scholarly journals Impact of serum levels of IL-18 and soluble IL-2 receptor on the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP regimen

2019 ◽  
Vol 5 (9) ◽  
pp. FSO414 ◽  
Author(s):  
Hussein M Khaled ◽  
Thoraya M Abdelhamid ◽  
Fouad M Abu-Taleb ◽  
Niveen M El-Hifnawi ◽  
Ahmad B Waley
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Serum Levels ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Pretreatment Serum ◽  
Large B Cell

Aim & methods: To assess the impact of pretreatment serum levels of IL-18 and soluble IL-2 receptor (sIL-2R) on the clinical outcome of patients with diffuse large B-cell lymphoma treated with an R-CHOP protocol. Total 73 patients were included. Results: Elevated serum IL-18 (using mean as cutoff) was associated with numerically lower complete remission, and 3-year disease-free survival rates; however, the difference was not statistically significant. Nevertheless, the 3-year overall survival rates were significantly more favorable for the lower serum level group. Correspondingly, the complete remission, 3-year disease-free survival and overall survival rates for patients with low pretreatment sIL-2R levels were significantly better than individuals with higher levels. Conclusion: There is a growing body of evidence supporting the utility of pretreatment serum levels of sIL-2R and IL-18 as prognostic factors in diffuse large B-cell lymphoma patients.

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.

Pretreatment Serum Level of Osteopontin and Vascular Endothelial Growth Factor Might Have a Prognostic Value in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1609-1609
Author(s):  
Antica Duletic Nacinovic ◽  
Tajana Juranovic ◽  
Toni Valkovic ◽  
Duska Petranovic ◽  
Ivan Host ◽  
...  
Keyword(s):  
Serum Level ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Serum Levels ◽  
Large B Cell Lymphoma ◽  
Pretreatment Serum ◽  
Large B Cell

Abstract Abstract 1609 Background: Angiogenesis is gaining importance in hematological malignancies; it is regulated by a balance of various enhancing and inhibiting angiogenic factors. However, studies related to the prognostic value of angiogenic factors and aggressive Non-Hodgkin lymphomas are limited compared to solid tumors. The aim of this study was to determine pretreatment serum level of vascular endothelial growth factor (VEGF) and osteopontin (OPN) in patients with diffuse large B cell lymphoma (DLBCL) and to investigate whether these factors provide prognostic information. METHODS: We measured pretreatment serum levels of VEGF and OPN by Enzyme-Linked Immunosorbent Assay (ELISA) in 67 patients newly diagnosed as diffuse large B-cell lymphoma and in 30 healthy controls. All patients were treated with rituximab-CHOP chemotherapy. RESULTS: The serum OPN levels were found elevated in untreated DLBCL patients compared to controls: in newly diagnosed patients it ranged from 25 to 238 pg/ml; median 94.2 pg/ml while in the healthy controls it ranged from 13 to 46.5 pg/ml; median 30.0 pg/ml (P=0.00008). There were significant differences in the serum VEGF levels between DLBCL patients and controls (median 480.96 pg/ml vs. 163.8 pg/ml, P=0.001). Serum OPN levels higher than the median level were related to advanced Ann Arbor stage (P=0.026), International Prognostic Index of 2 or higher (P=0.005), ECOG III-V (P=0.004). The complete remission rate after treatment was higher in patients with low OPN serum levels than in those with high OPN serum levels (67.5% versus 32.4%, P=0.002). Elevated serum levels of OPN were strongly associated with shorter overall survival (P=0.007) and event-free survival (P=0.04). In multivariate analysis with International Prognostic Index criteria, OPN remained a significant predictor for overall survival (P=0.033). VEGF level was significantly correlated with age (P=0.01) and serum lactate dehydrogenase level (P=0.02), but not strongly correlated with other potential prognostic factors, and it failed to show prognostic significance. CONCLUSION: Our results showed that pretreatment serum level of OPN is significantly related to outcome in DLBCL patients. Ongoing extension study and additional follow-up will provide more information moving forward. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bcl-2 protein frequency in patients with high-risk diffuse large B-cell lymphoma

2010 ◽  
Vol 128 (1) ◽  
pp. 14-17 ◽  
Author(s):  
Abrahão Elias Hallack Neto ◽  
Sheila Aparecida Coelho Siqueira ◽  
Frederico Luiz Dulley ◽  
Alfredo Chauobah ◽  
Marcelo Belesso ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9%) were GCB-like and 49 (67.1%) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37%) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37% of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.

scholarly journals Effects of Concurrent Expression of Myc and Bcl-2 on the Treatment and Prognosis in Extranodal Diffuse Large B Cell Lymphoma

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 34s-34s
Author(s):  
M. Sonmez ◽  
C. Konca
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

Aim: We aimed to investigate the effects of immunohistochemical and molecular presence of double-hit lymphomas (DHL) (combined expression of myc and bcl-2) on overall and progression-free survival rates of patients with extranodal diffuse large B-cell lymphoma (DLBCL). Methods: A total of 31 patients (17 female, 14 male; mean age 57 years) with diagnosis of extranodal DLBCL were included into the study. Patients transforming from low grade B cell lymphoma, and patients with HIV positivity were not included. In a retrospective manner, patient characteristics were noted (age at diagnosis, sex, sites of extranodal involvement, stage, high-risk group, histopathological diagnosis, IPI score, LDH level at diagnosis, bone marrow involvement, and treatment modalities). Histopathological specimens underwent immunohistochemical (bcl-6, bcl-2, myc, CD10, Mum-1) and molecular (bcl-2 and myc, by means of PCR) analysis. All patients was treatment with R-CHOP protocol. Results: DHL was observed immunohistochemically in only one patient, while molecular studies found 6 cases. Three-month overall survival rates were 50% and 88% in DHL positive and negative groups, respectively. Six-month overall survival rates were 16% and 76% in DHL positive and negative groups, respectively. Progression-free 3-month survival rates were 51% and 88% in DHL positive and negative groups, respectively. Progression-free 6-month survival rates were 33% and 76% in DHL positive and negative groups, respectively. No relation with histopathological type of the disease was noted. Conclusion: We conclude that DHL presence in patients with extranodal DLBCL was an independent factor leading to shortened overall or progression-free survival.

scholarly journals Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP

Blood ◽  
2012 ◽  
Vol 120 (22) ◽  
pp. 4400-4406 ◽  
Author(s):  
Mamta Gupta ◽  
Matthew J. Maurer ◽  
Linda E. Wellik ◽  
Mark E. Law ◽  
Jing Jing Han ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Potential Marker ◽  
Germinal Center B Cell ◽  
Tnf Α ◽  
Pretreatment Serum ◽  
Large B Cell

Abstract STAT3 regulates cell growth by up-regulating downstream targets, such as Myc. The frequency of phosphorylated STAT3 (pSTAT3) and Myc expression and their prognostic relevance is unknown within diffuse large B-cell lymphoma (DLBCL) germinal center B-cell (GCB) and non-GCB subtypes. pSTAT3 and Myc were studied by immunohistochemistry (IHC) on tumors from 40 DLBCL patients uniformly treated on a clinical trial of epratuzumab/rituximab-CHOP. A total of 35% of cases were pSTAT3-positive, and pSTAT3 positivity was more frequent in the non-GCB (P = .06) type but did not correlate with event-free survival (EFS). Myc expression was observed in 50% of cases and was more frequent in non-GCB type (P = .07). Myc-positive cases had inferior EFS in all patients, including the GCB and pSTAT3-positive cases, were more likely to express Myc (P = .06). Myc translocations involving the major breakpoint regions were found in 10% (3 of 29) of cases, and all 3 cases were GCB and had an inferior EFS (P = .09). pSTAT3, but not Myc expression, was correlated with elevated pretreatment serum cytokines, such as IL-10 (P = .05), G-CSF (P = .03), and TNF-α (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway–directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients.

Lenalidomide plus R-GDP (R2-GDP) in relapsed/refractory diffuse large B-cell lymphoma: Final results of the R2-GDP-GOTEL trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8019-8019 ◽  
Author(s):  
Luis de la Cruz Merino ◽  
Alejandro Martin ◽  
Esteban Nogales Fernández ◽  
Fernando Carnicero González ◽  
Eduardo Ríos Herranz ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Induction Phase ◽  
Cell Transplant ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Immune Biomarkers ◽  
Large B Cell

8019 Background: Lenalidomide is an immunomodulatory drug that could reverse rituximab refractoriness in lymphoma patients (pts). We conducted an open label multicenter phase 2 trial testing the efficacy and toxicity of a combination of lenalidomide and rituximab (R2) plus GDP schedule (R2-GDP) in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) pts, not suitable for autologous stem cell transplant (ASCT). Methods: Patients with R/R DLBCL previously treated with at least 1 prior line of immunochemotherapy including rituximab, and not candidates for ASCT, were eligible. After a run-in phase period, treatment consisted of an induction phase with lenalidomide (LEN) 10 mg po d1-14, rituximab 375 mg/m2 iv d1, cisplatin 60 mg/m2 iv d1, gemcitabine 750 mg/m2 iv d1 and d8 and dexamethasone 20 mg d1-3, up to a maximum of 6 cycles. Pts without disease progression (DP) entered into a maintenance phase with LEN 10 mg, or last LEN dose received in the induction phase, d1-21 in cycles every 28 days. Primary endpoint was overall response rate (ORR) by investigator assessment. Secondary endpoints included disease free survival (DFS), event free survival (EFS), overall survival (OS), safety and response by cell of origin (COO), type of DLBCL (double-triple hit) and other microenvironment and genomic biomarkers. Results: 79 pts were enrolled between April 2015 and September 2018. Median age was 70 years (range 23-86), 48,7% women. 78 pts were considered for efficacy and safety in the intention to treat (ITT) analysis. With a median follow-up of 13 months at the time of cut-off (November 2019), ORRwas 59.0%, with 32.1% complete responses (CR) and 26.9% partial responses (PR). In the primary refractory population (n = 33), ORR was 45.5%, with 21.2% CR and 24.3% PR. There were no statistically significant differences in ORR with respect to COO. In Double-Hit R/R DLBCL (n = 16), ORR was 37.5% with 25% CR. Median OS was 12.0 months (6.9-17.0). Most common grade 3/4 (G3/4) adverse events were thrombocytopenia (60.2%), neutropenia (60.2%) and anemia (26.9%). Febrile neutropenia occurred in 14.1% pts. Most frequent non-hematologic G3/4 events were asthenia (19.2%), infection (15.3%) and renal insufficiency (6.4%). There were 4 toxic deaths related to the R2-GDP schedule. Conclusions: LEN with Rituximab and GDP (R2-GDP) is feasible and active in R/R DLBCL. Results in the primary refractory DLBCL population are particularly promising. Analysis of COO did not revealed differences in response rates. Immune biomarkers results will be showed at the meeting. Clinical trial information: EudraCT 2014-001620-29 .

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