Expression of the c-Met Oncogene Correlates with Favorable Progression Free Survival In Classical Hodgkin Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3880-3880
Author(s):  
Chuanhui Xu ◽  
Anke Van Den Berg ◽  
Wouter Plattel ◽  
Nele Ruther ◽  
Huang Xin ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Line ◽  
Hodgkin Lymphoma ◽  
Signaling Pathway ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Free Survival

Abstract Abstract 3880 Background The HGF/c-Met signaling pathway regulates a variety of biological processes, including proliferation, survival and migration. Aberrant c-Met activation has been implicated in the pathogenesis of many human cancers. Furthermore, c-Met is of prognostic significance in several types of cancer such as diffuse large B cell lymphoma, bladder cancer, breast cancer, colorectal cancer and ovarian cancer. Expression of c-Met in Hodgkin lymphoma (HL) patients, as well as increased levels of HGF in the urine of HL patients has been reported, but no prognostic studies or functional data have been reported. Methods We studied the prognostic significance of c-Met expression by immunohistochemistry on paraffin sections of classical HL (cHL) patients from two independent patient cohorts. Functional studies were performed on HL cell line L428 that showed high c-Met levels, constitutive phosphorylated c-Met and no HGF expression. The effect of stimulation by HGF and inhibition by c-Met kinase inhibitor SU11274 was investigated by Western blot, cell proliferation and cell cycle progression analysis. Results Expression of c-Met was detected in Hodgkin Reed-Sternberg (HRS) cells in 52% (79/152) of primary cHL tissue samples and expression of its ligand, hepatocyte growth factor (HGF), was detected in HRS cells in 8% (10/120) of the cHL patients. Co-expression of HGF and c-Met in HRS cells was observed in only 3% (4/120) of cHL patients. A variable percentage of infiltrating cells stained positive for HGF, supporting a predominant paracrine activation route. In contrast to its adverse prognostic impact in other cancers, high c-Met expression significantly correlated with favorable 5 year progression free survival in both patient cohorts. To explain these unexpected findings we studied the c-Met/HGF signaling pathway in the L428 cHL cell line. The levels of phosphorylated c-Met, Akt, and Erk1/2 were upregulated upon HGF stimulation and this induction could be blocked by inhibiting c-Met activation with SU11274. Activation with HGF did not effect cell growth, while SU11274 alone suppressed cell growth. SU11274, as well as inhibitors of PI3K, MEK1/2 and Erk1/2 (downstream targets of the HGF/c-Met signaling pathway) induced G2/M cycle arrest. Conclusion Expression of c-Met in tumor cells was observed in 52% of cHL patients. In contrast to its prognostic value in other cancers, expression of c-Met in HRS cells of cHL patients correlated with favorable prognosis in two independent cohorts. Although triggering of c-Met in L428 cells with HGF induced activation of its downstream factors, no effect was observed on proliferation. Remarkably, the c-Met inhibitor did suppress cell growth of L428 cells. Disclosures: No relevant conflicts of interest to declare.

Coexpression of MYC and BCL-2 Predicts Inferior Survival in Pgi-DLBCL Treated with CHOP-like Regimen/Rituximab

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5404-5404 ◽  
Author(s):  
Le Zhang ◽  
Bing Xia ◽  
Shanqi Guo ◽  
Xiaowu Li ◽  
Fulian Qu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Chemotherapy Response ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Expression Levels ◽  
Stage Disease

Abstract MYC protein expression has been identified to be associated with inferior overall survival (OS) and progression-free survival (PFS) when coexpressed with BCL-2 protein in patients with diffuse large B cell lymphoma (DLBCL). But the concurrent expression of MYC and BCL-2 proteins in primary gastrointestinal (PGI)-DLBCL has not been clearly understood. Here, we investigated whether this coexpression has prognostic significance in PGI-DLBCL patients and explored its associations with patients’ clinical parameters. We enrolled 60 PGI-DLBCL patients and 30 age- and sex-matched healthy controls. Expression levels of MYC and BCL-2 were detected from both protein and mRNA levels by immunohistochemistry and real-time RT-PCR. Positive expression levels of MYC and BCL-2 proteins were detected in 35% and 45% of patients, respectively. MYC+/BCL-2+ protein was present in 30% of patients. MYC and BCL-2 protein were correlated with high MYC and BCL-2 mRNA expression, respectively (both p<0.05). We found that patients with advanced-stage disease (at IIE-IV) having higher MYC and BCL-2 coexpression levels (p<0.05). In addition, MYC+/BCL-2+ patients had more difficulty achieving complete remission than others (p<0.05). Presence of MYC protein expression only affected OS and PFS when BCL-2 protein was coexpressed. The adverse prognostic impact of MYC+/BCL-2+ protein on PFS remained significant (p<0.05) even after adjusting for age, Lugano stage, IPI, and BCL-2 protein expression in a multivariable model. MYC+/BCL-2+ patients have poorer chemotherapy response and poorer prognosis than patients who only express one of the two proteins, suggesting that assessment of MYC and BCL-2 expression by immunohistochemistry has clinical significance in predicting prognosis of PGI-DLBCL patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Overexpression of the OCT-1 Gene Is a Biomarker Associated with Poor Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) - Data from a Retrospective Cohort from Latin America: Defining a Very High-Risk Clinical-Molecular Subgroup

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Gisele Rodrigues Gouveia ◽  
Suzete Cleusa Ferreira ◽  
Sheila Aparecida Coelho de Siqueira ◽  
Abrahão Elias Hallack Neto ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
B Cell ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Molecular Subgroup ◽  
Free Survival ◽  
Very High

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy, representing 30-40% of all non-Hodgkin's lymphomas (NHLs). They comprise a group of aggressive and heterogeneous neoplasms in terms of clinical presentation, response to therapy and prognosis. The OCT-1 gene is a member of the homodomain-POU family of transcriptional regulators of B-lymphoid differentiation. OCT-1 acts by controlling the expression of specific B-cell genes, such as BCL-2, a potent inhibitor of apoptosis that is essential for the differentiation of B-cells in the germinal center. These genes can be expressed in DLBCL, but the role of BCL-2 in its prognosis has been contradictory and the prognostic impact of the OCT-1 gene has not yet been tested in this lymphoma. Methods: In this observational, retrospective, single-center study, we investigated the prognostic impact of BCL-2 and OCT-1 gene expression in Brazilian patients with DLCBL treated with immunopolychemotherapy R-CHOP in a real-world context. The BCL-2 and OCT-1 genes were assessed in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR (qRT-PCR) was isolated from formalin-fixed and paraffin-embedded (FFPE) samples. The values obtained for gene expression were transformed into categorical variables according to their medians (6.27 for BCL-2 and 24.5 for OCT-1). The association between clinical and laboratory variables and results of gene expression was verified by the Fischer test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate analysis was performed using Cox's bivariate regression method and multivariate analysis using Cox multiple regression methodology. Results: The median age of the cohort was 54.5 years (15-84), 50% (49/98) were male, 49.4% (38/77) and 51.4% (40/77) showed expression of OCT-1 and BCL- 2 ≥ median, respectively. The clinical characteristics of the 98 Brazilian patients with DLBCL that comprised our cohort are summarized in Table 1. The overall response rate (ORR) in all patients was 68.4% (67/98), 65.3% (64/98) showed a complete response (CR), and 3.1% (3/98) showed partial response (PR), while 6.1% (6/98) were primary refractory. With a median follow-up of 3.77 years (95% CI: 3.2-4.1), the median overall survival (OS) was 5.43 years (95% CI: 2.2-NR) and the median progression-free survival (PFS) was 5.15 years (95% CI: 2.9-NR). The 5-year OS and PFS was 54.2% (42.2% -64.8%) and 52.0% (40.1-62.6%), respectively. In the univariate analysis OCT-1 ≥ median was associated with shortened OS (HR: 2.45, 95% CI: 1.21-4.96, p = 0.013) and PFS (HR: 2.27, 95% CI: 1.14-4.51, p = 0.019). Overexpression of BCL-2 was associated with worse PFS (HR: 2.00, 95% CI: 1.02-3.95, p = 0.043). Subgroup analysis showed that OCT-1 overexpression predominated in elderly individuals (≥ 60 years) in a statistically significant mode (29/38 cases - 76.3%, p = 0.029). It was also observed that overexpression of OCT-1 was associated with worse OS in the high-risk adjusted International Prognostic Index (aIPI) subgroup (p = 0.048) - Figure 1, and worse PFS in patients ≥ 60 years old (p = 0.025) - Figure 2. In the multivariate analysis, overexpression of OCT-1 was associated with poor PFS (HR: 2.22, 95% CI: 1.06-4.76, p = 0.035). Conclusion: In this study, we demonstrated that overexpression of the OCT-1 gene was an independent prognostic factor associated with adverse outcomes in Brazilian patients with DLCBL. We also show that in patients with unfavorable risk, such as the elderly and those with intermediate-high and high-risk IPI, overexpression of OCT-1 contributed to the identification of a very high-risk clinical-molecular subgroup, where the results with standard R-CHOP therapy are unsatisfactory, and they may benefit from intensified therapeutic strategies. Our results are preliminary and need to be validated in subsequent studies of prospective nature and with an expanded sample. Disclosures No relevant conflicts of interest to declare.

Results of a Phase II Study of Lenalidomide in Combination with Rituximab for the Treatment of Indolent Non Follicular Non Hodgkin Lymphoma (NHL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1645-1645
Author(s):  
Stefano Sacchi ◽  
Samantha Pozzi ◽  
Marina Cesaretti ◽  
Luigi Marcheselli ◽  
Eliana Valentina Liardo ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Conflicts Of Interest ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
Open Label ◽  
Free Survival ◽  
Small Series

Abstract Abstract 1645 Background: Indolent non follicular B-Cell Lymphomas (INFL) are an eterogenous group of lymphomas and include small lymphocityic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL). Relapsed INFLs in advanced stage have a relatively poor prognosis, with low complete response to conventional chemotherapy and short survival. Lenalidomide (R®) is an immunomodulatory drug with effects on the innate immune system that may enhance antibody-dependent cell mediated cytotoxicity as well as the development of specific anti-tumor immune responses. These immunologic effects may synergize with the action of rituximab (R). To test the efficacy of R® combined with R (R2), we have conducted a multi center, open label phase II clinical trial in patients (pts) with relapsed INFL. Methods: Eligible pts must have indolent non follicular B-cell lymphoma relapsed after at least 2 but less than 4 prior lines of R-containing immuno-chemotherapy with measurable disease. Patients received oral R® 20 mg once daily on days 1–21. R is administered at a dose of 375 mg/m2 at day 14 of every course. Treatment is repeated every 28 days for up to 6 courses. The primary objectives of the study were to evaluate the antitumor activity of oral R® when given in combination with R and to assess the safety of R2 evaluated by standard criteria (CTC-NCI 3.0). The secondary objectives were progression free survival (PFS), event free survival (EFS) and duration of remission (DR). Results: From July 2010 and June 2012, 39 patients were enrolled: 19 had SLL, 11 had LPL, 4 splenic MZL, 3 extranodal MZL and a 2 nodal MZL. Median age was 68 years (51–76) and 58% were male. LDH value was increased in 17% of pts and β-2-microglobulin in 87%; 41% of pts had Hb<12 g/dL and 62% were bone marrow positive. At time of current analysis treatment and response data were available in 27 pts. Overall treatment was completed in 18 pts (67%); in 9 cases treatment was interrupted prematurely primarily due to hematological toxicity (n=5) and due to disease progression (n=4). Of the 27 pts, 5 achieved a complete remission and 9 a partial remission with an ORR of 52%. In general, the regimen R2 was relatively well-tolerated. Grade 3–4 hematological events included neutropenia occurring in 50% of pts, infection in 7% and piastrinopenia in 3%. Growth factors were administered in 60% of pts. The median dose intensity was 0.94 for R and 0.92 for R®. With a median follow-up of 13 months (range 1–36), overall 9 pts had a lymphoma progression and 2 of them died. The 1-year overall survival and the 1-year PFS were 92% (IC95% 57–99%) and 78 months (IC95% 54–91%) respectively. Conclusions: In our trial follicular histology was an exclusion criteria and all pts were relapsed/refractory to immuno-chemotherapy rituximab-containing regimens. Thus the results observed with the chemo-free R2 scheme compare favorably with other previously reported results observed in relapsed indolent lymphoma treated with standard immuno-chenotherapy. Further the R2 combination was relatively well tolerated. In conclusion our results, although obtained in a small series of patient are encouraging and support further evaluation of R2 scheme in a larger cohort of patients. Disclosures: No relevant conflicts of interest to declare.

The 18F-FDG SUVmax Reduction After Two Cycles of R-CHOP Regimen Predicts Progression Free Survival of Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2931-2931 ◽  
Author(s):  
Rene-Olivier Casasnovas ◽  
Anne Laure Saverot ◽  
Alina Berriolo-Riedinger ◽  
Michel Toubeau ◽  
Emmanuelle Ferrant ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Visual Analysis ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Induction Treatment ◽  
Free Survival ◽  
Residual Mass ◽  
Fdg Uptake ◽  
18F Fdg

Abstract Abstract 2931 Poster Board II-907 Introduction: PET assessment of early response allows to predict outcome of patients with DLBCL, but the more accurate criteria for early PET interpretation remain to be define. So we evaluated the prognostic value of PET after two cycles of immuno-chemotherapy and compared a semiquantitative approach using FDG uptake reduction, with two methods of visual analysis. Patients and methods: Forty five consecutive patients with newly diagnosed DLBCL treated in a single institution with rituximab and CHOP or CHOP-like regimen underwent 18F-FDG PET at baseline (PET0) and after 2 cycles of induction treatment (PET2). Images were interpreted visually according to two separate methods: - Juweid criteria (JCO 2007; 25: 571) (visual analysis-1) – A visual comparison of the FDG uptake between the residual mass and the normal hepatic tissue, a PET being considered as positive when the uptake of at least one residual mass was found greater than the liver (visual analysis-2). The quantitative approach was based on the lymphoma FDG uptake estimated by the maximal standardized uptake value (SUVmax) corrected to body weight. The SUV reduction between PET0 and PET2 (ΔSUVmax) was calculated for each patient. The ΔSUVmax cut-off was estimated to 65% by ROC analysis. Results: Patient median age was 50 years (range, 24 – 79) and 37 patients (73%) were younger than 61 years. The age-adjusted IPI score was, 2 or 3, 1 and 0 in 26 (49%), 16 (36%) and 7 (16%) patients respectively. With a median follow-up of 25 months, 6 (13%) out of 45 patients progressed or relapsed after treatment and 4 died from progressive disease. According to the visual analysis-1, PET2 was interpreted as negative in 16 (36%) patients and positive in the 29 remaining patients. Using the visual analysis-2, PET2 was negative in 25 cases (56%) and positive in 20 cases. The quantitative analysis showed a ΔSUVmax < 65% in 9 patients and a ΔSUVmax >= 65% in 36 patients (80%). The estimated efficiency of the three methods to predict patient outcome is detailed below: The probability of 2-years progression-free survival (PFS) for patients with a negative PET2 according to the visual analysis was slightly higher than those with a positive PET2 when using as well the Juweid criteria (93% vs 83%; p = 0.3), as the visual analysis-2 (95% vs 75%: p = 0.04). However, the quantitative aproach allows to better identify and split up the population of patients with a good outcome from those with a poor outcome, since the 2-years PFS was 56% in patients with a ΔSUVmax reduction less than 65% compared to a 94% 2-years PFS probability in patients with a ΔSUVmax higher than 65% (p=0.0009). A multivariate analysis was performed including the IPI score and the ΔSUVmax reduction as explanatory variables for PFS, showing that the PET2 result assessed by the ΔSUVmax reduction remains the only independant prognosis factor for PFS (p = 0.008; RR = 10). Conclusion: SUV-based assessment of PET after two courses of immuno-chemotherapy is more reliable to patient outcome than visual analysis. The SUVmax reduction is an early prognostic factor for DLBCL patients that may help to reduce false positive interpretations, and provides a useful tool to guide risk-adapted treatment. Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of Mid-Treatment PET in Patients with Diffuse Large B-Cell Lymphoma Who Achieved Metabolic CR at Post-Treatment PET

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3949-3949 ◽  
Author(s):  
Changhoon Yoo ◽  
Jeong-Eun Kim ◽  
Byeong Seok Sohn ◽  
Dok Hyun Yoon ◽  
Shin Kim ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Post Treatment ◽  
Prognostic Impact ◽  
Positron Emission ◽  
Age Range

Abstract Abstract 3949 Poster Board III-885 Background Mid-treatment positron emission tomography (PET) has been found to predict clinical outcomes in patients with aggressive non-Hodgkin's lymphoma. Currently, risk-adapted therapy based on mid-treatment PET has been widely evaluated. This study was intended to assess the prognostic value of mid-treatment PET in patients who achieved metabolic complete response (mCR) at post-treatment PET. Methods From February 2002 to March 2009, total 130 patients in whom post-treatment PET showed mCR were included in this study. We performed retrospective analysis of progression-free survival (PFS) and overall survival (OS) according to the results of mid-treatment PET. Results Median age (range) was 51 (16-85) years old, and 70 (54%) patients were male. International Prognostic Index (IPI) was low (0-2) in 91 (70%) patients and high (3-5) in 39 (30%) patients. As a front-line chemotherapy, most frequently administered regimen was R-CHOP (76%). Eighty-seven (67%) patients were mCR, and 43 (33%) patients were metabolic partial response (mPR) in mid-treatment PET. With 24 months of median follow-up, 3 year-rates of PFS and OS in overall patients were 74% and 87%, respectively. Differences of survival outcomes between patients with mCR and mPR at mid-treatment PET were not statistically significant in terms of PFS (p=0.13) and OS (p=0.76). Conclusions In patients with metabolic CR at post-treatment PET, survival outcome was not influenced by the results of mid-treatment PET. Therefore, risk-adapted therapy solely based on mid-treatment PET might be inappropriate in the management of newly diagnosed DLBCL. Disclosures: No relevant conflicts of interest to declare.

Prognostic Significance of Cell of Origin Subclassification in Diffuse Large B Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5081-5081
Author(s):  
Muath Dawod ◽  
Juan Gomez-Gelvez ◽  
Ahmad Mattour ◽  
Kedar V. Inamdar ◽  
Nalini Janakiraman
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Free Survival ◽  
Large B Cell Lymphoma

Abstract Abstract 5081 Background: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that has been divided into three different prognostic subgroups: Germinal Center B cell-like (GC), Activated B cell-like (ABC) and type 3 according to gene expression profile using cDNA. Immunohistochemistry (IHC) has been used as surrogate to identify these cell-of-origin subgroups. Data about the prognostic value of IHC has been conflicting. Patients and methods: In this retrospective study, we reviewed the charts of 252 patients diagnosed with DLBCL at Henry Ford Hospital from 1999 to 2012. We excluded patients with HIV, transformed lymphomas and unavailable samples. Data was collected on a total of 157 patients. The following data was gathered: age, sex, race, IPI score, disease stage, hemoglobin, white blood and platelet counts, best response achieved and dates of treatment start, relapse, death or last follow up. Tissue microarray slides with the following IHC stains (CD10, MUM1, Bcl6) were prepared and reviewed when needed. Using Hans Algorithm, samples were divided into two major groups (GC-like and non-GC-like). 3-year progression free and overall survivals were compared between all subgroups using a log-rank test. Continuous variables were reported as median and range, and compared using Wilcoxon rank-sum tests. Categorical variables were reported as median and range, and compared using Chi-square tests. Statistical significance was set at p<0. 05. Results: Eighty patients (51%) were classified as GC-like, and 77 patients (49%) as non-GC-like. GC-like subgroup had a significantly longer 3-year progression free survival (90% vs 74%, P=0. 024), as compared with the non-GC-like subgroup. There was a trend toward longer overall survival but it didn't reach statistical significance (74% vs 67%, P=0. 161). For all patients, IPI stands as a strong prognostic index with 3-year overall survival of (85% and 46%, P=<. 001) in patients with low IPI (0 to 2) and high IPI (3 to 5) respectively. Interestingly, in patients with low IPI, cell of origin stands as a prognostic factor with 3-year progression free survival of (96% and 81%, P=0. 032) in GC-like and non-GC-like groups respectively. While in patients with high IPI, there was no significant difference in progression free survival in cell-of-origin subgroups. Conclusion: Cell of origin subclassification as determined by IHC surrogate markers predict for better progression free survival in GC-like subgroup but not for overall survival. While this prognostic value was maintained in patients with low IPI, there was no prognostic significance in patients with high IPI. IPI is still a valuable prognostic tool in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

Incorporation of ABVD Increases Cure Rates of Patients with Limited Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3887-3887
Author(s):  
Kerry Joanne Savage ◽  
Brian Skinnider ◽  
Mubarak Al Mansour ◽  
Laurie H Sehn ◽  
Randy D. Gascoyne ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Treatment Guidelines ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Initial Therapy ◽  
Aggressive Lymphoma ◽  
Limited Stage ◽  
Non Hodgkin Lymphoma ◽  
Extended Field

Abstract Abstract 3887 Background: The appropriate therapy for limited stage NLPHL is the subject of debate. With favorable outcomes frequently reported, attempts have been made to reduce acute toxicity. In contrast to classical Hodgkin lymphoma, chemotherapy (CT) is often omitted; however, whether this omission affects outcome is unknown. At the BC Cancer Agency (BCCA), treatment guidelines are centrally driven and practiced throughout the province, facilitating survival comparisons across different treatment eras. Herein, we evaluated the outcome of patients with limited stage NLPHL treated with incorporation of ABVD (CT era) compared to those treated in the radiotherapy (RT) era. Patients and methods: The BCCA Lymphoid Cancer Database was used to identify all patients with limited stage NLPHL (non-bulky (<10cm) stage IA, 1B, 2A). Initially 106 patients were identified, however, following pathology and chart review 17 were excluded due to: an alternate lymphoma diagnosis (n=3); (non Hodgkin lymphoma not otherwise specified n=1; diffuse large B-cell lymphoma n=1; composite lymphoma n=1); diffuse morphology and blocks were not available for immunohistochemistry (n=2); benign histology (n=2); concurrent epithelial cancer (n=1); diagnosis out of province (n=9). Of the remaining 89 patients, 78 (88%) had a confirmed diagnosis of NLPHL and in 11 cases (12%), the slides or paraffin blocks were unavailable for re-review. In general, patients were treated according to era-specific guidelines: Before 1993 (n=33) extended field radiotherapy (RT); 1993-present (n=56) ABVD-like CT for 2 cycles with extended field RT (1993-1995), involved field RT (1995-2001) or involved nodal RT (2001-present) with the exception of 11 patients who received ABVD alone. Results: The majority of patients were male (67%), with a median age of 36.5 y (15-77) and 55 had stage I disease (62%). With a median follow-up of 6.4 y for living patients (range 1.2–40.5 y), the 10 y time to progression (TTP), progression-free survival (PFS) and overall survival (OS) for all 89 patients were 86%, 78% and 88%, respectively. Most patients were treated using the above guidelines except for 2 patients who were treated with MOPP CT + RT (physician's discretion) in the RT era and 6 patients treated solely with RT in the CT era (initial therapy out of province (n=1); high neck presentation (n=3); CT refusal (n=1); cardiac disease (n=1). In addition, 2 patients had undergone surgical resection alone in the RT era because the diagnosis of NLPHL was made retrospectively. In an era to era comparison, the 10 y TTP (98% v 74% p=0.0043, see figure 1), PFS (91% v 63%, p=0.0015) and OS (93% v 82%, p=0.053) favored the CT treatment era (> 1993) compared to the RT treatment era. Interestingly, there have been 5 cases of transformation to aggressive lymphoma in patients treated in the RT era and none in the CT era. In an ‘as treated’ analysis, patients given CT (n=52) had a superior 10 y TTP (97% v 77.5, p=0.0108) and PFS (90% v 66.5%, p=0.0035) versus those treated exclusively with RT (n=35). The sole patient who relapsed after CT had received MOPP. No patients treated with ABVD (n=50) have relapsed or developed transformed lymphoma. In multivariate analysis including treatment era, age >40 y, stage II disease, mass size > 5 cm and male sex, treatment in the CT era was the only factor impacting TTP (p=0.022, HR .088 (CI .011, .702)) and PFS (p=0.001, HR .126 (CI .028, .464)) and there was a trend towards an improved OS (p=.089 HR .156 (CI .018, 1.324). Conclusion: Since the introduction of ABVD CT into the treatment of patients with limited stage NLPHL, outcomes have improved considerably and patients are more likely to be cured of their lymphoma. Disclosures: No relevant conflicts of interest to declare.

Addition of Rituximab to Chemotherapy Alters the Prognostic Impact of Tumor-Associated Macrophages in Diffuse Large B-Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2650-2650
Author(s):  
Sari Riihijärvi ◽  
Maria Pöyhönen ◽  
Minna Taskinen ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Sirpa Leppä
Keyword(s):  
De Novo ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
Control Group ◽  
High Dose ◽  
Prognostic Impact ◽  
Tumor Associated Macrophages ◽  
Kaplan Meier

Abstract Abstract 2650 Background: Tumor associated macrophages (TAM) have at least two potential roles in promoting tumor growth: suppression of immune responses and potentiation of angiogenesis. In numerous cancer types, including lymphomas, high M2 type TAM content has been associated with worse prognosis. Rarely, high TAM content correlates with better survival. We have recently shown that CD68 positive TAMs in DLBCL contribute to unfavorable survival after high dose chemotherapy. Here we have extended our analyses on M2 type macrophages and questioned how combination of rituximab with chemotherapy influences TAM-associated clinical outcome. Patients and Methods: Expression of CD163 and CCL18, which are primarily expressed in M2 type macrophages, were identified immunohistochemically from samples of 101 de novo DLBCL patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen (immunochemotherapy). With a median follow-up of 65 months, (range 16–114 months), 5-year progression free survival (PFS) was 70% and overall survival (OS) 73%. 29 DLBCL patients previously treated with up front high dose chemotherapy served as a control group. Results: Correlation between CD163 and CCL18 positive TAMs was found (rs=0.427, p<0.001). In the Kaplan-Meier analyses the cutoff level of 67% was found to best discriminate between subgroups with different outcomes. Consistent with previous data, chemotherapy-treated patients with high CD163 or CCL18 positive TAM counts displayed a significantly inferior OS and PFS than the low group (Table). In contrast, after rituximab containing regimen, the patients with high CD163 and CCL18 positive TAM content tended to have favorable survival. Among the patients with low counts in both CD163 and CCL18 positive TAMs, PFS and OS were found to be significantly worse in comparison to others. Conclusions: In contrast to data on chemotherapy treated DLBCL or other lymphoma types, M2 type TAM content is associated with favorable prognosis in DLBCL patients after immunochemotherapy. Disclosures: No relevant conflicts of interest to declare.

Pre-Transplantation FDG-PET Predicts Early but Not Late Survival Outcomes Following Allogeneic Transplantation in Chemo-Sensitive Hodgkin Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1225-1225
Author(s):  
Yasmin Reyal ◽  
Irfan Kayani ◽  
Ronjon Chakraverty ◽  
Adrian Bloor ◽  
Christopher P Fox ◽  
...  
Keyword(s):  
T Cell ◽  
Hodgkin Lymphoma ◽  
Visual Analysis ◽  
Conflicts Of Interest ◽  
Survival Outcomes ◽  
Prognostic Impact ◽  
Data Set ◽  
Free Survival ◽  
Relapse Risk ◽  
Number Of Patients

Abstract Positron emission tomography (PET) is increasingly employed both to guide response-adjusted therapeutic strategies and to provide prognostic information in patients with Hodgkin Lymphoma (HL). The presence of residual [18-F]FDG-avid lesions prior to autologous stem cell transplantation (ASCT) confers a poor prognosis in terms of relapse risk and event-free survival outcomes, even when analysis is restricted to those with chemo-sensitive disease. The prognostic power of PET in the setting of allogeneic SCT remains more contentious, with relatively little data currently published. Information is particularly sparse in terms of outcomes relating to specific histological subtypes of lymphoma. We identified 160 patients transplanted for HL at four UK transplant centers using T-cell depleted conditioning regimens, based either on fludarabine-melphalan-alemtuzumab (FM-C) or the BCNU-etoposide-cytarabine-melphalan-alemtuzumab (BEAM-C) backbone, in whom pre-transplantation PET data were available. These represent the primary data set. Median age was 30 (12-66) years; 59 had failed a prior ASCT and these patients more commonly received FM-C (56/59 vs 26/101, p<0.001); median number of prior lines of treatment was 4 (2-10); median follow-up was 3.1 years in patients remaining alive. A Deauville score could be assigned according to a visual analysis 5-point scale in 137 cases following central review of digital file data; D1-2 (metabolic complete response) n=54, D3 n=13, D4 n=36, D5 n=34. Of those with a D5 score, 18 were non-progressive, and 16 progressive (D5p) prior to transplant. Overall survival (OS) was significantly worse in the D5p subset (19% [0-41%] at 4 years, p=0.001); it did not differ significantly between D1-2 vs D3-5 (78%[66-90%] vs 67%[54-80%], p=0.626), although the OS curves demonstrated early divergence from years 1-4 followed by convergence at later time points (Figure). The worse OS in the D5p cohort related both to a higher non-relapse-related mortality (NRM)(29%[12-65%] at 1 year) and a higher relapse risk (RR)(38%[19-76%] at 4 years). The latter were equivalent for the D1-2 vs D3-5 cohorts (NRM 17%[9-31%] vs 17% [10-30%] at 1 year; RR 23%[13-40%] vs 24% [15-38%] at 4 years respectively)(Figure). Interestingly the kinetics of relapse differed between the latter 2 groups, with relapse occurring later in the D1-2 cohort, again illustrated by early divergence (RR 16%[9-31%] vs 24%[15-38%] at 2 years) followed by later convergence from year 4. Progression free survival was also equivalent (57%[43-72%] vs 54%[41-67%] at 4 years respectively, p=0.347). Although the number of patients with non-progressive D5 scores was relatively small, exploratory analyses revealed no significant differences in survival outcomes between those with D4 vs D5 scores. Analysis of survival outcomes of D1-3 vs D4-5 also revealed no statistically significant differences. In summary, these data from a large cohort of patients with HL undergoing T-cell depleted allogeneic SCT illustrate inferior outcomes in those with progressive disease prior to transplantation, an altered kinetic of relapse and early survival advantage for those with Deauville 1-2 PET scores compared to those with non-progressive Deauville 3-5 PET scores, but no statistically significant differences in longer term outcomes including relapse risk, PFS and OS. Importantly, these data suggest that the allogeneic graft-versus-tumor activity likely overcomes the poor prognostic impact that has been demonstrated with residual metabolically active disease in the context of conventional dose escalation and ASCT, supporting further exploration of response-adjusted transplantation algorithms. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Two distinct prognostic groups in advanced-stage Hodgkin lymphoma revealed by the presence and site of bulky disease

2020 ◽  
Vol 4 (9) ◽  
pp. 2064-2072 ◽  
Author(s):  
Shunan Qi ◽  
Sarah Milgrom ◽  
Bouthaina Dabaja ◽  
Richard Tsang ◽  
Mario Levis ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Bone Marrow Involvement ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Maximum Diameter ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Free Survival ◽  
Disease Characteristics ◽  
Kaplan Meier

Abstract Controversy exists regarding the definition and prognostic significance of bulk in advanced-stage (stage III/IV) Hodgkin lymphoma (ASHL), and bulk location (mediastinum vs other sites) further complicated the setting. This retrospective, multi-institutional study comprised 814 ASHL patients between 2000 and 2010 and aimed to evaluate the significance of bulk in ASHL. End points of interest included progression-free survival (PFS) and overall survival (OS). Covariates included maximum diameter and the site of bulky disease. SmoothHR and Kaplan-Meier analyses were used to assess for an association of PFS and OS with covariates. In the exploratory cohort (n = 683), maximum diameter had no association with PFS and a complex, U-shaped association with all-cause mortality on smoothHR analysis. Using 5 cm as a cutoff for bulk, Kaplan-Meier analyses confirmed the smoothHR results. The site of bulk was incorporated to divide patients into 2 groups. The mediastinal bulk (MB) type had more favorable characteristics than the nonbulky/non-MB (NB/NMB) type on age, histology, and bone marrow involvement (P &lt; .001). The MB type was associated with better OS than the NB/NMB-type on univariable analysis (5-year OS, 92% vs 86%; HR, 0.53; 95% confidence interval, 0.34-0.84; P = .007). These findings persisted in the subgroup treated with chemotherapy alone and were confirmed in an independent validation cohort (n = 131). Our findings indicate that mediastinal bulk was associated with more favorable disease characteristics and improved OS in ASHL, and may be a surrogate of a more favorable biology.

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