Mucosa-Associated Lymphoid Tissue (MALT) lymphoma or MALToma is a type of non-Hodgkin lymphoma arising in the gastric mucosa that has largely been associated with Helicobacter pylori (H. pylori) infection. However, less than 10% of gastric MALTomas can occur with a negative H. pylori status, and the disease seems to have a different course.

Patients diagnosed with MALToma from 2000 to 2021 were included in the study. H. pylori-negative (HPN) status was confirmed when patients had at least 2 negative tests among the following: urea breath test, rapid urease test, serological test, or histology. The patients were divided into H. pylori positive (HPP) and HPN groups.

The final analysis included 52 gastric MALToma patients, 25 (48.1 %) were HPN. Demographics and disease stages were comparable between the two groups, although a higher prevalence of HPN cases emerged in patients diagnosed from 2011 to 2021 compared to the 2000-2010 period (55.3 % vs. 28.6 %, p = 0.09). All patients in the HPP group received eradication therapy (ET) compared to only 40 % in the HPN group. ET success in the stage 1 HPN group was 25 % compared to 78.6 % in the HPP group (p = 0.03). More patients in the HPN group received chemo and/or radiotherapy compared to the HPP (86.4 % vs 57.1 %, p = 0.033). Treatment outcomes were similar between both groups. Comparing stage 1 MALToma patients who responded to ET versus non-responders revealed that responders were more likely to be HPP (76.8 % vs. 33.3 %, p = 0.026) and diagnosed in the earlier period (2000-2010, p = 0.048).

HPN MALToma patients were similar to HPP patients in clinical features. However, there was an increase in diagnosis of HPN MALToma and a decrease in response to ET in more recent years.

H. pylori eradication therapy (HPE) can lead to tumor regression in H. pylori-positive (HPP) gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, some patients do not have detectable H. pylori (HP) infection (H. pylori-negative [HPN]) and the guidelines differ in their initial approach to HPN patients. The National Comprehensive Cancer Network (NCCN) recommends proceeding to radiation therapy, whereas European Society for Medical Oncology suggests HPE for every patient, even those who are HPN. To address this issue, we evaluated the effectiveness of HPE in limited-stage gastric MALT lymphoma.

We retrospectively reviewed patients newly diagnosed with stage IE gastric MALT lymphoma between January 2002 and December 2022. The primary outcome was the complete remission (CR) rate defined as no macroscopic findings of lymphoma and negative gastric biopsy at the follow-up gastric endoscopy.

Fifty-two patients were reviewed, and HP infection was detected in 19 (36.5%) patients-14 by immunostaining, three by serology, and one each by stool antigen and urea breath test. All 19 HPP and eight of the 33 HPN patients received HPE treatment. The CR rate was 63% (12/19) in HPP patients and 13% (1/8) in HPN patients (P = .033). After a median follow-up of 89.7 months, only two of the 12 HPP patients achieving CR have relapsed; the one HPN patient who received HPE remains in CR at 12+ months.

For limited-stage HPP gastric MALT lymphoma, HPE is an effective and durable first-line treatment and should be used. For HPN patients, the CR rate with HPE is very low in our experience and is thus in support of the NCCN guideline.

Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach.

We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment.

Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths.

Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity.

National Cancer Institute.

Marginal zone lymphomas (MZLs) are a rare, indolent group of non-Hodgkin lymphomas with different diagnostic, genetic and clinical features and therapeutic implications. The most common is extranodal MZL of mucosa-associated lymphoid tissue, followed by splenic MZL and nodal MZL. Patients with MZL generally have good outcomes with long survival rates but frequently have a relapsing/remitting course requiring several lines of therapy. The heterogeneous presentation and relapsing course present the clinician with several diagnostic and therapeutic challenges. This position statement presents evidence-based recommendations in the setting of Australia and New Zealand.

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma, trailing behind diffuse large B-cell lymphoma and follicular lymphoma. Gastric mucosa-associated lymphoid tissue lymphoma (GML) is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori (H. pylori)-induced chronic gastritis. On the other hand, a specific subset of individuals diagnosed with GML does not exhibit H. pylori infection. In contrast to its H. pylori-positive counterpart, it was previously believed that H. pylori-negative GML was less likely to respond to antimicrobial therapy. Despite this, surprisingly, in-creasing evidence supports that a considerable proportion of patients with H. pylori-negative GML show complete histopathological remission after bacterial eradication therapy. Nonetheless, the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended. In recent years, there has been growing interest in investigating the role of non-H. pylori gastric helicobacters (NHPHs) in the pathogenesis of H. pylori-negative GML. However, additional research is required to establish the causal relationship between NHPHs and GML. In this minireview, we examined the current understanding and proposed prospects on the involvement of NHPHs in H. pylori-negative GML, as well as their potential response to bacterial eradication therapy.

The first convincing evidence for a causal relationship between bacterial infection and lymphomagenesis came from the link between gastric lymphoma and chronic Helicobacter pylori gastritis. This review will summarize the current epidemiological, clinical, and biological evidence of a causative role of bacteria in the development of malignant lymphomas, particularly, the extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type.

Other microorganisms have been associated with specific extranodal lymphoma sites with variable and not always definitive, evidence, including Chlamydia psittaci , Borrelia burgdorferi , Campylobacter jejuni and, most recently, Coxiella Burnetii . According to most plausible models, lymphoma growth is a consequence of continuous antigenic stimulation induced by chronic infection. However, some evidence of a direct oncogenic role of H. pylori has been provided, too.

Lymphomas are not the result of a single cause but multifactorial diseases, influenced by a variety of genetic and environmental elements. Hence, ascertaining the specific contribution of bacterial infections is not always easy. Nevertheless, the eradication of the associated chronic infection may result in sustained lymphoma regression. Moreover, the association between infections and lymphoma may offer opportunities for reducing lymphoma incidence by preventing the predisposing infections or treating them early.

Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.

Helicobacter pylori (HP)-unrelated mucosa-associated lymphoid tissue (MALT) lymphoma includes the majority of extragastric MALT lymphomas and a small proportion of gastric MALT lymphomas. Although the role of first-line antibiotics in treating HP-negative gastric MALT lymphomas remains controversial, HP eradication therapy (HPE)-like regimens may result in approximately 20-30% complete remission (CR) for patients with localized HP-negative gastric MALT lymphoma. In these patients, H. heilmannii, H. bizzozeronii, and H. suis were detected in sporadic gastric biopsy specimens. Extragastric MALT lymphoma is conventionally treated with radiotherapy for localized disease and systemic chemotherapy for advanced and metastatic diseases. However, a proportion of extragastric MALT lymphomas, such as ocular adnexal lesions and small intestinal lesions, were reported to be controlled by antibiotics for Chlamydophila psittaci and Campylobacter jejuni, respectively. Some extragastric MALT lymphomas may even respond to first-line HPE. These findings suggest that some antibiotic-responsive tumors may exist in the family of HP-negative MALT lymphomas. Two mechanisms underlying the antibiotic responsiveness of HP-negative MALT lymphoma have been proposed. First, an HPE-like regimen may eradicate the antigens of unknown bacteria. Second, clarithromycin (the main component of HPE) may have direct or indirect antineoplastic effects, thus contributing to the CR of these tumors. For antibiotic-unresponsive HP-negative MALT lymphoma, high-dose macrolides and immunomodulatory drugs, such as thalidomide and lenalidomide, have reported sporadic success. Further investigation of new treatment regimens is warranted.

Introduction: Marginal zone lymphoma (MZL) is a heterogeneous disease with a wide range of possible frontline therapies depending on the subtype; there are no shared guidelines for the treatment of relapsed/refractory MZLs. The growing evidence of the importance of the BCR pathway in the pathogenesis of B lymphoproliferative forms has led researchers to consider BTK as a potential therapeutic target in MZL.Area covered: The authors provide the reader with an evaluation of ibrutinib as a treatment option for refractory marginal zone lymphoma. The review includes an overview of the drug's pharmacokinetics and pharmacodynamics, efficacy, and safety. The authors also provide the reader with their expert perspectives on the drug and its place in the treatment of MZL.Expert opinion: The availability of new non-chemotherapeutic agents represents an important opportunity to spare excessive exposure to cytotoxic compounds. Immunomodulators and targeted agents, alone or often in combination with immunotherapy, have been shown to be effective and safe therapies in patients with relapsed/refractory (R/R) MZL. In addition, numerous studies involving new generation targeted agents, alone or in combination, are currently active in both R/R and untreated patient populations, some with encouraging preliminary results.

The role of eradication therapy in Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma remains controversial. The aim of this study was to investigate the efficacy of H. pylori eradication therapy as a first-line treatment for H. pylori-negative gastric MALT lymphoma.

A literature search of studies published until October 2019 was performed using electronic databases. Studies that reported treatment response to eradication therapy as an initial treatment for patients with H. pylori-negative gastric MALT lymphoma were eligible for inclusion. The primary outcome was the complete remission rate after eradication therapy.

Twenty-five studies were included in the analyses. The overall pooled complete remission rate was 29.3% (95% confidence interval [CI], 22.2%-37.4%, I2  = 41.5%). There was no publication bias, and the sensitivity analyses showed consistent results. The pooled complete remission rates were lower in the subgroups of studies that had a higher incidence of translocation t(11;18)(q21;q21) (19.9%, 95% CI, 11.6%-32.0%), studies that used serological tests to exclude H. pylori infection (27.5%, 95% CI, 20.1%-36.4%), and studies where non-response to eradication therapy was determined at <12 months after treatment (27.0%, 95% CI, 15.5%-42.7%). Meta-regression analysis revealed that the pooled estimate was not significantly different in terms of the characteristics of individual studies.

Although the complete remission rate after eradication therapy is not high, it can be used as an initial treatment option in a subset of patients with H. pylori-negative gastric MALT lymphoma. Further studies to identify subgroups of patients who may benefit from eradication therapy are needed.