Helicobacter pylori and mucosa-associated lymphoid tissue: what's new

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Sung-Hsin Kuo ◽  
Ann-Lii Cheng
Keyword(s):  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Early Stage ◽  
Eradication Therapy ◽  
Gastric Malt Lymphoma ◽  
High Grade ◽  
First Line ◽  
Histological Evidence ◽  
H Pylori

AbstractLow-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach, gastric MALT lymphoma, is associated with Helicobacter pylori infection. The eradication of H pylori using antibiotics is successful in 60% to 80% of affected patients. In contrast to the previous paradigm, we and other investigators have shown that a certain proportion of patients with H pylori–positive early-stage diffuse large B-cell lymphoma (DLBCL) of the stomach with histological evidence of MALT lymphoma, including high-grade transformed gastric MALT lymphoma and gastric DLBCL(MALT), achieved long-term complete pathological remission (pCR) after first-line H pylori eradication therapy, indicating that the loss of H pylori dependence and high-grade transformation are separate events in the progression of gastric lymphoma. In addition, patients with H pylori–positive gastric DLBCL without histological evidence of MALT (gastric pure DLBCL) may also respond to H pylori eradication therapy. A long-term follow-up study showed that patients who achieved pCR remained lymphoma free. Gastric MALT lymphoma is indirectly influenced by H pylori infection through T-cell stimulation, and recent studies have shown that H pylori–triggering chemokines and their receptors, H pylori–associated epigenetic changes, H pylori–regulated miRNA expression, and tumor infiltration by CD4+CD25+ regulatory T cells contribute to lymphomagenesis of gastric MALT lymphoma. Recent studies have also demonstrated that the translocation of CagA into B lymphocytes inhibits apoptosis through p53 accumulation, BAD phosphorylation, and the up-regulation of Bcl-2 and Bcl-XL expression. In gastric MALT lymphoma, CagA may stimulate lymphomagenesis directly, through the regulation of signal transduction, and intracellular CagA is associated with H pylori dependence. These findings represent a substantial paradigm shift compared with the classical theory of H pylori–reactive T cells contributing indirectly to the development of MALT lymphoma. In conclusion, a wide range of H pylori–related gastric lymphomas have been identified. The use of antibiotics as the sole first-line therapy for early-stage gastric pure DLBCL requires validation in a prospective study. The clinical and biological significance of the CagA oncoprotein in the lymphomagenesis of gastric MALT lymphoma warrants further study.

scholarly journals MALT lymphoma: epidemiology, clinical diagnosis and treatment

2018 ◽  
Vol 11 (3) ◽  
pp. 187-193 ◽  
Author(s):  
Petruta Violeta Filip ◽  
◽  
Denisa Cuciureanu ◽  
Laura Sorina Diaconu ◽  
Ana Maria Vladareanu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
B Cell ◽  
Malt Lymphoma ◽  
Cell Lymphoma ◽  
Gastric Lymphoma ◽  
Eradication Therapy ◽  
B Cell Lymphoma ◽  
Gastric Malt Lymphoma ◽  
H Pylori

Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.

scholarly journals Clinical Outcome of Eradication Therapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma according toH. pyloriInfection Status

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Ju Seok Kim ◽  
Sun Hyung Kang ◽  
Hee Seok Moon ◽  
Jae Kyu Sung ◽  
Hyun Yong Jeong
Keyword(s):  
Complete Remission ◽  
Malt Lymphoma ◽  
Eradication Therapy ◽  
Gastric Malt Lymphoma ◽  
Clinicopathologic Characteristics ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Multiple Lesions ◽  
H Pylori

Background. To evaluate the long-term outcome ofH. pylorieradication therapy for gastric MALT lymphoma according to the presence ofH. pyloriinfection.Methods. We retrospectively reviewed the medical records of patients between January 2001 and June 2014. The clinicopathologic characteristics and clinical outcomes were compared betweenH. pylori-positive andH. pylori-negative gastric MALT lymphoma groups.Results. Fifty-four patients were enrolled: 12H. pylori-negative and 42H. pylori-positive patients. The tumor was located more frequently in both the proximal and distal parts of the stomach (P=0.001), and the percentage of multiple lesions was significantly greater in theH. pylori-negative group (P=0.046). Forty-seven patients received initial eradication therapy, and 85% (35/41) ofH. pylori-positive patients and 50% (3/6) ofH. pylori-negative patients achieved complete remission after eradication therapy. The presence of multiple lesions was a predictive factor for unresponsiveness toH. pylorieradication (P=0.024). The efficacy of eradication therapy (P=0.133), complete remission (CR) maintenance period, and relapse after eradication therapy were not significantly different between the two groups.Conclusions.H. pylorieradication therapy could be an effective first-line treatment for localizedH. pylori-negative gastric MALT lymphoma, especially for single lesions.

scholarly journals Antibiotic Therapy of H. Pylori Negative Gastric MALT Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1735-1735
Author(s):  
Seung Tae Lee ◽  
Purnima Teegavarupu ◽  
Anusha Karri ◽  
Saswatha Anireddy ◽  
Fredrick B. Hagemeister ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Antibiotic Therapy ◽  
Malt Lymphoma ◽  
Cell Transformation ◽  
Early Stage ◽  
Large Cell ◽  
Cancer Center ◽  
Gastric Malt Lymphoma ◽  
First Line ◽  
H Pylori

Abstract Introduction The causal association between H. pylori and gastric MALT lymphoma has been well demonstrated and H. pylori eradication with antibiotics has emerged as the standard therapy for Stage I H. pylori positive (HPP) gastric MALT lymphoma. As per the NCCN Guidelines, radiation therapy is the preferred treatment option for early stage H. pylori negative (HPN) gastric MALT lymphoma and antibiotic therapy is not indicated. However, successful treatment of HPN early stage gastric MALT lymphoma with antibiotics was reported in small series of patients by Raderer et al, Gut, 2006 [(5/6 patients achieved complete remission (CR)] and Asano et al, Tohoku J Exp Med, 2012 (5/17 patients achieved CR). Here, we report the outcome of Stage I HPP and HPN gastric MALT lymphoma patients treated with antibiotics at MD Anderson Cancer Center, Houston, Texas, USA over a period of 20 years. Methods We reviewed medical records of all pathologically proven gastric MALT lymphoma patients (n=128) referred to MD Anderson Cancer Center at initial diagnosis between 1991 and 2011. Only patients with Stage IAE disease were considered for this analysis. Patients with large cell transformation were excluded. H. pylori status was determined by histopathology and serum antibody assay. Clinical staging was determined by upper GI endoscopy with biopsy, bone marrow biopsy, and CT scans of neck, chest, abdomen, and pelvis and/or PET-CT scan. Response was assessed by upper GI endoscopy every 3-6 months until complete resolution of lymphoma. Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsies. Results Of the 128 patients reviewed, 81 patients had Stage IAE disease without histologic evidence of large cell transformation. The 81 Stage IAE patients were assigned to HPP (39/81, 48%) or HPN group (42/81, 52%) based on histopathologic evidence of H. pylori. The higher-than-expected proportion of HPN patients might be due to referral bias to a tertiary care cancer center. The results of H. pylori antibody serology are shown in Table 1. There was no significant difference in age, gender, and race between HPP and HPN groups. First-line antibiotic therapy was administered for all 39 (100%) HPP patients and 28/42 (67%) HPN patients. The CR rate after antibiotic therapy was significantly higher in HPP compared with HPN patients (22/39, 56% vs 7/28, 25%; p=0.019). The median time to achieve a CR was similar for the two groups (HPP: 7.8 mo, range 3-40 mo; HPN: 9.7 mo, range 3-35 mo; p=0.385). After a median follow-up of 110 mo for the HPP group and 91.5 mo for the HPN group, 3/22 (14%) and 2/7 (28%) responders relapsed, respectively (p=0.362). Patients who failed to achieve a CR with antibiotic therapy were mostly treated with radiation: 14/17 in the HPP group and 19/21 in the HPN group. All patients that received radiation achieved a CR. Of the patients in both groups who received upfront antibiotic therapy, there were no differences in time to progression (HPP, 90% vs HPN, 92% at 8 years; p=0.543) and overall survival (HPP, 93% vs HPN, 100% at 8 years; p=0.068). Conclusions Our results demonstrate that a substantial proportion of patients with Stage IAE HPN gastric MALT lymphoma achieve durable remission with antibiotic therapy alone. It is possible that such responses may be because of false-negative H. pylori test results or due to association of HPN gastric MALT lymphoma with other unidentified bacteria. We also observed that HPN gastric MALT lymphoma patients failing antibiotic therapy could be effectively salvaged with radiation therapy and their long-term outcome is not affected by delay from initial trial of antibiotic therapy. Thus, the results of this largest series-to-date of HPN patients treated with first-line antibiotic therapy, combined with results of smaller series reported previously, suggest that 1) antibiotic therapy should be considered as first-line therapy for Stage IAE HPN gastric MALT lymphoma patients, and 2) radiation therapy could be avoided in a subset of these patients. Table 1. H. pylori status in Stage IAE gastric MALT lymphoma as determined by histopathology and H. pylori antibody. H. pylori positive by histology (n=39) H. pylori negative by histology (n=28) CR (n=22) Non-CR(n=17) CR (n=7) Non-CR(n=21) H. pylori Ab Positive 4 4 0 3 H. pylori Ab Negative 8 2 1 7 Not available 10 11 6 11 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Prospective Study of Helicobacter pylori Eradication Therapy in Stage IE High-Grade Mucosa-Associated Lymphoid Tissue Lymphoma of the Stomach

2001 ◽  
Vol 19 (22) ◽  
pp. 4245-4251 ◽  
Author(s):  
Li-Tzong Chen ◽  
Jaw-Town Lin ◽  
Rong-Yaun Shyu ◽  
Chang-Ming Jan ◽  
Chi-Long Chen ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Prospective Study ◽  
Lymphoid Tissue ◽  
Remission Rate ◽  
Early Stage ◽  
Eradication Therapy ◽  
Stage I ◽  
High Grade ◽  
H Pylori

PURPOSE: High-grade mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach are generally believed to be Helicobacter pylori–independent, autonomously growing tumors. However, anecdotal cases of regression of high-grade lymphomas after the cure of H pylori infection had been described. The present prospective study was conducted to evaluate the effect of anti–H pylori therapy in stage IE high-grade gastric MALT lymphomas. PATIENTS AND METHODS: Sixteen patients with H pylori infection and stage IE gastric high-grade MALT lymphoma consented to a brief antibiotic therapy as first-line treatment from June 1995 through April 2000. Then, patients underwent intensive endoscopic follow-up examinations (± endoscopic ultrasonography) with biopsy to evaluate tumor response. Patients with significant improvement of gross lesions that accompanied regression of large cells were followed up without additional treatment. Patients without significant improvement were immediately referred to systemic chemotherapy. RESULTS: Eradication of H pylori was achieved in 15 patients and was accompanied by rapid gross tumor regression and disappearance of large cells in 10. All 10 of these patients with early response had subsequent complete histologic remission of lymphoma. The complete remission rate was 62.5% (95% confidence interval, 35.8% to 89.1%). The response rate was not affected by the tumor grading (proportion of large blast cells within the tumor) but was adversely affected by the depth of tumor invasion. At a median follow-up of 43.5 months (range, 21.1 to 67.4 months), all 10 of these patients remained lymphoma-free. The median duration of complete response was 31.2 months (range, 14.4 to 49.1 months). CONCLUSION: These results suggest that high-grade transformation is not necessarily associated with the loss of H pyloridependence in early-stage MALT lymphomas of the stomach.

Nuclear Expression of BCL10 or Nuclear Factor Kappa B Predicts Helicobacter pylori–Independent Status of Early-Stage, High-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphomas

2004 ◽  
Vol 22 (17) ◽  
pp. 3491-3497 ◽  
Author(s):  
Sung-Hsin Kuo ◽  
Li-Tzong Chen ◽  
Kun-Huei Yeh ◽  
Ming-Shiang Wu ◽  
Hui-Chen Hsu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Lymphoid Tissue ◽  
Nuclear Factor Kappa B ◽  
Early Stage ◽  
Gastric Malt Lymphoma ◽  
Nuclear Factor ◽  
High Grade ◽  
Nuclear Expression ◽  
H Pylori

Purpose A high percentage of early-stage, high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori dependent. t(11;18)(q21;q21), a genetic aberration highly predictive of H pylori–independent status in low-grade gastric MALT lymphoma, is rarely detected in its high-grade counterpart. This study examined whether nuclear expression of BCL10 or nuclear factor kappa B (NF-κB) is useful in predicting H pylori–independent status in patients with stage IE high-grade gastric MALT lymphomas. Patients and Methods Twenty-two patients who had participated in a prospective study of H pylori eradication for stage IE high-grade gastric MALT lymphomas were studied. The expression of BCL10 and NF-κB in pretreatment paraffin-embedded lymphoma tissues was evaluated by immunohistochemistry and confocal immunofluorescence microscopy. The presence of t(11;18)(q21;q21) was identified by a multiplex reverse transcriptase polymerase chain reaction of the API2-MALT1 chimeric transcript. Results Aberrant nuclear expression of BCL10 was detected in seven (87.5%) of eight H pylori–independent and in none of 14 H pylori–dependent high-grade gastric MALT lymphomas (P < .001). All seven patients with nuclear BCL10 expression had nuclear expression of NF-κB, compared with only two of 15 patients without nuclear BCL10 expression (P = .002). As a single variable, the frequency of nuclear expression of NF-κB was also significantly higher in H pylori–independent tumors than in H pylori–dependent tumors (seven of eight [87.5%] v two of 15 [12.3%]; P = .002). The API2-MALT1 fusion transcript was detected in only one (12.5%) of eight H pylori–independent lymphomas. Conclusion Nuclear expression of BCL10 or NF-κB is highly predictive of H pylori–independent status in high-grade gastric MALT lymphoma, and coexpression of these two markers in the nuclei is frequent.

scholarly journals Nhân một trường hợp bệnh Malt lymphoma dạ dày

2020 ◽  
Author(s):  
Thanh Ái Nguyễn
Keyword(s):  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Marginal Zone ◽  
Early Stage ◽  
Gastric Lymphoma ◽  
Gastric Malt Lymphoma ◽  
Term Survival ◽  
Stage Disease

CASE STUDY: GASTRIC MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT) LYMPHOMA Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (EMZL-MALT) have been linked to chronic immune stimulation due toinfection or autoimmune stimuli.The causal association between Helicobacter pylori(HP) and gastric MALT lymphoma has been well demonstrated. HPeradication with antibiotics has emerged as the standard therapy for early stage HPpositive gastric MALT lymphoma.High response rates and long-term survival have been reported inpatients with localized gastric MALT lymphomatreated with low-doseradiationtherapy.Monoclonal antibody and chemotherapy are reserved forpatients failing or recurring after RT and those with advanced stage disease. Key words: mucosa-associated lymphoid tissue, gastric lymphoma

Long-Term Persistence of Monoclonal B Cells After Cure of Helicobacter pylori Infection and Complete Histologic Remission in Gastric Mucosa–Associated Lymphoid Tissue B-Cell Lymphoma

2001 ◽  
Vol 19 (6) ◽  
pp. 1600-1609 ◽  
Author(s):  
Christian Thiede ◽  
Thomas Wündisch ◽  
Birgit Alpen ◽  
Beatrix Neubauer ◽  
Andrea Morgner ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
B Cells ◽  
Sequence Analysis ◽  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Gastric Malt Lymphoma ◽  
Low Grade ◽  
H Pylori

PURPOSE: Cure of Helicobacter pylori infection is associated with remission induction in the majority of patients with low-grade gastric mucosa associated lymphoid tissue (MALT) lymphoma in localized stages; however, limited data exist as to whether these patients may be cured of their lymphoma. The present study was performed to investigate whether the polymerase chain reaction (PCR) for the rearranged immunoglobulin heavy chain region may be used to define “molecular” remission. PATIENTS AND METHODS: Ninety-seven patients who suffered from low-grade gastric MALT lymphoma stage IE were observed with central pathology and molecular biology after cure of H pylori infection. PCR was performed with the use of consensus primers for the framework regions 1, 2, and 3 and monoclonality was corroborated by sequence analysis. In selected cases, microdissection was performed to study the origin of the monoclonal B cells. RESULTS: Of the 97 patients, 77 obtained complete endoscopic and histologic remission (CR). Twenty of 44 patients with PCR monoclonality at diagnosis and with sufficient molecular follow-up displayed monoclonal bands for a median time of 20.5 months after CR (range, 0 to 50.4 months). These B cells were related to the original lymphoma clone by sequence analysis. Microdissection analysis identified basal lymphoid aggregates as the source of these monoclonal B cells. Local relapse occurred in and was observed by PCR in four patients. All four patients displayed monoclonal PCR before relapse, and three of these four showed ongoing PCR monoclonality throughout their course, indicating the persistence of malignant cells. CONCLUSION: Half of all patients with gastric MALT lymphoma show long-term PCR monoclonality up to several years after cure of H pylori infection and CR. Patients with monoclonal PCR should be observed closely, whereas long-term PCR negativity may indicate cure of the disease.

scholarly journals CXCR4 PET/MRI for follow-up of gastric mucosa-associated lymphoid tissue lymphoma after first-line H. pylori eradication

Blood ◽  
2021 ◽  
Author(s):  
Marius Mayerhoefer ◽  
Markus Raderer ◽  
Wolfgang Lamm ◽  
Michael Weber ◽  
Barbara Kiesewetter ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Control Group ◽  
Gastric Malt Lymphoma ◽  
First Line ◽  
Cell Counts ◽  
Standardized Uptake Values ◽  
H Pylori

Post-treatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G-protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate PET with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow-up biopsies for assessment of residual disease (non-complete remission (CR)) after first-line H. pylori (HP) eradication. Forty-six post-HP eradication [68Ga]Pentixafor-PET/MRI examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard, and showed CR in six cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive value of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up, were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r=0.51 and r=0.52 (P=0.008 and P=0.006). In conclusion, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after HP eradication.

scholarly journals Successful Endoscopic Resection of Primary Rectal Mucosa-Associated Lymphoid Tissue Lymphoma by Endoscopic Submucosal Dissection: A Case Report

2021 ◽  
Vol 8 ◽  
Author(s):  
Jian Han ◽  
Zhe Zhu ◽  
Chao Zhang ◽  
Hua-ping Xie
Keyword(s):  
Endoscopic Submucosal Dissection ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Early Stage ◽  
Rectal Mucosa ◽  
Complete Response ◽  
Gastric Malt Lymphoma ◽  
Submucosal Dissection ◽  
Rectal Malt Lymphoma ◽  
H Pylori

Mucosa-associated lymphoid tissue (MALT) lymphoma arises in extra-nodal sites from the malignant transformation of B lymphocytes that are mainly triggered by infection or autoimmune process. MALT lymphoma is frequently detected in the gastrointestinal tract. As the causal relationship between Helicobacter pylori (H. pylori) infection and gastric MALT lymphoma, it was well-established that early-stage gastric MALT lymphoma could be cured by H. pylori eradication, and about 50–95% of cases achieved complete response with anti-H. pylori treatment. Compared to the stomach which is the most involved site due to the high prevalence of H. pylori infection, the colorectum is rarely affected. Primary rectal MALT lymphoma is a rare malignancy, and there are no specific therapeutic strategies so far. Here we report a case of rectal MALT lymphoma successfully resected by endoscopic submucosal dissection (ESD). ESD serves as a novel strategy to cure small localized rectal MALT lymphomas to avoid unnecessary surgery or chemo-radiotherapy.

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