Low-grade B-cell lymphomas arising in mucosa-associated lymphoid tissue (MALT) are most frequently localized in the gastrointestinal tract. More than 90% of gastric MALT lymphomas are diagnosed in patients with chronic, Helicobacter pylori-associated gastritis. High remission rates for these lymphomas have been observed after the cure of H. pylori infection. Data are lacking, however, with regard to the duration of the remissions. To address this question of remission duration, we have followed 50 patients in whom H. pylori infections were eradicated, and we determined whether the patients in complete remission displayed evidence of residual monoclonal B cells during follow-up.Patients were treated with amoxycillin and omeprazole for 2 weeks in an attempt to cure H. pylori infections. Follow-up included endoscopic investigations with biopsy sampling. Monoclonal B cells in biopsy specimens were detected by means of a polymerase chain reaction (PCR)-based assay.H. pylori infections were cured in all 50 patients. The median follow-up for the 50 patients is currently 24 months (729 days; range, 135-1411 days). Forty patients achieved complete remission of their lymphomas, but five have subsequently relapsed. The median time of continuous complete remission for the 40 patients was 15.4 months (468 days; range, 0-1198 days). Among six patients whose Iymphomas did not respond to H. pylori eradication, four revealed high-grade lymphomas upon surgery. PCR indicated the presence of monoclonal B cells during follow-up in 22 of 31 assessable patients in complete remission.Complete remissions of low-grade gastric MALT Iymphomas after the cure of H. pylori infection appear to be stable, although most patients display evidence of monoclonal B cells during follow-up. Whether these patients are truly cured of their Iymphomas remains to be determined.
Background: Low grade gastric MALT lymphomas are frequently observed on the background of H. pylori induced gastritis. We and others have shown that these lymphomas harbour a high remission rate after cure of H. pylori infection. Methods: The first fifty patients of our trial (lancet 345: 1591-4; 1995) have been followed for a median of 24 months. Endoscopies were performed every six months. Molecular and histological studies were performed as described(Lancet 345: 1591-4; 1995). Results: We observed a complete remission in fourty patients, a partial remission in four patients, and no change was seen in six patients. Of the 40 patients in CR, four have relapsed so far; one clonally not related relapse was seen in the nasal cavity, whereas the other three were local relapses, all H. pylori negative. Most patients in CR are still PCR-positive for clonal B-cells. However, the patients with the longest follow-up (up to 1.000 days) are PCR-negative. Four patients with no change were operated, and in all four patients a high-grade lymphoma was detected not previously appreciated on gastric biopsies. Conclusion: Cure of H.pylori infection may induce long-term remissions in low grade gastric MALT lymphomas. Whether this may induce cure of the disease, remains to be seen.
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 I E 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.
The Role of Helicobacter pylori Infection for the Development and Treatment of Gastric MALT Lymphomas Since 1983, it is well known that mucosa-associated lymphoid tissue (MALT)-type lymphoma of the stomach is due to chronic Helicobacter pylori (H. pylori) infection. Many epidemiological, biological, and moleculargenetic studies have implicated the role of H. pylori in lymphomagenesis. Nowadays, more than 650 patients with gastric MALT lymphoma worldwide have been treated with antibiotics for H. pylori infection, achieving a complete remission in about 75% of cases. Clinical predictive factors help to stratify patients into risk groups, and help to predict the probability of lymphoma remission. New insights into cytogenetics have also contributed to the understanding of lymphomagenesis, and with the newly identified translocation t(11;18)(q21;q21) we might have also a genetic factor at hand to predict treatment response.
Background: Low-grade gastric B-cell lymphomas of the mucosa associated lymphoid tissue(MALT) are frequently associated with chronic H. pylori (Hp) infection. The fact that eradication of Hp induces regression of the lymphoma in the majority of the patients together with the presence of Hp-specific T-cells supports the notion that these lymphomas are Hp-responsive. Recent work suggests that autoreactivity may also be important in the development of lymphomas. In addition, other autoreactive diseases like systemic lupus erythematosus or rheumatoid arthritis are often associated with autoantibodies encoded by specific germline VH segments. This study was initiated to analyze VH segment usage and the pattern of somatic mutations in 25 patients with primary gastric low-grade MALT lymphoma. Methods: PCR on VHDJH rearrangements was performed using genomic DNA and generic primers for the VH-framework and JH regions. Monoclonal PCR-products were cloned and sequenced. Results: The VH-sequences detected were homologous to VH1-family segments in 20% and to VH3 and VH4-family segments in 60% and 20% respectively. All five VH1-sequences were derived from the same germline segment (DP-10, V1-69) and five of the fourteen VH3 sequences used the V3-7 (DP54) segment. Somatic mutations were found in 24 out of 25 sequences, with higher incidence of replacement mutations in the antigen contacting complementarity determinating regions(CDRs). 18 out of 25 germline VH segments had previously been isolated from various autoreactive antibodies. Conclusion: These findings support the notion that gastric MALT lymphomas develop from B-cells that have been exposed to antigen, most likely post germinal center B-cells. The high incidence of VH-alleles associated with autoreactivity and preferrence of specific germline VH segments points to the fact that autoreactivity may be important in the genesis of these lymphomas.
Gastric marginal-zone B-cell lymphoma (MZBCL) of the mucosa-associated lymphoid tissue (MALT) is associated with chronic Helicobacter pylori gastritis. Stable complete remission (CR) can be induced by H pylori eradication. Whether this is paralleled by cure of the lymphoma remains unclear. Persisting monoclonal bands for immunoglobulin heavy chain variable region (VH) representing the lymphoma clone have been described in up to 50% of patients in CR. This retrospective study investigated whether this phenomenon also occurs after radiochemotherapy.Biopsy samples of 20 patients receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone and irradiation were analyzed before and after therapy. Study patients had Ann Arbor stage I/II primary gastric cancer, including four cases of MZBCL of MALT type, 12 cases of diffuse large-cell lymphomas (DLCL), and four cases of mixed MALT type/DLCL. Polymerase chain reaction (PCR) for VH rearrangement was performed. Monoclonal PCR products were cloned and sequenced.Fourteen of 20 patients had a monoclonal or oligoclonal band distribution at diagnosis converted into polyclonal pattern after radiochemotherapy. Of the remaining six patients, two were lost to follow-up. One patient did not respond and died of progressive disease. PCR in this patient showed persistent B-cell clonality. In three patients, the initial PCR showed a polyclonal pattern and thus could not be evaluated during follow-up.In contrast with H pylori eradication alone, radiochemotherapy results in clearing of monoclonal cells during follow-up. This may result in better elimination of residual lymphoma cells. Further study is needed to determine whether this translates into lower risk of relapse.
