How should I treat a patient with an atypical B‑cell lymphoid proliferation (low‑grade gastric marginal‑zone lymphoma) of the gastric mucosa?

Treatment of Gastric Marginal Zone B-Cell Lymphoma (MALT Lymphoma)

For localized H. pylori-positive gastric MALT lymphoma, H. pylori eradication with triple therapy (PPI + clarithromycin + amoxicillin or metronidazole for 10-14 days) should be the sole initial treatment, achieving complete remission in approximately 62% of patients with stage I disease. 1

Initial Diagnostic Workup

Before initiating treatment, confirm the diagnosis and stage appropriately:

• Obtain multiple biopsies from all gastric regions, duodenum, and gastroesophageal junction—not just the visibly abnormal areas—as MALT lymphoma is often multifocal throughout the gastric mucosa 1, 2
• Confirm diagnosis by expert hematopathologist using WHO classification criteria with immunohistochemistry panel (CD20, CD10, CD5, cyclin D1) to exclude other indolent B-cell lymphomas 1
• Test for H. pylori using histochemistry, urea breath test, stool antigen, or serology if histochemistry is negative 1
• Perform FISH or PCR for t(11;18) translocation—this identifies patients unlikely to respond to antibiotics and potentially resistant to alkylating agents 1, 3
• Complete staging with endoscopic ultrasound (assess wall depth and lymph nodes), CT chest/abdomen/pelvis, bone marrow biopsy, CBC, LDH, and β2-microglobulin 1

Treatment Algorithm Based on H. pylori Status and Stage

Stage I-II, H. pylori-Positive Disease

First-line: H. pylori eradication therapy

• Administer PPI-based triple therapy for 10-14 days: omeprazole 20 mg twice daily + clarithromycin 250-500 mg twice daily + either amoxicillin 1000 mg twice daily or metronidazole 400 mg twice daily 1, 4
• Confirm eradication with urea breath test or stool antigen at least 6 weeks after therapy and ≥2 weeks after stopping PPI 1
• If eradication fails, attempt second-line quadruple therapy with alternative antibiotics 1

Post-eradication monitoring:

• Perform endoscopy with biopsies at 2-3 months to document H. pylori eradication 1
• Continue endoscopy with biopsies every 6 months for 2 years to assess histological regression 1, 4
• Complete histological remission occurs at median 10 months; molecular remission takes longer at median 18 months 4, 5
• Observe for at least 12 months even if residual histologic lymphoma persists, as long as clinical and endoscopic remission is achieved—persistent monoclonal B-cells after histologic regression do not require immediate treatment 1, 5

Important caveat: Four of 56 patients (7%) with complete remission relapsed between 6-15 months, with one case due to H. pylori reinfection, emphasizing the need for continued surveillance 4

Stage I-II, H. pylori-Negative or Antibiotic-Refractory Disease

Preferred treatment: Involved-field radiotherapy

• Deliver 30-40 Gy in 1.5-1.8 Gy daily fractions over 3-4 weeks to the stomach and perigastric nodes 1, 6, 7
• Complete response rate is 94-100% with radiotherapy alone 6, 7
• Stage I1 disease (confined to mucosa/submucosa by endoscopic ultrasound) has higher regression rates than stage I2 (muscularis propria or beyond) 4
• Surgery is not recommended—it offers no survival advantage over conservative approaches and impairs quality of life 1

Special consideration for t(11;18)-positive patients:

• These patients have very low likelihood of responding to antibiotics and should proceed directly to radiotherapy for localized disease 1, 3
• The t(11;18) translocation may also predict reduced response to alkylating agents as monotherapy 3

Stage IV or Systemic Disease

Asymptomatic patients:

• Watchful waiting is appropriate even with disseminated disease 8
• If H. pylori-positive, still attempt eradication therapy 8
• Surveillance every 6 months with endoscopy, biopsies, and abdominal ultrasound 8

Symptomatic patients (bulky disease, organ compromise, or patient preference):

• Rituximab + chlorambucil is the evidence-based first-line regimen supported by randomized trial data 8, 3
• Alternative options include rituximab + bendamustine (high response rates in non-randomized studies) or rituximab monotherapy 8, 3, 9
• Oral alkylating agents (cyclophosphamide or chlorambucil) with or without rituximab are acceptable 1
• Avoid purine analogues (fludarabine, cladribine) as first-line due to increased risk of secondary myelodysplasia 8, 3
• Do not use aggressive anthracycline regimens (R-CHOP) unless there is histologic transformation to diffuse large B-cell lymphoma 8, 3
• Rituximab maintenance is not recommended as routine practice 8

Common Pitfalls to Avoid

• Do not perform surgery as initial treatment—multiple studies show no superiority over conservative approaches 1
• Do not skip H. pylori testing even in advanced stage disease, as eradication can contribute to disease control 8
• Do not treat persistent monoclonal B-cells immediately after histologic remission—observe for at least 12 months as these often resolve spontaneously 1, 5
• Do not assume single-site biopsies are adequate—MALT lymphoma is multifocal, requiring multiple biopsies from all gastric regions 2
• Do not use antibiotics alone in t(11;18)-positive patients—proceed directly to radiotherapy or systemic therapy 1, 3
• Do not stop surveillance after apparent cure—patients require indefinite follow-up as late relapses can occur, and there is increased risk of gastric adenocarcinoma 4, 2

Long-Term Surveillance

• Annual endoscopy with biopsies indefinitely to detect late relapses and monitor for secondary gastric adenocarcinoma 4, 2
• Annual blood counts and imaging as clinically indicated 1
• Patients with complete remission after H. pylori eradication have an 18% recurrence rate at median 4.5 years follow-up, underscoring the need for lifelong monitoring 7