Project description:BackgroundWhile the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known about the pathological characteristics and outcome of DLBCL arising in patients with HBV infection.MethodsWe retrospectively studied a cohort of 420 patients with DLBCL for the incidence of HBV infection, and the clinicopathologic features and prognostic factors in HBsAg-positive DLBCL patients in China, a hepatitis B endemic area.ResultsIn our study, 127 (30.2%) patients were HBsAg-positive. HBsAg-positive DLBCL displayed a younger median onset age (50 vs. 54 years, P = 0.002), more frequent involvement of the spleen (19.7% vs. 6.1%, P < 0.001), less frequent involvement of the small and large intestine (2.3% vs. 11.2%, P = 0.003), more advanced disease (stage III/IV: 56.7% vs. 45.1%, P = 0.028), and lower expression rate of MYC (49.1% vs. 66.7%, P = 0.026). The median follow-up time was 61.9 months. Univariate analysis showed that there was no significant difference in overall survival (OS) between HBsAg-negative and -positive DLBCL (P = 0.577). In the HBsAg-positive DLBCL subgroup, age older than 60 years, advanced disease, elevated lactate dehydrogenase (LDH), spleen involvement, B symptoms (fever, night sweats, weight loss), and double expressers of MYC and BCL2 had a significantly worse outcome, and patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) had a better prognosis. Multivariate analysis further confirmed that spleen involvement and rituximab use were independent prognostic factors in HBsAg-positive DLBCL patients.ConclusionsOur study indicates that HBsAg-positive DLBCL has unique clinicopathological features and independent prognostic factors. Moreover, under antiviral prophylaxis, the survival of DLBCL patients with HBV infections was comparable to that of HBV-negative patients, and the use of rituximab significantly improved OS in HBsAg-positive DLBCL patients.
Project description:ObjectiveThe worldwide incidence of primary small intestinal lymphoma (PSIL) is increasing. However, little is known about the clinical and endoscopic characteristics of this disease. The aim of this study was to investigate the clinical and endoscopic data of patients with PSIL, with the goal of enhancing our understanding of the disease, improving diagnostic accuracy, and facilitating more accurate prognosis estimation.MethodsNinety-four patients diagnosed with PSIL were retrospectively studied at Qilu Hospital of Shandong University between 2012 and 2021. The clinical data, enteroscopy findings, treatment modalities, and survival times were collected and analyzed.ResultsNinety-four patients (52 males) with PSIL were included in this study. The median age of onset was 58.5 years (range: 19-80 years). Diffuse large B-cell lymphoma (n=37) was the most common pathological type. Abdominal pain (n=59) was the most frequent clinical presentation. The ileocecal region (n=32) was the most commonly affected site, and 11.7% of patients had multiple lesions. At the time of diagnosis, the majority of patients (n=68) were in stages I-II. A new endoscopic classification of PSIL was developed, including hypertrophic type, exophytic type, follicular/polypoid type, ulcerative type, and diffusion type. Surgery did not show a significant increase in overall survival; chemotherapy was the most commonly administered treatment. T-cell lymphoma, stages III-IV, "B" symptoms, and ulcerative type were associated with poor prognosis.ConclusionThis study provides a comprehensive analysis of the clinical and endoscopic features of PSIL in 94 patients. This highlights the importance of considering clinical and endoscopic characteristics for accurate diagnosis and prognosis estimation during small bowel enteroscopy. Early detection and treatment of PSIL is associated with a favorable prognosis. Our findings also suggest that certain risk factors, such as pathological type, "B" symptoms, and endoscopic type, may affect the survival of PSIL patients. These results underscore the need for careful consideration of these factors in the diagnosis and treatment of PSIL.
Project description:ObjectiveDe novo CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) has different clinical characteristics compared with CD5-negative (CD5-) DLBCL. However, few studies have been reported in Chinese cohorts. We investigated the clinical features and prognosis of patients with CD5+ DLBCL and summarized the related literature.MethodsData from 245 patients with newly diagnosed DLBCL were retrospectively assessed.ResultsThirty-one and 214 patients were diagnosed with CD5+ DLBCL or CD5- DLBCL, respectively. In the CD5+ DLBCL group, there were significantly higher proportions of patients with older age (≥60 years), International Prognostic Index (IPI) ≥3, Eastern Cooperative Oncology Group (ECOG) scores ≥ 2, bone marrow involvement, positive B-cell lymphoma 2 expression, and positive MYC expression. Survival analysis showed that CD5+ DLBCL had a markedly poorer 2-year progression-free survival than CD5- DLBCL (18.2% vs. 56.2%). Univariate analysis indicated that age ≥60 years, ECOG score ≥ 2, IPI ≥ 3, B symptoms, and no rituximab-based treatment were poor predictive factors for overall survival (OS). Multivariate analysis revealed that B symptoms and no rituximab-based treatment, but not positive CD5 expression, were independent factors for OS.ConclusionsPatients with CD5+ DLBCL had heterogeneous clinical characteristics and poor survival. The development of more targeted and effective therapies is needed.
Project description:Diffuse large B-cell lymphoma (DLBCL) patients that fail to achieve a complete metabolic response with frontline immunochemotherapy have a poor prognosis. Genomic profiling has led to a broader understanding of the molecular drivers in DLBCL, but it is unknown how well current classifiers identify patients that will experience primary treatment resistance (PTR). Using whole exome and RNA sequencing data from newly diagnosed DLBCL patients, we evaluated the genomic landscape of PTR and compared it to that of non-PTR DLBCL. We found a significant increase in the frequency of TP53 (34% vs. 15%, p = 0.005) and ARID1A mutations (21% vs. 7%, p = 0.007) in PTR cases, with pathway analysis further demonstrating a downregulation of TP53 and an increase in chromatin modifying pathways. These results suggest that TP53 and ARID1A may be key mediators of PTR and important pathways contributing to the poor outcomes. We found that the current molecular classifiers were unable to identify PTR cases at diagnosis. However, our newly identified high-risk signature identified 46% of PTR cases at diagnosis. Overall, these results contribute to our understanding of the genomic landscape of patients with primary treatment resistance.
Project description:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of large lymphoid B cell malignancy with distinct clinical and genetic features. Recently, NOTCH1 mutations were identified in DLBCL cases by Next-generation sequencing (NGS), but the clinical features and prognostic impact were not systematically studied. Here, NOTCH1 genes in 161 DLBCL samples were sequenced by NGS. The prognostic value of NOTCH1 mutations was assessed in the context of clinical and laboratory factors, such as international prognostic index (IPI), cell-of-origin classification, double expression of BCL2 and c-MYC. The combined data from three Western cohorts were used to validate these results. As a result, NOTCH1 mutations were found in 17(10.6%) patients, and three patients had a hotspot mutation of c.7541_7542delCT. The presence of NOTCH1 mutations was significantly associated with poor complete response and progression free survival(PFS), which was independent of established clinical and laboratory parameters. In addition, 30 (1.92%) of 1562 patients treated with R-CHOP regimen in those combined Western cohorts had NOTCH1 mutations. Meta-analysis of the Western cohorts confirmed that NOTCH1 mutations were also associated with poor PFS and OS. In conclusion, DLBCL patients with the NOTCH1 mutations have worse PFS and OS, and the NOTCH1 mutations can be used as an independent predictor for patients with DLBCL.
Project description:BackgroundThe influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing.MethodsThis matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures.ResultsPatients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively (P = .206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%; P = .772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14; 95% CI: 0.66-6.96; P = .206) and OS (HR: 1.26; 95% CI: 0.27-5.93; P = .772).ConclusionPatients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required.
Project description:BackgroundCo-stimulatory molecules have been shown to enhance antitumor immune responses, but their role in Diffuse Large B-cell Lymphoma (DLBCL) remains unexplored.MethodsThis study aimed to explore the molecular typing of DLBCL with co-stimulatory molecule genes and to construct a prognostic profile to improve treatment decisions and clinical outcomes.ResultsWe conducted the first comprehensive analysis of co-stimulatory molecules in DLBCL patients and identified five co-stimulatory molecule genes with prognostic and diagnostic values. Consensus cluster analysis based on these five co-stimulatory molecule genes revealed that the two identified clusters had different distribution patterns and prognostic differences. Co-stimulatory molecular correlation signatures were then constructed based on these five co-stimulatory molecular genes and validated in an external dataset, showing good performance in predicting patient prognosis. The signature is an independent risk factor for DLBCL patients and significantly correlates with clinical factors in patients and can be used as a complement to clinical factors. Furthermore, the signature was associated with the tumor immune microenvironment. Patients identified as being at high risk according to our signature exhibit high levels of immune cell infiltration microenvironment.ConclusionsIn conclusion, our signature can provide clinicians with prognostic predictions and help guide the treatment of patients with DLBCL.
Project description:ObjectiveDiffuse large B-cell lymphoma (DLBCL) is a highly aggressive malignant tumor, accounting for 30-40% of non-Hodgkin's lymphoma. Our aim was to construct novel prognostic models of candidate genes based on clinical features.MethodsRNA-seq and clinical data of DLBCL were retrieved from TCGA database. Coexpression modules were constructed by WGCNA. Then, we investigated the interactions between modules and clinical features. By overall survival analysis, prognostic candidate genes from modules of interest were identified. A coexpression network of prognostic candidate genes was then constructed through WGCNA. GEPIA was used to analyze the expression of a candidate gene between DLBCL and normal samples.Results19 coexpression modules were constructed by 12813 genes from 52 DLBCL samples. The number of genes in modules ranged from 34 to 5457. We found that the purple module was significantly related with histological type (p value = 1e-04). Overall survival analysis revealed that MAFA-AS1, hsa-mir-338, and hsa-mir-891a were related with prognosis of DLBCL (p value = 0.027, 0.039, and 0.022, respectively). A coexpression network was constructed for the three prognostic genes. MAFA-AS1 was interacted with 36 genes, hsa-mir-891a was interacted with 11 genes, while no gene showed interaction with hsa-mir-338. Using GEPIA, we found that MAFA-AS1 showed low expression in DLBCL samples (p < 0.01).ConclusionWe constructed a coexpression module related with histological type and identified three candidate genes (MAFA-AS1, hsa-mir-338, and hsa-mir-891a) that possessed potential value as prognostic biomarkers and therapeutic targets of DLBCL.
Project description:The biology and clinical impact of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear in the rituximab era. We retrospectively analyzed 232 patients diagnosed with DLBCL at our center between 1999 and 2014. Concordant-presence of large cells similar to those of the lymph node biopsy- and discordant-infiltration by small cells forming lymphoid aggregates, lacking cytological atypia-BM infiltration was defined by histological criteria and further characterized by flow cytometry (FCM). Cell of origin (COO) was determined using Hans' algorithm. For the clonal relationship between tumor and discordant BM, the VDJH rearrangement was analyzed. Survival analyses were restricted to 189 patients treated with rituximab and chemotherapy. Thirty-six (16%) had concordant, and 37 (16%) discordant BM infiltration. FCM described different indolent lymphomas among discordant cases, clonally related with DLBCL in 10/13 available samples. Median follow-up was 58 months. 5-year-progression-free survival (PFS) for non-infiltrated, discordant and concordant groups was 68%, 65% and 30%, respectively (p < 0.001). Combining COO and BM infiltration, patients with discordant BM and non-germinal center B-cell COO also had decreased 5-year-PFS (41.9%). In multivariate analysis, concordant BM had an independent effect on PFS (HR 2.5, p = 0.01). Five-year cumulative incidence of central nervous system (CNS) relapse was 21%, 4% and 1% in concordant, discordant and non-infiltrated groups, respectively (p < 0.001). In conclusion, concordant BM infiltration represents a subset with poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to non-CGB cases.
Project description:A number of studies suggest an association between miRNAs and diffuse large B-cell lymphoma (DLBCL). The present study aimed to investigate the prognostic value of microRNA (miR-150) in primary gastrointestinal (PGI)-DLBCL, by assessing the association between miR-150 expression and clinicopathological characteristics in patients with PGI-DLBCL. A total of 84 patients diagnosed with PGI-DLBCL were recruited and both tumor and adjacent non-tumor tissue samples were collected. miR-150 expression was assessed via reverse transcription-quantitative (RT-q)PCR analysis. The results demonstrated that miR-150 expression was significantly lower in PGI-DLBCL tissues compared with adjacent non-tumor tissues. Furthermore, receiver operating characteristic (ROC) curve analysis indicated that the optimal cut-off value of miR-150 for predicting survival was 8.965 with high sensitivity (79.8%) and specificity (77.1%). Patients were divided into two groups according to this cut-off value, as follows: High (n=18) and low expression (n=66) groups. Low miR-150 expression was significantly associated with clinical stage, International Prognostic Index (IPI), Eastern Cooperative Oncology Group status and use of rituximab. RT-qPCR analysis demonstrated that miR-150 expression was significantly lower in patients with high IPI scores compared with patients with low IPI scores. Downregulated miR-150 expression was significantly associated with shorter overall survival (OS) time and progression-free survival (PFS) time in patients with PGI-DLBCL. Furthermore, miR-150 level and IPI score were identified as two risk factors for OS and PFS. The diagnostic value of miR-150 was evaluated via ROC curve analysis, with an area under the curve value of 0.882. Taken together, the results of the present study suggest that miR-150 is a potential diagnostic marker of PGI-DLBCL, and may also serve as a useful prognostic factor for survival outcomes in patients with PGI-DLBCL.