Diffuse large B-cell lymphoma (DLBCL), known as the predominant type of aggressive B-cell lymphoma, is biologically and clinically heterogeneous. The prognosis of DLBCL is quite different among subtypes. Hypoxia is one of the key elements in tumor microenvironment, promoting tumor progression by means of various mechanisms, such as increased proliferation, altered metabolism, enhanced angiogenesis, and greater migratory capability, among others. The primary purpose of this research is to investigate the connection between hypoxia-featured genes (HFGs), prognosis in DLBCL, and their capacity association with the immune microenvironment. Various hypoxia-associated patterns for DLBCL patients from GEO and TCGA databases were identified by means of an unsupervised consensus clustering algorithm. CIBERSORT and IOBR package is used to identify different immune infiltration status. To develop a predictive model using hypoxia-related genes, we conducted univariate Cox regression, multivariate Cox regression, and LASSO regression assessment. Subsequently, we confirmed the predictive importance of these hypoxia-associated genes, highlighting hypoxia-associated characteristics, and explored the connection between the hypoxia model and the immune environment. Three hypoxia clusters were identified. We also observed that each pattern of hypoxia response was significantly related to different prognoses. It was found that the immune status among hypoxia clusters is different. After developing a prognostic risk model using 5 hypoxia-related genes, we discovered that the risk score is related to immune factors and how effective drugs are in treating DLBCL. In DLBCL patients, varying hypoxia patterns correlate with both prognostic outcomes and the immune microenvironment. Hypoxia-featured genes (HFGs) function as a standalone predictive element in these patients. It is also potentially a reliable indicator for predicting clinical responses to ICI therapy and traditional drugs.

Secondary ion mass spectrometry (SIMS) using a gas cluster ion beam (GCIB), in this case 40 keV (CO2)7k+, was used to map the intact lipid signals across 14 lymph node samples representing diffuse large B-cell lymphoma (DLBCL), a common and aggressive form of lymphoma, and nonmalignant controls. The analysis allowed the samples to be classified as malignant or nonmalignant and also highlighted additional aggressive cancer signature in a DLBCL sample with an unusually high proliferation index. A complementary, combined k-means/image PCA approach was used to interrogate the data, highlighting the pros and cons of the different approaches and potential sources for misclassification/diagnoses resulting from the heterogeneity of the DLBCL samples. Compared to other cancer types, lymphoma results in a reduction of non-neoplastic inflammatory cells and their characteristic signals that are often classed as cancer-related, highlighting the need to consider disease heterogeneity when examining MS data. While delivering new information regarding the chemistry of lymphoma, the results also highlight the need for cellular precision with high chemical specificity and sensitivity, and the challenges associated with spectral/spatial classification of such complex samples and data where differently aggressive cancer samples show different signatures and pockets of different cell types, in this case histiocytes, can show intermediate cancer/healthy lipid profiles.

Symptoms of lymphomas include peripheral lymphadenopathy, B-symptoms, and other organ-specific symptoms; however, data on initial symptoms incidence in diffuse large B-cell lymphoma (DLBCL) remain limited. We aimed to investigate real-world patterns of initial DLBCL symptoms, correlating them with baseline characteristics and symptom onset-to-diagnosis interval. Patients with DLBCL diagnosed between 2010 and 2021 receiving R-CHOP were screened. 706 individuals with reported initial symptoms were analyzed. 682 (97%) patients had documented symptoms; remaining 24 patients (3%) had incidental findings discovered during examinations for unrelated reasons. Abdominal/gastrointestinal complaints were the most prevalent symptoms (26%), followed by peripheral lymphadenopathy (22%), and B-symptoms (13%). The median symptom-to-diagnosis interval was 10 weeks. Peripheral lymphadenopathy and testicular tumors correlated with low-risk characteristics, with testicular DLBCL featuring a shorter symptom-to-diagnosis interval. Limb pain/swelling and back pain were associated with high-risk characteristics and prolonged symptom-to-diagnosis interval. This analysis enhances our understanding of DLBCL symptomatology, aiding in timely recognition and management.

Circular RNAs (circRNAs) make up approximately 10% of the human transcriptome. CircRNAs belong to the broad group of non-coding RNAs and characteristically are formed by backsplicing into a stable circular loop. Their main role is to regulate transcription through the inhibition of miRNAs' expression, termed miRNA sponging. CircRNAs promote tumorigenesis/lymphomagenesis by competitively binding to miRNAs at miRNA binding sites. In diffuse large B-cell lymphoma (DLBCL), several circRNAs have been identified and their expression is related to both progression and response to therapy. DLBCL is the most prevalent and aggressive subtype of B-cell lymphomas and accounts for about 25% to 30% of all non-Hodgkin lymphomas. DLBCL displays great heterogeneity concerning histopathology, biology, and genetics. Patients who have relapsed or have refractory disease after first-line therapy have a very poor prognosis, demonstrating an important unmet need for new treatment options. As more circRNAs are identified in the future, we will better understand their biological roles and potential use in treating cancer, including DLBCL. For example, circAmotl1 promotes nuclear translocation of MYC and upregulation of translational targets of MYC, thus enhancing lymphomagenesis. Another example is circAPC, which is significantly downregulated in DLBCL and correlates with disease aggressiveness and poor prognosis. CircAPC increases expression of the host gene adenomatous polyposis coli (APC), and in doing so inactivates the canonical Wnt/β-catenin signaling and restrains DLBCL growth. MiRNAs belong to the non-coding regulatory molecules that significantly contribute to lymphomagenesis through their target mRNAs. In DLBCL, among the highly expressed miRNAs, are miR-155-5p and miR-21-5p, which regulate NF-ĸB and PI3K/AKT signaling pathways. The aim of this review is to describe the function and mechanism of regulation of circRNAs on miRNAs' expression in DLBCL. This will help us to better understand the regulatory network of circRNA/miRNA/mRNA, and to propose novel therapeutic targets to treat DLBCL.

Klippel-Feil syndrome (KFS) is a rare congenital disorder characterized by the fusion of cervical vertebrae, with a clinical presentation that can vary widely due to genetic and phenotypic diversity. While KFS can occur as an isolated anomaly, it is often associated with other congenital conditions, such as Sprengel deformity, which may present with or without an omovertebral bone, complicating diagnosis and management. This particular case also involves diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma. We hereby present a complex case of a 60-year-old male with the co-occurrence of KFS, Sprengel deformity, and DLBCL. Diagnostic imaging revealed an ill-defined right neck mass on ultrasound which was confirmed on neck CT. The CT also demonstrated an elevated left scapula and a left omovertebral bone, indicative of Sprengel deformity. There was fusion of the C5 and C6 vertebrae consistent with KFS. A whole-body F-18 FDG PET scan demonstrated significant uptake in the neck mass, leading to a biopsy that confirmed DLBCL. This case highlights the importance of comprehensive medical and imaging evaluations in diagnosing and managing the complexities associated with these disorders. In particular, awareness of the potential co-existence of congenital abnormalities and aggressive malignancies is critical in such cases.

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30-40% of all non-Hodgkin lymphoma cases. Organs located DLBCL such as lymph node, stomach, gastrointestinal tract, or skin were reported. However, the adrenal gland DLBCL was not been well explored. We performed RNA sequencing of ten DLBCL samples from adrenal gland, integrated analyzed DLBCL RNA data from multiple organs, defined the new subtypes of adrenal gland DLBCL and explored their molecular signatures. The special expression pattern and microenvironment immunology scores of adrenal glands DLBCL were observed when compared with other organs. Natural killer T cells was predicted to significantly enrichment in adrenal gland DLBCL, canonical cancer pathways such as programmed death protein 1 signaling pathways, tumor necrosis factor signaling pathways and peptide antigen binding pathways were found to be correlated with adrenal gland DLBCL. Further analysis defined two distant adrenal gland DLBCL sub-type by RNA expression pattern. Our study revealed the special expression, defined the molecular subtype of adrenal gland DLBCL. These results expanded the organ related DLBCL data, provided the new knowledge of adrenal gland DLBCL expression profile.

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.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin's lymphoma that arises from the germinal center. It represents a heterogeneous disease characterized by different pathological, clinical, and molecular entities. Gene expression profiling based on the alleged cell of origin differentiates transcriptional subtypes such as germinal center and activated B cell-like. DLBCL accounts for around 40% of all non-Hodgkin's lymphomas worldwide. Its incidence generally increases with age. The international prognostic index remains the most important tool for disease stratification.The diagnosis of DLBCL is best made through an excisional biopsy of a suspicious lymph node. Nowadays, advanced techniques are employed to accurately diagnose and determine the clinical outcomes of patients. Immunohistochemistry, next-generation sequencing, and array-based comparative hybridization facilitate the global identification of diverse and numerous genetic alterations. However, further validation should be necessary to apply advanced techniques in clinical practice. In this review, we summarize the current literature and discuss the pathophysiology, epidemiology, and diagnostic advancements of DLBCL.

The incidence of central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) varies, and the optimum strategy of CNS prophylaxis remains to be defined. We aimed to evaluate the incidence of CNS relapse in DLBCL patients and the role of CNS prophylaxis.

Data on patients diagnosed with DLBCL at our institution from January 2011 to June 2019 were retrospectively collected from the charts and computerized hospital information system for patient demographics, lymphoma stage at diagnosis, CNS international prognostic index (IPI) scores, extra-nodal sites, chemotherapy type, CNS prophylaxis, and CNS relapse. CNS prophylaxis comprised intrathecal (IT) chemotherapy and was administered based on the presence of high-risk features. Patients with primary CNS lymphoma and CNS involvement at diagnosis were excluded.

Of 101 patients, 58 (57.5%) were males with a median age of 56 (range: 16 - 87) years. Ann Arbor stages of I - IV were confirmed in nine, 21, 17, and 50 patients, respectively. The lung was the most common extranodal site involved (27, 26.7%). Twenty-five (24.75%) patients had a high-risk CNS-IPI score. Ninety-three percent of patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Sixteen patients received CNS prophylaxis as IT methotrexate (± cytarabine and hydrocortisone). Despite high-risk CNS-IPI scores, nine (36%) patients did not receive CNS prophylaxis. After a median follow-up of 36 (range: 4 - 114) months, two patients with high-risk CNS-IPI score developed CNS relapse and died shortly.

CNS relapse of DLBCL was uncommon in this patient population. Low incidence of CNS relapse despite limited use of IT prophylaxis may suggest adequacy of IT prophylaxis in these patients.

Background/Objectives: This study evaluates the diagnostic accuracy of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) using bone marrow biopsy (BMB) and clinical follow-up as reference standards. It further identifies predictive factors for bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) patients. Methods: NHL patients who underwent [18F]FDG PET and BMB at diagnosis in a tertiary cancer center were included in this study. Diagnostic accuracy was analyzed, and logistic regression was performed to identify BMI predictors using Stata software version 17. A retrospective analysis of 262 NHL patients was conducted. Results: Concordance rates between [18F]FDG PET and BMB and between [18F]FDG PET and clinical follow-up were 75.6% and 88.1%, respectively. The primary cause of discordance between [18F]FDG PET and BMB was the detection of extra-iliac focal hypermetabolic bone marrow lesions by [18F]FDG PET, which were negative on BMB. The sensitivity, specificity, and accuracy of [18F]FDG PET were 62.9%, 80%, and 75.6%, respectively, with BMB as a reference, and 74.1%, 97.5%, and 88.2%, respectively, with clinical follow-up as a reference. The focal bone marrow [18F]FDG pattern was the most reliable indicator of BMI. Univariate logistic regression showed that advanced NHL stage, elevated alkaline phosphatase, thrombocytopenia, leukopenia, and elevated lactate dehydrogenase were significant predictors of BMI. Multivariate analysis revealed advanced NHL stage and thrombocytopenia as clinical predictors. Conclusions: [18F]FDG PET is a reliable tool for assessing BMI, providing comprehensive total-body evaluation and identifying extra-iliac involvement beyond the scope of BMB. The collective interpretation of molecular imaging, clinical, and biochemical factors is crucial for predicting BMI.

SPiReL is a phase II clinical trial evaluating combination immunotherapy, pembrolizumab and cyclophosphamide, with maveropepimut-S, in survivin-expressing relapsed/refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL). We describe baseline tumor survivin expression and associations with clinico-pathological variables in 25 participants. The median number of survivin-expressing cells was 99%, and the intensity of survivin expression within tumors was heterogeneous by semi-quantitative immunohistochemistry assessment. Tumors with higher numbers of cells expressing 2+/3+ survivin were associated with characteristics of poor outcome, (Lactate dehydrogenase and cell-of-origin). Greater total baseline tumor area was associated with lower proportions of 1+ cells and greater proportions of 2+/3+ cells. High intensity survivin expression is associated with aggressive clinical features supporting a pathobiological role in R/R DLBCL. Future prognostic models incorporating survivin as a clinical biomarker require assessment of intensity, overall expression and should include potential threshold effects of survivin in DLBCL pathobiology.

Tumor lysis syndrome (TLS) is a life-threatening complication that can arise after initiation of cytotoxic chemotherapy in highly proliferative hematological malignancies, such as leukemias or lymphomas. Prophylactic measures, such as allopurinol, rasburicase, and hydration, are commonly initiated in these types of malignancies prior to chemotherapy to prevent TLS. However, in rare instances, TLS can still occur despite the initiation of prophylactic treatment. When TLS develops, the patient can experience various complications, such as kidney injury, muscle fatigue, paralysis, cardiac arrhythmias, and even death. Our case presents an 83-year-old male with newly diagnosed stage IV diffuse large B-cell lymphoma (DLBCL) who developed TLS following chemotherapy despite receiving the standard prophylactic treatment of IV fluids, rasburicase, and allopurinol. This case highlights the importance of identifying signs of TLS and initiating appropriate treatment even in patients receiving prophylaxis.

Tumor whole-cell vaccines are designed to introduce a wide range of tumor-associated antigens into the body to counteract the immunosuppression caused by tumors. In cases of lymphoma of which the specific antigen is not yet determined, the tumor whole-cell vaccine offers distinct advantages. However, there is still a lack of research on an effective preparation method for the lymphoma whole-cell vaccine. To solve this challenge, we prepared a whole-cell vaccine derived from non-Hodgkin B-cell lymphoma (A20) via the photothermal effect mediated by Prussian blue nanoparticles (PBNPs). The immune activation effect of this vaccine against lymphoma was verified at the cellular level. The PBNPs-treated A20 cells underwent immunogenic cell death (ICD), causing the loss of their ability to form tumors while retaining their ability to trigger an immune response. A20 cells that experienced ICD were further ultrasonically crushed to prepare the A20 whole-cell vaccine with exposed antigens and enhanced immunogenicity. The A20 whole-cell vaccine was able to activate the dendritic cells (DCs) to present antigens to T cells and trigger specific immune responses against lymphoma. Whole-cell vaccines are primarily administered through direct injection, a method that often results in low delivery efficiency and poor patient compliance. Comparatively, the microneedle patch system provides intradermal delivery, offering enhanced lymphatic absorption and improved patient adherence due to its minimally invasive approach. Thus, we developed a porous microneedle patch system for whole-cell vaccine delivery using Gelatin Methacryloyl (GelMA) hydrogel and n-arm-poly(lactic-co-glycolic acid) (n-arm-PLGA). This whole-cell vaccine combined with porous gel microneedle patch delivery system has the potential to become a simple immunotherapy method with controllable production and represents a promising new direction for the treatment of lymphoma.

Malignant ascites (MA), a common and serious complication of various cancers in the abdominal cavity, originates from the extensive infiltration, metastasis, and growth of cancer cells in or on the abdominal cavity, leading to abnormal accumulation of fluid in the abdominal cavity and the formation of MA. MA seriously reduces the quality of life of cancer patients, shortens their survival period, and generally has a poor prognosis. Modern medicine has developed various strategies for the treatment of MA, including targeted supportive treatment, diuretic treatment, abdominal paracentesis, surgical intervention, and intraperitoneal administration therapy. Among them, chemotherapy, as one of the important treatment methods, includes both systemic chemotherapy and intraperitoneal chemotherapy, especially pressurized intraperitoneal aerosol chemotherapy (PIPAC), hyperthermic intraperitoneal chemotherapy (HIPEC), and foam-based intraperitoneal chemotherapy (FBIC), providing a new choice for the treatment of MA. In addition, innovative treatment methods such as gas-based intra-abdominal hyperthermia (GIH) combined with dehydration therapy have also shown promising application prospects. This article delves into multiple aspects of MA, including its concept, mechanism of occurrence, clinical manifestations, differential diagnostic methods, and current treatment status and research progress. This comprehensive review aims to provide valuable references for effectively controlling MA, improving cancer patients' quality of life, and prolonging the survival cycle of cancer patients in clinical practice. Malignant ascites (MA) is a common complication of cancer, which originates from the extensive infiltration, metastasis, and growth of cancer cells in the abdominal cavity or peritoneum, leading to abnormal accumulation of peritoneal fluid. It is a common clinical manifestation in the late stage of cancer. Its symptoms are stubborn and recurrent, which can lead to abdominal pain, bloating, poor appetite, fatigue, breathing difficulties, and even multiple organ failure. The median survival time for cancer patients with MA is generally 5 to 6 months. The prognosis is poor, and it is imperative to seek more active and effective treatment plans. This article reviews the research and treatment status of MA, aiming to provide certain value for controlling MA and improving the quality of life of patients.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults, constituting a significant portion of global incidence rates. DLBCL can be further classified via genetic expression profiling into molecular subsets consisting of not-otherwise specified (NOS) subset being the most prevalent, germinal center B-cell-like (GCB) subset, and activated B-cell-like (ABC) subset. The ABC subset, marked by abnormal NF-κB signaling, is associated with poorer outcomes. This report presents an unusual case of a 30-year-old male with no past medical history who was found to have advanced-stage ABC-type DLBCL-NOS, featuring rare symptoms such as hypothermia, autonomic dysfunction, and atrial fibrillation, illustrating the unpredictable clinical manifestations of this aggressive lymphoma and the importance of molecular subtyping in treatment and prognosis.

Mitogen-activated protein kinase 12 (MAPK12), also known as p38γ, is a member of the p38 MAPK family and plays a crucial role in tumor occurrence and invasion. However, there is still uncertainty regarding MAPK12 involvement in diffuse large B-cell lymphoma (DLBCL).

Our study investigated the expression of MAPK12 mRNA in various types of cancer using bioinformatic analysis. Furthermore, we performed immunohistochemistry (IHC) to detect the expression of MAPK12 in patients with DLBCL and compared clinical indicators and survival rates.

We found that the high expression rate of MAPK12 was 43.1% in DLBCL patients. Several clinical indicators, including IPI scores, Hans classifications, LDH levels, and Ki-67 expression were closely associated with MAPK12 expression. Survival analysis revealed that higher expression of MAPK12 was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) in DLBCL patients. In addition, both univariate and multivariate analyses revealed IPI score, MAPK12 expression, and rituximab use as the independent OS risk factors (P < 0.05). To explore the functional role of MAPK12 in DLBCL, weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) were used to confirm the involvement of MAPK12 in the regulation of type II interferon production, positive regulation of lymphocyte proliferation, and other related biological processes.

DLBCL patients have poor prognoses when MAPK12 levels are high, which is expected to be a therapeutic target and prognostic factor.

Single-cell RNA sequencing (scRNA-seq), which profiles gene expression at the cellular level, has effectively explored cell heterogeneity and reconstructed developmental trajectories. With the increasing research on diseases and biological processes, scRNA-seq datasets are accumulating rapidly, highlighting the urgent need for collecting and processing these data to support comprehensive and effective annotation and analysis. Here, we have developed a comprehensive Single-Cell transcriptome integration database for human and mouse (SCInter, https://bio.liclab.net/SCInter/index.php), which aims to provide a manually curated database that supports the provision of gene expression profiles across various cell types at the sample level. The current version of SCInter includes 115 integrated datasets and 1016 samples, covering nearly 150 tissues/cell lines. It contains 8016,646 cell markers in 457 identified cell types. SCInter enabled comprehensive analysis of cataloged single-cell data encompassing quality control (QC), clustering, cell markers, multi-method cell type automatic annotation, predicting cell differentiation trajectories and so on. At the same time, SCInter provided a user-friendly interface to query, browse, analyze and visualize each integrated dataset and single cell sample, along with comprehensive QC reports and processing results. It will facilitate the identification of cell type in different cell subpopulations and explore developmental trajectories, enhancing the study of cell heterogeneity in the fields of immunology and oncology.

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.

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.

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.

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.

In this comprehensive review, we delve into the transformative role of artificial intelligence (AI) in refining the application of multi-omics and spatial multi-omics within the realm of diffuse large B-cell lymphoma (DLBCL) research. We scrutinized the current landscape of multi-omics and spatial multi-omics technologies, accentuating their combined potential with AI to provide unparalleled insights into the molecular intricacies and spatial heterogeneity inherent to DLBCL. Despite current progress, we acknowledge the hurdles that impede the full utilization of these technologies, such as the integration and sophisticated analysis of complex datasets, the necessity for standardized protocols, the reproducibility of findings, and the interpretation of their biological significance. We proceeded to pinpoint crucial research voids and advocated for a trajectory that incorporates the development of advanced AI-driven data integration and analytical frameworks. The evolution of these technologies is crucial for enhancing resolution and depth in multi-omics studies. We also emphasized the importance of amassing extensive, meticulously annotated multi-omics datasets and fostering translational research efforts to connect laboratory discoveries with clinical applications seamlessly. Our review concluded that the synergistic integration of multi-omics, spatial multi-omics, and AI holds immense promise for propelling precision medicine forward in DLBCL. By surmounting the present challenges and steering towards the outlined futuristic pathways, we can harness these potent investigative tools to decipher the molecular and spatial conundrums of DLBCL. This will pave the way for refined diagnostic precision, nuanced risk stratification, and individualized therapeutic regimens, ushering in a new era of patient-centric oncology care.

Etoposide to standard R-CHOP is used for high-risk diffuse large B-cell lymphoma (DLBCL) in some countries. Due to the lack of randomized trials, a real-world data study using matching methods was used to test the potential effectiveness of R-CHOEP over R-CHOP.

This study included patients from the Danish Lymphoma Register diagnosed between 2006 and 2020 at the age of 18-60 years with de novo DLBCL and age-adjusted IPI ≥2. R-CHOEP treated patients were matched 1:1 without replacement to R-CHOP treated patients using a hybrid exact and genetic matching technique. Primary endpoints were progression-free survival (PFS) and overall survival (OS).

In total, 396 patients were included; 213 received R-CHOEP and 183 received R-CHOP. Unadjusted 5-year PFS and OS for R-CHOEP were 69% (95% Confidence intervals [CI]; 63%-76%) and 79% (CI;73%-85%) versus 62% (CI;55%-70%) and 76% (CI;69%-82%) for R-CHOP (log-rank test, PFS p = .25 and OS p = .31). A total of 127 patients treated with R-CHOEP were matched to 127 patients treated with R-CHOP. Matching-adjusted 5-year PFS and OS were 65% (CI; 57%-74%) and 79% (CI; 72%-84%) for R-CHOEP versus 63% (CI; 55%-73%) and 79% (CI;72%-87%) for R-CHOP (log-rank test, PFS p = .90 and OS p = .63).

The present study did not confirm superiority of R-CHOEP over R-CHOP for young patients with high-risk DLBCL.

Diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin's lymphoma (NHL), is substantially heterogeneous. Approximately 5-10% of DLBCLs express CD5, which makes CD5+ DLBCL a rare subgroup. Different studies have shown that CD5+ DLBCL patients are often older and female and have higher lactate dehydrogenase levels, an Eastern Cooperative Oncology Group (ECOG) performance status > 1, and higher International Prognostic Index (IPI) scores. Moreover, patients often have advanced stage disease with a high incidence of central nervous system (CNS) relapse and bone marrow involvement. CD5+ DLBCL cells are more likely to express MYC, BCL-2, and MUM-1, less likely to express CD10, and most belong to the activated B-cell-like (ABC) subtype. The potential mechanisms underlying the poor prognosis of CD5+ DLBCL patients may be related to CD5-mediated B-cell receptor (BCR)-dependent and -independent pathways. The efficacy of the traditional rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen is unsatisfactory in CD5+ DLBCL patients. Despite supporting evidence from retrospective studies, it is currently unclear whether dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) can improve outcomes in this population. Several new drugs, such as Bruton tyrosine kinase inhibitors (BTKi), BCL-2 inhibitors, and CXCR4 antagonists, as well as immunotherapy, may help to improve the prognosis of CD5+ DLBCL patients, but additional clinical explorations are needed to determine the optimal therapeutic strategy for this disease.

NK cells are essential for the detection, identification and prediction of cancer. However, so far, there is no prognostic risk model based on NK cell-related genes to predict the prognosis and treatment outcome of DLBCL patients. This study aimed to explore a risk assessment model that could accurately predict the prognosis and treatment efficacy of DLBCL.

Bioinformatics analysis of the expression profiles of DLBCL samples in the GEO database was performed. Cox regression and LASSO regression analysis were used to determine NK cell-related genes associated with patient's prognosis. Based on these genes, a risk assessment model was constructed to predict the prognosis of patients and the effectiveness of treatment. Finally, qRT-PCR was used to verify the expression of gene tags in clinical samples.

We identified seven prognosis-related NK cell-related genes (MAP2K1, PRKCB, TNFRSF10B, IL18, LAMP1, RASGRP1, and SP110), and DLBCL patients were divided into low- and high-risk groups based on these genes. Survival analysis showed that the prognosis of patients with low-risk group was better. Pathway enrichment analysis showed that the differentially expressed genes between the two risk groups were related to immune response pathways. Compared with the high-risk group, the low-risk group had higher infiltration of immune cells in tumor tissues. Besides, compared with high-risk group, low-risk patients by immunotherapy or other commonly used anti-tumor drugs might have better efficacy after treatment. In addition, qRT-PCR showed that the expression of risk genes including TNFRSF10B, IL18 and LAMP1 were significantly increased in most DLBCL samples compared to control samples, while the expression of protective genes including MAP2K1, PRKCB, RASGRP1 and SP110 were significantly decreased.

The NK cell-related gene signatures were proved to be a reliable indicator of the success of immunotherapy in patients with DLBCL, thus providing a unique evaluation method.

A 67-year-old male with a past medical history of coronary artery disease, hypertension, and obesity presented with severe left knee pain and severe tricompartmental osteoarthritis. After failing conservative treatments and completing a preoperative medical workup, the patient was scheduled for total knee arthroplasty. Intraoperatively, a pathologic fracture of the distal femur was discovered, and the procedure was aborted. Histopathologic evaluation of the femur fracture revealed diffuse large B-cell lymphoma. Intraoperative discovery of a pathologic fracture should be treated as an underlying malignancy until proven otherwise. In these cases, surgery should be aborted until definitive diagnosis and management can be planned.

Diffuse large B-cell lymphoma (DLBCL) represents the most common tumor in non-Hodgkin's lymphoma. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor highly expressed in healthy tissues but downregulated in many cancers. Although cell proliferation-related metabolism rewiring has been well characterized, less is known about the mechanism of metabolic changes with DLBCL. Herein, we investigated the expressions of NDRG2, MYC and Myc-interacting zinc finger protein 1 (MIZ-1) in seven human lymphoma (mostly DLBCLs) cell lines. NDRG2 expression was inversely correlated with the expressions of MYC and MIZ-1. Further, we explored the regulatory mechanism and biological functions underlying the lymphomagenesis involving NDRG2, MYC and MIZ-1. MYC and MIZ-1 promoted DLBCL cell proliferation, while NDRG2 induced apoptosis in LY8 cells. Moreover, NDRG2 methylation was reversed by the 5-Aza-2'-deoxycytidine (5-Aza-CDR) treatment, triggering the downregulation of MYC and inhibiting DLBCL cell survival. MYC interacts with NDRG2 to regulate energy metabolism associated with mTOR. Remarkably, supporting the biological significance, the converse correlation between NDRG2 and MYC was observed in human DLBCL tumor tissues (R = -0.557). Bioinformatics analysis further validated the association among NDRG2, MYC, MIZ-1, mTOR, and related metabolism genes. Additionally, NDRG2 (P = 0.001) and MYC (P < 0.001) were identified as promising prognostic biomarkers in DLBCL patients through survival analysis. Together, our data demonstrate that the MYC/MIZ-1 complex interplays with NDRG2 to influence the proliferation and apoptosis of DLBCL cells and show the characterizations of NDRG2, MYC and MIZ-1 for metabolism features and prediction prognosis in DLBCL.

Ferroptosis has been regarded as a critical event in the process of diffuse large B cell lymphoma (DLBCL). Sentrin-specific protease 1 (SENP1) has emerged as an oncogene in multiple human malignancies. The present work was to investigate the effects of SENP1 on the progression of DLBCL and the possible regulatory mechanism involving ferroptosis. SENP1 expression in DLBCL tissues, parental and cisplatin-resistant DLBCL cells were, respectively, tested by GEPIA database, RT-qPCR, and Western blot. Cell viability was estimated via CCK-8 assay. Flow cytometry analysis estimated cell apoptosis and cycle. Western blot examined the expression of apoptosis-, cell cycle-, and ferroptosis-associated proteins. TBARS assay and BODIPY 581/591 C11 probe measured lipid peroxidation. Related assay kit assessed total iron levels. CCK-8 and flow cytometry evaluated cisplatin resistance. SENP1 expression was raised in DLBCL tissues and cells. SENP1 knockdown reduced cell viability, boosted cell apoptosis, cell cycle arrest, and elevated cisplatin sensitivity in DLBCL. SENP1 depletion drove the ferroptosis of both parental and cisplatin-resistant DLBCL cells and ferroptosis inhibitor Fer-1 reversed the influences of SENP1 inhibition on cell viability, apoptosis, cell cycle, and cisplatin resistance in DLBCL. Anyway, SENP1 absence might facilitate ferroptosis to obstruct the development of DLBCL and cisplatin resistance.

To evaluate whether BeEAM is an alternative to BEAM for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Data of 60 patients with relapsed or refractory DLBCL who underwent ASCT from January 2018 to June 2023 in our center, including 30 patients in the BeEAM group and 30 patients in the BEAM group, were retrospectively analyzed. The time to hematopoietic reconstitution, treatment-related adverse events, number of hospitalization days, hospitalization cost, and survival benefit were compared between the two groups.

The clinical characteristics of the patients did not significantly differ between the two groups. The median number of reinfused CD34 + cells was 5.06 × 106/kg and 5.17 × 106/kg in the BeEAM and BEAM groups, respectively, which did not significantly different (p = 0.8829). In the BeEAM and BEAM groups, the median time to neutrophil implantation was 10.2 and 10.27 days, respectively (p = 0.8253), and the median time to platelet implantation was 13.23 and 12.87 days, respectively (p = 0.7671). In the BeEAM and BEAM groups, the median hospitalization duration was 30.37 and 30.57 days, respectively (p = 0.9060), and the median hospitalization cost was RMB 83,425 and RMB 96,235, respectively (p = 0.0560). The hospitalization cost was lower in the BeEAM group. The most common hematologic adverse events were grade ≥ 3 neutropenia and thrombocytopenia, whose incidences were similar in the two groups. The most common non-hematologic adverse events were ≤ grade 2 and the incidences of these events did not significantly differ between the two groups. Median overall survival was not reached in either group, with predicted 5-year overall survival of 72.5% and 60% in the BeEAM and BEAM groups, respectively (p = 0.5872). Five-year progression-free survival was 25% and 20% in the BeEAM and BEAM groups, respectively (p = 0.6804).

As a conditioning regimen for relapsed or refractory DLBCL, BeEAM has a desirable safety profile and is well tolerated, and its hematopoietic reconstitution time, number of hospitalization days, and survival benefit are not inferior to those of BEAM. BeEAM has a lower hospitalization cost and is an alternative to BEAM.

Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. Assigning patients to different risk categories and cytogenetic abnormality and genetic mutation groups has been widely applied for prognostic stratification of DLBCL. Increasing evidence has demonstrated that dysregulated metabolic processes contribute to the initiation and progression of DLBCL. Metabolic competition within the tumor microenvironment is also known to influence immune cell metabolism. However, metabolism- and immune-related stratification has not been established. Here, 1660 genes involved in 84 metabolic pathways were selected and tested to establish metabolic clusters (MECs) of DLBCL. MECs established based on independent lymphoma datasets distinguished different survival outcomes. The CIBERSORT algorithm and EcoTyper were applied to quantify the relative abundance of immune cell types and identify variation in cell states for 13 lineages comprising the tumor micro environment among different MECs, respectively. Functional characterization showed that MECs were an indicator of the immune microenvironment and correlated with distinctive mutational characteristics and oncogenic signaling pathways. The novel immune-related MECs exhibited promising clinical prognostic value and potential for informing DLBCL treatment decisions.

This article presents a case study of diffuse large B-cell lymphoma in an elderly patient whose initial clinical manifestation was rapidly developing abdominal distension. The article delves into the patient's diagnostic and treatment journey, highlights treatment insights, and reviews relevant literature. The aim is to enhance the clinical diagnosis accuracy for elderly lymphoma patients presenting with a singular atypical symptom, ultimately optimizing treatment plans and enriching clinicians' knowledge of the disease.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with varying characteristics, in terms of genomic variation, cell morphology and clinical presentation. At present, only ~66% of patients are cured with initial treatment and those with refractory DLBCL exhibit a poor prognosis. Thus, further investigations into novel effective treatment options for DLBCL are required. The present study reports the case of a patient resistant to multiple therapies, including rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus enzastaurin (trial no. CTR20171560), GemOx plus lenalidomide and selinexor (trial no. ATG-010-DLBCL-001). The patient harbored a CD274 amplification, as identified via next-generation sequencing (NGS), and exhibited a high programmed death-ligand 1 Tumor Proportion Score of up to 95%. Consequently, the patient was treated with sintilimab monotherapy and the response lasted for 12 months of follow-up without major immune-related adverse events. This case highlights the role of NGS technology in selecting treatment options for refractory DLBCL. Furthermore, the results of the present study suggest that sintilimab may have potential in the treatment of patients with refractory DLBCL.

Cell fate is tightly controlled by a continuous balance between cell survival and cell death inducing mechanisms. B-cell lymphoma 2 (Bcl-2)-family members, composed of effectors and regulators, not only control apoptosis at the level of the mitochondria but also by impacting the intracellular Ca2+ homeostasis and dynamics. On the one hand, anti-apoptotic protein Bcl-2, prevents mitochondrial outer membrane permeabilization (MOMP) by scaffolding and neutralizing proapoptotic Bcl-2-family members via its hydrophobic cleft (region composed of BH-domain 1-3). On the other hand, Bcl-2 suppress pro-apoptotic Ca2+ signals by binding and inhibiting IP3 receptors via its BH4 domain, which is structurally exiled from the hydrophobic cleft by a flexible loop region (FLR). As such, Bcl-2 prevents excessive Ca2+ transfer from ER to mitochondria. Whereas regulation of both pathways requires different functional regions of Bcl-2, both seem to be connected in cancers that overexpress Bcl-2 in a life-promoting dependent manner. Here we discuss the anti-apoptotic canonical and non-canonical role, via calcium signaling, of Bcl-2 in health and cancer and evolving from this the proposed anti-cancer therapies with their shortcomings. We also argue how some cancers, with the major focus on diffuse large B-cell lymphoma (DLBCL) are difficult to treat, although theoretically prime marked for Bcl-2-targeting therapeutics. Further work is needed to understand the non-canonical functions of Bcl-2 also at organelles beyond the mitochondria, the interaction partners outside the Bcl-2 family as well as their ability to target or exploit these functions as therapeutic strategies in diseases.

The objective of the present study was to assess the levels of circulating cytokines in patients with diffuse large B-cell lymphoma (DLBCL), and to examine the associations between the cytokine levels, clinicopathological manifestations and patient prognosis. The study enrolled 49 patients with DLBCL, 11 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and 67 healthy controls from Zhejiang Provincial People's Hospital (Hangzhou, China) between January 2017 and January 2020. The serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were measured using flow cytometry. The IL-6, IL-10 and IFN-γ levels were significantly raised in patients with DLBCL compared with those in the healthy controls (P<0.05). The levels of IL-10 were significantly higher in patients with raised levels of circulating lactate dehydrogenase (P<0.05), while increases in both IL-6 and IL-10 were associated with raised C-reactive protein (CRP) levels, with IL-6 levels positively associated with those of serum CRP (P<0.01; r=0.66). Additionally, International Prognostic Index (IPI) risk stratification of patients with DLBCL was strongly associated with circulating IL-6 and IL-10 levels. Raised IL-6, IL-10 and TNF-α levels were linked with worse short-term treatment efficacies (P<0.05). Moreover, the accuracy of the model predicting short-term treatment response in patients with DLBCL, obtained using the support vector machine algorithm, was 81.63%. It was also found that raised serum IL-6 and IL-10 levels, together with reduced levels of IL-17, were associated with survival of <1 year in patients with DLBCL (P<0.05), although no significant link was found between cytokine levels and long-term overall survival. In conclusion, the serum levels of IL-6, IL-10, IL-17, TNF-α and IFN-γ can potentially serve as biological indicators of DLBCL tumor immune status, and combined application with the IPI score can be a robust prognostic indicator in patients with DLBCL.

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.

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.

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.

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.

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.

Despite being the most common primary tumor of the spleen, in the past, few studies have predicted the prognosis of primary spleen diffuse large B cell lymphoma. This study aimed to establish a nomogram prediction model of overall survival in primary DLBCL of the spleen. We screened out 347 patients with primary splenic DLBCL from surveillance, epidemiology, and end results database. According to the Cox regression results (age, Ann Arbor Stage, splenectomy and chemotherapy was the independent risk factor for primary splenic DLBCL), the nomogram was constructed. We evaluated the predictive ability of nomogram with C-Index (training cohort: 0.719 [0.669-0.769]; validation cohort: 0.711 [0.641-0.781]) and 3-year/5-year receiver operating characteristic area under curve (3-year/5-year ROCAUC, training cohort: 0.731/0.742; validation cohort: 0.721/0.742). Calibratioin plot shows that our predicted values fluctuate around the actual value, indicating good agreement with nomogram. The decision curve analysis (DCA) results showed that our nomogram could benefit more than Ann Arbor Stage for predicts the prognosis of the primary splenic DLBCL. The Kaplan-Meier and landmark analysis showed that a great discrimination between high-risk group and low-risk group (P < 0.05) and indicating that our nomogram has the good ability to identify high-risk patients. In this study, a nomogram prediction model for primary spleen DLBCL was established, which has good ability of prediction and generalization. It can help clinicians carry out individualized treatment measures.

Advanced diffuse large B cell lymphoma (DLBCL) is a common malignant tumor with aggressive clinical features and poor prognosis. At present, there is lack of effective prognostic tool for patients with advanced (stage III/IV) DLBCL. The aim of this study is to identify prognostic indicators that affect survival and response and establish the first survival prediction nomogram for advanced DLBCL. A total of 402 patients with advanced DLBCL were enrolled in this study. COX multivariate analysis was used to obtain independent prognostic factors. The independent prognostic factors were included in the nomogram, and the nomogram to predict the performance of the model was established by R rms package, C-index (consistency index), AUC curve and calibration curve. The training and validation cohorts included 281 and 121 patients. In the training cohort, multivariate analysis showed that Ki-67 (70% (high expression) vs ≤ 70% (low expression), p < 0.001), LDH (lactate dehydrogenase) (elevated vs normal, p = 0.05), FER (ferritin) (elevated vs normal, p < 0.001), and β2-microglobulin (elevated vs normal, p < 0.001) were independent predictors and the nomogram was constructed. The nomogram showed that there was a significant difference in OS among the low-risk, intermediate-risk and high-risk groups, with 5-year survival rates of 81.6%, 44% and 6%, respectively. The C-index of the nomogram in the training group was 0.76. The internal validation of the training group showed good consistency. In the internal validation cohort of the training group, the AUC was 0.828, and similar results were obtained in the validation group, with a C-index of 0.74 and an AUC of 0.803. The proposed nomogram provided a valuable individualized risk assessment of OS in advanced DLBCL patients.

Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL. We reveal transcriptomic differences between macrophages within RLTs (light zone /dark zone, germinal center/ interfollicular), and between disease states (RLTs/ DLBCL), which we then use to generate six spatially-derived macrophage signatures (MacroSigs). We proceed to interrogate these MacroSigs in macrophage and DLBCL single-cell RNA-sequencing datasets, and in gene-expression data from multiple DLBCL cohorts. We show that specific MacroSigs are associated with cell-of-origin subtypes and overall survival in DLBCL. This study provides a spatially-resolved whole-transcriptome atlas of macrophages in reactive and malignant lymphoid tissues, showing biological and clinical significance.

Introduction Diffuse large B-cell lymphoma (DLBCL) may be complicated by hypercalcemia at various stages of treatment. The impact of hypercalcemia on chemotherapy admission outcomes in DLBCL is not well described.  Methods In a retrospective analysis, using the National Inpatient Sample database (2018 - 2020), patients with DLBCL admitted for chemotherapy were dichotomized based on the presence of hypercalcemia. Our primary outcome was all-cause mortality. Secondary outcomes included length of stay (LOS), total charge, rate of acute kidney injury (AKI), tumor lysis syndrome (TLS), hyperkalemia, metabolic acidosis, acute encephalopathy, septic shock, Clostridiodes difficile infection, acute respiratory failure, and venous thromboembolic events (VTE). Results We identified 78,955 patients, among whom 1,375 (1.74%) had hypercalcemia. Hypercalcemia was associated with higher odds of all-cause mortality (aOR:3.05, p-value:0.020), TLS (aOR:8.81, p-value<0.001), acute metabolic encephalopathy (aOR:4.89, p-value<0.001), AKI (aOR:5.29, p-value<0.001), hyperkalemia (aOR:2.84, p-value:0.002), metabolic acidosis (aOR:3.94, p-value<0.001) and respiratory failure (aOR:2.29, p-value:0.007) and increased LOS by 1 day and total charge by 12, 501 USD. Conclusions In patients with DLBCL admitted for inpatient chemotherapy, those with hypercalcemia compared to a cohort without had higher odds of; all-cause mortality, TLS, AKI, acute encephalopathy, acute metabolic acidosis, hyperkalemia, and acute respiratory failure as well as higher LOS and total charge.