The impact of Epstein-Barr virus status on primary CNS lymphoma survival.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13528-e13528
Author(s):  
Isabel P Prado ◽  
Frank Barbiero ◽  
Joachim M. Baehring ◽  
Kevin Becker ◽  
Zachary Corbin

e13528 Background: Primary CNS lymphoma (PCNSL) incidence is increasing among the elderly and immunocompromised. Especially for these vulnerable populations, a deeper understanding of the prognostic value of tumor biomarkers is necessary to recommend more targeted therapies. Our primary objective is to evaluate the predictive strength of immunohistochemical markers on PCNSL overall survival. Secondary objectives include estimating the impact of these biomarkers on event-free survival. Methods: We retrospectively analyzed PCNSL patients treated at Yale between 2000 and 2018. The primary endpoint is overall survival. Event-free survival, measured by time to relapse or death, is the secondary endpoint. Kaplan-Meier survival curves with log-log confidence intervals were used to estimate survival outcomes. Cox proportional hazards regression models were used to evaluate the statistical significance (at alpha = 0.05) of immunohistochemical markers. Results: One hundred ten subjects were analyzed. Not all biomarkers were available for every subject. The median age of the cohort is 64 years. Sixty-three patients died, and seventy-six experienced an event (progression or death). Surviving patients had a median follow-up of 4.36 years. The median overall survival is 2.63 years (95% confidence interval (CI): 1.13 to 5.98 years). Epstein-Barr virus (EBV) status by immunohistochemistry significantly impacted overall survival. Adjusting for age and immunocompromised status, EBV-positive patients had a higher risk of death than EBV-negative patients (n = 13, hazard ratio (HR) = 33.75, 95% CI: 1.61-708.68). Other significant biomarkers include the GFAP and S100 proteins. The median event-free survival is 1.13 years (95% CI: 0.66 to 2.12 years), and EBV-positive patients had an increased risk of event (HR = 38.23, 95% CI: 2.32-630.88). CD10, BCL2, BCL6, and MUM1 were not significant to predict either survival outcome. Conclusions: We describe a large cohort of PCNSL patients treated at a single institution with comparable survival outcomes to similar research yet conflicting evidence of biomarker significance. Multi-institutional studies may further clarify the prognostic role of immunohistochemistry for improved PCNSL patient survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3121-3121
Author(s):  
Alexander Claviez ◽  
Markus Tiemann ◽  
Heike Lueders ◽  
Reza Parwaresch ◽  
Guenther Schellong ◽  
...  

Abstract The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin’s lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available due to small series. 842 children and adolescents (55% male) with a median age of 13.7 years (range, 2–20) from consecutive pediatric DAL/GPOH multicenter treatment studies HD-90 and HD-95 were studied for the presence of latent EBV infection in Hodgkin and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Histology subtypes were as follows: nodular sclerosis (NSHL) 549, mixed cellularity (MCHL) 190, lymphocyte predominance (NLPHL) 90, lymphocyte depletion (LDHL) 6, lymphocyte-rich classical HL (LRCHL) 5, not specified 2. 88 patients had stage I, 470 had stage II, 172 had stage III and 112 had stage IV. B symptoms were present in 274 patients (33%). LMP status was compared with clinical parameters and established risk factors. A total of 263 patients (32%) were LMP positive. EBV infection correlated with gender (male 39% vs. female 23%; p<.001), histological subtype (MCHL 69% vs. NSHL 22% vs. NLPHL 6%; p<.001) and age (<10 years 67% vs ≥10 years 28%, p<.001. With a median follow-up of 4.9 years (0.3–12) 820 patients (97%) are alive. Probability of overall survival at 10 years (±SD) for EBV negative and positive patients was 98±1% and 95±1%, respectively (p=.017 by log-rank test). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89±2% and 84±4%, respectively (p=.86). With respect to LMP status, a negative effect of latent EBV infection on overall survival became evident only for patients treated for advanced stages (p=.003), those with nodular sclerosis subtype Bennett II (p=.02) and B symptoms (p=.05). In a multivariate regression analysis, allocation to treatment group (RR=3.7) and LMP positivity (RR=3.01) were independent factors for overall survival and presence of B symptoms (RR=2.4) for FFS. Under current highly effective polychemotherapy with or without involved field radiotherapy in pediatric HL, latent EBV infection has no influence on FFS in univariate and multivariate analysis. LMP positivity, however, seems to be associated with an inferior overall survival in some subgroups.


2017 ◽  
Vol 1 (11) ◽  
pp. 681-684 ◽  
Author(s):  
Jennifer J. G. Welch ◽  
Cindy L. Schwartz ◽  
Meghan Higman ◽  
Lu Chen ◽  
Allen Buxton ◽  
...  

Key Points EBV DNA in cell-free blood in patients with Hodgkin lymphoma correlated with the presence of virus in tumor. Persistence of EBV DNA in cell-free blood 1 week after initiation of therapy predicted inferior event-free survival.


2016 ◽  
Vol 34 (19) ◽  
pp. 2212-2220 ◽  
Author(s):  
Jan Styczynski ◽  
Gloria Tridello ◽  
Lidia Gil ◽  
Per Ljungman ◽  
Jennifer Hoek ◽  
...  

Purpose We investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Patients and Methods The study included 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT. Results Patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors (hazard ratio [HR], 1.05; 95% CI, 0.97 to 1.12; P = .23). Seropositive donors also had no influence on relapse-free survival (HR, 1.04; 95% CI, 0.97 to 1.11; P = 0.31), relapse incidence (HR, 1.03; 95% CI, 0.94 to 1.12; P = .58), and nonrelapse mortality (HR, 1.05; 95% CI, 0.94 to 1.17; P = .37). However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P < .001; HR, 1.42; 95% CI, 1.30 to 1.56). When adjusting for confounders, higher risk was identified for both acute and chronic GVHD. In seronegative patients with seropositive donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P < .001) for chronic GVHD. Seropositive patients with seronegative donors did not have an increased risk of GVHD. Conclusion Our data suggest that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT.


Neurology ◽  
1993 ◽  
Vol 43 (11) ◽  
pp. 2358-2358 ◽  
Author(s):  
R. Bashir ◽  
J. Luka ◽  
K. Cheloha ◽  
M. Chamberlain ◽  
F. Hochberg

1999 ◽  
Vol 17 (2) ◽  
pp. 554-554 ◽  
Author(s):  
A. Antinori ◽  
G. De Rossi ◽  
A. Ammassari ◽  
A. Cingolani ◽  
R. Murri ◽  
...  

PURPOSE: To determine the diagnostic capability of thallium-201 (201Tl) single-photon emission computed tomography (SPECT) combined with Epstein-Barr virus DNA (EBV-DNA) in CSF for the diagnosis of AIDS-related primary CNS lymphoma (PCNSL).PATIENTS AND METHODS: All human immunodeficiency virus (HIV)–infected patients with focal brain lesions observed between June 1996 and March 1998 underwent lumbar puncture and201Tl SPECT. Each CSF sample was tested with polymerase chain reaction (PCR) for EBV-DNA.RESULTS: Thirty-one patients were included, 13 with PCNSL and 18 with nontumor disorders. In 11 PCNSL patients, EBV-DNA was positive. Thallium-201 uptake ranged from 1.90 to 4.07 in PCNSL cases (mean, 2.77; 95% confidence interval [CI], 2.35 to 3.19) and from 0.91 to 3.38 in nontumor patients (mean, 1.62; 95% CI, 1.30 to 1.94) (P < .0002). Using a lesion/background ratio of 1.95 as cutoff, a negative SPECT was found in one PCNSL case and 16 nonneoplastic cases. A cryptococcoma and a tuberculoma showed highly increased201Tl uptake. Epstein-Barr virus DNA was never detected in nonneoplastic patients. For PCNSL diagnosis, hyperactive lesions showed 92% sensitivity and 94% negative predictive value (NPV), whereas positive EBV-DNA had 100% specificity and 100% positive predictive value. The presence of increased uptake and/or positive EBV-DNA had 100% sensitivity and 100% NPV.CONCLUSION: Combined SPECT and EBV-DNA showed a very high diagnostic accuracy for AIDS-related PCNSL. Because PCNSL likelihood is extremely high in patients with hyperactive lesions and positive EBV-DNA, brain biopsy could be avoided, and patients could promptly undergo radiotherapy or multimodal therapy. On the contrary, in patients showing hypoactive lesions with negative EBV-DNA, empiric anti-Toxoplasma therapy is indicated. In patients with discordant SPECT/PCR results, brain biopsy seems to be advisable.


Author(s):  
Xiao-Yun Li ◽  
Dong-Hua Luo ◽  
Ling Guo ◽  
Hao-Yuan Mo ◽  
Rui Sun ◽  
...  

PURPOSE Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, –4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.


2005 ◽  
Vol 9 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Aurelia Fallo ◽  
Elena De Matteo ◽  
María Victoria Preciado ◽  
María Cristina Cerqueiro ◽  
Susana Escoms ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jieti Wang ◽  
Ruochen Li ◽  
Yifan Cao ◽  
Yun Gu ◽  
Hanji Fang ◽  
...  

AbstractStudies that examined an association between CD8+T and prognosis in gastric cancer are inconsistent, and a distinct population of CXCR5+CD8+T associated with better overall survival has been reported among various malignancies. Here, we show that the abundance of intratumoral CXCR5+CD8+T cells is associated with better overall survival in patients with gastric cancer. Patients with TNM II + III gastric cancer with higher intratumoral CXCR5+CD8+T cell infiltration are more likely to benefit from adjuvant chemotherapy. Microsatellite-unstable and Epstein–Barr virus positive tumors are enriched with CXCR5+CD8+T cells. Gastric cancer infiltrating CXCR5+CD8+T cells represent a specific subtype of stem-like CD8+T with effector memory feature. Identification of the clinical significance and phenotype of gastric cancer infiltrating CXCR5+CD8+T provides a roadmap for patient stratification and trials of targeted therapies.


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