High Skp2 Expression Is an Independent Predictor of Unfavorable Outcome in 333 Patients with Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1560-1560
Author(s):  
Ritsuko Seki ◽  
Koichi Ohshima ◽  
Fumio Kawano ◽  
Toshihiko Murayama ◽  
Yukiyoshi Moriuchi ◽  
...  
Keyword(s):  
Clinical Stage ◽  
Combined Treatment ◽  
B Cell Lymphoma ◽  
Similar Distribution ◽  
Prognostic Impact ◽  
Advanced Clinical Stage ◽  
Treatment Groups ◽  
Skp2 Expression ◽  
New Treatment

Abstract The addition of rituximab to CHOP (CHOP-R) chemotherapy has resulted in an improved outcome for patients with DLBCL and has recently been shown to diminish the prognostic impact of several recognized biomarkers. S-phase kinase-associated protein 2 (Skp2) is a proto-oncogene that has been shown to be expressed in a number of tumors. We have reported that Skp2 expression in tumor cells is an unfavorable prognostic factor in DLBCL. In the present study, we investigated the significance of Skp2 expression in the patients with DLBCL treated with CHOP or CHOP-R. DLBCL patients (333 cases) were entered into this study, based on the availability of paraffin blocks for interpretable immunohistochemistry for all antigens (CD10, Bcl-6, MUM1, Bcl-2, Skp2). All patients were treated with either CHOP (201) or CHOP-R (132) from 1996 to 2005, and were diagnosed as having DLBCL at the twenty different hospitals. All specimens were histopathologically reviewed before entering into this study. Their clinical characteristics, including either the IPI or R-IPI factors, were evenly matched. The median follow-up of living patients was 3.7 and 2.1 y for CHOP vs CHOP-R, respectively. DLBCL were assigned to GCB subtype (40.8%: 136/333) or non-GCB subtype (59.2%: 197/333) based on the method of Hans et al., Blood 103: 275–82 (2004), with similar distribution in both treatment groups. Expression of bcl-6 (p<0.05) or GCB subtypes (p<0.05) was associated with better overall survival (OS), whereas expression of bcl-2 (p<0.05) was associated with worse OS in CHOP treatment group. The addition of R was associated with an improved survival in the non-GCB subtype and resulted in same as that of GCB subtype. The survival benefit of both low Bcl-2 and high Bcl-6 expressions diminished in combined treatment with R to CHOP. There were 97 patients with high Skp2 expression (>60% positive cells) (97/333: 29.1%). High Skp2 expression was found in both GCB subtype (28.6%) and non-GCB subtype (30.3%). In advanced clinical stage or extranodal involvement (>2), the patients with high Skp2 expression had worse survival than those with low Skp2 expression (p<0.05). Interestingly, in CHOP-R group, high Skp2 expression was the strong biomarker of worse prognosis (p<0.05). DLBCL patients with high Skp2 expression did not benefit from the addition of R to CHOP. Therefore, Skp2 may be a useful prognostic marker in recent rituximab era. The new treatment strategy is necessary for the DLBCL patients with high Skp2 expression. Figure Figure

Regulation of p27 by S-Phase Kinase- Associated Protein 2 Is Associated with Aggressiveness in Diffuse Large B Cell Lymphoma (DLBCL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3760-3760
Author(s):  
Ritsuko Seki ◽  
Koichi Ohshima ◽  
Tomoaki Fujisaki ◽  
Naokuni Uike ◽  
Fumio Kawano ◽  
...  
Keyword(s):  
B Cell ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
S Phase ◽  
Prognostic Impact ◽  
Treatment Groups ◽  
Skp2 Expression ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract The F-box protein S-phase kinase-associated protein 2 (Skp2) is one of the positive regulators of the cell cycle that promote ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. In this study, we investigated the significance of Skp2 and p27 expression in diffuse large B cell lymphoma (DLBCL) treated with CHOP or CHOP-R. All patients (671) were diagnosed as having DLBCL at the twenty different hospitals and were treated with either CHOP (425) or CHOP-R (246) from 1996 to 2005. All specimens were histopathologically recomfirmed by one pathologist with expertise before entering into this study. Their clinical characteristics, including either the IPI or R-IPI factors, were evenly matched in both treatment groups. The median follow-up of living patients was 3.7 and 2.1 y for CHOP vs CHOP-R, respectively. Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. There were 257 patients with high Skp2 expression (cutoff value >40% positive cells) (257/671,39.0%). High Skp2 expression was found in all IPI groups. Expression of p27 (P<.001) was associated with better overall survival (OS), whereas expression of Skp2 was associated with worse OS in CHOP treatment groups (P<.001). We also examined the prognostic impact of Skp2 according to various expression degree of Skp2, Skp2 expression remained a significant predictor of survival (<40%,40–79%,≥80%, P<.001). The multivariant analysis revealed that both the IPI score and the expression of Skp2 and p27 were independent predictors of OS and PFS in both treatment groups (P<.001). The patients with high Skp2 expression in combination with low p27 expression were related to worst survival in CHOP group (Fig1A). Interestingly, even in CHOP-R group, both high Skp2 expression and low p27 expression were the strong biomarker of worse prognosis (Fig 1B). DLBCL patients with high Skp2 expression did not benefit from the addition of R to CHOP. Conclusion: Addition of rituximab did not provide a beneficial outcome to DLBCL with high Skp2 and low p27 expression. Therapeutic strategies other than CHOP-R will be needed for DLBCL patients exhibiting a high Skp2 and low p27 expression at the time of diagnosis. Figure Figure

scholarly journals Interim Serum Soluble Interleukin-2 Receptor Levels Are Strongly Associated with Prognosis in Newly Diagnosis DLBCL Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4118-4118
Author(s):  
Haruya Okamoto ◽  
Akihiro Miyashita ◽  
Hiroaki Nagata ◽  
Yasuhiko Tsutsumi ◽  
Yuri Kamitsuji ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Interleukin 2 ◽  
B Cell Lymphoma ◽  
Clinical Variable ◽  
Rank Test ◽  
Prognostic Impact ◽  
Interleukin 2 Receptor ◽  
Log Rank Test ◽  
Soluble Interleukin 2 Receptor

<Background> Serum soluble interleukin-2 receptor (sIL2R) levels are often measured to evaluate the state of lymphoma. The serum sIL2R level at diagnosis has been reported to be correlated with the prognosis of diffuse large B cell lymphoma (DLBCL) patients treated with the R-CHOP regimen. However, it is unclear whether interim sIL2R levels are associated with prognosis in DLBCL. Here, we analyzed the prognostic impact of interim serum sIL2R levels in DLBCL. <Patients and Methods> We retrospectively examined data for DLBCL patients who started receiving chemotherapy at the Japanese Red Cross Society Kyoto Daini Hospital between January 2012 and December 2018. All of the patients received R-CHOP-like regimens (rituximab plus pirarubicin or adriamycin, cyclophosphamide, vincristine, and prednisolone). The interim sIL2R level (I-IL2R) was defined as the value measured after the third chemotherapy cycle. I-IL2R levels of >700 U/ml were regarded as positive. The primary endpoints of this study were progression-free survival (PFS) and overall survival (OS). The unadjusted probabilities of PFS and OS were estimated using the Kaplan-Meier method. The log-rank test and multivariate Cox regression analysis were used to assess the prognostic value of each clinical variable. <Results> In total, 102 patients were enrolled. The patients' median age was 73.5 years (range, 35-88), 58 patients (56.9%) were male, and 52 (51.0%) had poor revised International Prognostic Index scores. The median follow-up time was 25.2 months (range, 3.7-88.6). Twenty-three patients (22.5%) were I-IL2R-positive (>700 U/ml). Univariate analysis revealed that I-IL2R-positivity was associated with a poor prognosis. The 3-y PFS rates of the I-IL2R-negative (<700 U/ml) and I- IL2R-positive (>700 U/ml) patients were 60.4% (95% confidence interval [95%CI], 46.2-71.9) and 37.5% (95%CI, 15.7-59.4; p<0.001, log-rank test), respectively, and their 3-y OS rates were 82.2% (95%CI, 69.7-89.9) and 37.4% (95%CI, 13.8-61.4; p<0.001, log-rank test), respectively. Multivariate analysis confirmed that the I-IL2R level is independently associated with prognosis. <Conclusion> The I-IL2R level of >700 U/ml patients had poor prognosis. The I-IL2R level can be used to predict the outcomes of DLBCL patients. IL2R levels should be measured during chemotherapy, and I-IL2R-positive patients could be targeted with high-dose or novel therapies. As this study was based on a retrospective analysis and involved a small cohort and a limited follow-up period, further studies are needed to confirm the prognostic impact of I-IL2R. Figure Disclosures No relevant conflicts of interest to declare.

Alprazolam and Exposure Alone and Combined in Panic Disorder with Agoraphobia

1993 ◽  
Vol 162 (6) ◽  
pp. 776-787 ◽  
Author(s):  
Isaac M. Marks ◽  
Richard P. Swinson ◽  
Metin Başoǧlu ◽  
Klaus Kuch ◽  
Homa Noshirvani ◽  
...  
Keyword(s):  
Panic Disorder ◽  
Combined Treatment ◽  
Randomised Trial ◽  
Treatment Groups ◽  
End Of Treatment ◽  
Group A ◽  
Contrast Group ◽  
Drop Outs ◽  
Cross National

A cross-national randomised trial of alprazolam for chronic panic disorder with agoraphobia was run. Compared with previous trials it had three new features: an exposure therapy contrast group, a six-month treatment-free follow-up, and a low rate of early placebo drop-outs (‘non-evaluables’). The dose of alprazolam was high (5 mg/day). The 154 patients had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo and exposure; or placebo and relaxation (double placebo). Drug taper was from weeks 8 to 16. Follow-up was to week 43. Results were similar at both sites. Treatment integrity was good. All four treatment groups, including double placebo, improved well on panic throughout. On non-panic measures, by the end of treatment, both alprazolam and exposure were effective, but exposure had twice the effect size of alprazolam. During taper and follow-up, gains after alprazolam were lost, while gains after exposure were maintained. Combining alprazolam with exposure marginally enhanced gains during treatment, but impaired improvement thereafter. The new features put previous trials in a fresh light. By the end of treatment, though gains on alprazolam were largely as in previous studies, on phobias and disability they were half those with exposure. Relapse was usual after alprazolam was stopped, whereas gains persisted to six-month follow-up after exposure ceased. Panic improved as much with placebo as with alprazolam or exposure.

scholarly journals The Fate of Patients with Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5413-5413
Author(s):  
Pavel Otahal ◽  
Andrea Janikova ◽  
David Belada ◽  
Vit Prochazka ◽  
Heidi Mocikova ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Clinical Stage ◽  
B Cell Lymphoma ◽  
Refractory Disease ◽  
First Line ◽  
Advisory Committees ◽  
Advanced Clinical Stage ◽  
Line Therapy

Abstract Background: The outcome of DLBCL patients is improving, it however seems to be very poor for those who are refractory to the therapy. We have decided to analyze this group of patients. Methodology: As part of an observational clinical study NiHiL (GovTrial No NCT03199066) we identified the patients treated in the first line by R-CHOP like immunochemotherapy who met at least one criterium: 1. refractory (stable disease - SD or progression) on 1st line therapy (1st l- R), 2. refractory (SD or progression) on salvage (platinum based regimen) (Salv-R), 3. refractory to or relapse/progression within 12 months after ASCT (ASCT-R/R). There were 210 patients diagnosed in the period 2001-2017 who fulfilled the criteria. Progression-free survival (PSF) and overall survival (OS) were estimated from the time of determination of a refractory disease. Results: The cohort consisted of 163 patients primarily resistant to the first-line therapy, 31 patients were resistant to the salvage therapy and 16 patients progressed within 12 months after ASCT . At the time of the diagnosis, the median age was 65 years (22-91) (the same as at the refractory disease), 54% were males, 74% had advanced clinical stage (III+IV), 68% had IPI >3, 77% had above-normal LDH, and 45% had a tumor mass >10cm. The OS from the time of determination of refractory disease was 0.53 years, median PFS was 0.29 years. Patients under 65 years had median survival 0.8 years compared to 0.4 years in the group of patients above 65 years of age. The median PFS for 1st l-R, Salv-R and ASCT-R/R resp. was 0.3, 0.26 and 0.35 years resp. and 5y survival 22%, 0% and 6% resp. The median OS for 1st l-R, Salv-R and ASCT-R/R resp. was 0.55, 0.39 and 0.65 y resp. and 5y survival was 28%, 0% and 13% resp. Our results demonstrate that resistant DLBCL has an extremely poor prognosis, clearly new effective therapeutic strategies such as CAR-based therapies or others are required. This work was supported by a research program Progres Q28-9. Disclosures Belada: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Prognosis in Patients with Human Immunodeficiency Virus Infection and Advanced Clinical Stage Classic Hodgkin's Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5281-5281
Author(s):  
Juan J delMoral-Diez ◽  
Elena Juventina Tuna-Aguilar ◽  
Alvaro Aguayo ◽  
Antonio Olivas-Martinez ◽  
Gladys P Agreda-Vasquez
Keyword(s):  
Prognostic Factors ◽  
Hodgkin’S Lymphoma ◽  
Clinical Stage ◽  
Univariate Analysis ◽  
Cd4 Count ◽  
Hodgkin's Lymphoma ◽  
Advanced Stage ◽  
Advanced Clinical Stage ◽  
Histologic Subtype

Classic Hodgkin's lymphoma (cHL) represents 95% of all Hodgkin lymphomas, and is responsible of 0.5% of all cancer types (Siegel, Miller & Jemal, 2016). In HIV positive patients, the incidence of cHL is high (5-20 fold). The use of combination antiretroviral therapy (CART) and CD4 count >200 cells/uL appears to increase the risk; nonetheless, the risk for developing cHL in HIV infected patients remains high, regardless of CD4 count. The median patients' age of HIV-associated classic Hodgkin's lymphoma (HIV-cHL) ranges from 40 to 49 years old, slightly higher than the age observed in general population. It is more common in men, and tends to manifest with extranodal disease (67% vs 32%), B-symptoms (77% vs 43%), and stage III or IV disease (82% vs 42%) (Shiels et al, 2014). Recent recommendations state that HIV-cHL should receive first-line ABVD chemotherapy treatment while continuing CART (Blanca et al, 2007)(Montoto et al, 2012). To determine the prognosis of de novo advanced stage HIV-cHL and compare it with non-HIV-cHL, we designed an observational, descriptive study, including all HIV-cHL (WHO 2016 criteria) from August 2004 to December 2018, paired with a non-HIV-cHL group by clinical stage and gender. Clinical features between positive and negative HIV groups were compared by standard statistical methods. Overall survival (OS) and relapse-free survival (RFS) were calculated by Kaplan-Meier methodology. Analysis for mortality predictors was performed with a univariate Cox regression model. Data was collected from 21 patients with HIV-cHL, all male and with advanced clinical stage, and compared with 58 non-HIV-cHL patients with the same characteristics. The mean age observed was 42.9 (± 10.88) years in HIV-cHL, and 45.1 (± 17.56) years in non-HIV-cHL (p = 0.50). Among the clinical characteristics, the presence of B symptoms was documented in 85.7% of HIV-cHL, and in 91.4% of non-HIV-cHL (p = 0.43). Among biochemical characteristics in both groups, we observed a significantly lower leucocyte count in HIV-cHL (4.6x103 cells/uL) compared with non-HIV-cHL (6.7x103 cells/uL) (p = 0.02). In the monocyte line, we found that HIV-cHL had lower absolute counts (340 cells/uL) than non-HIV-cHL (708 cells/uL) (p = 0.01). A high IPS was reported in 66.7% of HIV-cHL, and in 67.2% of non-HIV-cHL (p = 1.00). The most common reported histologic subtype was mixed cellularity for both groups, with a prevalence of 38.1% and 38.9%, respectively (p = 0.25). The positivity for Epstein-Barr virus was tested in the biopsies of 18 HIV-cHL, and was 100%. Regarding HIV status in infected patients, a 40-month period was the median time between HIV and cHL diagnosis. The median CD4 cell count was 109 cells/uL. 90.5% of patients were treated with CART at time of cHL diagnosis. Other clinical, biochemical and prognostic characteristics are in Table 1. The median follow-up time for all patients was 31 months; the median follow-up time for HIV-cHL was 10 months, shorter than the median follow-up time for non-HIV-cHL (45 months) (p = 0.01). 85.7% of HIV-cHL and 96.6% of non-HIV-cHL received chemotherapy, with a median of 6 cycles (p = 0.11). Complete response (CR) was documented in 61.1% of HIV-cHL, and in 66.1% of non-HIV-cHL (p = 0.77). RFS was 36.5 months for all patients, being less for HIV-cHL (24 months) compared with non-HIV-cHL (51 months) (p = 0.03). The OS median at the time of last follow-up had not yet been reached in all patients (Figure 1). The univariate analysis showed that age ≥45 years old and stage IV cHL are adverse prognostic factors (p = 0.02, p = 0.03, respectively). IPS ≥4 was an adverse outcome factor for mortality, with statistical significance (p = 0.01) (Figure 2). At last follow-up, 22 (27.8%) patients had died, 6 (28.6%) HIV-cHL and 16 (27.6%) non-HIV-cHL (p = 1.00). Clinical, biochemical and prognostic variables, as well as treatment outcomes were similar between HIV-cHL and non-HIV-cHL. Although follow-up time in the HIV-cHL group is shorter, prognosis in terms of OS is similar. RFS is statistically different between both groups and is shorter in HIV-cHL, but as the OS in both groups remains similar, it is possible that rescue chemotherapy is effective in relapsed patients. There was no difference observed in the likelihood of achieving CR in both groups. IPS ≥4 and CR were independent prognostic factors for OS. IPS as an adverse factor and CR as a favorable one. Prognosis of advanced stage HIV-cHL is similar to non-HIV-cHL patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic Impact of lncRNA MCM3AP-AS1 Expression in Malignant Solid Tumors: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
qi le ◽  
wei chen ◽  
Lei Jiang ◽  
Wenwen Hu ◽  
Nan Yao
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Malignant Tumors ◽  
Meta Analysis ◽  
Clinical Stage ◽  
Prognostic Impact ◽  
China National Knowledge Infrastructure ◽  
Poor Overall Survival ◽  
Advanced Clinical Stage ◽  
High Level

Abstract Objectives: MCM3AP-AS1 is a newly discovered long non-coding RNA that functions as a biomarker in many different cancer types. However, the pooled role of lncRNA MCM3AP-AS1 in the prognosis of human cancers remains unclear. We performed a systematic review and meta-analysis to explore its potential prognosis for malignant tumors. Materials and methods: A literature survey was conducted by searching in the PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang databases for studies published as of September 1, 2021. The pooled hazard ratio (HR) and 95% confidence interval (95% CI) were calculated to evaluate the relationship between MCM3AP-AS1 expression and overall survival (OS). The endpoints also included various clinical parameters. Results: A total of 14 studies containing 921 cancer patients were finally included into this meta-analysis. The results comprehensively showed that increased MCM3AP-AS1 expression was significantly correlated with poor overall survival (HR = 1.83, 95% CI: 1.56-2.14, P<0.00001). A subgroup meta-analysis for overall survival was conducted. Additionally, high level of lncRNA MCM3AP-AS1 was significantly associated with worse differentiation (OR = 1.76, 95 % CI: 1.12–2.75, P = 0.01), larger tumor size (OR = 2.70, 95 % CI: 1.13–6.46, P = 0.03), advanced clinical stage (OR = 2.52, 95 % CI: 1.32–4.81, P = 0.005) and lymph node metastasis (OR = 2.85, 95 % CI: 1.16–7.00, P = 0.02), respectively. Conclusions: LncRNA MCM3AP-AS1 might be a potential and unfavorable prognostic biomarker of cancer.

Strong p53 Expression Is an Independent Predictor of Outcome in De Novo Diffuse Large B Cell Lymphoma (DLBCL) Treated with Either CHOP or CHOP-R.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 812-812 ◽  
Author(s):  
Pedro Farinha ◽  
Laurie Sehn ◽  
Brian Skinnider ◽  
Lin Wu ◽  
Nancy Patten ◽  
...  
Keyword(s):  
Overall Survival ◽  
De Novo ◽  
Mutational Analysis ◽  
B Cell Lymphoma ◽  
Similar Distribution ◽  
Prognostic Impact ◽  
P53 Mutations ◽  
P53 Expression ◽  
P53 Status ◽  
Diagnostic Biopsies

Abstract Background: The addition of rituximab to CHOP (CHOP-R) chemotherapy has resulted in an improved outcome for patients with DLBCL and has recently been shown to diminish the prognostic impact of two recognized biomarkers, namely Bcl-2 and Bcl-6. In the CHOP era, p53 mutations in DLBCL were associated with an aggressive clinical course and shortened survival. Using immunohistochemistry and mutational analysis, p53 over-expression and mutational status were examined in a population-based cohort of DLBCL patients treated with CHOP or CHOP-R (Sehn et al, J Clin Oncol2005; 23: 5027–33). Method: We analyzed 155 patients from a total cohort of 292 patients based on available paraffin blocks with sufficient tissue for interpretable immunohistochemistry for all antigens. All were initial diagnostic biopsies of de novo DLBCL cases accrued between 1999 and 2002 at the BCCA. HIV+ patients or those with active secondary malignancies were excluded. Tissue microarrays (TMA) were built using duplicate 0.6mm cores from paraffin embedded formalin fixed (FFPE) diagnostic biopsies and stained with antibodies against CD10, Bcl-6, MUM1, Bcl-2, p53 and p21. DLBCL cases were assigned to GCB or non-GCB subgroups based on the method of Hans et al., Blood 103: 275–82 (2004). Strong nuclear expression of the p53 antibody (clone DO7) was defined as high intensity (3/3) expression in &gt;50% of the malignant cells. The p53 gene mutational analysis was performed on this subset of cases with DNA extracted from FFPE samples using the AmpliChip™ p53 test (developed in Roche Molecular Systems, Inc.). Results: Patients were treated with either CHOP (n = 77) or CHOP-R (n = 78). Their clinical characteristics, including the IPI factors, were evenly matched. The two treatment cohorts represent consecutive eras of therapy and thus the median follow-up of living patients was 5.1 and 4.0 y for CHOP vs CHOP-R, respectively. Of the 155 patients, 75 had a GCB phenotype and 80 non-GCB, with similar distribution in both treatment groups. There were 19 strong p53-positive cases (19/155 or 12.3%). Ten p53-positive cases were GCB and 9 were non-GCB. All 19 strong p53-positive cases were negative for p21 expression and 16/17 analyzable cases had p53 mutations. Univariate analysis of the entire cohort (n = 155) revealed that both IPI and p53 expression were of prognostic importance (p &lt; 0.0001). In multivariate analysis, strong p53 and IPI were independent predictors of OS (p = 0.005 and p &lt; 0.0001, respectively). Importantly, when analyzed by treatment era, strong p53 expression remained significant in both CHOP (p=0.015) and CHOP-R groups (p=0.012). Conclusion: Strong p53 protein expression correlates with p53 mutations and is an independent prognostic factor for patients with DLBCL even when treated with CHOP-R. p53 mutations were found in both GCB and non-GCB subtypes. Importantly the prognostic impact of p53 is not diminished in the era of CHOP-R, identifying a subgroup of patients with inferior survival. Overall Survival for 155 DLBCL Based on p53 Status Overall Survival for 155 DLBCL Based on p53 Status

Clinicopathological Differences Between Asian and Western Patients with De Novo Diffuse Large B Cell Lymphoma Treated with R-CHOP

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2665-2665
Author(s):  
Natalie Sinclair ◽  
Brady E Beltran ◽  
Moo-Kon Song ◽  
Ivana Ilic ◽  
Sirpa Leppa ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Research Funding ◽  
De Novo ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Advanced Clinical Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2665 Introduction: Little is known on the racial differences in characteristics and outcomes of patients with a diagnosis with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-containing regimens. The aim of this retrospective study is to compare the clinicopathological characteristics, prognostic factors and outcomes of Asian and Western patients with a diagnosis of de novo DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Patients and Methods: Patient-level data was collected from 8 centers (USA, Italy, Sweden, Finland, Croatia, Japan, Korea and China). This study was approved by the Institutional Review Board at each of the participant centers. All patients were diagnosed with de novo DLBCL and treated with R-CHOP administered every 3 weeks. HIV-positive and primary brain DLBCL were excluded. The requested clinical data included age, sex, performance status, lactate dehydrogenase (LDH) levels, number of extranodal sites, clinical stage, expression of CD10, BCL6 and MUM1/IRF4, response to chemotherapy, outcome and overall survival (OS). Patients were divided in Asian and Western, according to the country of report. Comparison between groups was performed with Mann-Whitney and Chi square tests for continuous and categorical variables, respectively. Univariate survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional-hazard regression test. P-values of <0.05 were considered statistically significant. Results: A total of 712 patients, 455 Asian and 257 Western patients were included in this study. Western patients were more likely to present with elevated LDH levels (70% vs. 48%; p<0.001), advance clinical stage (58% vs. 49%; p=0.02) and a non-germinal center immunohistochemical profile (53% vs. 43%; p=0.01). Additionally, Western patients were more likely to present with low risk IPI scores (p=0.003 for trend), and had higher complete response (CR) rates (91% vs. 76%; p<0.001). There were no statistical differences between the 2 groups on age at diagnosis, sex distribution, ECOG performance status, number of extranodal sites, overall response rates and proportion of deaths. After a median follow-up of 36 months, there was no difference in median overall survival (OS; not reached in both groups) or estimated 5-year OS (66% vs. 62%; p=0.67) (Figure). In the univariate analyses, ECOG >1, elevated LDH levels and advanced clinical stage were significantly associated with a worse median OS in Westerners (p<0.01 each factor) while ECOG >1, >1 extranodal sites and advanced clinical stage were significant adverse factors for Asians (p<0.01 each factor). In the multivariate analyses, ECOG >1 and advanced clinical stage were independent prognostic factors associated with a worse median OS in Westerners and Asians (p<0.01, p=0.03, and p<0.01, p<0.01, respectively). Elevated LDH level was an adverse independent prognostic factor for Western patients only (p=0.04). Conclusions: Asian and Western patients with de novo DLBCL present with distinct clinical and pathological characteristics, and although the CR rate to standard R-CHOP was higher in Westerners than in Asians, the final outcome, prognostic factors and median and 5-year OS rates are similar in both populations. Disclosures: Castillo: GlaxoSmithKline: Research Funding; Millennium Pharmaceuticals: Research Funding.

Prognostic Impact Of Gender In Diffuse Large B Cell Lymphoma Patients Treated With R-CHOP Therapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5079-5079
Author(s):  
Hiroyuki Takahashi ◽  
Naoto Tomita ◽  
Rika Kawasaki ◽  
Chizuko Hashimoto ◽  
Etsuko Yamazaki ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Clinical Stage ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Female Patients ◽  
Large B Cell Lymphoma ◽  
Male Patients ◽  
Bulky Mass ◽  
Large B Cell

Abstract Background Since the introduction of rituximab, an anti-CD20 monoclonal antibody, the prognosis of patients with CD20-positive non-Hodgkin lymphoma has significantly improved. Recent reports have shown a gender-associated difference in rituximab clearance and clinical response, suggesting that rituximab may be more effective in female patients. However, the prognostic impact of gender with regard to rituximab clearance in diffuse large B-cell lymphoma (DLBCL) patients has not been elucidated thus far. Methods We retrospectively analyzed data from 368 consecutive DLBCL patients, uniformly treated with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-21) therapy in 7 institutions in Japan, between 2001 and 2009. Patients with a dose reduction greater than 20%, mainly elderly patients with low performance status, were excluded from this study. The median age of the cohort was 64 years (range, 18–80 years), and 209 (57%) of the patients were male. Results With respect to the International Prognostic Index (IPI) factors, a significantly higher proportion of female patients had elevated serum lactate dehydrogenase (sLDH) levels than male patients (56% vs. 44%, P = 0.02). A difference was also observed in the frequency of bone marrow (BM) involvement, which was primarily observed in male patients (8% in women vs. 18% in men, P = 0.006). No difference was observed between sexes in other baseline factors (additional IPI factors, bulky mass over 10 cm, B symptoms). Complete remission rate for R-CHOP-21 was 86% in female patients and 91% in male patients (P = 0.1). After a median follow-up of 36 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 74.9% and 84.5%, respectively. The IPI on diagnosis was low for 158 (42.9%) patients, low-intermediate for 93 (25.3%) patients, high-intermediate for 57 (15.5%) patients, and high for 60 (16.3%) patients, with significant differences in survival among the 4 groups (3-year OS: 93.8%, 85.2, 82.6%, and 60.2%, respectively, P < 0.001). Univariate analysis revealed that advanced clinical stage, poor performance status (PS 2-4), elevated sLDH, more than 1 extranodal involvement, BM involvement, bulky mass over 10 cm, and B symptoms had prognostic impact for both PFS and OS. However, there was no significant difference in the survival rate between female and male patients (3-year PFS; 72.7% vs. 78.0%, P = 0.4; 3-year OS; 82.7% vs. 76.5%, P = 0.4). Moreover, gender did not have an impact on prognosis among younger (<60 years)/elderly (>60 years), normal/elevated sLDH, and positive/negative BM involvement patients’ cohort. Multivariate analysis revealed that clinical stage (P = 0.001 for PFS, 0.02 for OS), sLDH (P = 0.03 for PFS), PS (P= 0.005 for OS), and bulky mass (0.02, 0.04) had a prognostic impact, whereas gender was not identified as a prognostic factor. Conclusion Although a difference in the rate of rituximab clearance has been previously reported, gender was not found to be a prognostic factor among DLBCL patients receiving uniform R-CHOP therapy in this study. Disclosures: No relevant conflicts of interest to declare.

Predictive Value of Bcl-2 and Bcl-6 Protein Expression in Diffuse Large B-Cell Lymphoma Patients from a Single Institution.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4546-4546
Author(s):  
Ewa Paszkiewicz-Kozik ◽  
Olga Mioduszewska ◽  
Irena Federowicz ◽  
Ewa Kraszewska ◽  
Elzbieta Kulczycka ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Predictive Value ◽  
Death Rate ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
B Cell Lymphoma ◽  
Advanced Clinical Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Bcl-2 and Bcl-6 protein expression has been reported to predict progression-free (PFS) and overall (OS) survival of patients with Diffuse Large B-cell Lymphoma (DLBCL) in retrospective and prospective clinical studies. Reports on Bcl-2 expression frequency and predictive value have been conflicting. In the current study, paraffin-embedded tissue specimens from 79 newly diagnosed DLBCL patients subsequently treated with CHOP-like chemotherapy without rituximab were studied retrospectively using immunohistochemistry to evaluate expected influence of Bcl-2 and Bcl-6 on clinical outcome. Bcl-2 and Bcl-6 positivity was defined as staining in any of lymphoma cells and it was demonstrated in 78% of Bcl-2 and 58% of Bcl-6 patients. Frequency of Bcl-2 protein expression in our study was much higher then reported by others. Combinations of possible positive/negative staining results: Bcl2+/Bcl6+, Bcl-2+/Bcl-6-, Bcl-2-/Bcl-6+, Bcl-2-/Bcl-6- were found in 46%, 33%, 13%, and 9% of cases, respectively. Complete remission (CR) after initial chemotherapy was achieved in 54 of 74 evaluable patients (73%) and 6 patients (8%) had progressive disease (PD). CR rate was higher and relapse and death rate was lower in patients with Bcl-6+ tumor irrespective of Bcl-2 status. In patients with Bcl-6 negative lymphoma CR rate was higher when Bcl-2 was positive, but relapse and death rate was not affected by Bcl-2. Median OS and PFS were not reached after 21.3 months of follow-up in this group of patients. In the analysis using multivariate proportional hazards regression model, advanced clinical stage (CS III and IV vs. CS I and II) was the only significant factor predicting OS (p&lt;0.002). Risk of relapse or PD was significantly lower in patients with IPI score of 0 or 1 vs. &gt; 1 (p&lt;0.001), and in patients with both Bcl-2 and Bcl-6 positive lymphoma (p=0.04) as compared to patients with all other protein expression combinations. When analyzed separately, Bcl-6 positivity alone predicted PFS (p=0.025) while Bcl-2 was not significant (p=0.98). These results support predictive value of Bcl-6 protein expression for response to CHOP and PFS in DLBCL patients and are in agreement with the recent findings from the E4494 trial group (Blood102:101a, Abstr. 345, 2003). Unlike the findings of the GELA study (Blood101: 4279, 2003), our data fail to confirm predictive role of Bcl-2 protein. Figure Figure

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