Search

Plant viruses are naturally occurring nanoparticles and adjuvants that interact with the mammalian immune system. This property can be harnessed in vaccines and immunotherapy. We have previously demonstrated that intratumoral immunotherapy with cowpea mosaic virus (CPMV) stimulates systemic and durable antitumor immunity in mouse tumor models and canine cancer patients. Here we compared the antitumor efficacy of CPMV with potato virus X (PVX) using a mouse model B-cell lymphoma (A20 and BALB/c mice). Despite their diverse morphologies and physiochemical properties, both plant viruses elicited systemic and long-lasting antitumor immune memory, preventing the recurrence of A20 lymphoma in rechallenge experiments. Data indicate differences in the underlying mechanism: CPMV persists longer in the tumor microenvironment (TME) compared to PVX; CPMV is a potent and multivalent toll-like receptor (TLR) agonist (activating TLRs 2, 4 and 7) while PVX may only weakly engage with TLR7. While CPMV and PVX recruit myeloid cells (neutrophils)─CPMV also recruits macrophages. Data further indicate that antiviral T cells may play a role in antitumor efficacy in the case of CPMV immunotherapy, however this may not be the case for PVX. Regardless of the mechanism of action, both CPMV and PVX elicited a durable antitumor response against a B-cell lymphoma tumor model and thus are intratumoral immunotherapy candidates for clinical development.

Background: Treatment for refractory or relapsed primary CNS lymphoma (r/r PCNSL) is challenging. Salvage whole-brain radiation therapy (WBRT) is an option but has a short duration of disease control, so additional treatment modalities are warranted. Case: A 75-year-old female with r/r PCNSL who had multiple progressions after multiple lines of treatment underwent salvage WBRT. The patient received ibrutinib, a Brutons tyrosine kinase inhibitor, as maintenance therapy for 18 months following WBRT with the intention of increasing survival duration after salvage WBRT. She survived 81 months from diagnosis, including 57 months after completion of WBRT. Conclusion: This case presentation describes the experience of using ibrutinib as maintenance therapy in treating r/r PCNSL after salvage WBRT.

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]

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]

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]

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]

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]

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]

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]

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.

INTRODUCTION: Fluorescence in situ hybridization (FISH) is an essential ancillary study used to identify clinically aggressive subsets of large B-cell lymphomas that have MYC, BCL2, or BCL6 rearrangements. Small-volume biopsies such as fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are increasingly used to diagnose lymphoma and obtain material for ancillary studies such as FISH. However, the performance of FISH in small biopsies has not been thoroughly evaluated or compared to surgical biopsies. METHODS: We describe the results of MYC, BCL2, and BCL6 FISH in a series of 222 biopsy specimens, including FNAB with cell blocks, CNBs, and surgical excisional or incisional biopsies from 208 unique patients aggregated from 6 academic medical centers. A subset of patients had FNAB followed by a surgical biopsy (either CNB or excisional biopsy) obtained from the same or contiguous anatomic site as part of the same clinical workup; FISH results were compared for these paired specimens. RESULTS: FISH had a low hybridization failure rate of around 1% across all specimen types. FISH identified concurrent MYC and BCL2 rearrangements in 20 of 197 (10%) specimens and concurrent MYC and BCL6 rearrangements in 3 of 182 (1.6%) specimens. The paired FNAB and surgical biopsy specimens did not show any discrepancies for MYC or BCL2 FISH; of the 17 patients with 34 paired cytology and surgical specimens, only 2 of the 49 FISH probes compared (4% of all comparisons) showed any discrepancy and both were at the BCL6 locus. One discrepancy was due to necrosis of the CNB specimen causing a false negative BCL6 FISH result when compared to the FNAB cell block that demonstrated a BCL6 rearrangement. DISCUSSION: FISH showed a similar hybridization failure rate in all biopsy types. Ultimately, MYC, BCL2, or BCL6 FISH showed 96% concordance when compared across paired cytology and surgical specimens, suggesting FNAB with cell block is equivalent to other biopsy alternatives for evaluation of DLBCL or HGBCL FISH testing.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Background: Lenalidomide is a thalidomide analog that has immunomodulatory and anti-angiogenic properties. The ECOC-ACRIN E1412 Phase II trial demonstrated that lenalidomide, when combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), extended survival in diffuse large B-cell lymphoma (DLBCL) patients. This study aimed to evaluate the cost-effectiveness of combining lenalidomide with R-CHOP (R2-CHOP) versus R-CHOP alone as the initial treatment for DLBCL from the perspective of the Chinese healthcare system. Methods: We developed a 5-year partitioned survival model to compare the cost-effectiveness of R2-CHOP versus R-CHOP alone. The clinical data came from the ECOG-ACRIN E1412 clinical trial. The costs of drugs and examinations were obtained from publicly available Chinese medical databases and literatures. Model robustness was assessed by sensitivity analysis and scenario analysis. And subgroup analysis was also performed. Key outcomes include total cost, quality-adjusted life years, and the incremental cost-effectiveness ratio (ICER). Results: Over a 5-year time horizon, the basic analysis results of the partitioned survival model showed that the ICER of $35,159.06 per QALY for R2-CHOP compared to R-CHOP. Deterministic sensitivity analysis revealed that the price of lenalidomide is the main factor affecting cost-effectiveness. Probabilistic sensitivity analysis indicated a 67.9% chance of lenalidomide plus R-CHOP being cost-effective at the willingness-to-pay threshold, compared to R-CHOP alone. Scenario analysis showed R2-CHOP scenarios to be cost-effective for 10–30 years. And subgroup analysis showed that treating activated B cell-like type DLBCL with R2-CHOP was more cost-effective. Conclusion: In the Chinese healthcare system, R2-CHOP is a cost-effective approach for DLBCL compared to R-CHOP, but the costs of lenalidomide and rituximab warrant attention. [ABSTRACT FROM AUTHOR]

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

Background: Infections are common complications and causes of death during immunochemotherapy in diffuse large B-cell lymphoma (DLBCL). The gut microbiota plays a significant role in bacterial infection, but its relationship and predictive capacity with infectious complications in DLBCL are unknown. Methods: We performed 16S rRNA gene sequencing of fecal samples collected from 41 patients with newly diagnosed DLBCL at baseline, after every two cycles of standard immunochemotherapy, during infection, and after infection recovery. Analysis of the diversity and species composition of these samples was used to evaluate the relationship between gut microbiota and bacterial infection. Results: Our findings demonstrate the dynamic changes of Enterobacteriaceae in patients with DLBCL during immunochemotherapy. The abundance of Enterobacteriaceae was markedly higher at baseline in patients who subsequently developed bacterial infection during immunochemotherapy than in those who did not (P < 0.0001), and showed a further increase during infection (P < 0.01), after recovery from the infection, the Enterobacteriaceae was significantly decreased (P < 0.001). While there was no significant change in patients who did not develop bacterial infection. The univariate and multivariate analysis showed that baseline abundance of Enterobacteriaceae > 4.5% was independently associated with post-immunochemotherapy bacterial infection. Conclusions: Our findings suggest that the gut microbiota signatures differ between patients with DLBCL who do and do not develop bacterial infection. The baseline abundance of Enterobacteriaceae is associated with the post-immunochemotherapy bacterial infection, and it has certain predictive value. Detecting the changes of gut microbiota can help predict the risk of bacterial infection after immunochemotherapy. [ABSTRACT FROM AUTHOR]