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Diffuse large B-cell lymphoma (DLBCL) is the leading cause of mortality from invasive hematological malignancies worldwide. MicroRNA-7-5p (miR-7-5p) has been shown to be a tumor suppressor in several types of tumors. However, its role in DLBCL is not fully understood. This study explored the role of miR-7-5p in the progression of DLBCL and pursued the underlying mechanism. Quantitative real-time PCR and transfection of miRNA mimic and inhibitors were used to assess the effects of miR-7-5p on autophagy and apoptosis in SU-DHL-4 and SU-DHL-10 cells. Dual-luciferase reporter assay was used to identify target genes of miR-7-5p. Immunofluorescence, flow cytometry, and western blotting (WB) were performed to explore the underlying mechanism and downstream pathways of miR-7-5p and AMBRA1 in DLBCL cells. MiR-7-5p was upregulated in DLBCL cells. Luciferase reporter assays implicated AMBRA1 as a downstream target of miR-7-5p in DLBCL. WB and flow cytometry showed that an increase in miR-7-5p level and a decrease in AMBRA1 expression led to a decrease in autophagy and apoptosis-related protein expression. Furthermore, miR-7-5p prevented c-MYC dephosphorylation through AMBRA1 downregulation. On the contrary, c-MYC increased the expression of miR-7-5p, thereby establishing positive feedback on miR-7-5p transcription. The addition of hydroxychloroquine, an autophagy inhibitor, reduced autophagy and increased apoptosis in DLBCL cells. In vivo experiments further proved that the increase of miR-7-5p played a regulatory role in the expression of downstream AMBRA1 and c-MYC. These results demonstrate that c-MYC-dependent MiR-7-5p suppressed autophagy and apoptosis by targeting AMBRA1 in DLBCL cells. MiR-7-5p also suppressed autophagy and apoptosis by targeting AMBRA1 in DLBCL cells. Therefore, these data suggest that targeting miR-7-5p may be a promising strategy in DLBCL therapy. [ABSTRACT FROM AUTHOR]

Primary uterine non-Hodgkin lymphoma (NHL) is rarely reported, as its incidence is extremely low. We describe a 72 year old patient with primary uterine non-Hodgkin's lymphoma stage IV, diffuse B-cell large cells, who responded well to cytotoxic chemotherapy (R-CHOP). Radiological investigations exhibited certain characteristics, including magnetic resonance T2 weighted imaging, enhanced scanning, diffusion weighted imaging and apparent diffusion coefficient values. The lesion in the anterior wall of the uterine body was relatively large, with a size of about 34mm×47mm×43mm. The gold standard for diagnosis is still the pathological examination of a biopsy specimen, which revealed diffuse large cell of B lineage. This article reviews data collected from 141 patients in the literature. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma (DLBCL) has been reported previously. However, the detailed mechanisms of CCR7 in DLBCL, particularly regarding its interaction with lenalidomide treatment, are not fully understood. Methods: Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups. Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL. Furthermore, in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment. Results: Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL. Notably, 31.14% and 36.0% (44/122) of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively, establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis. Additionally, our studies demonstrated that the external application of the protein CCL21 promoted proliferation, migration, invasion, and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression. This effect was mitigated by CCR7 silencing through siRNA, application of ERK inhibitors, or lenalidomide treatment. In vivo experiments reinforced the efficacy of lenalidomide, significantly reducing tumor growth rate, tumor mass, serum total LDH levels, and expression of CCR7 and p-ERK1/2 in a SU-DHL-2 xenograft model in nude mice (p < 0.05). Conclusion: Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prognostic value of lactate dehydrogenase (LDH), serum albumin (ALB) and the lactate dehydrogenase/albumin ratio (LAR) in diffuse large B-cell lymphoma (DLBCL) before primary treatment. Methods: The clinical data of 212 primary adult DLBCL patients admitted to the First People's Hospital of Lianyungang from January 2017 to December 2022 were analyzed retrospectively. The optimal cutoff values of LDH, ALB, and LAR were determined using ROC curves. Survival curves of LDH, ALB, and LAR were plotted and analyzed using the Cox regression model and Kaplan–Meier method with the log-rank test. Results: Among the 212 patients admitted, the study derived the optimal cutoff values for ALB, LDH, and LAR as 38, 301, and 6, respectively. The Kaplan–Meier method and log-rank test analysis indicated a significant association between lower ALB levels, elevated LDH levels, elevated LAR levels, and shorter overall survival (OS) and progression-free survival (PFS) (P < 0.05). Additionally, the critical values of ALB and LDH were grouped into three categories. The differences in OS and PFS among these three groups were statistically significant (P < 0.05). Cox multifactorial analysis revealed that the LAR was an independent factor influencing the prognosis of OS and PFS, with a higher prognostic value than LDH and ALB alone. Conclusion: Decreased ALB levels and elevated LDH and LAR levels at the time of initial diagnosis are indicative of a poor prognosis in DLBCL patients. Furthermore, the study highlighted that the LAR has a higher prognostic value than LDH and ALB alone. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the expression levels and biological significance of CKS2 in Burkitt cell lymphoma (BL) and diffuse large B‐cell lymphoma (DLBCL). Additionally, the potential synergistic anti‐tumor effects of CKS2 knockdown in combination with etoposide in BL and DLBCL were explored for the first time. Methods: Bioinformatics analysis was utilized to explore the transcriptional levels, prognostic value, and gene function enrichment of CKS2 in BL and DLBCL. Specific shRNA sequences were designed to target CKS2 for the purpose of constructing a lentiviral expression vector, and therapeutic effects were assessed through analyses of cell proliferation, cell cycle distribution, and cell apoptosis. Results: First, the study examined the increased transcriptional and protein levels of CKS2 in BL and DLBCL through analysis of various databases and immunohistochemistry tests. Elevated CKS2 expression was found to be correlated with a worse prognosis in BL and DLBCL patients, as evidenced by data from the TCGA and GEO databases. Enrichment analysis indicated that CKS2 functions were primarily linked to protein kinase regulatory activity, G1/S phase transition of the cell cycle, and the p53 signaling pathway, among others. Second, stable suppression of CKS2 gene expression in Raji and SUDHL6 cells using shRNA resulted in a significant inhibition of cell proliferation. Moreover, CKS2‐shRNA induced G0/G1 cell cycle arrest and apoptosis by activating the p53 signaling pathway in Raji and SUDHL6 cells. Third, the combined treatment of CKS2‐shRNA and etoposide exhibited a synergistic effect on the proliferation and apoptosis of Raji and SUDHL6 cells. Conclusions: Our findings suggest that CKS2 may play a critical role in the progression of BL and DLBCL and provide evidence for the potential therapeutic application of combining CKS2‐shRNA and etoposide agents in the treatment of BL and DLBCL. [ABSTRACT FROM AUTHOR]

Objective·To analyze the clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma (DLBCL), including clinical characteristics, pathological characteristics, gene mutation profiles, and prognostic factors.Methods·One hundred and forty-nine patients with kidney-involved DLBCL, admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from July 2005 to November 2021, were retrospectively analyzed for their clinicopathological data, survival and prognostic factors, which included therapeutic methods, clinical outcomes, staging, etc. Gene mutation profiles were evaluated by targeted sequencing of 54 lymphoma-related genes. Prognostic factors were also analyzed based on the information mentioned above.Results·A total of 149 kidney-involved DLBCL cases were included, of which 89 patients (58.4%) were aged over sixty, 121 patients (81.2%) were staged Ann Arbor Ⅲ‒Ⅳ, 27 patients (18.1%) had an Eastern Cooperative Oncology Group (ECOG) performance status of two or more, 121 patients (81.2%) had elevated serum lactate dehydrogenase (LDH) level, 111 patients (74.5%) had extranodal invasion in at least two organs and 131 patients (87.9%) scored over 2 points on the international prognosis index (IPI). The estimated 5-year overall survival (OS) rate and progression-free survival (PFS) rate of kidney-involved DLBCL patients were 52.2% and 50.4% respectively. Univariate analysis revealed that elevated serum LDH levels were an adverse prognostic factor for both OS (P=0.048) and PFS (P=0.033). In pathological characteristics, 145 patients (97.3%) belonged to DLBCL, not otherwise specified (NOS) and 39 patients (26.3%) belonged to germinal center B-cell (GCB) according to Hans classification. Among 144 patients who could be evaluated for clinical outcomes, 87 patients (60.4%) got complete response (CR). Targeted sequencing data from 75 kidney-involved DLBCL patients showed high mutation frequency in PIM1 (n=23, 31%), MYD88 (n=22, 29%), CD79B (n=21, 28%) and KMT2D (n=18, 24%), with CD79B mutation indentified as an adverse prognostic factor for OS in patients with kidney-involved DLBCL (P=0.034).Conclusion·Elevated serum LDH level is an adverse prognostic factor in patients with kidney-involved DLBCL. The prognosis of patients with CD79B mutations is poor.

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Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous non-Hodgkin lymphoma that is extremely aggressive and has an intermediate to high malignancy. Some patients still experience treatment failure, relapse, or resistance to rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) therapy. Therefore, there is an urgent need for further research on new agents for the treatment of DLBCL. AP-48 is an aaptamine alkaloid analog with potent anti-tumor effects that originates from marine natural products. In this study, we found that AP-48 exhibits dose-dependent cytotoxicity in DLBCL cell lines. Flow cytometry showed that AP-48 induced cell cycle arrest in the G0/G1 phase in SU-DHL-4 and Farage cells and in the S phase in WSU-DLCL-2 cells. AP-48 also accelerated apoptosis via the caspase-3-mediated intrinsic apoptotic pathway. Further experiments demonstrated that AP-48 exerted its anti-DLBCL effects through the PI3K/AKT/mTOR pathway, and that the PI3K agonist YS49 partially alleviated the inhibition of cell proliferation and apoptosis induced by AP-48. Finally, in a tumor xenograft model, AP-48 inhibited tumor growth and promoted apoptosis in tumor tissues, indicating its therapeutic potential in DLBCL. [ABSTRACT FROM AUTHOR]

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. Methods: CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandemmass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Results: Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. Discussion: This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Chimeric antigen receptor T-cell (CAR T) therapies have transformed diffuse large B-cell lymphoma (DLBCL) treatment. It is important to better understand their use in Medicare Fee-for-Service (FFS) patients, who often differ from commercially insured populations in important ways. Methods: We analyzed Medicare FFS claims data, focusing on the utilization patterns across three CAR T products—lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), and axicabtagene autoleucel (axi-cel)—which are indicated for the treatment of DLBCL. Our investigation covered the period from 2021 through 2022. This analysis spanned a 180-day period prior to CAR T procedure and extended to a 90-day post-CAR T. Utilization of healthcare services, healthcare spending, and comorbidities were assessed in the pre- and post-periods. Clinical trial and PPS-exempt center claims were removed from the analysis. Statistical comparisons between inpatient and outpatient cohorts were made using Wilcoxon's rank-sum tests for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables. Results: Among the total 391 CAR T claims assessed, most of the CAR T therapies were administered in the inpatient setting (79%) compared to outpatient (21%). CAR T therapy in the inpatient setting received an average Medicare cost of US$498,723 ($276,138—$1,066,524), while the average Medicare cost for outpatient CAR T claims was $414,393 ($276,980—$849,878). There was a higher 3-month average post-period cost for those hospitals utilizing CAR T in the outpatient setting than the inpatient setting ($15,794 vs. $10,244). Despite the higher post-period cost, when looking at the CAR T procedure and pre- and post-periods as a single episode, beneficiaries receiving outpatient CAR T had less cost for the total episode of care ($587,908 vs. $529,188). Follow-up inpatient claims were also assessed post-CAR T procedure for 30 days. The rate of post-CAR T inpatient re-admission was significantly lower for beneficiaries receiving the index CAR T in the inpatient setting (21%) compared to outpatient CAR T (59%). Days between index CAR T discharge and IP admission were also significantly shorter for OP CAR T compared to IP CAR T (8.0 vs. 14.1 days, p < 0.0001). Additionally, IP CAR T had a longer ALOS on the admission claim (6.9 vs. 6.2 days). Conclusion: CAR T therapy for the treatment of LBCL has become more common within the Medicare population, primarily in the inpatient setting. This study helps understand providers' cost and associated patient care around CAR T administration. The data show that the average cost received by hospitals encompasses the expenses related to both the CAR T drug and the medical services delivered to patients. [ABSTRACT FROM AUTHOR]

Here, we have discussed the molecular mechanisms of p53-responsive microRNAs dysregulation in response to genotoxic stress in diffuse large B-cell lymphoma (DLBCL) patients. The role of micro ribonucleic acids (microRNAs) in p53-signaling cellular stress has been studied. MicroRNAs are the small non-coding RNAs, which regulate genes expression at post-transcriptional level. Many of them play a crucial role in carcinogenesis and may act as oncogenes or suppressor of tumor growth. The understanding of the effect of p53-responsive microRNA dysregulation on oncogenesis achieved in recent decades opens wide opportunities for the diagnosis, prediction and of microRNA-based cancer therapy. Development of new bioinformatics tools and databases for microRNA supports DLBCL research. We overview the studies on the role of miRNAs in regulating gene expression associated with tumorigenesis processes, with particular emphasis on their role as tumor growth-suppressing factors. The starting point is a brief description of the classical microRNA biogenesis pathway and the role of p53 in regulating the expression of these molecules. We analyze various molecular mechanisms leading to this dysregulation, including mutations in the TP53 gene, DNA methylation, changes in host-genes expression or microRNA gene copy number, mutations in microRNA and microRNA biogenesis genes.

Primary uterine non-Hodgkin lymphoma (NHL) is rarely reported, as its incidence is extremely low. We describe a 72 year old patient with primary uterine non-Hodgkin’s lymphoma stage IV, diffuse B-cell large cells, who responded well to cytotoxic chemotherapy (R-CHOP). Radiological investigations exhibited certain characteristics, including magnetic resonance T2 weighted imaging, enhanced scanning, diffusion weighted imaging and apparent diffusion coefficient values. The lesion in the anterior wall of the uterine body was relatively large, with a size of about 34mm×47mm×43mm. The gold standard for diagnosis is still the pathological examination of a biopsy specimen, which revealed diffuse large cell of B lineage. This article reviews data collected from 141 patients in the literature.

Objectives: The aim of this review is to focus on the possibility of patients with squamous cell carcinoma to develop a second primary disease such as DLBCL, perhaps because of the irradiation of the head and neck area. Materials and methods: A case of an 89-year-old man is reported, who initially underwent surgical and complementary treatment for neck squamous cell carcinoma of occult primary and later for tonsillar diffuse large B-cell non-Hodgkin lymphoma. Results: The second primary was considered a recurrence in the neck of the original cancer of unknown primary, so a new surgical management was decided. The final pathology report described a diffuse large B-cell non-Hodgkin lymphoma. Conclusions: The importance of maintaining follow-ups for patients with occult primary cancers who are at an elevated risk of developing a metastasis or a second primary carcinoma outbreak is highlighted. [ABSTRACT FROM AUTHOR]

• This EHA–ESMO Clinical Practice Guideline provides key recommendations for managing primary DLBCL of the CNS. • The guideline covers clinical, imaging and pathological diagnosis, staging and risk assessment, treatment and follow-up. • Algorithms for first-line and salvage treatments are provided. • The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe. • Recommendations are based on available scientific data and the authors' collective expert opinion. [ABSTRACT FROM AUTHOR]

Lymphoma is one of the most frequent hematopoietic tumors in dogs and shares similar features with human counterparts. MicroRNAs (miRNA, small noncoding RNAs) are pivotal in gene regulation fine tuning and cancer hallmarks are influenced by their aberrant expression. Consequently, miRNA biomarkers may assist predicting therapeutic response and clinical outcome by providing less-invasive novel diagnostics tools. The aim of this study was to detect dysregulated miRNAs in lymphomatous lymph node tissues in comparison to lymph node material or PBMCs from healthy control dogs. Potential significant differences in miRNA expression profiles between four lymphoma entities were evaluated. A customized PCR array was utilized to profile 89 canine target miRNAs. Quantification was performed using qPCR, relative expression was determined by the delta-delta Ct method, and p-values were calculated with student's t-test. In the 14 diffuse large B-cell lymphoma (DLBCL) patients, 28 and 24 different miRNAs were significantly dysregulated compared to lymph node material or PBMCs. Sixteen miRNAs occurred in both control groups, with 12 miRNAs being down- and four miRNAs being upregulated. The six peripheral T-cell lymphoma (PTCL) samples showed 24 and 25 dysregulated miRNAs when compared to the healthy controls. A combined analysis of DLBCL and PTCL samples revealed seven shared and 19 differently expressed miRNAs. Potential biomarkers in T- and B-cell lymphoma could be the miRNA-17/92 cluster and miRNA-181-family together with miRNA-34a and miRNA-150. Diagnostic utility of potential biomarkers must be validated in larger, prospective cohorts of canine lymphoma cases and in higher numbers of physiological patient material. [ABSTRACT FROM AUTHOR]

With the outbreak of coronavirus disease 2019 (COVID-19), there has been an increasing focus on exploring the relationship between SARS-CoV-2 infection and tumors. However, there is no consensus on the association between COVID-19 and lymphoma. In this study, genome-wide association study (GWAS) summary data sets for COVID-19 and lymphoma were obtained from the OPEN GWAS website. Single nucleotide polymorphisms (SNPs) were selected as genetic instrument variants for fulling P < 5 × 10−8 and linkage disequilibrium [LD] r2 < 0.001. Both palindromic and outlier SNPs were removed. Cochran's Q test, the MR‒Egger intercept test, and leave-one-out analysis were employed to assess the sensitivity of the effect of COVID-19 on lymphoma. The results showed that COVID-19 patients with very severe respiratory symptoms have an increased risk of developing diffuse large B-cell lymphoma (IVW, OR = 1.765, 95% CI 1.174–2.651, P = 0.006). There was no association between COVID-19 with very severe respiratory symptoms and Hodgkin's lymphoma or other types of non-Hodgkin's lymphoma. No horizontal or directional pleiotropy was observed in the Mendelian randomization analysis. In conclusion, SARS-CoV-2 infection with very severe respiratory symptoms may be a potential risk factor for diffuse large B-cell lymphoma (DLBCL), and follow-up studies with larger samples are needed. [ABSTRACT FROM AUTHOR]

Hirudin is one of the specific inhibitors of thrombin, which has been confirmed to have strong bioactivities, including inhibiting tumors. However, the function and mechanism of hirudin and protease‐activated receptor 1 (PAR‐1) in diffuse large B‐cell lymphoma (DLBCL) have not been clear. Detecting the expression PAR‐1 in DLBCL tissues and cells by RT‐qPCR and IHC. Transfected sh‐NC, sh‐PAR‐1, or pcDNA3.1‐PAR‐1 in DLBCL cells or processed DLBCL cells through added thrombin, Vorapaxar, Recombinant hirudin (RH), or Na2S2O4 and co‐culture with EA.hy926. And built DLBCL mice observed tumor growth. Detecting the expression of related genes by RT‐qPCR, Western blot, IHC, and immunofluorescence, measured the cellular hypoxia with Hypoxyprobe‐1 Kit, and estimated the cell inflammatory factors, proliferation, migration, invasion, and apoptosis by ELISA, CCK‐8, flow cytometry, wound‐healing and Transwell. Co‐immunoprecipitation and pull‐down measurement were used to verify the relationship. PAR‐1 was highly expressed in DLBCL tissues and cells, especially in SUDHL2. Na2S2O4 induced SUDHL2 hypoxia, and PAR‐1 did not influence thrombin‐activated hypoxia. PAR‐1 could promote SUDHL2 proliferation, migration, and invasion, and it was unrelated to cellular hypoxia. PAR‐1 promoted proliferation, migration, and angiogenesis of EA.hy926 or SUDHL2 through up‐regulation vascular endothelial growth factor (VEGF). RH inhibited tumor growth, cell proliferation, and migration, promoted apoptosis of DLBCL, and inhibited angiogenesis by down‐regulating PAR‐1‐VEGF. RH inhibits proliferation, migration, and angiogenesis of DLBCL cells by down‐regulating PAR‐1‐VEGF. [ABSTRACT FROM AUTHOR]

Diffuse large B‐cell lymphoma (DLBCL) is a heterogeneous and prevalent subtype of aggressive non‐Hodgkin lymphoma that poses diagnostic and prognostic challenges, particularly in predicting drug responsiveness. In this study, we used digital pathology and deep learning to predict responses to immunochemotherapy in patients with DLBCL. We retrospectively collected 251 slide images from 216 DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP), with their immunochemotherapy response labels. The digital pathology images were processed using contrastive learning for feature extraction. A multi‐modal prediction model was developed by integrating clinical data and pathology image features. Knowledge distillation was employed to mitigate overfitting on gigapixel histopathology images to create a model that predicts responses based solely on pathology images. Based on the importance derived from the attention mechanism of the model, we extracted histological features that were considered key textures associated with drug responsiveness. The multi‐modal prediction model achieved an impressive area under the ROC curve of 0.856, demonstrating significant associations with clinical variables such as Ann Arbor stage, International Prognostic Index, and bulky disease. Survival analyses indicated their effectiveness in predicting relapse‐free survival. External validation using TCGA datasets supported the model's ability to predict survival differences. Additionally, pathology‐based predictions show promise as independent prognostic indicators. Histopathological analysis identified centroblastic and immunoblastic features to be associated with treatment response, aligning with previous morphological classifications and highlighting the objectivity and reproducibility of artificial intelligence‐based diagnosis. This study introduces a novel approach that combines digital pathology and clinical data to predict the response to immunochemotherapy in patients with DLBCL. This model shows great promise as a diagnostic and prognostic tool for clinical management of DLBCL. Further research and genomic data integration hold the potential to enhance its impact on clinical practice, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

A novel antibody-drug conjugate (ADC), Polatuzumab vedotin has emerged as a promising player in the oncology field. This comprehensive review aims to elucidate the intricate details of Polatuzumab vedotin, encompassing its molecular structure, mechanisms of action, clinical applications, therapeutic efficacy, and ongoing research endeavors. With a focus on precision and targeted therapy, Polatuzumab vedotin stands as a beacon of hope in the battle against various malignancies. It has been regarded as a significant advancement in the field of targeted treatment of diffuse large B-cell lymphoma. As research continues to expand, our understanding of Polatuzumab vedotin, it is evident that its potential to improve patient outcomes and reduce the burden of cancer will remain a topic of great interest for the medical community.

Simple Summary: Here, we assessed clinical outcomes, predictors of survival, and compared responses and toxicities among different therapeutic modalities in a large cohort of older adults with DLBCL. A total of 185 Brazilian patients were included from 2009 to 2020. After a long follow-up, we demonstrated a 5-year OS of 50.2%. The R-MiniCHOP regimen was associated with a lower ORR; however, these patients were more malnourished and had a higher risk on prognostic indexes. Although associated with higher rates of severe neutropenia, the R-CHOP regimen was associated with substantial OS and PFS advantages. We also identified independent prognostic factors associated with poor outcomes, including age ≥ 75 years, high LDH, B-symptoms, clinical stage III/IV, neutrophilia, and reduced lymphocyte/monocyte ratio. Although a significant portion of older DLBCL patients are highly fragile and ineligible for enhanced regimens, attenuated protocols promoted remarkably inferior outcomes compared to those achieved by the R-CHOP. Background: Diffuse large B-cell lymphoma (DLBCL) especially affects the older population. Old (≥60 years) and very old age (≥80 years) DLBCL patients often present high-risk molecular alterations, lower tolerability to conventional immunochemotherapy, and poor clinical outcomes. In this scenario, attenuated therapeutic strategies, such as the R-MiniCHOP and R-MiniCHOP of the elderly regimens, have emerged for this particularly fragile population. However, the responses, clinical outcomes, and toxicities of these regimens currently remain poorly understood, mainly because these individuals are not usually included in controlled clinical trials. Methods: This retrospective, observational, and single-center real-world study included 185 DLBCL, NOS patients older than 70 years treated at the largest oncology center in Latin America from 2009 to 2020. We aimed to assess the outcomes, determine survival predictors, and compare responses and toxicities between three different primary therapeutic strategies, including the conventional R-CHOP regimen and the attenuated R-MiniCHOP and R-MiniCHOP of the elderly protocols. Results: The median age at diagnosis was 75 years (70–97 years), and 58.9% were female. Comorbidities were prevalent, including 19.5% with immobility, 28.1% with malnutrition, and 24.8% with polypharmacy. Advanced clinical stage was observed in 72.4%, 48.6% had bulky disease ≥7 cm, 63.2% had B-symptoms, and 67.0% presented intermediate–high/high-risk IPI. With a median follow-up of 6.3 years, the estimated 5-year OS and PFS were 50.2% and 44.6%, respectively. The R-MiniCHOP of the elderly regimen had a lower ORR (p = 0.040); however, patients in this group had higher rates of unfavorable clinical and laboratory findings, including hypoalbuminemia (p = 0.001), IPI ≥ 3 (p = 0.013), and NCCN-IPI ≥ 3 (p = 0.002). Although associated with higher rates of severe neutropenia (p = 0.003), the R-CHOP regimen promoted increased OS (p = 0.003) and PFS (p = 0.005) in comparison to the attenuated protocols. Additionally, age ≥ 75 years, high levels of LDH, B-symptoms, advanced clinical stage (III/IV), neutrophilia, and low lymphocyte/monocyte ratio were identified as poor prognostic factors in this cohort. Conclusions: In this large and real-life Latin American cohort, we demonstrated that patients with DLBCL, NOS older than 70 years still do not have satisfactory clinical outcomes in 2024, with half of cases not reaching 5 years of life expectancy after diagnosis. Although the conventional R-CHOP offers response and survival advantages over attenuated regimens, its myelotoxicity is not negligible. Therefore, the outcomes reported and the prognostic factors here identified may assist clinicians in the appropriate selection of therapeutic strategies adapted to the risk for old and very old DLBCL patients. [ABSTRACT FROM AUTHOR]

The majority of patients with Diffuse Large B-cell Lymphoma (DLBCL) will respond to first-line treatment and be cured. However, the disease is heterogeneous, and biomarkers able to discriminate patients with suboptimal prognosis are needed. M2 CD163-positive tumor-associated macrophages (TAMs) were shown to be implicated in DLBCL disease activity regulation. Serum-soluble CD163 (sCD163) functions as a scavenger receptor for haptoglobin–hemoglobin complexes and is mostly expressed by monocytes and macrophages. Its levels are used to determine macrophage activation. We aimed to determine serum sCD163 in a sample of DLBCL patients and study eventual correlations with parameters of disease activity or survival. Serum sCD163 levels were measured in 40 frozen sera from patients diagnosed with DLBCL and 30 healthy individuals (HIs) using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using SPSS version 28. The results showed that patients who achieved complete response after standard-of-care immunochemotherapy and were alive and disease-free after 12 months of follow-up but had elevated sCD163 levels (above median) at diagnosis presented a significantly worse overall survival compared to those with initial serum sCD163 levels below the median (p = 0.03). Consequently, serum sCD163 levels in patients with DLBCL may constitute a marker of long-term response to chemoimmunotherapy. [ABSTRACT FROM AUTHOR]

Anti-CD20 monoclonal antibodies (mAbs) have revolutionized the treatment of lymphomas by improving the survival of patients, particularly in conjunction with chemotherapy. Until recently, the gold standard was based on the utilization of Rituximab (RTX) combined with chemotherapy. With our better understanding of monoclonal antibody (mAb) engineering, anti-CD20 mAb therapy has evolved to enhance clinical outcomes by improving pharmacokinetics, safety, activity and immunogenicity. Efforts to improve the on-targeting CD20 expressed on lymphomas through novel bioengineering techniques have led to the development of newer anti-CD20 mAbs that have accentuated complement-dependent cytotoxicity (CDC), antibody-dependent cell medicated cytotoxicity (ADCC), and/or a direct killing effect. There are several anti-CD20 monoclonal antibodies that have been evaluated for the treatment of lymphomas, some of which are now approved in addition to RTX. [ABSTRACT FROM AUTHOR]

Aims: Primary bone diffuse large B‐cell lymphoma (PB‐DLBCL) is not recognized as a separate entity by the current classification systems. Here we define and highlight its distinctive clinical presentation, morphology, phenotype, gene expression profile (GEP), and molecular genetics. Methods: We collected 27 respective cases and investigated their phenotype, performed gDNA panel sequencing covering 172 genes, and carried out fluorescence in situ hybridization to evaluate MYC, BCL2, and BCL6 translocations. We attempted to genetically subclassify cases using the Two‐step classifier and performed GEP for cell‐of‐origin subtyping and in silico comparison to uncover up‐ and downregulated genes as opposed to other DLBCL. Results: Most cases (n = 22) were germinal centre B‐cell‐like (GCB) by immunohistochemistry and all by GEP. Additionally, PB‐DLBCL had a mutational profile similar to follicular lymphoma and nodal GCB‐DLBCL, with the exception of more frequent TP53 and B2M mutations. The GEP of PB‐DLBCL was unique, and the frequency of BCL2 rearrangements was lower compared to nodal GCB‐DLBCL. The Two‐step classifier categorized eight of the cases as EZB, three as ST2, and one as MCD. Conclusion: This study comprehensively characterizes PB‐DLBCL as a separate entity with distinct clinical and morpho‐molecular features. These insights may aid in developing tailored therapeutic strategies and shed light on its pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effect of kaempferol on the growth, apoptosis, and motility of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) cells, and to elucidate its mechanism of action. Methods: Human DLBCL cells were used to generate EBV-positive (EBV +) cell line Pfeiffer. CCK-8, colony formation, flow cytometry (FCM), and immunoblot assays were employed to determine the effects of kaempferol on the growth and apoptosis of EBV + DLBCL cells. Cell motility was evaluated by Transwell and immunoblot assays. Immunoblot assay was further conducted to unravel the mechanism of action. Results: Kaempferol inhibited the growth of EBV + DLBCL cells. It also enhanced the apoptosis of EBV + DLBCL cells, but inhibited the motility of the cells. Furthermore, kaempferol inhibited PI3K/AKT axis, thereby suppressing DLBCL. Conclusion: Kaempferol inhibits the growth and motility of EBV + DLBCL cells via PI3K/AKT axis. It is therefore a potential drug for the treatment of DLBCL. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) stands as a formidable challenge in the landscape of non-Hodgkin's lymphomas. This review illuminates the remarkable strides made in comprehending DLBCL's molecular intricacies and devising targeted treatments. DLBCL, the most prevalent non-Hodgkin's lymphoma, has seen transformative progress in its characterization. Genetic investigations, led by high-throughput sequencing, have unveiled recurrent mutations in genes such as MYC, BCL2, and BCL6, casting light on the underlying genetic chaos propelling DLBCL's aggressiveness. A pivotal facet of this understanding centers on cell signaling pathways. Dysregulation of B-cell receptor (BCR) signaling, NF-κB, PI3K/Akt/mTOR, JAK/STAT, Wnt/β-Catenin, and Toll-like receptor pathways plays a critical role in DLBCL pathogenesis, offering potential therapeutic targets. DLBCL's complex tumor microenvironment (TME) cannot be overlooked. The dynamic interplay among tumor cells, immune cells, stromal components, and the extracellular matrix profoundly influences DLBCL's course and response to therapies. Epigenetic modifications, including DNA methylation and histone changes, add another layer of intricacy. Aberrant epigenetic regulation plays a significant role in lymphomagenesis, offering prospects for epigenetic-based therapies. Promisingly, these molecular insights have spurred the development of personalized treatments. Targeted therapies and immunotherapies, guided by genomic profiling and molecular classification, are emerging as game-changers in DLBCL management. In conclusion, this review underscores the remarkable strides in understanding DLBCL's molecular underpinnings, spanning genetics, cell signaling, the tumor microenvironment, and epigenetics. These advances pave the way for more effective, personalized treatments, renewing hope for DLBCL patients. [ABSTRACT FROM AUTHOR]

Lymphoma is one of the most frequent hematopoietic tumors in dogs and shares similar features with human counterparts. MicroRNAs (miRNA, small non-coding RNAs) are pivotal in gene regulation fine tuning and cancer hallmarks are influenced by their aberrant expression. Consequently, miRNA biomarkers may assist predicting therapeutic response and clinical outcome by providing less-invasive novel diagnostics tools. The aim of this study was to detect dysregulated miRNAs in lymphomatous lymph node tissues in comparison to lymph node material or PBMCs from healthy control dogs. Potential significant differences in miRNA expression profiles between four lymphoma entities were evaluated. A customized PCR array was utilized to profile 89 canine target miRNAs. Quantification was performed using qPCR, relative expression was determined by the delta–delta Ct method, and p-values were calculated with student’s t-test. In the 14 diffuse large B-cell lymphoma (DLBCL) patients, 28 and 24 different miRNAs were significantly dysregulated compared to lymph node material or PBMCs. Sixteen miRNAs occurred in both control groups, with 12 miRNAs being down- and four miRNAs being upregulated. The six peripheral T-cell lymphoma (PTCL) samples showed 24 and 25 dysregulated miRNAs when compared to the healthy controls. A combined analysis of DLBCL and PTCL samples revealed seven shared and 19 differently expressed miRNAs. Potential biomarkers in T- and B-cell lymphoma could be the miRNA-17/92 cluster and miRNA-181-family together with miRNA-34a and miRNA-150. Diagnostic utility of potential biomarkers must be validated in larger, prospective cohorts of canine lymphoma cases and in higher numbers of physiological patient material.

Abstract Diffuse large B‐cell lymphoma (DLBCL) is a heterogeneous and prevalent subtype of aggressive non‐Hodgkin lymphoma that poses diagnostic and prognostic challenges, particularly in predicting drug responsiveness. In this study, we used digital pathology and deep learning to predict responses to immunochemotherapy in patients with DLBCL. We retrospectively collected 251 slide images from 216 DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP), with their immunochemotherapy response labels. The digital pathology images were processed using contrastive learning for feature extraction. A multi‐modal prediction model was developed by integrating clinical data and pathology image features. Knowledge distillation was employed to mitigate overfitting on gigapixel histopathology images to create a model that predicts responses based solely on pathology images. Based on the importance derived from the attention mechanism of the model, we extracted histological features that were considered key textures associated with drug responsiveness. The multi‐modal prediction model achieved an impressive area under the ROC curve of 0.856, demonstrating significant associations with clinical variables such as Ann Arbor stage, International Prognostic Index, and bulky disease. Survival analyses indicated their effectiveness in predicting relapse‐free survival. External validation using TCGA datasets supported the model's ability to predict survival differences. Additionally, pathology‐based predictions show promise as independent prognostic indicators. Histopathological analysis identified centroblastic and immunoblastic features to be associated with treatment response, aligning with previous morphological classifications and highlighting the objectivity and reproducibility of artificial intelligence‐based diagnosis. This study introduces a novel approach that combines digital pathology and clinical data to predict the response to immunochemotherapy in patients with DLBCL. This model shows great promise as a diagnostic and prognostic tool for clinical management of DLBCL. Further research and genomic data integration hold the potential to enhance its impact on clinical practice, ultimately improving patient outcomes.

Objective·To analyze the clinicopathologic characteristics, gene mutation profile, and prognostic factors of thyroid diffuse large B-cell lymphoma (DLBCL).Methods·From November 2003 to December 2021, a total of 66 patients with thyroid DLBCL [23 cases (34.8%) with primary thyroid DLBCL, and 43 cases (65.2%) with secondary thyroid DLBCL] admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data, survival and prognostic factors. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes) in 40 patients.Results·Compared to primary thyroid DLBCL, secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ‒Ⅳ (P=0.000), elevated serum lactate dehydrogenase (LDH) (P=0.043), number of affected extranodal involvement ≥2 (P=0.000), non-germinal center B cell (non-GCB) (P=0.030), BCL-2/MYC double expression (DE) (P=0.026), and international prognostic index (IPI) 3‒5 -scores (P=0.000). The proportion of patients who underwent thyroid surgery (P=0.012) was lower than that of patients with primary thyroid DLBCL. The complete remission (CR) rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients (P=0.039). Fifty-five patients (83%) received rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-based first-line regimen. The estimated 5-year progression free survival (PFS) rate of primary thyroid DLBCL patients was 95.0%, higher than the 49.7% of the secondary patients (P=0.010). Univariate analysis showed that Ann Arbor Ⅲ‒Ⅳ (HR=4.411, 95%CI 1.373‒14.170), elevated LDH (HR=5.500, 95%CI 1.519‒19.911), non-GCB (HR=5.291, 95%CI 1.667‒16.788), and DE (HR=6.178, 95%CI 1.813‒21.058) were adverse prognostic factors of PFS in patients with thyroid DLBCL. Ann Arbor Ⅲ‒Ⅳ (HR=7.088, 95%CI 0.827‒60.717), elevated LDH (HR=6.982, 95%CI 0.809‒60.266), and DE (HR=18.079, 95%CI 1.837‒177.923) were adverse prognostic factors of overall survival (OS). Multivariate analysis showed that Ann Arbor Ⅲ‒Ⅳ (HR=4.693, 95%CI 1.218‒18.081) and elevated LDH (HR=5.058, 95%CI 1.166‒21.941) were independent adverse prognostic factors of PFS in patients with thyroid DLBCL. Targeted sequencing data showed mutation frequency >20% in TET2 (n=14, 35%), KMT2D (n=13, 32%), TP53 (n=11, 28%), GNA13 (n=10, 25%), KMT2C (n=9, 22%), and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL (P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL. Ann Arbor Ⅲ‒Ⅳ, elevated LDH, non-GCB, and DE (MYC and BCL2) are adverse prognostic factors in thyroid DLBCL. TET2, KMT2D, TP53, GNA13, and KMT2C are commonly highly mutated genes in thyroid DLBCL, and the prognosis of patients with TP53 mutations is poor.

Chimeric antigen receptor T (CAR T)-cell therapy has become a standard treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). Mutations in the PPM1D gene, a frequent driver alteration in clonal hematopoiesis (CH), lead to a gain of function of PPM1D/Wip1 phosphatase, impairing p53-dependent G1 checkpoint and promoting cell proliferation. The presence of PPM1D mutations has been correlated with reduced response to standard chemotherapy in lymphoma patients. In this study, we analyzed the impact of low-frequency PPM1D mutations on the safety and efficacy of CD19-targeted CAR T-cell therapy in a cohort of 85 r/r DLBCL patients. In this cohort, the prevalence of PPM1D gene mutations was 20% with a mean variant allele frequency (VAF) of 0.052 and a median VAF of 0.036. CAR T-induced cytokine release syndrome (CRS) and immune effector cell-associated neuro-toxicities (ICANS) occurred at similar frequencies in patients with and without PPM1D mutations. Clinical outcomes were globally worse in the PPM1D mutated (PPM1Dmut) vs. PPM1D wild type (PPM1Dwt) subset. While the prevalent treatment outcome within the PPM1Dwt subgroup was complete remission (56%), the majority of patients within the PPM1Dmut subgroup had only partial remission (60%). Median progression-free survival (PFS) was 3 vs. 12 months (p = 0.07) and median overall survival (OS) was 5 vs. 37 months (p = 0.004) for the PPM1Dmut and PPM1Dwt cohort, respectively. Our data suggest that the occurrence of PPM1D mutations in the context of CH may predict worse outcomes after CD19-targeted CAR T-cell therapy in patients with r/r DLBCL.

Abstract To establish a nomogram for elderly patients with diffuse large B‐cell lymphoma (DLBCL) based on nutritional and imaging features. The data of 221 elderly pretreatment DLBCL patients were retrospectively analyzed. All cases were randomly separated into the training group and validation group. A nomogram was built based on the results of multivariate analysis. A nomogram was established based on maximum standardized uptake value (SUVmax), geriatric nutritional risk index (GNRI), and lactate dehydrogenase. The concordance index (C‐index) of the nomogram was 0.772 for the training group and 0.729 for the validation group, and similar results were found in the area under the curve (AUC). The calibration curve showed favorable consistency between prediction and real survival. The decision curve analysis (DCA) also showed that the nomogram had favorable clinical effectiveness. The new risk‐stratification model divided patients into three groups with obvious survival. The C‐index and AUCs for the new model were greater than those of IPI and NCCN‐IPI. The DCA curve suggested that the new model had better clinical effectiveness than the IPI and NCCN‐IPI. The nomogram prognostic model based on SUVmax and GNRI performed superior to NCCN‐IPI and equal to IPI for risk stratification of elderly DLBCL patients.

Abstract Background Owing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment. Results The established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (r s = 0.284, P

Objective·To analyze the clinical characteristics and prognostic risk factors of patients with diffuse large B-cell lymphoma (DLBCL), and evaluate the prognostic effects of autologous stem cell transplantation (ASCT) and rituximab maintenance therapy on DLBCL patients.Methods·The clinical data of 160 patients with DLBCL who were first diagnosed by pathology and immunotyping were collected from the Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from January 2015 to January 2020, and the risk factors affecting the efficacy and prognosis of patients were analyzed. Moreover, the clinical characteristics of patients with relapsed/refractory DLBCL and the effect of salvage ASCT on overall survival (OS) were assessed. For those high-risk patients who achieved complete remission (CR) in the interim assessment, the impact of ASCT and rituximab maintenance therapy on survival outcomes was further assessed.Results·Patients with initial age of treatment >60 years (P=0.005), International Prognostic Index (IPI) 3‒5 scores (P=0.032), low albumin level (P=0.001) and anemia (P=0.007) had poor efficacy. Multivariate analysis showed that the initial age of treatment >60 years (HR=2.788, 95%CI 1.575‒4.936, P=0.000), non-GCB subtype (HR=2.230, 95%CI 1.150‒4.324, P=0.018), elevated lactate dehydrogenase level (HR=2.064, 95%CI 1.006‒4.234, P=0.048) and low albumin level (HR=2.052, 95% CI 1.169‒3.602, P=0.012) were the independent risk factors for progression-free survival (PFS). The initial age of treatment >60 years (HR=2.269, 95% CI 1.060‒4.860, P=0.035) and IPI scores of 3 to 5 (HR=2.557, 95%CI 1.132‒5.778, P=0.024) were independent factors affecting OS. For patients with relapsed/refractory DLBCL, salvage ASCT was found to significantly improve the prognosis of these patients and was a protective factor for the death event of patients (P=0.030). For patients in the high-risk group who achieved CR in the interim evaluation after chemotherapy, there were no deaths in patients on maintenance therapy with consolidation ASCT and rituximab to the end point of follow-up; however, it did not prolong the OS of the patients (P>0.05).Conclusion·In patients with relapsed/refractory DLBCL, salvage ASCT can significantly prolong the OS, whereas in the high-risk patients of DLBCL, consolidation ASCT and rituximab maintenance therapy can't prolong the OS.

Background: Tocilizumab is a well-practiced strategy to manage cytokine release syndrome (CRS) after chimeric antigen receptor T cell (CAR-T) therapy. However, varied efficiency in CRS mitigation by tocilizumab has been reported to highlight affecting variables such as tumor types and timing of the administration. Objective: The objective of this study is to identify different curative effect between diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL) by early use of tocilizumab for prophylaxis and treatment of CRS. Methods: By retrospectively summarizing our institution's experience with a CAR-T clinical trial targeting CD19, 11 cases were analyzed: 5 DLBCL, and 6 ALL. The two groups were compared with patient characteristics, CRS information and clinical outcomes. 3 patients were pretreated with tocilizumab for prophylaxis and the rest were treated with tocilizumab at CRS diagnosis. Results: CRS occurred in 81.8% of patients (9/11), grade 3 or higher occurred in 55.6% of the CRS patients (5/9). The two group were similar in patient characteristics, CAR-T and CRS profile. However, tocilizumab produced much better efficacy against CRS in DLBCL group compared with ALL group (80% versus 16.7%, P ​= ​0.08). Conclusions: Despite the statistical was non-significant, possibly due to small case pool and bias was unavoidable, our analysis suggested that early use of tocilizumab was more effective for DLBCL than ALL in the prophylaxis and treatment of CRS. A treatment algorithm for management of CRS with regard to DLBCL and ALL is proposed, which may extend to other local or systemic malignancies and warrant further investigation.

Introduction: This case report describes a serious complication of delayed human immunodeficiency virus (HIV) diagnosis in a patient initially misdiagnosed with palliative-stage cancer and subsequently diagnosed with B-cell lymphoma. This situation highlights the diagnostic challenges and treatment implications following HIV diagnosis, and underscores the critical importance of accurate and timely HIV detection in oncology patients. Case presentation: A 39-year-old man was initially diagnosed with lung cancer based on computed tomography and histopathologic findings. He was treated with 2 lines of chemotherapy over an 8-month period, the neoplastic lung lesions progressed, and he was referred to palliative care. Two years after his initial diagnosis, during the management of an actively bleeding gastric tumor, he was diagnosed with HIV and referred to an infectious disease unit. Immediate antiretroviral treatment was initiated after diagnosis, and further evaluation confirmed the presence of B-cell lymphoma. A retrospective review suggested that the initial cancer diagnosis was likely misinterpreted and was in fact lymphoma, a malignancy commonly associated with HIV. Lymphoma treatment was initiated, and after 1 year, the patient achieved HIV-1 virologic suppression and near-complete remission of all lesions. Conclusions: This case highlights the consequences of delayed HIV diagnosis, which can significantly alter treatment course and patient prognosis. The initial misdiagnosis of cancer and subsequent ineffective treatment highlights the importance of HIV testing, particularly in patients presenting with malignancy. It also highlights the role of multidisciplinary collaboration, the need for prompt initiation of antiretroviral therapy, and the efficacy of targeted anticancer therapies for HIV-associated malignancies. [ABSTRACT FROM AUTHOR]

We herein report a case of diffuse large B-cell lymphoma (DLBCL) of the palate secondary to Sjögren syndrome. A 55-year-old woman was found to have redness of the palate at a nearby dental clinic and was referred to the oral surgery department of another hospital in February 2007. It was difficult to distinguish mucosa-associated lymphoid tissue (MALT) lymphoma from severe inflammation based on a biopsy, so the patient was referred to our department. The mass showed redness, measuring 25 × 20 mm, and was smooth-surfaced and elastic hard. The results of a rebiopsy in our department suggested the possibility of MALT lymphoma, but the diagnosis could not be confirmed. At the same time, a systemic examination revealed complications with Sjögren's syndrome. The mass subsequently increased in size, and the entire mass was resected to confirm the diagnosis. The pathological final diagnosis was DLBCL. Complete remission has been maintained for over 14 years since therapy was performed. [ABSTRACT FROM AUTHOR]

Background: Primary non-Hodgkin's lymphoma with multiple extra- and intra-calvarial extensions without systemic spread in an immunocompetent patient is extremely rare. They masquerade commonly as meningioma and can present as mass lesions with raised intracranial pressure. Case Description: We report one such case of primary diffuse large B-cell lymphoma (DLBCL) in a young female involving the scalp, dural involvement in the right frontal region, left parietal, and posterior fossa and mimicking both clinically and radiologically as meningioma. She was managed surgically. Histological examination showed features suggestive of DLBCL (germinal center type). She was planned for adjuvant therapy. However, at 2 months following surgery, she succumbed due to systemic involvement of the disease. Conclusion: DLBCL is seen rarely in neurosurgical practice. They can present as tumors with adjacent extra- and intra-cranial masses. They pose a diagnostic challenge as it can be easily confused with meningioma. Tumor resection is performed to confirm diagnosis and in patients who present with raised intracranial pressure. Chemotherapy is the preferred treatment, and adjuvant therapy should be started early. [ABSTRACT FROM AUTHOR]

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Objective: Diffuse Large B-Cell Lymphoma (DLBCL) is a common and frequently occurring subtype of Non-Hodgkin Lymphoma (NHL). The effective treatment and prognosis of DLBCL are still urgently needed to be explored. This article aims to shed light on the connection between DLBCL survival and NR3C1 expression levels. Methods: First, we divided the 952 DLBCL patients into an NR3C1 high-expression group and an NR3C1 low-expression group and compared the baseline characteristics of the two groups. Second, we used multivariate analysis to predict the dependent variable for age, pathology, ECOG score, lactate dehydrogenase (LDH) ratio, and NR3C1 expression level. Finally, we analyzed the progression-free survival (PFS) and overall survival rate (OS) of DLBCL patients with high or low NR3C1 expression. Results: DLBCL patients with high NR3C1 expression had a better prognosis than those with low NR3C1 expression (OS, P < 0.0001). In DLBCL patients of CHOP therapy, high NR3C1 expression was associated with a good survival prognosis in OS (OS, P = 0.028). Conclusion: In multivariate analysis, NR3C1 high expression was an independent prognostic factor that predicted a longer OS of DLBCL (OS, P = 0.0003). NR3C1 is considered an independent predictor of DLBCL patients and can be used as a biomarker for the prognosis of DLBCL. [ABSTRACT FROM AUTHOR]

This study comprehensively incorporates pathological parameters and novel clinical prognostic factors from the international prognostic index (IPI) to develop a nomogram prognostic model for overall survival in patients with diffuse large B-cell lymphoma (DLBCL). The aim is to facilitate personalized treatment and management strategies. This study enrolled a total of 783 cases for analysis. LASSO regression and stepwise multivariate COX regression were employed to identify significant variables and build a nomogram model. The calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) curve were utilized to assess the model's performance and effectiveness. Additionally, the time-dependent concordance index (C-index) and time-dependent area under the ROC curve (AUC) were computed to validate the model's stability across different time points. The study utilized 8 selected clinical features as predictors to develop a nomogram model for predicting the overall survival of DLBCL patients. The model exhibited robust generalization ability with an AUC exceeding 0.7 at 1, 3, and 5 years. The calibration curve displayed evenly distributed points on both sides of the diagonal, and the slopes of the three calibration curves were close to 1 and statistically significant, indicating high prediction accuracy of the model. Furthermore, the model demonstrated valuable clinical significance and holds the potential for widespread adoption in clinical practice. The novel prognostic model developed for DLBCL patients incorporates readily accessible clinical parameters, resulting in significantly enhanced prediction accuracy and performance. Moreover, the study's use of a continuous general cohort, as opposed to clinical trials, makes it more representative of the broader lymphoma patient population, thus increasing its applicability in routine clinical care. [ABSTRACT FROM AUTHOR]

Background Primary cardiac lymphoma (PCL) is an extremely rare tumour that typically affects the right heart chamber. It is a life-threatening tumour presenting with rapid growth; therefore, early diagnosis and treatment are crucial for improving the prognosis of patients with PCL. Case summary An 81-year-old female with a history of dermatomyositis and interstitial pneumonia was referred to the cardiology department for cardiomegaly detected on chest radiography and computed tomography (CT). She experienced shortness of breath on exertion. Electrocardiography revealed negative T-waves in various leads. Transthoracic and transoesophageal echocardiography revealed a large mass on the epicardial free wall of the left atrium and ventricle. Coronary CT angiography showed feeding vessels from the left circumflex artery and the posterolateral branch of the right coronary artery. Positron emission tomography showed elevated mass uptake and no systemic metastasis. Needle biopsy with total endoscopic anterolateral mini-thoracotomy was performed. Histopathological examination revealed diffuse large B-cell lymphoma. She received systemic chemotherapy and achieved a complete metabolic response. Discussion Herein, we report an extremely rare case of PCL located on the left side of the heart. Owing to the location of the tumour, percutaneous or transcatheter biopsy could not be performed. Early diagnosis with needle biopsy via anterolateral mini-thoracotomy and systemic chemotherapy resulted in good outcomes. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR T)-cell therapy has become a standard treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). Mutations in the PPM1D gene, a frequent driver alteration in clonal hematopoiesis (CH), lead to a gain of function of PPM1D/Wip1 phosphatase, impairing p53-dependent G1 checkpoint and promoting cell proliferation. The presence of PPM1D mutations has been correlated with reduced response to standard chemotherapy in lymphoma patients. In this study, we analyzed the impact of low-frequency PPM1D mutations on the safety and efficacy of CD19-targeted CAR T-cell therapy in a cohort of 85 r/r DLBCL patients. In this cohort, the prevalence of PPM1D gene mutations was 20% with a mean variant allele frequency (VAF) of 0.052 and a median VAF of 0.036. CAR T-induced cytokine release syndrome (CRS) and immune effector cell-associated neuro-toxicities (ICANS) occurred at similar frequencies in patients with and without PPM1D mutations. Clinical outcomes were globally worse in the PPM1D mutated (PPM1Dmut) vs. PPM1D wild type (PPM1Dwt) subset. While the prevalent treatment outcome within the PPM1Dwt subgroup was complete remission (56%), the majority of patients within the PPM1Dmut subgroup had only partial remission (60%). Median progression-free survival (PFS) was 3 vs. 12 months (p = 0.07) and median overall survival (OS) was 5 vs. 37 months (p = 0.004) for the PPM1Dmut and PPM1Dwt cohort, respectively. Our data suggest that the occurrence of PPM1D mutations in the context of CH may predict worse outcomes after CD19-targeted CAR T-cell therapy in patients with r/r DLBCL. [ABSTRACT FROM AUTHOR]

Simple Summary: Double/triple-hit lymphomas (DHLs/THLs) are an aggressive type of high-grade B-cell lymphomas (HGBLs), characterized by translocations in MYC and BCL2/BCL6. DHL patients respond poorly to standard chemoimmunotherapy regimens; thus, timely and accurate diagnosis is of paramount importance for their proper clinical management. The standard technique used for the identification of these translocations is fluorescence in situ hybridization (FISH), which is not routinely performed at every medical center to all potential patients. In the current study, we employed an image-based, artificial intelligence, deep learning algorithmic tool for the identification of DHL/THL cases by analyzing scanned histopathological H&E-stained tissue slide images. Our preliminary results demonstrate high performances, suggesting the potential use of such a solution in the clinical workflow to support the management of HGBL patients. Deep learning applications are emerging as promising new tools that can support the diagnosis and classification of different cancer types. While such solutions hold great potential for hematological malignancies, there have been limited studies describing the use of such applications in this field. The rapid diagnosis of double/triple-hit lymphomas (DHLs/THLs) involving MYC, BCL2 and/or BCL6 rearrangements is obligatory for optimal patient care. Here, we present a novel deep learning tool for diagnosing DHLs/THLs directly from scanned images of biopsy slides. A total of 57 biopsies, including 32 in a training set (including five DH lymphoma cases) and 25 in a validation set (including 10 DH/TH cases), were included. The DHL-classifier demonstrated a sensitivity of 100%, a specificity of 87% and an AUC of 0.95, with only two false positive cases, compared to FISH. The DHL-classifier showed a 92% predictive value as a screening tool for performing conventional FISH analysis, over-performing currently used criteria. The work presented here provides the proof of concept for the potential use of an AI tool for the identification of DH/TH events. However, more extensive follow-up studies are required to assess the robustness of this tool and achieve high performances in a diverse population. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T-cell therapy (CAR-T) has been widely applied in the clinical practice of relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) due to its promising effects. Hyperprogressive disease (HPD) has gained attention for rapid tumor progression and has become a therapeutic and prognostic challenge. Here, we present a patient who had suffered from several recurrences previously and controlled well with a very small tumor lesion left was infused with CD19/CD22 bispecific CAR-T, with no immune effector cell-associated neurotoxicity syndrome, or cytokine release syndrome observed. However, rapid deterioration, subsequent imaging examination, circulating tumor DNA, and serum biomarkers detection identified HPD. The patient did not respond to salvage treatment and died 40 days after infusion. To our knowledge, only one case of HPD in DLBCL after CAR-T therapy has been reported. This fatal case alarmed the risk of HPD and the ctDNA profile monitoring we used was performed as a non-invasive method to diagnose HPD, providing far-reaching practical instruction for CAR-T therapy.

Background: Owing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment. Results: The established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P < 0.01). DLBCLRP expressions were also significantly or tended to be positively correlated with international prognostic index (IPI) (rs = 0.306, P < 0.05), lg(total metabolic tumor volume, TMTV) (r = 0.298, P < 0.05) and lg(total lesion glycolysis, TLG) (r = 0.233, P = 0.064). Though no significant correlation of DLBCLRP expression was found with Ann Arbor staging or tumor SUVmax (P > 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (rs = 0.284, P < 0.05) and IPI (rs = 0.297, P < 0.05). Conclusions: The proposed DLBCLRP would lay the foundation for further investigating the cerebral dysfunction related to DLBCL itself and/or treatments. Besides, the expression of DLBCLRP was associated with the tumor burden of lymphoma, implying a potential biomarker for prognosis. [ABSTRACT FROM AUTHOR]

Summary: The transcriptional factor ETS1 is upregulated in 25% of diffuse large B cell lymphoma (DLBCL). Here, we studied the role of ETS1 phosphorylation at threonine 38, a marker for ETS1 activation, in DLBCL cellular models and clinical specimens. p‐ETS1 was detected in activated B cell‐like DLBCL (ABC), not in germinal centre B‐cell‐like DLBCL (GCB) cell lines and, accordingly, it was more common in ABC than GCB DLBCL diagnostic biopsies. MEK inhibition decreased both baseline and IgM stimulation‐induced p‐ETS1 levels. Genetic inhibition of phosphorylation of ETS1 at threonine 38 affected the growth and the BCR‐mediated transcriptome program in DLBCL cell lines. Our data demonstrate that ETS1 phosphorylation at threonine 38 is important for the growth of DLBCL cells and its pharmacological inhibition could benefit lymphoma patients. [ABSTRACT FROM AUTHOR]