens, but few studies have evaluated the prognostic impact of the frequency of VH SHMs in DLBCL. The BIOMED‐2 protocol is the gold standard polymerase chain reaction (PCR) for clonality analysis in lymphoid malignancies, but can produce false negatives due to the presence of IgH VH SHMs. To overcome this problem, three primer sets were designed for the three framework regions (FR1, FR2, and FR3). We evaluated the predictive value of this PCR pattern in patients with DLBCL. To evaluate the prognostic impact of complete detection of the clonal amplifications (VHFR1–JH, VHFR2–JH, and VHFR3–JH) in the BIOMED‐2 protocol, we retrospectively analyzed 301 DLBCL patients who were initially treated with anthracycline‐based immunochemotherapy. Complete detection of the FR1 to FR3 primer‐based IgH VH PCR patterns in the BIOMED‐2 protocol was associated with low frequency of VH SHMs (p

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a malignant tumour. Although some standard therapies have been established to improve the cure rate, they remain ineffective for specific individuals. Therefore, it is meaningful to find more novel therapeutic approaches. Macrophage polarisation is extensively involved in the process of tumour development. Recombinant hirudin (rH) affects macrophages and has been researched frequently in clinical trials lately. Our article validated the regulatory role of rH in macrophage polarisation and the mechanism of PAR-1 by collecting clinical samples and subsequently establishing a cellular model to provide a scientifically supported perspective for discovering new therapeutic approaches. Method We assessed the expression of macrophage polarisation markers, cytokines and PAR-1 in clinical samples. We established a cell model by co-culture with THP-1 and OCI-Ly10 cell. We determined the degree of cell polarisation and expression of validation cytokines by flow cytometry, ELISA, and RT-qPCR to confirm the success of the cell model. Subsequently, different doses of rH were added to discover the function of rH on cell polarisation. We confirmed the mechanism of PAR-1 in macrophage polarisation by transfecting si-PAR-1 and pcDNA3.1-PAR-1. Results We found higher expression of M2 macrophage markers (CD163 + CMAF+) and PAR-1 in 32 DLBCL samples. After inducing monocyte differentiation into M0 macrophages and co-culturing with OCI-Ly10 lymphoma cells, we found a trend of these expressions in the cell model consistent with the clinical samples. Subsequently, we discovered that rH promotes the polarisation of M1 macrophages but inhibits the polarisation of M2 macrophages. We also found that PAR-1 regulates macrophage polarisation, inhibiting cell proliferation, migration, invasion and angiogenic capacity. Conclusion rH inhibits macrophage polarisation towards the M2 type and PAR-1 regulates polarisation, proliferation, migration, invasion, and angiogenesis of DLBCL-associated macrophages.

Abstract Many therapies are available for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of therapy, albeit with scant evidence on the comparative effectiveness of these therapies. This study used inverse probability of treatment weighting to indirectly compare treatment outcomes of epcoritamab from the EPCORE NHL-1 trial with individual patient data from clinical practice cohorts treated with chemoimmunotherapy (CIT) and novel therapies (polatuzumab-based regimens, tafasitamab-based regimens, and chimeric antigen receptor T-cell [CAR T] therapies) for third-line or later R/R large B-cell lymphoma (LBCL) and DLBCL. In this analysis, epcoritamab demonstrated significantly better response rates and overall survival rates than CIT, polatuzumab-based regimens, and tafasitamab-based regimens. No statistically significant differences in response rates or survival were found for epcoritamab compared with CAR T in R/R LBCL.

Background and Objectives Natural killer T-cell lymphoma (NKTCL) and diffuse large B-cell lymphoma (DLBCL) are the two most prevalent subtypes of lymphoma in the sinonasal region. Accurately differentiating between sinonasal DLBCL and NKTCL is crucial for determining the appropriate treatment and prognosis. The present study compared the clinical characteristics of these two conditions. Methods We conducted a retrospective review of 173 patients diagnosed with sinonasal lymphoma at a single institute between 2004 and 2017. This review included only patients with DLBCL and NKTCL who had more than 6 months of follow-up records. We analyzed patient data encompassing clinical characteristics, pathologic findings, radiologic findings, treatment modalities, recurrence, and survival. Results Among the patients analyzed, 117 patients were diagnosed with NKTCL and 45 with DLBCL. Endoscopic evaluation revealed a significantly higher incidence of crusting (p

Herein, we report a case of plasmablastic lymphoma (PBL) and diffuse large B-cell lymphoma (DLBCL) that occurred concurrently in the large intestine. An 84-year-old female presented with a palpable rectal tumor and ileocecal tumor observed on imaging analyses. Endoscopic biopsy of both lesions revealed lymphomatous round cells. Hartmann’s operation and ileocecal resection were performed for regional control. The ileocecal lesion consisted of a proliferation of CD20/CD79a-positive lymphoid cells, indicative of DLBCL. In contrast, the rectal tumor showed proliferation of atypical cells with pleomorphic nuclei and abundant amphophilic cytoplasm, with immunohistochemical findings of CD38/CD79a/MUM1/MYC (+) and CD20/CD3/CD138/PAX5 (–). Tumor cells were positive for Epstein-Barr virus–encoded RNA based on in situ hybridization and MYC rearrangement in fluorescence in situ hybridization analysis. These findings indicated the rectal tumor was most likely a PBL. Sequencing analysis for immunoglobulin heavy variable genes indicated a common B-cell origin of the two sets of lymphoma cells. This case report and literature review provide new insights into PBL tumorigenesis.

Abstract Background Diffuse large B-cell lymphoma (DLBCL) represents a prevalent malignant tumor, with approximately 40% of patients encountering treatment challenges or relapse attributed to rituximab resistance, primarily due to diminished or absent CD20 expression. Our prior research identified PDK4 as a key driver of rituximab resistance through its negative regulation of CD20 expression. Further investigation into PDK4’s resistance mechanism and the development of advanced exosome nanoparticle complexes may unveil novel resistance targets and pave the way for innovative, effective treatment modalities for DLBCL. Methods We utilized a DLBCL-resistant cell line with high PDK4 expression (SU-DHL-2/R). We infected it with short hairpin RNA (shRNA) lentivirus for RNA sequencing, aiming to identify significantly downregulated mRNA in resistant cells. Techniques including immunofluorescence, immunohistochemistry, and Western blotting were employed to determine PDK4’s localization and expression in resistant cells and its regulatory role in phosphorylation of Histone deacetylase 8 (HDAC8). Furthermore, we engineered advanced exosome nanoparticle complexes, aCD20@ExoCTX/siPDK4, through cellular, genetic, and chemical engineering methods. These nanoparticles underwent characterization via Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM), and their cellular uptake was assessed through flow cytometry. We evaluated the nanoparticles’ effects on apoptosis in DLBCL-resistant cells and immune cells using CCK-8 assays and flow cytometry. Additionally, their capacity to counteract resistance and exert anti-tumor effects was tested in a resistant DLBCL mouse model. Results We found that PDK4 initiates HDAC8 activation by phosphorylating the Ser-39 site, suppressing CD20 protein expression through deacetylation. The aCD20@ExoCTX/siPDK4 nanoparticles served as effective intracellular delivery mechanisms for gene therapy and monoclonal antibodies, simultaneously inducing apoptosis in resistant DLBCL cells and triggering immunogenic cell death in tumor cells. This dual action effectively reversed the immunosuppressive tumor microenvironment, showcasing a synergistic therapeutic effect in a subcutaneous mouse tumor resistance model. Conclusions This study demonstrates that PDK4 contributes to rituximab resistance in DLBCL by modulating CD20 expression via HDAC8 phosphorylation. The designed exosome nanoparticles effectively overcome this resistance by targeting the PDK4/HDAC8/CD20 pathway, representing a promising approach for drug delivery and treating patients with Rituximab-resistant DLBCL.

Abstract Background Lymphoid neoplasm is a common disease, arising from lymphoid cells. It is divided into Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma can be intranodular or extranodular, which happens in 25% of primary cases. The most common locations of extranodular non-Hodgkin lymphoma are the skin and gastrointestinal tract. The genital tract is a rare location; most lymphomas arise from the cervix and vagina, while the uterine corpus is an extremely rare location. In our case, the patient was diagnosed with primary extranodular non-Hodgkin lymphoma in different locations of her genital tract. Case presentation A 48-year-old nonparous Syrian woman complained of diffuse abdominal pain, fatigue, debility, high fever, vomiting, and urinary retention for a week. The last menstrual period of the patient was 5 years previously. The physical examination showed periodic abdominal pain with severe fatigue and increased abdominal size. The laboratory investigations were within normal limits except for a low level of hemoglobin and a high level of cancer antigen 125. The radiological investigations showed a uterine sizable lobulated mass with irregular borders and high and heterogeneous density, extending to the right and left ovaries, enlargement lymph nodes around the abdominal aortic and right iliac vessels, and severe right pleural effusion with right inferior lobe atelectasis. A total hysterectomy and oophorectomy were done. The histopathological examination showed that the patient had non-Hodgkin lymphoma (primary tumor). Conclusion Primary non-Hodgkin lymphoma in the female genital tract is an extremely rare disease. Fast diagnosis and treatment can improve the outcomes, so this differential diagnosis should be in our minds even in the absence of systematic manifestations of lymphoma. More studies are needed to explain the pathology of this disease and to put guidelines that determine the perfect methods for diagnosis and treatment.

Abstract Background The metabolic tumour area (MTA) was found to be a promising predictor of prostate cancer. However, the role of MTA based on 18F-FDG PET/CT in diffuse large B-cell lymphoma (DLBCL) prognosis remains unclear. This study aimed to elucidate the prognostic significance of MTA and evaluate its incremental value to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) for DLBCL patients treated with first-line R-CHOP regimens. Methods A total of 280 consecutive patients with newly diagnosed DLBCL and baseline 18F-FDG PET/CT data were retrospectively evaluated. Lesions were delineated via a semiautomated segmentation method based on a 41% SUVmax threshold to estimate semiquantitative metabolic parameters such as total metabolic tumour volume (TMTV) and MTA. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values. Progression-free survival (PFS) and overall survival (OS) were the endpoints that were used to evaluate the prognosis. PFS and OS were estimated via Kaplan‒Meier curves and compared via the log-rank test. Results Univariate analysis revealed that patients with high MTA, high TMTV and NCCN-IPI ≥ 4 were associated with inferior PFS and OS (P