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Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, with significant clinical heterogeneity. Recent studies suggest that the intratumoral microbiome may influence the tumor microenvironment, affecting patient prognosis and therapeutic responses. This study aims to identify microbiome-related subtypes in DLBCL and assess their impact on prognosis, immune infiltration, and therapeutic sensitivity. Methods: Transcriptomic and microbiome data from 48 DLBCL patients were obtained from public databases. Consensus clustering was used to classify patients into distinct microbiome-related subtypes. Functional enrichment analysis, immune infiltration assessments, and single-cell RNA sequencing were performed to explore the biological characteristics of these subtypes. Drug sensitivity predictions were made using the OncoPredict tool. Hub genes’ expression and biological function were validated and inferred in cell lines and independent cohorts of DLBCL. Results: Two distinct microbiome-related subtypes were identified. Patients in Cluster 1 exhibited significantly better overall survival (P < 0.05), with higher immune infiltration of regulatory T cells and M0 macrophages compared to Cluster 2, which was associated with poorer outcomes. Functional enrichment analysis revealed that genes in Cluster 1 were involved in immune regulatory pathways, including cytokine–cytokine receptor interactions and chemokine signaling, suggesting enhanced anti-tumor immune responses. In contrast, genes in Cluster 2 were enriched in immunosuppressive pathways, contributing to a less favorable prognosis. Single-cell RNA sequencing analysis revealed significant heterogeneity in immune cell populations within the tumor microenvironment. B cells exhibited the most notable heterogeneity, as indicated by stemness and differentiation potential scoring. Intercellular communication analysis demonstrated that B cells played a key role in immune cell interactions, with significant differences observed in MIF signaling between B-cell subgroups. Pseudo-time analysis further revealed distinct differentiation trajectories of B cells, highlighting their potential heterogeneity across different immune environments. Metabolic pathway analysis showed significant differences in the average expression levels of metabolic pathways among B-cell subgroups, suggesting functional specialization. Furthermore, interaction analysis between core genes involved in B-cell differentiation and microbiome-driven differentially expressed genes identified nine common genes (GSTM5, LURAP1, LINC02802, MAB21L3, C2CD4D, MMEL1, TSPAN2, and CITED4), which were found to play critical roles in B-cell differentiation and were influenced by the intratumoral microbiome. DLBCL cell lines and clinical cohorts validated that MMEL1 and CITED4 with important biologically function in DLBCL cell survival and subtype classification. Conclusions: This study demonstrates the prognostic significance of the intratumoral microbiome in DLBCL, identifying distinct microbiome-related subtypes that impact immune infiltration, metabolic activity, and therapeutic responses. The findings provide insights into the immune heterogeneity within the tumor microenvironment, focusing on B cells and their differentiation dynamics. These results lay the foundation for microbiome-based prognostic biomarkers and personalized treatment approaches, ultimately aiming to enhance patient outcomes in DLBCL. [ABSTRACT FROM AUTHOR]

AbstractThis is a retrospective study conducted to determine whether there is an optimal regimen for elderly diffuse large B-cell lymphoma (DLBCL) patients. We selected patients aged 80 years or older who received the frontline chemoimmunotherapy of standard-dose rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), reduced dose of R-CHOP (R-miniCHOP), or rituximab and bendamustine (BR). Patients with standard dose of R-CHOP presented a better overall response rate than those with R-miniCHOP (p = 0.047). However, there was no significant difference in progression-free survival (PFS) or overall survival (OS) among the groups. Eastern Cooperative Oncology Group performance status of 0 or 1, serum albumin ≥3.5 g/dL, early stage, and GCB subtype were the factors associated with superior PFS and OS. In conclusion, no single regimen was found to be superior for elderly DLBCL patients. Rather than selecting regimen depending on sole age, comprehensive evaluation should be done before chemotherapy initiation. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of different treatment strategies on the long-term survival of patients with diffuse large B-cell lymphoma (DLBCL). Methods A total of 117 DLBCL patients admitted to our hospital from April 2018 to April 2019 who had completed follow-up were selected and divided into group A (39 cases),group B (39 cases) and group C (39 cases). At the same time, patients were divided into survival group (96 cases) and death group (21 cases) according to the survival situation. Group A was treated with chop regimen, group B was treated with R-CHOP Regimen, and group C was treated with DA-R-EPOCH regimen. The clinical efficacy, adverse reactions and long-term survival of the three groups were compared, and the influencing factors of death in DLBCL patients were analyzed by COX regression model. Results After 4 cycles of treatment, the total effective rate of group C was 92. 31% (36/39),followed by group B[84. 62% (33/39) ] and group A[66. 67% (26/39) ],and the difference was statistically significant (P＜0. 05). During the treatment, there was no significant difference in the incidence of adverse reactions among the 3 groups (P＞0. 05). During the follow-up period, group C had the longest survival time[ (58. 08±6. 35) month] and the lowest mortality rate[10. 26% (4/39) ],followed by group B,group A had the shortest survival time and the highest mortality rate, and the difference were statistically significant (P＜0. 05). There were significant differences in Ann Arbor stage, Ki-67,International Prognostic Index (IPI) score and treatment scheme between the survival group and the death group (P＜0. 05). Ann Arbor stage (Ⅲ-Ⅳ stage),Ki-67 (＞80%),IPI score (＞2 points) and treatment plan (CHOP) were the independent risk factors of death in patients with DLBCL (HR＞1,P＜0. 05). Conclusion Both R-CHOP and DA-R EPOCH can effectively improve the clinical symptoms and prolong the survival of DLBCL patients without increasing the incidence of adverse reactions. At the same time, Ann Arbor stage, Ki-67,IPI score and treatment method are independent risk factors for death in DLBCL patients. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2DmutBTG2mut had poorer OS than those with KMT2Dwt BTG2mut (P=0.07) and KMT2Dwt BTG2wt (P=0.05). On the contrary, patients with KMT2Dmut CD79Bmut had better OS than those with KMT2Dmut CD79Bwt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ ( HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2DmutBTG2mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis. [ABSTRACT FROM AUTHOR]

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

AbstractT-cell/histiocyte-rich B-cell lymphoma (THRLBCL) is an uncommon variant of diffuse large B‐cell lymphoma (DLBCL). Historically, it is considered an aggressive variant with poorer outcomes; however, recent analyses suggest that outcomes may be better for patients treated in the rituximab era. We reviewed THRLBCL cases who were diagnosed in MSKCC from January 2000 to October 2019. A total of 67 patients were included with a median follow-up of 5.4 years (0.5–13.8). Frontline treatment included R-CHOP or R-CHOP-based treatment in 48%, R-EPOCH in 12%, R-CHOP/R-ICE in 33% and other palliative treatments in 7.5%. In the whole cohort, 5-year EFS and OS was 59% and 79%, respectively. In an analysis of patients who received therapy with R-CHOP-14 × 4 followed by ICE/R-ICE × 3 compared to patients who were treated with R-CHOP or R-CHOP based treatment, CR rates were 95% and 70%, respectively (p = 0.023). The R-CHOP/R-ICE regimen was also associated with higher event-free survival (5-year EFS of 80% vs 50%; p = 0.006) and overall survival (5-year OS of 100% vs 72%; p = 0013). Our study demonstrates better outcomes among patients with THRLBCL compared to historical data. Our findings suggest that treatment with a higher intensity regimen with noncross resistance, such as R-CHOP/R-ICE is reasonable approach for patients with newly diagnosed THRLBCL. [ABSTRACT FROM AUTHOR]

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

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

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

Introduction: Primary breast lymphoma (PBL) is a rare non-Hodgkin lymphoma, predominantly presenting as diffuse large B-cell lymphoma (DLBCL) and primarily affecting the breast, often misdiagnosed due to its nonspecific symptoms resembling breast carcinoma. Breast implants are among the most frequently used medical devices for esthetic and reconstructive purposes. Case Presentation: We present a 24-year-old female with a growing breast mass who was diagnosed with PBL (non-Hodgkin’s DLBCL). She underwent successful R-CHOP chemotherapy, resulting in complete remission. Follow-up imaging showed no distant metastasis or significant residual disease, with silicone implants intact and no pathological uptake. Conclusion: PBL is a rare malignancy that primarily affects postmenopausal women, with diagnosis relying on radiologic investigations and histopathology due to its clinical and imaging similarities to breast carcinoma. Treatment is controversial and often involves rituximab-based chemotherapy, intrathecal methotrexate, and radiotherapy, with improved outcomes observed in recent years. Introduction: Primary breast lymphoma (PBL) is a rare non-Hodgkin lymphoma, predominantly presenting as diffuse large B-cell lymphoma (DLBCL) and primarily affecting the breast, often misdiagnosed due to its nonspecific symptoms resembling breast carcinoma. Breast implants are among the most frequently used medical devices for esthetic and reconstructive purposes. Case Presentation: We present a 24-year-old female with a growing breast mass who was diagnosed with PBL (non-Hodgkin’s DLBCL). She underwent successful R-CHOP chemotherapy, resulting in complete remission. Follow-up imaging showed no distant metastasis or significant residual disease, with silicone implants intact and no pathological uptake. Conclusion: PBL is a rare malignancy that primarily affects postmenopausal women, with diagnosis relying on radiologic investigations and histopathology due to its clinical and imaging similarities to breast carcinoma. Treatment is controversial and often involves rituximab-based chemotherapy, intrathecal methotrexate, and radiotherapy, with improved outcomes observed in recent years. Introduction: Primary breast lymphoma (PBL) is a rare non-Hodgkin lymphoma, predominantly presenting as diffuse large B-cell lymphoma (DLBCL) and primarily affecting the breast, often misdiagnosed due to its nonspecific symptoms resembling breast carcinoma. Breast implants are among the most frequently used medical devices for esthetic and reconstructive purposes. Case Presentation: We present a 24-year-old female with a growing breast mass who was diagnosed with PBL (non-Hodgkin’s DLBCL). She underwent successful R-CHOP chemotherapy, resulting in complete remission. Follow-up imaging showed no distant metastasis or significant residual disease, with silicone implants intact and no pathological uptake. Conclusion: PBL is a rare malignancy that primarily affects postmenopausal women, with diagnosis relying on radiologic investigations and histopathology due to its clinical and imaging similarities to breast carcinoma. Treatment is controversial and often involves rituximab-based chemotherapy, intrathecal methotrexate, and radiotherapy, with improved outcomes observed in recent years. [ABSTRACT FROM AUTHOR]

Objectives Classic Hodgkin lymphoma (CHL) is characterized by infrequent neoplastic Hodgkin and Reed-Sternberg (HRS) cells in an inflammatory background. The diagnostic utility of CC-chemokine receptor 7 (CCR7) in CHL was explored using flow cytometry and immunohistochemistry (IHC). Methods Neoplastic specimens and non-neoplastic lymph nodes were immunophenotyped and CCR7 expression was measured semiquantitatively by flow cytometry (clone 3D12) and IHC (clone 150503). Results Our results showed that CCR7 was expressed on HRS cells in the vast majority of CHL cases (45/48 by flow cytometry, 57/59 by IHC) but rarely expressed in neoplastic cells in diffuse large B-cell lymphoma, not otherwise specified (1/25 by flow cytometry, 2/40 by IHC) and nodular lymphocyte predominant Hodgkin lymphoma (0/4 by flow cytometry, 1/13 by IHC). Primary mediastinal large B-cell lymphoma (PMLBCL) revealed weak CCR7 expression by flow cytometry in most cases (8/10) but only occasionally by IHC (2/12). Both cases (2/2) of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) also showed CCR7 expression detected by flow cytometry compared with IHC (0/7). The HRS cells demonstrated a greater percentage of positive cells and greater antigen intensity than the other B-cell lymphomas by IHC. The expression identified by flow cytometry in PMLBCL and THRLBCL but not by IHC suggests that there may be differences in the detection capabilities of the 2 techniques or the 2 CCR7 clones used. Conclusions The expression of CCR7 in HRS cells suggests its potential utility in differentiating CHL from other B-cell lymphomas. Incorporating CCR7 into flow cytometry and IHC panels may further enhance the diagnostic sensitivity of CHL. [ABSTRACT FROM AUTHOR]

Methotrexate is a commonly employed folate antagonist used as a disease modifying antirheumatic drug. It is recommended by the European League Against Rheumatism Guidelines as an add-on therapy for the treatment of polymyalgia rheumatica. Lymphoproliferative disease developing during methotrexate treatment is recognised as methotrexate-associated lymphoproliferative disorder. We describe a patient with polymyalgia rheumatica on long-term methotrexate treatment presenting with double vision and systemic symptoms concerning for giant cell arteritis. Two months prior, she had noticed a mass of the right nasal dorsum. Neuroimaging showed several lesions of the nasal cavity and a clival lesion. Nasal cavity biopsy revealed diffuse large B-cell lymphoma, and FDG-PET/CT 3 weeks after methotrexate cessation showed significant interval disease regression, confirming the diagnosis of methotrexate-associated lymphoproliferative disorder. Follow-up FDG-PET/CT 4 months after methotrexate cessation showed complete radiological regression of lymphoproliferative lesions. The cumulative incidence of methotrexate-associated lymphoproliferative disorder in patients with rheumatoid arthritis treated with methotrexate has been reported to be up to 4.7% at 10 years in a retrospective study. Cessation of methotrexate resulted in spontaneous regression in 59% of patients. It is important to include methotrexate-associated lymphoproliferative disorder on the differential diagnosis for patients on long-term methotrexate treatment who present with neuro-ophthalmic symptoms and signs as tissue diagnosis prior to commencing steroid treatment is essential to secure the diagnosis and guide treatment. [ABSTRACT FROM AUTHOR]

What is this summary about? In this article, we summarize results from a clinical study called LOTIS-2, in which researchers looked at patients with a type of blood cancer called diffuse large B-cell lymphoma, or DLBCL for short. Patients received the drug loncastuximab tesirine, or Lonca for short, which targets a marker on the surface of tumor cells called CD19. Patient information from the LOTIS-2 study, other studies of Lonca, and information from scientific publications was used to develop a quantitative systems pharmacology (QSP) model, which can predict how Lonca works in the body. The goal was to use the QSP model to see if CD19 levels can predict tumor size changes after Lonca treatment and if Lonca can still work to treat DLBCL when CD19 levels are very low. The prior LOTIS-1 and LOTIS-2 trials demonstrated an acceptable safety profile for Lonca, and therefore the current study did not evaluate safety data. What were the results? Researchers used immunohistochemistry, a common technique to evaluate CD19 expression. They found that there was no association between patients who responded to Lonca treatment and levels of CD19 on their tumor cells. Some patients with low or even undetectable levels of CD19 on their tumor cells had observable decreases in tumor size after Lonca treatment. What do the results of the study mean? While Lonca uses the CD19 target to find and destroy cancer cells, Lonca does not require a large amount of CD19 to kill tumor cells. These results mean that Lonca may be an effective treatment for patients with DLBCL, even if CD19 expression in tumors is undetectable by immunohistochemistry. [ABSTRACT FROM AUTHOR]

A 70-year-old woman presented to our hospital with abdominal pain. Imaging examinations showed diffuse and extensive wall thickening at the perihilar bile duct; however, the degree of stricture was mild, and the mucosal epithelium was smooth. A transpapillary biopsy was performed considering cholangiocarcinoma and IgG4 sclerosing cholangitis as differential diagnoses; however, no pathologic diagnosis was obtained. Peroral cholangioscopy revealed a regular epithelium at the stricture, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the enlarged lymph node confirmed the diagnosis of diffuse large B-cell lymphoma. Multiagent chemotherapy was administered, which led to complete remission. Because primary bile duct malignant lymphomas are rare and specific, clinical, and imaging findings are lacking, and many of those reported so far have been diagnosed by postoperative pathology. As chemotherapy is the first-line treatment for malignant lymphoma, obtaining an accurate diagnosis is crucial. Our findings support that smooth and mild biliary strictures with mainly submucosal wall thickening may be characteristic imaging findings of primary bile duct malignant lymphoma, and that peroral cholangioscopy and EUS-FNA may be helpful for an accurate diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this investigation is to explore the capability of baseline 18F-FDG PET/CT radiomics to predict the prognosis of diffuse large B-cell lymphoma (DLBCL) with extranodal involvement (ENI). Methods: 126 patients diagnosed with DLBCL with ENI were included in the cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to refine the optimum subset from the 1328 features. Cox regression analyses were employed to discern significant clinical variables and conventional PET parameters, which were then employed with radiomics score to develop combined model for predicting both progression-free survival (PFS) and overall survival (OS). The fitness and the predictive capability of the models were assessed via the Akaike information criterion (AIC) and concordance index (C-index). Results: 62 patients experienced disease recurrence or progression and 28 patients ultimately died. The combined model exhibited a lower AIC value compared to the radiomics model and SDmax/clinical variables for both PFS (507.101 vs. 510.658 vs. 525.506) and OS (215.667 vs. 230.556 vs. 219.313), respectively. The C-indices of the combined model, radiomics model, and SDmax/clinical variables were 0.724, 0.704, and 0.615 for PFS, and 0.842, 0.744, and 0.792 for OS, respectively. Kaplan––Meier curves showed significantly higher rates of relapse and mortality among patients classified as high-risk compared to those classified as low-risk (all P < 0.05). Conclusions: The combined model of clinical variables, conventional PET parameters, and baseline PET/CT radiomics features demonstrates a higher accuracy in predicting the prognosis of DLBCL with ENI. [ABSTRACT FROM AUTHOR]

Background: The significance of the controlling nutritional status (CONUT) score in predicting the prognostic outcomes of diffuse large B-cell lymphoma (DLBCL) has been widely explored, with conflicting results. Therefore, the present meta-analysis aimed to identify the prognostic significance of the CONUT in DLBCL by aggregating current evidence. Methods: The Web of Science, PubMed, Embase, CNKI and Cochrane Library databases were searched for articles from inception to October 15, 2024. The prognostic value of CONUT for DLBCL was analyzed by determining the pooled hazard ratios (HRs) with 95% confidence intervals (CIs). The Newcastle–Ottawa Scale (NOS) was used to analyze study quality. Results: Eight studies including 2687 cases were included in this work. The NOS scores of these studies were 7–9 (median, 8), demonstrating high quality. Our analyses revealed that an elevated CONUT score significantly predicted poor overall survival (OS) (HR = 1.63, 95%CI = 1.29–2.05, p < 0.001) and inferior progression-free survival (PFS) (HR=1.22, 95%CI = 1.12–1.33, p < 0.001) in patients with DLBCL. Further, the elevated CONUT score showed a significant correlation with the following clinicopathological factors in DLBCL: Ann Arbor stage III-IV, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2–4, presence of extranodal disease, ≥high intermediate National Comprehensive Cancer Network International Prognostic Index (NCCN IPI), presence of B symptoms, elevated lactose dehydrogenase (LDH) levels, and presence of bone marrow infiltration. Conclusions: An increased CONUT score was dramatically associated with poor OS and PFS in patients with DLBCL, as well as with clinicopathological characteristics representing DLBCL tumor development. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical manifestations, pathological features and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) with c-Myc gene amplification in the pancreas. Methods The clinicopathological features of two patients with primary pancreatic DLBCL with c-Myc gene amplification were retrospectively analyzed. Results Case 1,DLBCL,non-germinal center type; Case 2,DLBCL,germinal central type. Case 1 received no operation, case 2 received chemotherapy after duodenectomy. Two patients were treated with rituximab combined with doxorubicin, cyclophosphamide, vincristine, and prednisolone (R-CHOP regimen) . Overall survival was 18 days for case 1 and 15 months for case 2. Conclusion The clinical manifestations of patients with primary pancreatic DLBCL with c-Myc gene amplification are similar to those of pancreatic cancer. The disease is easy to progress and the prognosis is poor. R-CHOP regimen chemotherapy is not effective. It is recommended to adopt more radical treatment to improve the prognosis. [ABSTRACT FROM AUTHOR]

AbstractTreatment strategies for early stage diffuse large B-cell lymphoma (ES-DLBCL) include R-CHOP, with a similar schedule to that used in advanced stage, or a reduced number of cycles followed by radiation therapy (RT). We retrospectively analyzed 179 ES-DLBCL patients, managed according to the clinical practice. Treatment regimens include chemoimmunotherapy 4–6 cycles +/- RT as consolidation. First-line therapy was R-CHOP/CHOP-like in 88.8% of cases. RT as consolidation was administered to 29.9% of cases. Complete response rate was 87.2%, median PFS and OS were not reached. IPI 2–3 and first-line regimen with 3–4 cycles of R-CHOP without RT were the 2 prognostic variables for OS in multivariate analysis. After a median follow-up of 48 months, 31 patients died (17.3%). We suggest that both R-CHOP 6 cycles and 3–4 cycles followed by RT as consolidation seem to be valid first-line regimens, while an abbreviated strategy without RT could be associated to inferior outcome. [ABSTRACT FROM AUTHOR]

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

Background: Retrospective studies are often criticized for their susceptibility to case selection bias compared to prospective studies, which include all patients consecutively and are thus less prone to such limitations. However, the larger sample sizes typical of retrospective studies can sometimes offset this drawback. On behalf of the Fondazione Italiana Linfomi (FIL), a substantial retrospective study involving 946 patients was conducted to examine the use of non-pegylated liposomal anthracycline (Myocet). This was followed by a prospective study, the Prospective Elderly Project, which enrolled 308 patients treated with the same liposomal anthracycline regimen. Methods: The objective of this analysis was to determine whether the patient cohort from the retrospective study significantly differed from the cohort in the prospective study. Statistical hypothesis testing was applied to assess whether the samples from both studies originated from the same underlying population. The Anderson–Darling test, a non-parametric statistical method, was utilized to evaluate and compare the overall survival distributions between the two patient cohorts. Results: The statistical tests produced conflicting results, suggesting a potential selection bias in the retrospective study or the possibility that the two groups were from the same population. These discrepancies may have arisen due to the choice of statistical methods or the quality of the data analyzed. Conclusions: This study highlights the challenges of comparing retrospective and prospective cohorts and underscores the importance of selecting appropriate statistical methodologies. The findings provide valuable insights and lay the groundwork for developing innovative approaches to improve such comparisons in future research. [ABSTRACT FROM AUTHOR]

AbstractPatients with relapsed/refractory primary central nervous system lymphoma (R/R PCNSL) usually have a poor prognosis and limited treatment options. We respectively reviewed 38 patients with R/R PCNSL treated with zanubrutinib-based regimens in our center. The overall response rate, complete response rate and disease control rate were 76.3%, 47.4% and 92.1%, respectively. The median progression-free survival (PFS) was 31.0 months, the median overall survival (OS) was not reached. Unitivariate analysis by Cox’s proportional hazards model revealed that overall response (vs. no response, HR = 0.18, 95%CI:0.07,0.48, p = 0.001), long duration of zanubrutinib (≥6months vs 2-5 months, HR = 0.20, 95%CI:0.06,0.63, p = 0.006) were independent factors for prolonged PFS. The log-rank analysis indicated a prolongation of PFS among patients exhibiting a higher Tumor mutational burden (TMB, ≥14.75muts/Mb) following zanubrutinib-based treatment (p = 0.016). Our data showed promising efficacy with tolerable safety of zanubrutinib-based therapies in patients with R/R PCNSL. Long duration of zanubrutinib may be associated with prolonged PFS. [ABSTRACT FROM AUTHOR]

With the introduction of anti‐CD19 chimeric antigen receptor (CAR) T‐cell (CAR T) therapies, bispecific CD3/CD20 antibodies and anti‐CD19 antibodies, immunotherapy continues to transform the treatment of diffuse large B‐cell lymphoma (DLBCL). A number of novel immunotherapeutic strategies are under investigation to build upon current clinical benefit and offer further options to those patients who cannot tolerate conventional intensive therapies due to their age and/or state of health. Alongside immunotherapies that leverage the adaptive immune response, natural killer (NK) cell and myeloid cell‐engaging therapies can utilize the innate immune system. Monoclonal antibodies engineered for greater recognition by the patient's immune system can enhance antitumor cytotoxic mechanisms mediated by NK cells and macrophages. In addition, CAR technology is extending into NK cells and macrophages and investigational immune checkpoint inhibitors targeting macrophage/myeloid cell checkpoints via the CD47/SIRPα axis are in development. Regimens that engage both innate and adaptive immune responses may help to overcome resistance to current immunotherapies. Furthermore, combinations of immunotherapy and oncogenic pathway inhibitors to reprogram the immunosuppressive tumor microenvironment of DLBCL may also potentiate antitumor responses. As immunotherapy treatment options continue to expand, both in the first‐line setting and further lines of therapy, understanding how to harness these immunotherapies and the potential for combination approaches will be important for the development of future DLBCL treatment approaches. [ABSTRACT FROM AUTHOR]

AbstractThe cell of origin (COO) classification is an expression-based tumor algorithm identifying molecular subtypes of diffuse large B-cell lymphoma (DLBCL) with distinct prognostic characteristics. Traditional immunohistochemical methods for classifying COO subtypes have poor concordance and limited prognostic value in frontline DLBCL. In contrast, RNA-based metrics like the NanoString Lymphoma Subtyping Test (LST) define more robust subtypes with validated prognostic associations. This study introduces gneSeqCOO, an algorithm using bulk RNA Sequencing (RNASeq) profiles of individual tumor biopsies for COO classification based on a fixed reference. This method produced consistent per-sample results and was robust to variation in RNA quality and sequencing bias. Validation in >1000 DLBCL samples showed high concordance with the NanoString LST assay, even in cohorts containing only one COO subtype. gneSeqCOO presents a robust and versatile alternative to existing assays, potentially reducing the need for additional samples where RNASeq was already generated. The package is available at https://github.com/Genentech/gneSeqCOO. [ABSTRACT FROM AUTHOR]

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

Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma rarely presents with circulating lymphoma cells (CL) at diagnosis. Previous studies were limited by small sample size precluding robust analysis. Hence, we evaluated the prognostic relevance of CL cells in newly diagnosed DLBCL patients. Based on peripheral blood (PB) immunophenotyping, patients were grouped into CL + and CL−. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of DLBCL. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and diagnosis-to-treatment interval (DTI). Among the 1266 patients with DLBCL, 621 had PB flow at diagnosis, and after excluding patients not meeting eligibility criteria, 588 cases remained. Among these, 85 (15%) were CL + and 503 were CL- (85%). Patients in CL + group were younger (67 vs. 70 years, p = 0.03) with a higher proportion of non-bulky disease (85% vs. 56%, p < 0.0001), normal albumin (79% vs. 54%, p < 0.0001), and MYC/BCL2 and/or BCL6 rearrangements (18% vs. 7%, p = 0.003) compared to the CL − group. Patients with CL at diagnosis had significantly inferior PFS and OS compared with those without CL. After adjusting for factors associated with inferior PFS and OS in univariable analysis, presence of CL remained significantly associated with inferior PFS (HR = 2.04, 95%CI = 1.47–2.84, p < 0.0001) and OS (HR = 1.61, 95%CI = 1.1–2.36, p = 0.01), respectively. There was no significant difference in DTI between the two groups. Given the prognostic relevance associated with presence of CL, clinicians should consider checking PB flow at diagnosis in all newly diagnosed DLBCL patients. [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following hematopoietic stem cell transplantation (HSCT), with its occurrence post-autologous hematopoietic stem cell transplantation (auto-HSCT) being even rarer. Research on PTLD following auto-HSCT is exceedingly scarce. Here, we present a noteworthy instance wherein a patient with diffuse large B-cell lymphoma (DLBCL) developed PTLD, manifesting as classical Hodgkin lymphoma (cHL) two years after auto-HSCT. Additionally, we conducted an extensive review of existing literature, exploring the current research on PTLD following auto-HSCT and illuminating this scarcely examined area. [ABSTRACT FROM AUTHOR]

Lactate dehydrogenase (LDHA) activation induces tumorigenesis by activating tumor proliferation, growth, invasion, and metastasis. Whether LDHA mediates tumor metabolism that upon diffuse large B-cell lymphoma (DLBCL) occur remains unknown. Here, we investigated how LDHA adopt tumor metabolism after activation to regulate DLBCL-inducible. We investigated LDHA is highly expressed in peripheral blood mononuclear cells (PBMCs) of DLBCL patients. Knockdown of LDHA results in an increase in the apoptosis of cells, suppression of cell growth and migration in OCI-Ly1 and OCI-Ly10 cells. We show that LDHA gains a canonical enzyme activity to produce lactate and triggers NAD + in DLBCL cells. Furthermore, p-STAT5 was identified as a downstream target of LDHA, and the p-STAT5 protein level was significantly reduced related to decreased LDHA protein expression. Collectively, our findings identify the oncogenic role of LDHA in DLBCL and suggest that LDHA can be considered as a pivotal prognostic biomarker and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Patients with testicular lymphoma are at an increased risk of central nervous system (CNS) disease. Optimal strategy for CNS relapse prevention is unknown. We analyzed treatment strategies, cumulative incidence of CNS relapse and prognosis in 229 patients with diffuse large B-cell lymphoma (DLBCL) and testicular involvement: 157 primary testicular lymphomas (PTL) in clinical stages IE/IIE and 72 patients in advanced stages (T-DLBCL) IIIE/IV. Treatments for PTL vs. T-DLBCL included: rituximab-based chemotherapy (80.9% vs. 90.3%), orchiectomy (94.3% vs. 65.3%) and contralateral testicular irradiation (59.8% vs. 44.4%). Majority (84.3%) received CNS prophylaxis with similar rates of prophylactic methotrexate (intravenous 19.1% vs. 16.6%, intrathecal 40.8% vs. 40.4%, or both 24.2% vs. 27.8%) between PTL and T-DLBCL (p = 0.89). Median follow-up was 51.8 months. CNS relapses occurred in 14 (6.1%) of 63 relapsing patients. The 5-year cumulative incidence of CNS relapse in PTL was 4.5% and in T-DLBCL 12.1%. Median time to CNS relapse was 21.9 months. In univariate analyses, orchiectomy was the single significant factor associated with lower risk of CNS relapse in PTL (HR = 0.11 [95% CI, 0-0.124], p = 0.001). Rituximab significantly reduced CNS relapse risk in T-DLBCL (HR = 0.1002, p = 0.0005). Median progression-free survival (PFS) and overall survival (OS) following CNS relapse was dismal in T-DLBCL compared to PTL (PFS 1.6 vs. 37.8 months, p = 0.04 and OS 2.3 vs. 37.8 months, p = 0.05). This study confirmed a favorable impact of rituximab in prevention of CNS relapse in T-DLBCL. Methotrexate prophylaxis did not alter CNS relapse risk. Prognosis of CNS relapse is particularly poor in T-DLBCL. [ABSTRACT FROM AUTHOR]

Double-hit lymphoma (DHL) is a high-risk subtype of large B-cell lymphoma, defined by concurrent rearrangements MYC and BCL2. The diagnosis is confirmed through histologic and immunophenotypic examination and fluorescence in situ hybridization (FISH) to demonstrate the rearrangements. DHL morphology ranges from DLBCL to high-grade B-cell lymphoma which can resemble Burkitt lymphoma and is almost always germinal center B-cell like (GCB). Prognosis is influenced by elevated lactate dehydrogenase (LDH), advanced stage, and extranodal involvement, among other factors. Treatment outcomes vary, but intensive chemotherapy regimens such as dose-adjusted EPOCH-R have shown the most promising results, though low-risk cases do occur and may do well with less intensive treatments. Recent therapeutic advances such as CAR-T cells and bispecific antibodies offer promise for patients with relapsed/refractory disease. This review synthesizes data from recent literature to provide a comprehensive analysis of the molecular underpinnings, diagnostic criteria, prognostic factors, and therapeutic strategies for DHL. [ABSTRACT FROM AUTHOR]

Introduction: Chimeric antigen receptor T (CAR-T) cell therapy, emerging as an efficient treatment option for patients with secondary central nervous system (CNS) lymphoma, is frequently complicated with immune effector cell-associated neurotoxicity syndrome (ICANS). Case Presentation: We report a case of a 64-year-old woman with transformed follicular lymphoma, developing high-grade ICANS with eosinophilic pleocytosis following third-line therapy with CAR-T cells (tisagenlecleucel). During bridging therapy, she declined neurologically and was diagnosed with secondary CNS lymphoma. She received methotrexate-cytarabine-thiotepa-rituximab regimen with clinical and radiological improvement. Post-CAR-T cell infusion she developed cytokine release syndrome grade II and ICANS grade III. Given the lack of response to steroids, anakinra was initiated with complete ICANS resolution. Cerebrospinal fluid (CSF) analysis, performed only on day +10 due to thrombocytopenia, revealed eosinophils, while infections were excluded. Conclusion: This report emphasizes the importance of CSF analysis in individuals with CAR-T-related neurotoxicity for elucidating the role of specific immune cells in such complications. [ABSTRACT FROM AUTHOR]

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

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

Simple Summary: While many patients diagnosed with large B cell lymphomas (LBCL), specifically diffuse large B cell lymphoma (DLBCL) will be cured following treatment with first-line immunochemotherapy, those who are not are likely to die from complications of this disease. This discrepancy in outcome suggests biologic heterogeneity of this common lymphoid malignancy, and LBCL tumors can be both classified and risk-stratified by testing available in the clinical laboratory. Such testing may also identify opportunities to add targeted agents to first-line immunochemotherapy in homes of improving survival for patients whose tumors harbor high-risk pathologic features, examples of which are offered. Whether more complex comprehensive genomic analyses can be applied in clinical practice and enhance this effort remains to be determined. Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) and high-grade B cell lymphoma (HGBL) comprise the majority of large B-cell lymphomas (LBCL), and approximately two-thirds of patients diagnosed with these LBCLs are cured following treatment with first-line immunochemotherapy. While the International Prognostic Index (IPI) score is a validated prognostic tool used for patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), there is a growing body of evidence that suggests that LBCL tumor features, which can be detected by clinical laboratory testing, can predict patient survival following first-line immunochemotherapy. Conclusions: Clinical laboratory testing may also allow for rational identification of targeted agents that can be added to first-line immunochemotherapy for high-risk, pathologically defined subsets of LBCL patients, and this approach may result in better survival outcomes for the entire LBCL patient population as compared with adding pathologically "agnostic" agents for those defined as high risk by IPI score. [ABSTRACT FROM AUTHOR]

High‐dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is widely used in patients with diffuse large B‐cell lymphoma. HDCT/ASCT is associated with increased morbidity in elderly/unfit patients. We retrospectively evaluated the use of reduced intensity conditioning in DLBCL patients. Our study included 146 patients aged 60 years and older treated at our institution between 2005 and 2019; 86 patients received standard intensity conditioning (SI group) with BEAM or TEAM (BCNU or thiotepa, etoposide, cytarabine, melphalan). Sixty patients received reduced intensity high‐dose conditioning (RI group) with BM (BCNU, melphalan, 43.3%), TM (thiotepa, melphalan, 16.7%), BCNU or busulfan thiotepa (38.4%), or bendamustine melphalan (1.7%). Median follow‐up was 62.4 months. We observed comparable toxicities in the SI and RI groups. The cumulative incidence of relapse at 3 years was higher in the RI group (30.8% vs. 23.4%, p = 0.034). There was no difference in nonrelapse mortality (NRM). In univariate analyses, SI vs. RI conditioning resulted in superior progression‐free survival (PFS) (HR 1.80 CI 1.11–2.92, p = 0.017) but not in superior overall survival (OS) (HR 1.48 CI 0.86–2.56, p = 0.152). On multivariate analysis, we observed no difference in PFS (HR 0.74 CI 0.40–1.38, p = 0.345) and a trend toward better OS with RI conditioning (HR 0.45 CI 0.22–0.94, p = 0.032). Age 60–69 versus ≥ 70 years and remission prior to ASCT were the only factors predicting better PFS. Factors associated with better OS were RI conditioning, age 60–69 versus ≥ 70 years, ECOG 0 versus ≥ 1 performance status, bulky disease, and prior lines 1 versus ≥ 2. In conclusion, RI conditioning prior to ASCT may be feasible in elderly patients and led to a comparable outcome when corrected for several significant confounders. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

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

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

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

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

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