scholarly journals Hepatitis B Surface Antigen Positivity Is an Independent Unfavorable Prognostic Factor for Overall Survival in Patients with Diffuse Large B-Cell Lymphoma Treated with Standard Chemoimmunotherapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4235-4235
Author(s):  
Chieh-Lung Cheng ◽  
Erin Huang ◽  
Ming-Kai Chuang ◽  
Wen-Chien Chou ◽  
Hwei-Fang Tien
Keyword(s):  
Hepatitis B ◽  
B Cell ◽  
Cell Lymphoma ◽  
Hepatitis B Surface Antigen ◽  
B Cell Lymphoma ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Hbsag Positivity ◽  
Large B Cell Lymphoma ◽  
Significant Difference

Abstract Introduction Hepatitis B virus (HBV) is one of the most common viral infections in humans. Global prevalence of chronic HBV infection is heterogeneous, with 2-20% of a given population being infected with HBV. In some parts of Africa, Asia and South America, HBV infection is endemic and remains to be a significant public health issue.Previous studies have shown a positive association between hepatitis B surface antigen (HBsAg)-positive HBV infection and B-cell non-Hodgkin lymphoma (NHL), such as diffuse large B-cell lymphoma (DLBCL), the most common subtype of B-cell NHL. Nevertheless, the clinical characteristics of HBsAg positivity and negativity, as well as their prognostic implications in DLBCL patients treated with frontline standard chemoimmunotherapy remain to be clarified. Methods We conducted a single-institution retrospective study in a tertiary referral hospital in Taiwan, an HBV prevalent country in Asia. From January 2001 to December 2015, patients aged ≥20 years with newly diagnosed DLBCL treated with standard rituximab plus combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were selected. Retrospective chart review was performed to collect data on clinical features, laboratory profiles, serum markers for HBV infection such as HBsAg and HBV-DNA loads before chemotherapy, as well as data on treatment response and outcome. The cohort was followed up until the cutoff date of June 30, 2018. Results A total of 393 DLBCL patients were analyzed in this study, with a median age of 60.5 years (range, 23.5 years to 90.9 years) and the sex ratio of 1.38 to 1.The 5-year overall survival (OS) rates were 65.2% after a median follow-up time of 68.8 months. In this cohort, 100 patients (25.4%) were found to have HBsAg positivity before treatment.Eighty-two of them had received prophylactic antiviral therapy, including 28 with lamivudine, 44 with entecavir and 10 with others. Besides, forty-five of HBsAg-positive patients had data of serum HBV-DNA loads before treatment, and 44 of them had received prophylactic anti-HBV therapy. Compared to HBsAg-negative patients, HBsAg-positive patients had a younger median onset age (55.9 years vs. 61.4 years, P=0.004), a trend of more advanced stage (stage III/IV: 62% vs. 51.2%, P=0.064), higher serum LDH levels at diagnosis (62% vs. 50.2%, P=0.048), and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (high-intermediate/high: 50% vs. 41.6%, P=0.162). Regarding to treatment response and outcome, HBsAg-positive patients, compared to HBsAg-negative patients, had a trend of lower overall response rates (78% vs. 84.3%, P=0.169) and complete remission rates (73% vs. 79.9%, P=0.163). Furthermore, compared to HBsAg-negative patients, HBsAg-positive patientshad a poorer median OS (median OS, not reached vs. 95.8 months, P=0.001, Figure 1) and a shorter median progression-free survival (PFS) (median PFS, not reached vs. 34.3 months, P=0.031), respectively. By multivariate analysis, HBsAg positivity is an independent poor prognostic factor for OS irrespective of NCCN-IPI score, serum albumin levels and B symptoms. No significant difference was found in outcome between patients with high HBV-DNA loads (> 2000 IU/mL, n=21) and those with low HBV-DNA loads (≤2000 IU/mL, n=24). With respect to prophylactic anti-HBV treatment, patients without prophylactic therapy (n=18), compared to those with prophylactic therapy (n=82), had a trend of shorter median OS (27.9 months vs. 96.2 months, P=0.346). Moreover, no significant difference was found in median OS between HBsAg-positive patients when administrated with anti-HBV lamivudine and those when administrated with anti-HBV entecavir. Conclusions This study demonstrated that HBsAg positivity has unique clinical relevance to patients with DLBCL, as well as its impact in the efficacy of treatment. HBsAg positivity may serve as a relevant biomarker to predict clinical outcome in DLBCL patients treated with R-CHOP. Prophylactic anti-HBV therapy may be of great importance in HBsAg-positive DLBCL patients. Further studies to explore the etiopathogenesis of HBV infection in DLBCL may help to discovery new treatment targets to improve the outcome of this group of patients. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Prospective Analysis of Hepatitis B Virus Reactivation in Patients With Diffuse Large B-Cell Lymphoma After Rituximab Combination Chemotherapy

2010 ◽  
Vol 28 (34) ◽  
pp. 5097-5100 ◽  
Author(s):  
Nozomi Niitsu ◽  
Yuki Hagiwara ◽  
Ken Tanae ◽  
Mika Kohri ◽  
Naoki Takahashi
Keyword(s):  
Hepatitis B ◽  
B Cell ◽  
Cell Lymphoma ◽  
Hepatitis B Surface Antigen ◽  
B Cell Lymphoma ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
Large B Cell Lymphoma ◽  
B Virus ◽  
Large B Cell

Purpose Recently, there have been reports of hepatitis B virus (HBV) reactivation after rituximab combination chemotherapy in hepatitis B surface antigen (HBsAg) –negative patients with B-cell lymphoma. In this prospective study, the frequency of and risk factors for HBV reactivation in patients who were receiving rituximab chemotherapy were examined. Patients and Methods A total of 314 HBsAg-negative patients with diffuse large B-cell lymphoma were treated with rituximab chemotherapy. Antibody to hepatitis B surface antigen (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) tests were performed in all patients. In patients who were positive for anti-HBs and/or anti-HBc, serum HBV-DNA was measured. Results Of the 314 patients, 51 (16.2%) were HBV carriers. HBV reactivation occurred during or after rituximab chemotherapy in six patients (12%). All six patients who developed HBV reactivation were anti-HBc positive, and three of them were also anti-HBs positive. In these six patients, the pretreatment anti-HBs titer was low. Entecavir administration was started when serum HBV DNA became positive, and serum HBV-DNA became negative within 1 to 3 weeks. Rituximab chemotherapy was then continued. Risk factors for HBV reactivation were being male and having a low anti-HBs titer. Conclusion HBV reactivation occurred in some patients who had been anti-HBs negative or had a low anti-HBs level. In addition, HBV reactivation occurred at an early stage of rituximab chemotherapy, but rituximab chemotherapy could be continued after entecavir administration reduced the serum HBV-DNA level. Entecavir (BMS 200495) prophylaxis was not performed when rituximab chemotherapy was started, and it was thought that entecavir could be started when serum HBV-DNA increased.

Prospective Analysis of Hepatitis B Virus Reactivation In Patients with Diffuse Large B Cell Lymphoma After Rituximab Combination Chemotherapy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3950-3950
Author(s):  
Nozomi Niitsu ◽  
Yuki Hagiwara ◽  
Ken Tanae ◽  
Mika Kohri ◽  
Miyuki Hayama ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
Large B Cell Lymphoma ◽  
B Virus ◽  
Large B Cell

Abstract Abstract 3950 Reactivation of hepatitis B virus (HBV) was reported in patients who were being treated with rituximab-combination chemotherapy (R-chemotherapy). HBV reactivation was a well-known complication in lymphoma patients who were positive for hepatitis B surface antigen (HBsAg) in the pre-rituximab era. Recently, it was reported that HBV reactivation can occur in HBsAg-negative patients with past infection of HBV, upon administering R-chemotherapy for B-cell lymphoma. The association between rituximab and HBV reactivation is still unknown. There have been cases of HBV reactivation in patients with past HBV infection during the course of chemotherapy and/or immunotherapy, sometimes proving fatal. Nevertheless, it remains uncertain whether diffuse large B-cell lymphoma (DLBCL) patients with past HBV infection are at substantial risk for reactivation of latent HBV. We prospectively studied the frequency of and risk factors for HBV reactivation in DLBCL patients who received R-chemotherapy. A total of 356 HBsAg-negative patients with DLBCL were treated with R-chemotherapy. Anti-HBs and anti-HBc tests were performed in all patients. In patients who were positive for anti-HBs and/or anti-HBc, serum HBV-DNA was measured. The serum HBV-DNA load was determined by quantitative RT-PCR [COBAS® AmpliPrep/COBAS® TaqMan® HBV-Test, Roche Diagnostics K.K. Tokyo, Japan]. A total of 356 HBsAg-negative patients with DLBCL were enrolled in this study. Among the 51 (16.2%) HBV carriers, 6 patients developed HBV reactivation and 45 patients did not develop HBV reactivation during the study period. Exploratory analysis was conducted on potential factors associated with the development of HBV reactivation. Male gender and having a low anti-HBs titer before R-chemotherapy were significantly associated with HBV reactivation. Age, clinical stage, B symptoms, lactate dehydrogenase (LDH), performance status, international prognostic index, and chemotherapy regimen were not associated with HBV reactivation. Among the 51 HBV carriers, 8 patients (15.7%) were positive for only anti-HBs, 27 (53%) were positive for both anti-HBs and anti-HBc, and 16 (31.3%) were positive for only anti-HBc. HBV reactivation occurred during or after R-chemotherapy in the 6 patients (12%); two patients developed reactivation after three or seven cycles of R-CHOP, respectively, whereas four patients developed reactivation after completion of R-CHOP therapy at a median interval of 90 days (range, 20 to 143 days). All 6 patients who developed HBV reactivation were positive for anti-HBc, and 3 of them were also positive for anti-HBs. The pretreatment anti-HBs titer of the 6 patients was low (range, <2.0 to 40.2 mIU/ml). When HBV-DNA became detectable in the serum, entecavir administration was started and the serum HBV-DNA became negative within 13 weeks. Elevation of ALT and AST was not observed in any of the 6 patients. The serum HBV-DNA level did not increase after entecavir administration was started in any patient. When HBV reactivation occurred, the liver function did not become elevated and HBsAg remained negative in all six patients. After serum HBV-DNA became undetectable, R-chemotherapy was resumed. None of the 6 patients developed hepatitis B. In the 6 patients who developed HBV reactivation, the anti-HBs titer before R-chemotherapy and the anti-HBs titer at the time of HBV reactivation did not significantly differ. In the 45 patients who did not develop HBV reactivation, the anti-HBs titer before R-chemotherapy ranged from 11.6 to <1,000 mIU/ml. After the end of R-chemotherapy, the anti-HBs titer was lower in 42 of the 45 patients. The posttreatment anti-HBs titer of the 42 patients was 10.2–542 mIU/ml. The anti-HBs titer returned to the value before the start of R-chemotherapy 6–18 months after the end of R-chemotherapy. HBV reactivation occurred in some patients who had been anti-HBs-negative or had a low anti-HBs level. In addition, HBV reactivation occurred at an early stage of R-chemotherapy, but R-chemotherapy could be resumed after entecavir administration reduced the serum HBV-DNA level. Entecavir prophylaxis was not performed when R-chemotherapy was started, and it was thought that entecavir could be started when the serum HBV-DNA increased. Disclosures: No relevant conflicts of interest to declare.

Hepatitis B e Antibody Positive before Rituximab Combination Chemotherapy Is Associated with a Lower Risk of Hepatitis B Virus (HBV) Reactivation in HBV Carriers with Diffuse Large B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1655-1655
Author(s):  
Qingqing Cai ◽  
Kailin Chen ◽  
Qirong Geng ◽  
Guangzheng Zhong ◽  
Jianping Li ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Combination Chemotherapy ◽  
Lower Risk ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
B Virus

Abstract Background: With antivirus prophylaxis, reactivation of hepatitis B virus (HBV) also occurred in HBV carriers (hepatitis B surface antigen [HBsAg] positive) undergoing rituximab combination chemotherapy. It was reported that most HBV carriers with improved long-term outcomes were seropositive for hepatitis B e antibody (HBeAb). In this study on HBsAg-positive lymphoma patients with prophylaxis, the objectives were to determine the HBV reactivation rate in patients with HBeAb positive compared with the patients with HBeAb negative. Methods: We retrospectively analyzed the medical records of 113 HBV carriers with CD20(+) diffuse large B-cell lymphoma (DLBCL) received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy with antivirus prophylaxis between August 1, 2002 and November 31, 2011 at Sun Yat-sen University Cancer Center, China. Results: Among 113 HBV carriers with CD20(+) DLBCL, 68(60.2%) were hepatitis B e antibody (HBeAb) positive. There was no significant difference in terms of sex distribution, age, ECOG PS, stage, baseline HBV DNA detectable rate, or ALT, AST, bilirubin, or LDH between the HBeAb positive group and the HBeAb negative group. However, there were a significantly higher proportion of HBeAg seronegativity (94.1%v 24.4%; P< .001), and HBcAb seropositivity (100.0%v 82.2%; P< .001) in the HBeAb positive group. All the patients received antiviral therapy before chemotherapy. The antiviral treatments were used as follows: lamivudine in 68 (60.2%) patients, entecavir in 18 (15.2%) patients, others in 27 (23.8%) patients. Other antiviral treatments were including adefovir, lamivudine plus entecavir, lamivudine at beginning and then entecavir, and so on. No significant difference was observed in the antiviral drugs between the two groups. After R-CHOP chemotherapy, HBV reactivation was found in 23.0% of HBV carriers (26/113). And its incidence rate was lower in HBsAg- positive / HBeAb positive patients than in HBsAg-positive/ HBeAb negative patients (16.1% versus 33.3%; P =.034). Multivariate analysis showed that patients positive for HBeAb before chemotherapy was the only significant and independent protective factor associated with hepatitis due to HBV reactivation after chemotherapy. Chemotherapy was continued when the serum HBV-DNA level reduced or liver function improved. Survival was not affected by the occurrence of HBV reactivation or the status of HBeAb. Conclusion: HBeAb positive before rituximab combination chemotherapy was associated with a lower risk of HBV reactivation in HBV carriers with CD20(+) DLBCL. A more effective antivirus prophylaxis may be considered in HBV carriers with HBeAb negative in order to reduce HBV reactivation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Genetic landscape of hepatitis B virus–associated diffuse large B-cell lymphoma

Blood ◽  
2018 ◽  
Vol 131 (24) ◽  
pp. 2670-2681 ◽  
Author(s):  
Weicheng Ren ◽  
Xiaofei Ye ◽  
Hong Su ◽  
Wei Li ◽  
Dongbing Liu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hbv Infection ◽  
Disease Stage ◽  
Large B Cell Lymphoma ◽  
B Virus ◽  
Large B Cell

Hepatitis B virus (HBV) infection is endemic in some parts of Asia, Africa, and South America and remains to be a significant public health problem in these areas. It is known as a leading risk factor for the development of hepatocellular carcinoma, but epidemiological studies have also shown that the infection may increase the incidence of several types of B-cell lymphoma. Here, by characterizing altogether 275 Chinese diffuse large B-cell lymphoma (DLBCL) patients, we showed that patients with concomitant HBV infection (surface antigen positive [HBsAg+]) are characterized by a younger age, a more advanced disease stage at diagnosis, and reduced overall survival. Furthermore, by whole-genome/exome sequencing of 96 tumors and the respective peripheral blood samples and targeted sequencing of 179 tumors from these patients, we observed an enhanced rate of mutagenesis and a distinct set of mutation targets in HBsAg+ DLBCL genomes, which could be partially explained by the activities of APOBEC and activation-induced cytidine deaminase. By transcriptome analysis, we further showed that the HBV-associated gene expression signature is contributed by the enrichment of genes regulated by BCL6, FOXO1, and ZFP36L1. Finally, by analysis of immunoglobulin heavy chain gene sequences, we showed that an antigen-independent mechanism, rather than a chronic antigenic simulation model, is favored in HBV-related lymphomagenesis. Taken together, we present the first comprehensive genomic and transcriptomic study that suggests a link between HBV infection and B-cell malignancy. The genetic alterations identified in this study may also provide opportunities for development of novel therapeutic strategies.

scholarly journals Bone Marrow Molecular Markers Associated with Relapsed/Refractory Activated B-Cell-Like Diffuse Large B-Cell Lymphoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Di Wang ◽  
Peng Liu ◽  
Yue Zhang ◽  
Hui-Ying Liu ◽  
Di Shen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Molecular Markers ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Significant Finding ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin’s lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry. Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton’s tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients. The same smear could present positive expression of multiple proteins simultaneously. Positive combinations of protein expression were associated with resistance. The most significant finding was that the Stat3+NF-κB+ group developed resistance, which was significantly higher than that of the Stat3-NF-κB-group (80 vs. 14%). There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-κB (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001). Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears. At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.

Outcome of Diffuse Large B-Cell Lymphoma with First-line Chemotherapy

2021 ◽  
Vol 5 (01) ◽  
pp. 03-09
Author(s):  
Zulfia Zinat Chowdhury ◽  
Tamanna Bahar ◽  
Shaila Rahman ◽  
Salina Haque ◽  
A K M Mynul Islam ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Retrospective Data Analysis ◽  
Significant Difference ◽  
Line Chemotherapy ◽  
Large B Cell

Background: Diffuse Large B-Cell Lymphoma (DLBCL), most common Non-Hodgkin Lymphoma (NHL) variety, is an aggressive, fast-growing form comprising up to 40% of all cases globally. Objective: To observe the treatment outcome of different subtypes of Diffuse Large B-Cell Lymphoma (DLBCL) after first-line chemotherapy and also the association with IHC, presenting age, sex, and IPI score with outcome. Methodology: This is a retrospective data analysis included all DLBCL patients registered in the department of Haematology of National Institute of Cancer Research and Hospital (NICRH) between July 2016 to June 2019. Results: Total 188 cases were included in this study and mean age was 48 years with a Standard deviation of 15 years with Male (69.1%) predominance. We divide the cases into three different entities of DLBCL [Germinal Centre B-cell like (GCB), Non-GCB and others (NOS) among them Non-GCB variety was the prevalent (47.3%) one. After first line   chemotherapy 52.1% complete remission with 7% death was observed in overall outcome. There was no significant difference in outcome among different types of DLBCL after chemotherapy based on Han’s algorithm. Rituximab with CHOP has significantly better outcome than CHOP alone arm (p: 0.021). Conclusion: This limited database study of NICRH will help to ascertain the outcome of DLBCL after first-line chemotherapy in Bangladesh.

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