Treatment of low grade gastric mucosa-associated lymphoid tissue lymphoma in stage I with Helicobacter pylori eradication. Long-term results after sequential histologic and molecular follow-up

Abstract

BACKGROUND AND OBJECTIVES: Most cases of gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma are associated with H. pylori. In localized disease (stage I), eradication of H. pylori can result in histologic regression of the lymphoma in 50% to 100% of the patients. Moreover, in half of the apparently cured patients a monoclonal rearrangement of the IgH gene can be demonstrated. However, data on the long-term outcome of the patients are scarce. We report the evolution of a series of patients followed-up since 1994 in order to evaluate the long-term outcome of the apparently cured lymphoma. DESIGN AND METHODS: From January 1994 to July 2000, 19 consecutive patients with stage I gastric low grade MALT lymphoma were sequentially studied in our hospital. They had all been diagnosed by endoscopy and had had a complete staging (including CT-scan, contrast X-ray of the small bowel, bone marrow biopsies, immunophenotyping of bone marrow and peripheral blood and, in the later years, endoscopic ultrasonography). Diagnosis required established histologic criteria for low grade MALT lymphoma in the samples obtained by endoscopy. The investigation of H. pylori status included histologic search, serology and breath test urea-(13)C. Only patients in stage I disease associated with H. pylori were included in the study. Patients received standard triple therapy for eradication of H.pylori and after treatment were sequentially followed-up with endoscopies performed every 2-3 months in the first year, every 6 months in the second year and then yearly. Post-treatment biopsies were obtained by endoscopy for histologic studies, H. pylori cultures and molecular studies. The criteria of Wotherspoon et al. were used for the histological evaluation. Molecular studies were performed with a polymerase chain reaction analysis of the IgH gene using semi-nested procedures with consensus primers for the V(H) (Fr3A/Fr2A) and J(H) (LJH and VLJH) regions. RESULTS: After the eradication treatment, 18 of the 19 patients (94.7%) achieved histologic regression of the MALT lymphoma that occurred after a mean of 4.6 months (range 2-19). In 11 of the 18 histologically cured patients (61%) a monoclonal rearrangement of the IgH gene was demonstrated. In 2 patients the monoclonality disappeared completely, but 9 of the 11 patients (82%) had either persistent (3 patients) or intermittently persistent (5 patients) monoclonality for as long as 64 months. None of the patients who achieved a histologic remission (either with or without monoclonality) relapsed after a mean follow-up of 37 months (range 2-78). Two patients were lost to follow-up and another patient died of a gastric carcinoma; the remaining 15 patients are still in histologic remission after a mean period of 43 months (range 5-78). Ten patients studied between 1994 and the end of 1996 are in remission after a mean of 59 months (range 33-78). INTERPRETATIONS AND CONCLUSIONS: In most cases of gastric low-grade MALT lymphoma in stage I eradication of H. pylori can produce histologic regression of the lymphoma and this regression can be maintained for years. However, IgH gene monoclonality can be detected and persists in most cases. Although this persistent monoclonality seems to indicate the presence of a latent lymphoma population, over a period of 6 years it has not so far influenced the outcome. These findings indicate that in cases of localized gastric low-grade MALT lymphoma associated with H. pylori, the first step of treatment should be eradication of the H. pylori; however, a close and long follow-up is essential to determine the ultimate outcome of these patients and the possible significance of the persistent monoclonality.