Progression of Primary Gastric Diffuse Large B-Cell Lymphoma after Helicobacter pylori Eradication

In Helicobacter pylori-positive, localized primary gastric diffuse large B-cell lymphoma (DLBCL), an increasing number of reports have recently been published on the effectiveness of H. pylori eradication (HPE). However, HPE treatment strategies for gastric DLBCL, including its indications, have yet to be examined. No detailed report has been published on a case of gastric DLBCL unsuccessfully treated by HPE. A 64-year-old female and a 70-year-old male were pathologically diagnosed with chronic active gastritis and mucosa-associated lymphoid tissue lymphoma, respectively. Both patients were positive for H. pylori, so HPE was employed. The disease progressed within 1 year, and both patients were pathologically diagnosed with DLBCL by endoscopic biopsy. On reviewing the first pathology slide, both patients were diagnosed with DLBCL. That is, the 2 patients had primary gastric DLBCL; however, they exhibited progressive disease after HPE. This failure of HPE treatment may be due to the initial lymphomas being multiplex ulcerative lesions. In both cases, complete remission was achieved by chemotherapy (plus radiation therapy) without recurrence for more than 3 years.

Download Full-text

Helicobacter pylori infection disturbs the tumor immune microenvironment and is associated with a discrepant prognosis in gastric de novo diffuse large B-cell lymphoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002947 ◽

2021 ◽

Vol 9 (10) ◽

pp. e002947

Author(s):

Yuwei Deng ◽

Wenjia Su ◽

Junwen Zhu ◽

Hongfei Ji ◽

Xiaoping Zhou ◽

...

Keyword(s):

Helicobacter Pylori ◽

B Cell ◽

De Novo ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Immune Microenvironment ◽

Large B Cell Lymphoma ◽

Tumor Immune Microenvironment ◽

H Pylori ◽

Large B Cell

BackgroundGastric diffuse large B-cell lymphoma (gDLBCL) related to Helicobacter pylori infection exhibits a wide spectrum of prognosis, and the tumor immune microenvironment (TIME) affects tumor progression. However, there are few studies on the correlation between prognosis and changes of TIME induced by H. pylori infection in de novo gDLBCL.MethodsA retrospective study was performed to determine the prognostic value of TIME related to H. pylori infection in de novo gDLBCL. A total of 252 patients were included and have been treated with standard rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy or other similar regimens in addition to H. pylori eradication (HPE). All patients were stratified by H. pylori infection, HPE efficacy, and preliminary TIME evaluation using conventional criteria. Statistical analyses were conducted. To assess the mechanism, 30 subjects were assessed for H. pylori infection. The components and spatial distributions of TIME were analyzed.ResultsThe median follow-up of the 252 patients was 66.6 months (range 0.7–119.2), and the 5-year overall survival (OS) was 78.0%. A total of 109 H. pylori-positive cases with pathological complete remission and high tumor-infiltrating T lymphocytes (cohort 1) had significantly higher 5-year progression-free survival (88.1% vs 70.5%, p<0.001) and OS (89.2% vs 76.6%, p<0.001) than the other 143 patients (cohort 2). Among 30 patients, 19 were cytotoxin-associated gene A-marked as the cohort 1 subset. Compared with cohort 2, cohort 1 exhibited increased inflammatory factors (tumor necrosis factor-α, interferon γ, etc) and decreased immunosuppressive components (PD-L1, PD-1, IL-10, etc). There was reduced NF-kB activation. Cancer-promoting immune cells (PD-1hiTim-3+ CTL, Tregs, M2-like macrophages, etc) occupied a minor spatial distribution, while the antitumor subtypes increased, corresponding to favorable survival.ConclusionH. pylori-evoked inflammatory responses disturb the TIME, causing a differential prognosis in de novo gDLBCL, which can be used to identify patients who could benefit from HPE and immunochemotherapy.

Download Full-text

Early 18fluorodeoxyglucose PET Scan as a Prognostic Tool in Diffuse Large B-Cell Lymphoma Patients Treated with An Anthracycline-Based Chemotherapy Plus Rituximab.

Blood ◽

10.1182/blood.v114.22.98.98 ◽

2009 ◽

Vol 114 (22) ◽

pp. 98-98 ◽

Cited By ~ 5

Author(s):

Violaine Safar ◽

Jehan Dupuis ◽

Fabrice Jardin ◽

Christophe Fruchart ◽

Stéphane Bardet ◽

...

Keyword(s):

B Cell ◽

Prognostic Value ◽

Cell Lymphoma ◽

Treatment Strategies ◽

B Cell Lymphoma ◽

Rank Test ◽

Log Rank Test ◽

Large B Cell Lymphoma ◽

Dose Dense ◽

Large B Cell

Abstract Abstract 98 Background: 18Fluorodeoxyglucose PET has been quickly integrated to the diagnostic and therapeutic armamentarium in diffuse large-B cell lymphoma (DLBCL). Moreover, early PET appears a promising prognostic tool for tailoring treatment strategies. We evaluated the predictive value of early PET in a large prospective cohort of patients treated with immunochemotherapy. Patients and methods: 112 previously untreated patients from three institutions were treated between January 2000 and October 2008 for DLBCL using an anthracycline-based regimen plus Rituximab. Chemotherapy was either an R-CHOP21 regimen (n=57) or a dose-dense regimen (R-ACVBP, n=31 or R-CHOP14, n= 24). PET was performed at diagnosis and after two cycles of treatment. Early PET results were interpreted visually as positive (PET2p) or negative (PET2n), as previously described1, but did not modify the scheduled therapy. Results: Median age at diagnosis was 59 years (range 20–79 years) and 67% of patients were males, 44% were over 60 years, 81% presented with an advanced Ann Arbor stage (III–IV), 29% had a poor performance status (ECOG 2-4), 36% had more than one extra-nodal site involved and LDH were elevated in 68%. The repartition on the basis of the International Prognosis Index was the following: low=5%, low-intermediate =35%, intermediate-high=37% and high risk=23%. After two cycles, 70 patients (63%) were PET2n and 42 (38%) were PET2p (38 patients in partial response and 4 with stable disease). Median follow-up was 38 months for living patients. Ten of 70 (14%) PET2n patients showed progression versus 22 of 42 (52%) PET2p patients. The estimated 5-year progression free survival (PFS) was 81% for PET2n and 47% for PET2p patients (log rank test, p<0.0001). Prognostic value of early PET was significant in terms of PFS whether patients were treated with R-CHOP21 (p=0.0006) or with dose-dense regimens (p=0.0056). Nine of 70 (13%) PET2n and 15 of 42 (36%) PET2p patients died. The estimated 5-year overall survival (OS) was 88% for PET2n and 62% for PET2p patients (log rank test, p<0.0034). Prognostic value of early PET was significant in terms of OS for patients treated with R-CHOP21 (p=0. 0225) but not for those treated with dose-dense regimens (p=0.133). Conclusion: Early PET after 2 cycles of treatment is a powerful tool to predict outcome in DLBCL patients treated with Rituximab combined with an anthracycline-based chemotherapy. It brings promising opportunities in the designing of new treatment strategies for DLBCL. Reference : 1 Haioun et al. Blood 2005; 106(4):1376–81. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

A Retrospective Analysis of Gastric Diffuse Large B-Cell Lymphoma with or without MALT Component

Blood ◽

10.1182/blood.v120.21.4856.4856 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4856-4856

Author(s):

Xiaowu Li ◽

Bing Xia ◽

Shanqi Guo ◽

Eduardo M. Sotomayor ◽

Yong Yu ◽

...

Keyword(s):

Surgical Treatment ◽

B Cell ◽

Clinical Characteristics ◽

De Novo ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Advanced Stage ◽

Large B Cell Lymphoma ◽

H Pylori ◽

Large B Cell

Abstract Abstract 4856 Background: The aim of this study was to evaluate the clinical characteristics, prognostic factors and survival outcomes of patients with gastric diffuse large B-cell lymphoma (DLBCL). Patients and methods: 162 patients with gastric DLBCL were evaluated retrospectively. Comparisons were made between patients of gastric DLBCL with component of mucosa-associated lymphoid tissue lymphoma (DLBCL/MALT) and patients of gastric DLBCL without detectable MALT component (de novo DLBCL). Results: Results according to the distribution of sex, age, stage, performance status, and other clinical characteristics were similar between de novo DLBCL group and DLBCL/MALT group (p>0.05). The ratio of patients with the germinal center B-cell-like (GCB) subtype to non-GCB subtype did not differ significantly between the two groups (1:1.1 versus 1:1.6, p=0.319). However, the proportion of patients with the stage-modified international prognostic index (m-IPI) ≥2 was higher in DLBCL/MALT groups (18%) than taht in de novo DLBCL groups (34%) (p=0.026). In addition, the H. pylori infection rate was 75% in DLBCL/MALT versus 38% in de novo DLBCL (p<0.001). Patients with de novo DLBCL have better 5-year PFS and OS estimates than those DLBCL/MALT patients (p=0.037 and 0.019 for the 5-year PFS and OS estimates, respectively). Surgical treatment did not offer survival benefit when compared with chemotherapy (p=0.405 and 0.065 for the 5-year PFS and OS estimates, respectively). Multivariate analysis revealed that non-GCB classification and m-IPI≥2 were independently associated with shorter OS and advanced stage was independently associated with shorter PFS. Conclusion: Gastric DLBCL is a heterogeneous disease that included de novo DLBCL and DLBCL/MALT lymphoma. Compared with the former, the latter has a higher H. pylori infection rate. And what's more, the proportion of patients with m-IPI≥2 is higher in DLBCL/MALT groups. De novo DLBCL was associated with higher 5-year PFS and OS estimates. Non-surgical treatment should be a primary consideration for gastric DLBCL. Immunophenotype classification and m-IPI were the most reliable factors for OS, and advanced stage was for PFS. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Gastric Diffuse Large B-cell Lymphoma Cured with Helicobacter pylori Eradication Regardless of Whether it Contains Features of MALT Lymphoma

Internal Medicine ◽

10.2169/internalmedicine.53.1603 ◽

2014 ◽

Vol 53 (7) ◽

pp. 695-698 ◽

Cited By ~ 2

Author(s):

Kei Mitsuhashi ◽

Kentaro Yamashita ◽

Akira Goto ◽

Takeya Adachi ◽

Yoshihiro Kondo ◽

...

Keyword(s):

Helicobacter Pylori ◽

B Cell ◽

Malt Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Helicobacter Pylori Eradication ◽

Large B Cell Lymphoma ◽

Large B Cell

Download Full-text

Overexpression of B cell–activating factor of TNF family (BAFF) is associated with Helicobacter pylori–independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma

Blood ◽

10.1182/blood-2008-02-137513 ◽

2008 ◽

Vol 112 (7) ◽

pp. 2927-2934 ◽

Cited By ~ 31

Author(s):

Sung-Hsin Kuo ◽

Pei-Yen Yeh ◽

Li-Tzong Chen ◽

Ming-Shiang Wu ◽

Chung-Wu Lin ◽

...

Keyword(s):

Helicobacter Pylori ◽

B Cell ◽

Nuclear Translocation ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Histologic Evidence ◽

Nuclear Expression ◽

B Cell Activating Factor ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract We have recently demonstrated that nuclear expression of BCL10 predicts Helicobacter pylori (HP) independence of early-stage gastric diffuse large B-cell lymphoma (DLBCL) with histologic evidence of mucosa-associated lymphoid tissue (MALT). In this study, we examined the role of B cell–activating factor of TNF family (BAFF) in mediating BCL10 nuclear translocation and HP independence of gastric DLBCL (MALT). We used immunohistochemistry and immunoblotting to measure the expression of BAFF, pAKT, BCL3, BCL10, and NF-κB. Transactivity of NF-κB was measured by electromobility shift assay. In lymphoma samples from 26 patients with gastric DLBCL (MALT), we detected aberrant expression of BAFF in 7 of 10 (70%) HP-independent and in 3 of 16 (18.8%) HP-dependent cases (P = .015). BAFF overexpression was associated with pAKT expression (P = .032), and nuclear expression of BCL3 (P = .014), BCL10 (P = .015), and NF-κB (P = .004). In B-cell lymphoma Pfeiffer cells, BAFF activated NF-κB and AKT; the activated NF-κB up-regulated BCL10, and the activated AKT caused formation of BCL10/BCL3 complexes that translocated to the nucleus. Inhibition of AKT by LY294002 (a PI3K inhibitor) blocked BCL10 nuclear translocation, NF-κB transactivity, and BAFF expression. Our results indicate that autocrine BAFF signal transduction pathways may contribute to HP-independent growth of gastric DLBCL (MALT).

Download Full-text