Overview

Infection with Helicobacter pylori (H. pylori) is a significant contributor to gastric MALT lymphoma. Eliminating the infection using antibiotics can reduce the tumour in approximately 78% of early-stage instances, and more than 95% of individuals live for at least 5 years. However, approximately 10% of individuals with gastric MALT lymphoma do not show any evidence of H. pylori infection.¹

Gastric lymphoma that arises from mucosa-associated lymphoid tissue (MALT) typically progresses slowly over time. In recent years, there has been growing evidence suggesting that infection with Helicobacter pylori (H. pylori) may contribute to the onset of gastric MALT lymphoma.²

What is Gastric MALT Lymphoma?

To understand gastric malt lymphoma, we need to know what malt lymphoma is. Lymphoma refers to cancer of the lymphatic system, which is a part of the immune system. Mucosa-Associated Lymphoid Tissue (MALT). Gastric (MALT) lymphoma accounts for 5%–8% of all B-cell lymphomas.³

It denotes a group of lymphoid tissues located in the linings of mucous membranes across the body, including the digestive, respiratory, and urogenital systems. These tissues are essential in protecting the body from pathogens that invade through these mucosal surfaces. Gastric malt lymphoma simply means cancer associated with the stomach.

MALT lymphoma is a form of non-Hodgkin lymphoma (NHL) originating from B cells. Lymphoma occurs when lymphocytes, a type of white blood cell, proliferate excessively. They circulate within your bloodstream and your lymphatic vessels. The lymphatic system plays a crucial role in our immune defense. It contains tubes that extend throughout all areas of the body. 

These tubes are referred to as lymph vessels or lymphatic vessels, and they transport a straw-colored fluid known as lymph. This fluid flows throughout the body's tissues. It has a significant amount of white blood cells (lymphocytes) that combat infection. 

• MALT lymphoma is typically identified in older adults. It may be associated with specific infections or autoimmune disorders
• MALT lymphoma in the stomach is frequently associated with a persistent stomach infection due to the bacterium Helicobacter pylori⁴

Role of Helicobacter pylori (H. pylori) in MALT Lymphoma

Helicobacter pylori are spiral-shaped, gram-negative, microaerophilic bacteria that are part of the Campylobacterales order and Helicobacteraceae family. They can inhabit the challenging conditions of the human stomach. More than half of the global population is infected with this pathogen. H. pylori has inhabited the human stomach for ages. In nearly all infected individuals, H. pylori induces inflammation manifesting as chronic active gastritis, which advances in:

• 10%–20% of those affected have peptic ulcer disease, stomach adenocarcinoma, and/or mucosa-associated lymphoid tissue (MALT) lymphoma
• Merely a tiny fraction (1%–2%) of infected people will progress to a malignant condition. One of the most notable characteristics of H pylori is its genetic variability observed among clinical isolates⁵

Antibiotic therapy is less toxic and much more effective than conventional chemotherapy and radiotherapy, making it the preferred initial treatment. Helicobacter pylori is a flagellated, helical, Gram-negative bacterium that is becoming more widespread globally. Approximately half of the global population is estimated to have H. pylori infection or at least asymptomatic colonisation within the stomach. The World Health Organisation (WHO) has classified it as a Class I carcinogen.⁶

Recommended antibiotics and treatment approach for H. pylori Infection: Antibiotic Eradication Therapy

Eliminating H. pylori infection can be tough. However, effective treatment can resolve gastritis and assist in avoiding severe long-term issues. Treatment guidelines recommend eradicating H. pylori with a standard triple-therapy regimen that includes two antibiotics along with a proton pump inhibitor (PPI), and occasionally a bismuth compound, for a duration of 10 to 14 days. 

The antibiotics most frequently utilised are amoxicillin, clarithromycin, and metronidazole. Additional antibiotics that might be utilized are levofloxacin, tetracycline, and rifampicin. 

It is highly recommended that therapy strategies be modified depending on the sensitivity of local H. pylori strains to antibiotics. The objective is to reach a minimum of a 90% success rate in eradicating the infection.⁶ 

Quadruple therapy for H.pylori Eradication

In a case study, the patients underwent H. pylori eradication therapy with a standard triple treatment lasting 1 or 2 weeks, which included a proton pump inhibitor (PPI), clarithromycin, and amoxicillin. In cases where H. pylori eradication treatment was unsuccessful, patients were given a 1- or 2-week quadruple therapy that included PPI, metronidazole, bismuth, and tetracycline. The success or failure of the eradication treatment was evaluated through histology, a rapid urease test, or a urea breath test conducted at least 4 to 6 weeks post-treatment.⁷

Sequential treatment for H.pylori Eradication

Sequential therapy is advantageous for managing Helicobacter pylori infection as it enhances eradication success and aids in overcoming antibiotic resistance. Sequential treatment for H. pylori eradication consists of a two-step process. First, a proton pump inhibitor (PPI) and amoxicillin are used for 5-7 days, then followed by a PPI, clarithromycin, and a nitroimidazole (such as tinidazole) for an additional 5-7 days. This approach has demonstrated better eradication rates than conventional triple therapy, although both treatments exhibit comparable side effect profiles.⁸

Effectiveness of H. pylori Eradication in Treating Low-Grade Gastric MALT Lymphoma

A study conducted in Korea, an area with a high prevalence of H. pylori, examined the effectiveness of H. pylori eradication in patients diagnosed with low-grade gastric MALT lymphoma.

• Of the 111 patients infected, 99 finished the complete follow-up at Seoul National University Hospital
• Following effective eradication of H. pylori, 84.8% of patients attained complete remission (CR), with a median duration of 3 months
• The majority stayed in steady remission, yet 5 patients experienced a relapse after 10–22 months without being reinfected
• The cumulative recurrence rate over three years was minimal (9.3%). Tumours situated in the distal stomach showed a better response to treatment compared to those in the proximal stomach

In general, the research indicates that sole H. pylori eradication provides a significant likelihood of sustained remission and possible cure in the majority of patients with low-grade gastric MALT lymphoma. The location of the tumour could assist in forecasting treatment outcomes.⁹

When antibiotics fail: next steps

Watchful waiting (in slow-progressing disease)

There are no clear discussions on the course of action if the lymphoma persists after treating H. pylori. Below are the two potential scenarios: 

• If the condition deteriorates or reoccurs, Cancer treatment (such as radiation therapy or chemotherapy) is initiated
• If the disease stays stable but doesn't completely disappear, A "watch-and-wait" strategy is typically adopted. Doctors might observe the patient for as long as 24 months before deciding on the next step

Following this observation phase, the choice to initiate cancer therapy relies on the patient's unique circumstances.¹⁰

Second-line therapy:

Radiation therapy

• Ideal for localised illness (Stage I or II1)
• Extremely efficient with response rates ranging from 93% to 100%
• Typical dosage: 30–40 Gy administered across 15–20 sessions
• Chosen instead of chemotherapy for early-stage situations¹⁰

Immunotherapy and chemotherapy 

• These medicines are considered for cases when the sickness has spread (disseminated or progressed) or when the lymphoma has become more aggressive (e.g., DLBCL)

Common care alternatives: 

• R-CHOP (rituximab coupled with cyclophosphamide, doxorubicin, vincristine, and prednisolone) is effective but may be overly aggressive for indolent MALT lymphomas
• R-COP (rituximab combined with cyclophosphamide, vincristine, and prednisolone) is more tolerated and less harsh
• Oral alkylating agents (e.g., chlorambucil or cyclophosphamide): Simple and well tolerated
• Around 75% of patients show a complete response
• Relapse can occur in approximately 28% of instances¹⁰

Promising pairings 

Recent combinations containing rituximab have shown exceptional results in a variety of MALT lymphoma types, including stomach cases. These comprise: 

• Rituximab combined with chlorambucil 
• Rituximab combined with fludarabine
• Rituximab combined with bendamustine¹⁰

Summary

• Lymphoma is a type of cancer affecting the lymphatic system, which plays a role in the immune system. Mucosa-Associated Lymphoid Tissue (MALT) refers to tissue associated with Mucosa-Related Lymphocytes
• Gastric (MALT) lymphoma represents 5%–8% of all B-cell lymphomas
• Antibiotic therapy is less toxic and much more effective than conventional chemotherapy and radiotherapy, making it the preferred initial treatment
• MALT lymphoma in the stomach is frequently associated with a persistent stomach infection due to the bacterium Helicobacter pylori
•  Treatment guidelines recommend eradicating H. pylori with a standard triple-therapy regimen that includes two antibiotics along with a proton pump inhibitor (PPI), and occasionally a bismuth compound, for a duration of 10 to 14 days
• If the disease stays stable but doesn't completely disappear, A "watch-and-wait" strategy is typically adopted. Doctors might observe the patient for as long as 24 months before deciding on the next step