bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Analysis of Prognostic Significance of Absolute Lymphocyte Count and Lymphocyte-to-Monocyte Ratio in Diffuse Large B-Cell Lymphoma
Authors: Huang Haiwen , Liu Ying , Jin Zhengming , Depei Wu 
Published: October 2019

Abstract
【Objective】
To evaluate the prognostic value of absolute lymphocyte count (ALC)and lymphocyte-to-monocyte ratio (LMR) in Diffuse large B-cell lymphoma(DLBCL) when they are diagnosised.
【Methods】
Sixty-nine cases were analyzed retrospectively, including sex, age, stage, B symptoms, absolute lymphocyte count, absolute monocyte count, lymphocyte-to-monocyte ratio, lactate dehydrogenase, IPI score, bulky disease, ECOG performance status, number of extranodal involvement. Thirty-four received CHOP treatment (cyclophosphamide, vincristine, adriamycin, dexamethasone) , thirty-five received R-CHOP (rituximab plus CHOP). The ALC, AMC, LMR cutoff value for survival analysis were 1.0×109/L, 0.3×109/L, 2.6 respectively. All data were analyzed by statistical package for the social sciences (SPSS) software ‘‘version 18.’’ Chi-square test wasused to compare the difference between two groups of means. The Kaplan–Meier method was used to summarize OS and PFS and the logrank test was used for univariable analysis. The Cox proportional hazards model was used for multivariable analyses of measured factors.
【Results】
1. Patients with ALC<1.0×109/L had a high incidence of advanced Ann Arbor stage (P=0.003) , B symptoms (P=0.001) , elevated LDH level (P<0.001), high IPI score (P<0.001) and high ECOG score (P=0.001). Similar results were observed in patients with LMR<2.6. Patients with LMR<2.6 had a high incidence of advanced Ann Arbor stage (P<0.001) , B symptoms (P=0.005) , elevated LDH level (P<0.001), high IPI score (P<0.001) and high ECOG score (P=0.006).
2. In comparison with CHOP and RCHOP treatment, OS was significant longer with rituximab, as well as PFS(P＜0.05).
3. After a median 41.5 months follow-up, K-M analysis showed that lower ALC and LMR associated with inferior overall survival (OS) and progression free survival (PFS) (P＜0.001). In CHOP treatment group, patients with lower ALC and LMR seemed to have worse OS and PFS ( ALC: P=0.002 in OS,and P=0.005 in PFS; LMR: P=0.011 in OS, and P=0.027 in PFS). We got the same results in RCHOP set (ALC: P=0.001 in OS ; P=0.001 in PFS / LMR: P=0.001 in OS ; P=0.002 in PFS).
4. In multivariate analysis, only ALC were proven as an independent prognosis factor of survival(P<0.05).
【Conclusions】
the ALC and LMR at diagnosis were independent prognostic factors of both OS and PFS for patients with DLBCL. These data suggest that ALC can be used in combination with other prognostic features to better predict the outcome of DLBCL.

Disclosures
No relevant conflicts of interest to declare.
Hepatitis C Infection Is Associated with Hepatic Toxicity but Does Not Compromise the Survival of Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab-Based Chemotherapy
Authors: Bai Li-Yuan , Chen Tzu-Ting , Chiu Chang-Fang , Yang Tse-Yen , Yeh Su-Peng , Liao Yu-Min 
Published: October 2019

Abstract
Introduction: The influence of hepatitis C virus (HCV) infection on outcome of patients with diffuse large B cell lymphoma (DLBCL) treated with rituximab-based chemotherapy is still controversial.
Materials and Methods: We retrospectively analyzed the characteristic and clinical outcomes of patients with DLBCL newly diagnosed between Jan 2005 and Dec 2011. All patients were treated with at least one course of rituximab-containing chemotherapy. The clinical characteristics between groups (29 HCV-positive or 139 HCV-negative) were compared using a Chi-square method for categorical variables, a Student’s t-test for continuous variables, and a non-parametric method (Wilcoxon Sum-Rank test) for AST, AST and total bilirubin. Univariate analysis followed by multivariate analysis was used to identify the variables associated with hepatotoxicity.
Results: The medium follow-up duration was 3.0 (0.07-8.02) years. HCV infection resulted in more hepatic toxicity in both univariate (55.2% vs. 23.0%, P = 0.001) and multivariate (P = 0.003) analyses. In addition, HCV-positive DLBCL patients were more likely to have treatment delay (20.1% vs. 0.7%, P = 0.004). For patients who developed hepatic toxicity during immunochemotherapy, HCV-positive patients had significantly higher folds of aspartate aminotransferase elevation (3.39 folds vs. 2.06 folds, P = 0.042) and total bilirubin elevation (1.60 folds vs. 0.96 folds, P = 0.012) compared with those who were HCV negative. However, HCV did not influence the 5-year progression-free survival rate (P = 0.412) or 5-year overall survival rate (P = 0.410).
Conclusions: HCV infection is associated with increased incidence and severity of hepatic toxicity and delayed chemotherapy without compromised survival in DLBCL patients treated with rituximab-based chemotherapy.

Disclosures
No relevant conflicts of interest to declare.
The Prognostic Significance of Tumor-Associated Macrophages and NK Cells in Patients with Diffuse Large B-Cell Lymphoma Treated with RCHOP
Authors: Xie Muchen , Wei Yongqiang , Yang Lei , Huang Fen , Wei Xiaolei , Jing Hui , Hao Xiaoxiao , Zeng Hong , Feng Ru 
Published: October 2019

Abstract
Background
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). Although international prognostic index (IPI) has been widely used in DLBCL to evaluate the prognosis, there is need to find new biomarkers to predict outcome. Tumor microenvironment has been reported to be associated with both metastatic spread and diminished in some tumors. Tumor-associated macrophages (TAMs) and nature-killer (NK) cells play an important role in the tumor microenvironment. Therefore, we performed this study to investigate the prognostic implications of TAMs including M1 as well as M2 and NK cells in DLBCLs.
Materials and Methods
We reviewed 77 cases of DLBCL diagnosed between June 2004 and October 2012, who treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Patients were divided into GCB and non-GCB subgroups by Hans’ algorithm. We performed immunohistochemical stains using CD68, CD163 and CD57 to mark M1 macrophages, M2 macrophages and NK cells on paraffin tissue section. The percentage of TAMs was recorded and graded as: 0 if less than 5%, 1 if 5-25%, and 2 if greater than 25% of the total cells present in tumor cells rich nodules were positive for CD68 or CD163. And counting the mean number of the CD57+ cells in 5 fields under high-power magnification (400 times): 0 if less than 5 positive cellsG1 if more than 5 positive cells.
Results
Of the 77 DLBCL patients treated with R-CHOP, there were 51 males (66.2%), 26 females (33.8%). The median age was 52 years (range, 16-81 years). The median follow-up was 38.1 months. The median percentage for CD68 was 12.8 %( range, 2.4–50.84), for CD163 was 12.3 %( range, 1.0–39.2). The median counts of CD57 cells were 5 (range, 1.0-78) per unit area. In univariate analysis, an increase in CD68-positive cells was related to improved EFS (grade 0 vs. grade 2, p = 0.036). By contrast, an increased number of CD163-positive cells were significantly poor associated with OS, (grade0 vs grade2, p = 0.033). Patients with elevated NK cells tended to have no effect on prognosis. In multivariate analysis, an increased CD68 -positive cells was an independent predictors of EFS (HR 0.467, 95%CI 0.236-0.922, P=0.028), an decreased CD163-positive cells and lower LDH were independent predictors for OS (HR 2.287, 95%CI 1.043-5.013, P=0.039).
Conclusion
These results suggest that M1 macrophages might predict favorable clinical outcome and M2 macrophages predict poor clinical outcome. However, the NK cells have no prognostic significance in DLBCL patients treated with RCHOP.

Disclosures
No relevant conflicts of interest to declare.
Immunohistochemistry in Staging Bone Marrow Biopsy Specimens: a Useful Adjunct for Morphological Diagnosis in Non Hodgkin’s Lymphoma
Authors: Arami Siamak , Svec Alexandr 
Published: October 2019

Abstract
Background: Morphological examination of bone marrow trephine biopsy represents a standard method for non-Hodgkin’s lymphomas (NHL) staging. Immunohistochemistry staining of bone marrow trephine specimens has been widely used in haematological malignancies due to its high applicability and sensitivity at diagnosis. However, the routine use of immunohistochemistry in the clinical settings when there is no obvious morphological (light microscopic) evidence of lymphoma in the bone marrow trephine, is not yet well established universally. We assessed the value of immunohistochemistry (by using a standard basic panel of anti-CD20 and anti-CD3 staining) in detecting involvement by NHL in routinely processed bone marrow trephine specimens with no obvious morphological involvement with lymphoma.
Methods: This study involved 56 randomly selected paraffin wax embedded, formalin fixed bone marrow trephine specimens between February 2011 and September 2013 from three teaching hospitals in Northeast, UK. 49 patients (87%) had B-cell NHL: diffuse large B cell lymphoma (DLBCL) 43% (n=24), follicular lymphoma (FL) 18% (n=10), marginal zone lymphoma (MZL) 9% (n=5), mantle cell lymphoma (MCL) 7% (n=4), lymphoplasmacytic lymphoma (LPL) 6% (n=3) and Burkitt’s lymphoma (BL) 6% (n=3). 7 cases (12%) had T/NK lymphomas. There was no obvious morphological evidence of bone marrow infiltration as all samples were reviewed by two examiners. All specimens were stained with the anti-CD20 and anti-CD3 antibodies.
Results: Concordant results were found in 50 samples (89%), as both investigations were reported negative. 6 of the 56 cases (11%) with no morphological evidence of involvement by NHL on routine stains, were positive on immunohistochemistry. Considering histology, discrepant results were noted more frequently in T/NK lymphomas (42%; 3 of 7 cases) comparing to B-cell NHLs (6%; 2 cases of DLBCL and 1 case of FL). In all six cases the lymphoid infiltrates had diffuse pattern.
Conclusions: Our results indicate that immunohistochemistry can detect a subgroup of NHL patients with bone marrow involvement beyond discriminatory level of conventional stains (Haematoxylin & Eosin and Giemsa), thereby contributing to accuracy of staging and treatment planning. Rational application of immunohistochemistry is a cost-effective & valuable method in routine investigation of staging bone marrow trephine biopsies.

Disclosures
No relevant conflicts of interest to declare.
The Glasgow Prognostic Score (GPS) As a Significant Predictor of Diffuse Large B Cell Lymphoma Treated with the R-CHOP in China
Authors: Li Xiaoyang , Zhang Yunxiang , Zhu Hongming , Hu Jiong , Li Junmin 
Published: October 2019

Abstract
Background: The Glasgow Prognostic Score (GPS), consisting of C-reactive protein (CRP) and albumin (Alb), is clinically useful for tumor behavior and shows significant prognostic value in several types of tumors. Several studies showed that GPS could be a predictive marker for advanced solid tumor, such as colorectal cancer, gastric cancer, etc. Now we performed a retrospective study to evaluate the relationship between GPS and prognosis of 160 patients with diffuse large B cell lymphoma (DLBCL) receiving R-CHOP chemotherapy between January 2001 and May 2010 at Shanghai Ruijin Hospital.
Methods: Before treatment, the CRP and albumin were both tested for base line. Patients with both elevated CRP level (>10 mg/L) and hypoalbuminemia (<35 g/L) were given a score of 2. Patients with only one of these two biochemical abnormalities were allocated a score of 1. Patients in whom neither of these abnormalities was presented received a score of 0. We also identified International Prognostic Index (IPI) score of these patients.
Results: Patients were assorted into three groups based on GPS at diagnosis. Survival curves were performed using the Kaplan-Meier method. Results showed that the overall survival (OS) and progress-free survival (PFS) rates for all patients were 78.1% and 68.1%, respectively. Analyzed by log-rank test, there was significant difference between GPS 1, GPS 2 and GPS 3 for OS (90.8% vs. 76.6% vs. 38.5%, p<0.001) and PFS (86.2% vs. 66.0% vs. 15.4%, p<0.001) (Fig 1a and b). In addition, the IPI, as a well-accepted prognostic system, though showed significant difference between lower risk group (IPI 0-2) and higher risk group (IPI 3--5) for OS (89.1% vs. 54.0%, p<0.01), failed to identify patients with poor prognosis in the lower risk group, since the low risk (IPI=0-1) and low-intermediate risk groups (IPI=2) appeared closely overlapping (p>0.05). While combining with the IPI model, GPS can have powerful prognostic value in the lower-risk (IPI=0-2) DLBCL patients, since patients with GPS score=0 had better OS (P<0.001) and PFS (P<0.001) than those with GPS score=1--2(Fig 2a and b).
Conclusion: The GPS was a reliable and independent predictor of OS and PFS in patients with DLBCL treated with R-CHOP regimen. GPS combining with the IPI score may offer a more integrated prognostic system in the rituximab era of DLBCL. And inflammatory response might play an important role in the progression and survival of patients with DLBCL.
Figure 1 Figure 1.
Figure 2 Figure 2.

Disclosures
No relevant conflicts of interest to declare.
Predictive and Prognostic Significance of Immunohistochemical Markers and Blood Absolute Lymphocyte Count in Diffuse Large B-Cell Lymphoma in Rituximab Era: A Polish Lymphoma Research Group (PLRG) Multicenter Retrospective Analysis
Authors: Czyz Anna , Joks Monika , Drozd-Sokolowska Joanna E , Knopinska-Posluszny Wanda , Zawartko Magdalena , Mizera-Nyczak Ewa , Dytfeld Dominik , Zdziarska Barbara , Jedrzejczak Wiktor-Wieslaw , Komarnicki Mieczyslaw 
Published: October 2019

Abstract
This report is a retrospective analysis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP-21. The aim of the study was to determine the impact of peripheral blood absolute lymphocyte count (ALC), Ki67 proliferation index and immunohistochemical expression of Bcl-2 and Bcl-6 at diagnosis on complete response rate and survival.
The study group consisted of 161 patients with stage II-IV who were treated with six cycles of R-CHOP-21 between January 2004 and December 2013. With International Prognostic Index (IPI), 29% patients were low, 29% low-intermediate, 25% high-intermediate and 17% high risk. Bcl-2 and Bcl-6 expression was detected with immunohistochemical staining on paraffin sections in 83% and 77% of patients, respectively. Bcl-2 expression with high Ki67 proliferation index, greater than 80%, was found in 15% of patients. BcL-6 expression with Ki67 index of 80% or lower was detected in 52% of patients. Median ALC at diagnosis was 1.4 G/L (0.1-4.2). ALC below 1.0 G/L was revealed in 27% patients.
Results: The complete response rate to R-CHOP was 69%. In univariate logistic regression for complete response to immunochemotherapy, the variables that were correlated with lower response rate were IPI > 2 (p=0.016) and ALC < 1.0 G/L (p=0.014). In multivariate logistic regression, ALC < 1.0 G/L remained the only independent variable associated with failure to achieve complete response (OR 2.6; 95%CI 1.2-5.9; p=0.03). After the median follow-up time of 37 months (6-109), the 5-year progression free and overall survival (OS) estimated with Kaplan-Meier method were 67% (95% CI 56-76) and 66% (95% CI 55-75), respectively. In univariate analysis IPI (log-rank test, p=0.001), ALC (log-rank test, p=0.009) (fig.1), Bcl-2 expression with high Ki67 index (log-rank test, p=0.015) (fig.2) and Bcl-6 expression with low Ki67 index (log-rank test, p=0.05) were statistically significant for OS. In the multivariate analysis with Cox model, ALC at diagnosis (HR 2.9; 95%CI 1.1-7.3; p=0.024) and Bcl-2 expression with high Ki67 index (HR 2.8; 95%CI 1.1-7.5; p=0.039) remained significant for OS. IPI higher than 2 tended to impact negatively OS (HR 2.4; 95%CI 0.9-6.3; p=0.067).
In conclusion, our results indicate that low ALC at diagnosis is independent predictor of poor response to R-CHOP for patients with DLBCL. In addition, low ALC and Bcl-2 expression with high Ki67 index adversely influence patient survival in the rituximab era.
Figure 1 Figure 1. Figure 2 Figure 2.

Disclosures
No relevant conflicts of interest to declare.
Selective Inhibition of HDAC6 Decreases Viability of Cutaneous T-Cell Lymphoma and Improves Immune Recognition
Authors: Knox Tessa , Lienlaf Maritza , Perez-Villarroel Patricio , Lee Calvin , Sahakian Eva , Powers John J. , Cheng Fengdong , Canales Jorge , Marante Danay , Seto Ed , Sotomayor Eduardo M. , Villagra Alejandro , Horna Pedro 
Published: October 2019

Abstract
Cutaneous T-cell lymphoma (CTCL) includes a spectrum of non-Hodgkin’s T-cell lymphomas. While most patients with CTCL experience non-life threatening skin symptoms, those who do progress to later stages of the disease may develop serious complications. For patients with tumor stage or lymph node involvement there is a significant decline in treatment response & few treatment options are available. Current available therapeutic options include the use of histone deacetylase (HDAC) inhibitors as Romidepsin, Panobinostat and Vorinostat. However, their mechanism of action is still unknown. The role of histone deacetylases (HDACs) in cell biology, initially limited to their effects upon histones, now encompasses more complex regulatory functions that are dependent on their tissue expression, cellular compartment distribution, pathophysiological conditions and stage of cellular differentiation. Although major advances have been made in understanding the role of specific HDACs in cell proliferation and the survival of cancer cells, their individual participation in specific intracellular pathways is not completely understood. Here we present data demonstrating the changes in several immune-related pathways in two CTCL cell lines after exposure to both pan-HDAC inhibitors and selective HDAC6 inhibitors.
We compared the pharmacological effects of the pan-HDAC inhibitor LBH589 (Panbinostat), the class I selective Romidepsin, and the selective HDAC6 inhibitors such as TubastatinA and NexturstatB, on two CTCL cell lines (HuT78, HuT102). Our findings thus far demonstrate the following: First, we observed a marked inhibition of proliferation capacity of both cell lines when treated with either pan-HDACi or the more selective HDAC6 inhibitors. However, the selective HDAC6 inhibitors showed less cytotoxicity. Second, we observed important changes in the expression of the co-inhibitory molecules, such as PD-L1. Given our results, we conclude that the selective targeting of HDAC6 could recapitulate the anti-tumor effects of pan-HDAC inhibitors without having the non-target cytotoxic effects often encountered when using pan-HDAC inhibitors.

Disclosures
No relevant conflicts of interest to declare.
Imbalance in Alternative Splicing of MCL-1 Inhibits Apoptosis in Diffuse Large B-Cell Lymphoma
Authors: Rekers Nicolle H , Moesbergen Laura M , Hijmering Nathalie J , Vos Wim , Oudejans Joost , Ossenkoppele Gert J. , Meijer Chris JLM , Cillessen Saskia AGM 
Published: October 2019

Abstract
Diffuse large B-cell lymphoma (DLBCL) remains eventually fatal in 30-40% of the patients, despite intensive chemotherapy (CHOP) in combination with rituximab. A subgroup of chemotherapy-refractory DLBCL is characterized by high expression levels of both pro- and anti-apoptotic genes, including MCL-1. Alternative splicing of the MCL-1 gene results in a Bcl-2-like anti-apoptotic MCL-1L protein and a BH3-only pro-apoptotic MCL-1S protein. In the present study, we investigated if a switch in alternative splicing of MCL-1 is involved in apoptosis-resistance in primary lymphoma cells of 20 DLBCL patients and 5 DLBCL cell lines.
RT-MLPA analysis revealed that MCL-1L and MCL-1S are both expressed in all tested DLBCL samples and DLBCL cell lines, however expression levels varied strongly. An imbalance between the expression levels of MCL-1L and MCL-1S to an anti-apoptotic status was observed in DLBCL patient cells and DLBCL cell lines, especially in activated B-cell like (ABC)-DLBCL, compared to tonsillar germinal center B-cells. MCL-1 mRNA expression was confirmed at protein level using immunohistochemistry and western blot analysis. Co-immunoprecipitation demonstrated that MCL-1L inhibited apoptosis by binding of Bak in MCL-1L positive DLBCL cell lines. Knockdown of MCL-1L with siRNA analysis resulted in induction of apoptosis in both GCB- and ABC-DLBCL cell lines and also in increased sensitivity to the conventional chemotherapeutical drugs etoposide. Downregulation of MCL-1L using flavopiridol induced apoptotic cell death of MCL-1L-positive DLBCL cells with low Bcl-2 expression.
In summary, a switch in alternative splicing of MCL-1 occurs in a subgroup of DLBCL leading to an increase in the level of anti-apoptotic MCL-1L that contributes to therapy-resistance. These preclinical data suggest that targeting of MCL-1L might be a therapeutic option for MCL-1L positive DLBCL.

Disclosures
No relevant conflicts of interest to declare.
Impact of FDG-PET/CT in Staging, Response Evaluation and Decision of Radiotherapy for Pediatric Hodgkin Lymphoma
Authors: Khan Safia , Riaz Shazia , Ahmecd Mehoob , Kazmi Ather , Bashir Humayun 
Published: October 2019

Abstract
PURPOSE: To review the role of FDG-PET/CT in staging, assessment of treatment response, and decision of radiotherapy among Pediatric Hodgkin Lymphoma patients.
MATERIALS & METHOD: 125 hodgkin lymphoma patients up to 18 years of age who were evaluated with FDG-PET/CT for staging workup, treatment response and planning for radiatherapy during 2010-2013 in Shaukat Khanum Memorial Cancer Hospital & Research Center, Lahore, Pakistan were retrospectively reviewed for this study. 104 out of 125 patients were evaluated in mid treatment with FDG-PET/CT by giving F18 FDG dose 0.21mg/Kg intravenously in resting condition followed by imaging over 25-30 min; contrast enhanced CT was required as a part of PET/CT protocol. Remaining 21 patients were evaluated for treatment response with isolated contrast enhanced CT due to non-availability of FDG-PET/CT.
RESULTS: Majority (82%) of the patients fall under the age group of 5 to 15 years. However, ratio of male patients was greater than female i.e. about 3:1. From Chi square analysis it is revealed that there is substantial association between staging with FDG-PET/CT and conventinal CT. From cross tabulation it is concluded that FDG-PET/CT downstaged one patient and up staged eight patients. On the bases of interim CT, radiotherapy was given to 7 patients of which 5 relapsed. Based on FDG-PET/CT 19 patients received radiotherapy, out of these 19 patients 10 relapsed.
The 48% of 21 patients evaluated by conventional CT relapsed and 15% of 104 patients evaluated by FDG-PET replaped.
CONCLUSION:Based on our data , initial staging FDG-PET/CT upstaged more patients than convential CT, while at mid-treatment response evaluation less patients received radiation in FDG-PET/CT group. Relapse rate was lower in FDG-PET/CT group.

Disclosures
No relevant conflicts of interest to declare.