scholarly journals A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9658
Author(s):  
Hao Zhou ◽  
Chang Zheng ◽  
De-Sheng Huang
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Immune Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Penalized Regression ◽  
Gene Set Enrichment Analysis ◽  
Validation Dataset ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background Immune cells in the tumor microenvironment are an important prognostic indicator in diffuse large B-cell lymphoma (DLBCL). However, information on the heterogeneity and risk stratification of these cells is limited. We sought to develop a novel immune model to evaluate the prognostic intra-tumoral immune landscape of patients with DLBCL. Methods The ESTIMATE and CIBERSORT algorithms were used to estimate the numbers of 22 infiltrating immune cells based on the gene expression profiles of 229 patients with DLBCL who were recruited from a public database. The least absolute shrinkage and selection operator (Lasso) penalized regression analyses and nomogram model were used to construct and evaluate the prognostic immunoscore (PIS) model for overall survival prediction. An immune gene prognostic score (IGPS) was generated by Gene Set Enrichment Analysis (GSEA) and Cox regression analysis was and validated in an independent NCBI GEO dataset (GSE10846). Results A higher proportion of activated natural killer cells was associated with a poor outcome. A total of five immune cells were selected in the Lasso model and DLBCL patients with high PIS showed a poor prognosis (hazard ratio (HR) 2.16; 95% CI [1.33–3.50]; P = 0.002). Differences in immunoscores and their related outcomes were attributed to eight specific immune genes involved in the cytokine–cytokine receptor interaction and chemokine signaling pathways. The IGPS based on a weighted formula of eight genes is an independent prognostic factor (HR: 2.14, 95% CI [1.40–3.28]), with high specificity and sensitivity in the validation dataset. Conclusions Our findings showed that a PIS model based on immune cells is associated with the prognosis of DLBCL. We developed a novel immune-related gene-signature model associated with the PIS model and enhanced the prognostic functionality for the prediction of overall survival in patients with DLBCL.

scholarly journals Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients

Blood ◽  
2013 ◽  
Vol 122 (19) ◽  
pp. 3251-3262 ◽  
Author(s):  
Stefan K. Barta ◽  
Xiaonan Xue ◽  
Dan Wang ◽  
Roni Tamari ◽  
Jeannette Y. Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Pooled Analysis ◽  
Factors Affecting ◽  
Large B Cell Lymphoma ◽  
Key Points ◽  
Large B Cell

Key Points Rituximab use is associated with significant improvement in all outcomes for patients with HIV-associated CD20-positive lymphomas. Infusional EPOCH chemotherapy is associated with better overall survival in patients with AIDS-related diffuse large B-cell lymphoma (DLBCL).

scholarly journals miR-199a and miR-497 Are Associated with Better Overall Survival due to Increased Chemosensitivity in Diffuse Large B-Cell Lymphoma Patients

2015 ◽  
Vol 16 (8) ◽  
pp. 18077-18095 ◽  
Author(s):  
Katharina Troppan ◽  
Kerstin Wenzl ◽  
Martin Pichler ◽  
Beata Pursche ◽  
Daniela Schwarzenbacher ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma

2020 ◽  
Author(s):  
Hsu-Chih Chien ◽  
Deborah Morreall ◽  
Vikas Patil ◽  
Kelli M Rasmussen ◽  
Chunyang Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Line Treatment ◽  
Electronic Health Record Data ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000–2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan–Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.

scholarly journals Inflammatory Cells in Diffuse Large B Cell Lymphoma

2020 ◽  
Vol 9 (8) ◽  
pp. 2418
Author(s):  
Roberto Tamma ◽  
Girolamo Ranieri ◽  
Giuseppe Ingravallo ◽  
Tiziana Annese ◽  
Angela Oranger ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B cell lymphoma (DLBCL), known as the most common non-Hodgkin lymphoma (NHL) subtype, is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME), in which the tumor cells reside, is crucial in the regulation of tumor initiation, progression, and metastasis, but it also has profound effects on therapeutic efficacy. The role of immune cells during DLBCL development is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators and structural components present in the tumor microenvironment. Different immune cells are recruited into the tumor microenvironment and exert distinct effects on tumor progression and therapeutic outcomes. In this review, we focused on the role of macrophages, Neutrophils, T cells, natural killer cells and dendritic cells in the DLBCL microenvironment and their implication as target for DLBCL treatment. These new therapies, carried out by the induction of adaptive immunity through vaccination or passive of immunologic effectors delivery, enhance the ability of the immune system to react against the tumor antigens inducing the destruction of tumor cells.

scholarly journals Antiviral therapy improves overall survival in hepatitis C virus-infected patients who develop diffuse large B-cell lymphoma

2016 ◽  
Vol 139 (11) ◽  
pp. 2519-2528 ◽  
Author(s):  
Jeff Hosry ◽  
Parag Mahale ◽  
Francesco Turturro ◽  
Roberto N. Miranda ◽  
Minas P. Economides ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Antiviral Therapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Survival of Limited Stage Peripheral T-Cell Lymphoma Is Similar To Diffuse Large B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2817-2817 ◽  
Author(s):  
Kerry J. Savage ◽  
Mukesh Chhanabhai ◽  
Nicholas Voss ◽  
Shenkier Tamara ◽  
Randy D. Gascoyne ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Limited Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of diseases with an overall poor prognosis. Little information is available regarding the outcome of PTCL patients who present with limited stage disease. We sought to determine the outcome of PTCL patients presenting with limited disease in comparison with a cohort of patients with limited stage diffuse large B-cell lymphoma (DLBCL). Methods: In a retrospective analysis we identified all patients with limited stage (non-bulky (<10cm) stage I/II disease no symptoms) PTCL diagnosed at the British Columbia Cancer Agency (BCCA) between 1983 and 2004. Patients were excluded if they had cutaneous anaplastic large cell lymphoma (CutALCL) (n=13), NK/T-cell lymphoma nasal type (n=9) or primary CNS/ocular involvement (n=6). Results: Thirty-seven patients with PTCL were identified according to the World Health Organization Classification: ALK-neg ALCL 8 (22%); PTCL-unspecified (PTCLUS) 28 (78%); enteropathy associated TCL (EATL) 1 (3 %). The majority received CHOP-type chemotherapy (n=31, 86%), most with brief chemotherapy followed by involved-field radiation (n=19, 61%). The 5 y OS and PFS was similar between PTCLUS and ALK-neg ALCL. There was no difference in survival between extranodal and nodal cases. The outcome of PTCL patients (including ALK-neg ALCL and PTCLUS) was compared to a cohort of limited stage DLBCL patients (excluding CNS/ocular lymphoma) (n=305) diagnosed over the same time period and treated similarly. There was no difference in 5 y OS or PFS (Figure 1,2). Interestingly, there were no late relapses observed in PTCLUS, in marked contrast to DLBCL. Conclusions: Limited stage PTCL is rare, however outcomes appear to be comparable to early stage DLBCL, supporting that they should be treated in a similar manner. Unlike limited stage DLBCL where late relapses occur, a plateau in the progression-free survival curve is observed, highlighting a distinct natural history for limited stage PTCL. Overall Survival Limited Stage PTCL vs DLBCL p=.18 Overall Survival Limited Stage PTCL vs DLBCL p=.18 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07

Significance of c-myc Rearrangements in Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2030-2030
Author(s):  
Philip Bierman ◽  
Fausto Loberiza ◽  
Bhavana Dave ◽  
Warren Sanger ◽  
R. Gregory Bociek ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Overall Survival Rates

Abstract Rearrangements of the c-myc oncogene can be seen in 5–10% of patients with diffuse large B-cell lymphoma. However, studies examining the significance of this finding have yielded conflicting results. Therefore, we performed a retrospective analysis to determine the clinical significance of c-myc rearrangements in diffuse large B-cell lymphoma. The results of classical cytogenetic studies and FISH analyses were used to identify diffuse large B-cell lymphoma cases in the database of the Nebraska Lymphoma Study Group with or without c-myc rearrangements. Patients who were HIV positive and those with post-transplant lymphoproliferative disease were excluded. We identified 16 patients with diffuse large B-cell lymphoma and c-myc rearrangements. All patients were initially treated with doxorubicin- or mitoxantrone-containing chemotherapy regimens. The median age of these 16 patients was 61 years (range 40 to 80), and 5 (31%) were males. The International Prognostic Index (IPI) was 0–2 at diagnosis in 9 patients (56%), and 3–5 in 7 patients (44%). Eleven patients (69%) had bulky disease (≥ 5 cm) at diagnosis. No significant differences in outcome were identified when the 16 c-myc positive patients were compared with 97 c-myc negative diffuse large B-cell lymphoma patients in the same age range. The actuarial 5-year progression-free survival for the c-myc positive patients was 23% (95% CI 6% to 46%), as compared with 38% (95% CI 29% to 48%) for c-myc negative patients (p=0.17). The actuarial 5-year overall survival rates were 36% (95% CI 14% to 59%) and 47% (95% CI 36% to 56%), respectively (p=0.19). Classical cytogenetics and FISH analyses were also used to examine the 16 c-myc positive cases for bcl-2 rearrangements. Eight (50%) cases had rearrangements of bcl-2 in addition to c-myc rearrangements. These patients were similar to the c-myc positive/bcl-2 negative patients except for a higher likelihood of an elevated LDH level at diagnosis (88% vs. 25%; p=0.03). The actuarial 5-year progression-free survival for c-myc positive/bcl-2 positive patients was 0%, as compared to 33% (95% CI 6% to 66%) for patients with rearrangements of c-myc alone, and 37% (95% CI 28% to 47%) for c-myc negative patients. The actuarial 5-year overall survival rates were 12% (95% CI 1% to 42%), 47% (95% CI 12% to 76%), and 41% (95% CI 31% to 51%), respectively. A multivariate analysis, adjusting for IPI score, demonstrated that the relative risk (RR) of treatment failure was significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.86, 95% CI 1.32–6.23; p=0.008). Similarly, mortality was also significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.69, 95% CI 1.18–6.11; p=0.02). In contrast, no significant differences in treatment failure or overall survival were demonstrated when c-myc positive/bcl-2 negative patients were compared with c-myc negative patients. Our results demonstrate that the c-myc rearrangement is not associated with poorer survival in patients with diffuse large B-cell lymphoma. However, patients with rearrangements of bcl-2 in addition to c-myc had significantly worse progression-free survival and overall survival.

Outcome of Diffuse Large B Cell Lymphoma in the VA System: The Rituximab Era.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4729-4729
Author(s):  
Rami S. Komrokji ◽  
Sanjay Maraboyina ◽  
Rami Y. Haddad ◽  
Zeina A. Nahleh ◽  
Malek M. Safa
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Wilcoxon Test ◽  
P Value ◽  
Medical Centers ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Addition of rituximab to chemotherapy in patients with diffuse large B cell Lymphoma (DLBCL) has been shown to improve survival in several recent clinical studies. A study from British Columbia confirmed those results in a population-based cohort. No similar population based studies were conducted in the USA. Our study aims to address outcome of DLBCL in the era of rituximab in the VA health system. Methods: This was a retrospective analysis. The VA Central Cancer Registry (VACCR) database was used to identify patients with DLBCL diagnosed between 1995 and 2005. There are approximately 120 VA medical centers diagnosing and/or treating patients with cancer. The VACCR aggregates the data collected by the medical centers’ cancer registries. Data were extrapolated and analyzed using bio-statistical software SPSS. Variables included age, sex, stage of disease, histology subtype, date of diagnosis, date of last contact, date of relapse, vital status, whether patients received chemotherapy and or radiation. Use of rituximab was not specifically recorded in the registry. Due to that we divided the patients into two groups, patients diagnosed with DLBCL before 2001 (pre rituximab era group) and patients diagnosed after 2001 (rituximab era group). The initial results of rituximab in DLBCL were presented in 2000 and published in January 2002. Independent t test was used for comparing continuous variables and chi square test for categorical variables. Wilcoxon test was used to compare survival among the two groups. Results: There were 2792 patients with DLBCL at the VACCR between 1995 and 2005, 1772 patients in pre rituximab era and 1020 patients in the rituximab era. The mean age at diagnosis was to 64 in pre rituximab group and 66 in rituximab group (P-value 0.015). Race distribution was similar between the two groups. More patients were diagnosed at advanced stage (stage III and IV) 61 % in rituximab group compared to 57% in pre rituximab group (P-value &lt;0.005), IPI score data were not available. More patients in pre rituximab era did not receive multi-agent chemotherapy 28% versus 22% (P-value &lt; 0.005). More patients received radiation 21 % in pre rituximab group compared to 16% in rituximab era group (P-value &lt; 0.005). The 5-year overall survival was 26% in pre rituximab era and 36% after rituximab (P-value 0.0025). Using Cox regression multivariable analysis age, use of mutli-agent chemotherapy, radiation and whether patients were diagnosed and treated before or after 2001 were statistically significant independent variables affecting survival. Conclusions: Overall survival of DLBCL in VA patients had improved in the rituximab era. The magnitude of improvement observed in this study is similar to what was described in previous studies. Other factors contributing to improvement in outcomes such as supportive care could not be differentiated in this study. This is a population-based study suggesting improvement in survival in DLBCL in the rituximab era.

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