scholarly journals A Systemic Protein Deviation Score Linked to PD-1+ CD8+ T Cell Expansion That Predicts Overall Survival in Diffuse Large B Cell Lymphoma

Med ◽  
2020 ◽  
Author(s):  
Eivind Heggernes Ask ◽  
Astrid Tschan-Plessl ◽  
Thea Johanne Gjerdingen ◽  
Michelle Lu Sætersmoen ◽  
Hanna Julie Hoel ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Cell Expansion ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cd8 T Cell ◽  
Deviation Score ◽  
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

scholarly journals Elevated LDH greater than 400 U/L portends poorer overall survival in diffuse large B-cell lymphoma patients treated with CD19 CAR-T cell therapy in a real world multi-ethnic cohort

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Emma Rabinovich ◽  
Kith Pradhan ◽  
R. Alejandro Sica ◽  
Lizamarie Bachier-Rodriguez ◽  
Ioannis Mantzaris ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lactate Dehydrogenase ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
A Value ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractAnti-CD19 chimeric antigen receptor T-cell therapies have shown striking clinical activity in diffuse large B-cell lymphoma but robust biomarkers predictive of responsiveness are still needed. We treated a multi-ethnic cohort of 31 diffuse large B-cell lymphoma patients with axicabtagene ciloleucel with an overall response rate of 71%. Analysis of various biomarkers identified a significant decrease in overall survival with elevated lactate dehydrogenase, measured both at time of cell infusion and before lymphodepletion. Lactate dehydrogenase was prognostic in a multivariate analysis [HR = 1.47 (1.1–2.0)] and a value of 400 U/L at time of infusion and a value of 440 U/L before lymphodepletion provided the best prognostic cutoffs for overall survival in our cohort. These data demonstrate efficacy of anti-CD19 chimeric antigen receptor T-cell therapy in a diverse inner city population and demonstrate novel lactate dehydrogenase cutoffs as prognostic biomarkers.

scholarly journals Distinct Molecular Subtypes of Diffuse Large B Cell Lymphoma Patients Treated with Rituximab-CHOP Are Associated with Different Clinical Outcomes and Molecular Mechanisms

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Haifeng Yu ◽  
Shuailing Peng ◽  
Shuiyun Han ◽  
Xi Chen ◽  
Qinghua Lyu ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Molecular Mechanisms ◽  
Molecular Subtypes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Training Set ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Objective. Our purpose was to characterize distinct molecular subtypes of diffuse large B cell lymphoma (DLBCL) patients treated with rituximab-CHOP (R-CHOP). Methods. Two gene expression datasets of R-CHOP-treated DLBCL patients were downloaded from GSE10846 ( n = 233 , training set) and GSE31312 ( n = 470 , validation set) datasets. Cluster analysis was presented via the ConsensusClusterPlus package in R. Using the limma package, differential expression analysis was utilized to identify feature genes. Kaplan-Meier survival analysis was presented to compare the differences in the prognosis between distinct molecular subtypes. Correlation between molecular subtypes and clinical features was analyzed. Based on the sets of highly expressed genes, biological functions were explored by gene set enrichment analysis (GSEA). Several feature genes were validated in the molecular subtypes via qRT-PCR and western blot. Results. DLBCL samples were clustered into two molecular subtypes. Samples in subtype I displayed poorer overall survival time in the training set ( p < 0.0001 ). Consistently, patients in subtype I had shorter overall survival ( p = 0.0041 ) and progression-free survival time ( p < 0.0001 ) than those in subtype II. Older age, higher stage, and higher international prognostic index (IPI) were found in subtype I. In subtype I, T cell activation, lymphocyte activation, and immune response were distinctly enriched, while cell adhesion, migration, and motility were significantly enriched in subtype II. T cell exhaustion-related genes including TIM3 ( p < 0.001 ), PD-L1 ( p < 0.0001 ), LAG3 ( p < 0.0001 ), CD160 ( p < 0.001 ), and CD244 ( p < 0.001 ) were significantly highly expressed in subtype I than subtype II. Conclusion. Two molecular subtypes were constructed in DLBCL, which were characterized by different clinical outcomes and molecular mechanisms. Our findings may offer a novel insight into risk stratification and prognosis prediction for DLBCL patients.

Cutaneous Lymphomas: Single Institution Experience in Lima-Peru.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4619-4619
Author(s):  
Brady E. Beltrán-Gárate ◽  
José Malaga ◽  
Karen Portugal ◽  
Domingo Morales ◽  
Luis Riva ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
General Hospital ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Cutaneous Lymphomas ◽  
Large B Cell

Abstract Background: The clinicopathologic characteristics of malignant lymphomas may vary according to geography. We previously described Adult T -cell leukaemia/lymphoma (ATLL) cases associated with human T-cell lymphotropic virus type-I (HTLV-I) in their different clinical presentation: acute, lymphomatous, chronic and smoldering and the recently primary cutaneous subtype in Peru (EHA2001: abstract 129). The aim of this study is to determine the relative frequency of cutaneous lymphomas and evaluate the clinical relevance of the new WHO/EORTC classification in a General Hospital in Lima-Peru Methods: We conducted a clinicopathologic retrospective study of primary cutaneous lymphomas diagnosed from 1997 to 2004 in our General Hospital. Clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from 78 patients were reviewed. HTLV-1 serology was made using ELISA and Western Blot method. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: The mean age at time of presentation was 62 years and the female/male ratio 1,5:1. T-cell lymphomas were 88.6% and 11.4% were B-cell lymphomas. Eight-six percent (67/78) were primary cutaneous lymphomas and fourteen percent (11/78) were secondary cutaneous lymphomas. The most frequent primary cutaneous lymphomas was mycosis fungoides (MF): 44.7% (30/67); cutaneous / smoldering ATLL sutypes included 13/67 (19.4%) patients; unspecified peripheral T-cell lymphoma 4/67 (6%), lymphomatoid papulosis 2/67 (3%), leg-type diffuse large B-cell lymphoma 2/67 (3%), diffuse large B-cell lymphoma 2/67 (3%), subcutaneous panniculitis-like T-cell lymphoma 2/67 (3%), one case of the following lymphomas: anaplastic large cell, Sézary syndrome, nasal type extranodal NK/T-cell lymphoma, marginal zone B-cell lymphoma, follicle center lymphoma and intravascular lymphoma; finally unclassifiable lymphomas 5/67 (7.4%). Most frequent secondary cutaneous lymphomas were acute and lymphomatous subtypes of ATLL with 72% of the cases. Five-years overall survival for MF was 77%. The 5-years overall survival for primary cutaneous ATLL lymphomas was 18% and 0% for the secondary cutaneous ATLL group. Conclusions: In this retrospective analysis, both ATLL and MF are the most frequent cutaneous lymphomas in our General Hospital. ATLL has a poor overall survival.

The density of CD8+ T-cell infiltration and expression of BCL2 predicts outcome of primary diffuse large B-cell lymphoma of bone

2013 ◽  
Vol 464 (2) ◽  
pp. 229-239 ◽  
Author(s):  
Hajnalka Rajnai ◽  
Fenna H. Heyning ◽  
Lianne Koens ◽  
Anna Sebestyén ◽  
Hajnalka Andrikovics ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cd8 T Cell ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium

2020 ◽  
Vol 38 (27) ◽  
pp. 3119-3128 ◽  
Author(s):  
Loretta J. Nastoupil ◽  
Michael D. Jain ◽  
Lei Feng ◽  
Jay Y. Spiegel ◽  
Armin Ghobadi ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Complete Response ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Large B Cell

PURPOSE Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication. PATIENTS AND METHODS Data were collected retrospectively from all patients with relapsed/refractory LBCL who underwent leukapheresis as of September 30, 2018, at 17 US institutions with the intent to receive SOC axi-cel. Toxicities were graded and managed according to each institution’s guidelines. Responses were assessed as per Lugano 2014 classification. RESULTS Of 298 patients who underwent leukapheresis, 275 (92%) received axi-cel therapy. Compared with the registrational ZUMA-1 trial, 129 patients (43%) in this SOC study would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis. Among the axi-cel–treated patients, grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 7% and 31%, respectively. Nonrelapse mortality was 4.4%. Best overall and complete response rates in infused patients were 82% (95% CI, 77% to 86%) and 64% (95% CI, 58% to 69%), respectively. At a median follow-up of 12.9 months from the time of CAR T-cell infusion, median progression-free survival was 8.3 months (95% CI, 6.0 to15.1 months), and median overall survival was not reached. Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 and elevated lactate dehydrogenase had shorter progression-free and overall survival on univariable and multivariable analysis. CONCLUSION The safety and efficacy of axi-cel in the SOC setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.

scholarly journals MiRNA-340-5p mediates the functional and infiltrative promotion of tumor-infiltrating CD8+ T lymphocytes in human diffuse large B cell lymphoma

2020 ◽  
Author(s):  
Yangyang Xu ◽  
Zhenchuan Liu ◽  
Lixin Lv ◽  
Ping Li ◽  
Bing Xiu ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cd8 T Cell ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: CD8+ tumor-infiltrating T lymphocytes (T-TILs) in the tumor microenvironment (TME) play an important role in tumor development, and miRNAs regulate tumor cell interactions with the microenvironment. T-TIL-based tumor immunotherapy provides a promising treatment strategy in diffuse large B-cell lymphoma (DLBCL). MiRNAs tend to be attractive targets for novel antitumor interventions. Methods: Weighted gene coexpression network analysis (WGCNA), CIBERSORT analysis and Cox regression analysis were used to identify CD8+ T-TIL-related miRNAs. RT-PCR, western blotting, immunohistochemistry (IHC), in situ hybridization (ISH), luciferase reporter assay, coimmunoprecipitation and ubiquitination analyses were used to detect miRNA, mRNA and protein expression and their combination. The viability and function of CD8+ T cells after stimulation were evaluated by enzyme-linked immunosorbent assay (ELISA), cytotoxicity assay, functional avidity assessment, flow cytometry and Cell Counting Kit-8 (CCK-8) assay. DLBCL cell lines, primary cells and a murine xenograft model established with A20 cell injection were used as in vitro and in vivo experimental models. Results: MiR-340-5p was positively correlated with CD8+ T-TILs in DLBCL patients, and KMT5A was a direct target gene of miR-340-5p. CD8+ T-cell function was significantly enhanced by miR-340-5p mimics both in vitro and in vivo, which was reversed by KMT5A overexpression. We demonstrated that COP1/CD73 was involved in the downstream mechanism of the miR-340-5p/KMT5A axis involving ubiquitination. In vivo, we validated an improved CD8+ T-TIL infiltration rate and tumor suppression with miR-340-5p treatment. Furthermore, miR-340-5p directly regulated the biological activity of DLBCL cells without CD8+ T-cell participation. Conclusions: MiR-340-5p promoted CD8+ T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.

Sign in / Sign up

Export Citation Format

Share Document