B. Alpen

Publications (17)113.51 Total impact

• Article: Clonal relationship in multifocal non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT).

  B Alpen, T Wündisch, J Dierlamm, G Börsch, M Stolte, A Neubauer
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  ABSTRACT: To elucidate the progression of gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, we analyzed a case presenting simultaneously with MALT lymphoma of the stomach and lung, and a gastric high-grade diffuse large lymphoma. The rearranged immunoglobulin heavy chain (IgH) variable regions were analyzed using a polymerase chain reaction (PCR)-based assay. Clonal relationship was shown between the gastric high-grade and the pulmonary low-grade lymphoma. The gastric MALT lymphoma was not related to the other manifestations. Translocation t(11;18) was not detected in the gastric high-grade lymphoma. MALT lymphomas at various locations and with different histologies may derive from a common precursor cell. Lymphomas at identical sites may have different stem cells.
  Annals of Hematology 03/2004; 83(2):124-6. · 2.62 Impact Factor
• Article: Etiology and therapy of Helicobacter pylori-associated gastric lymphomas.

  T Wündisch, T D Kim, C Thiede, A Morgner, B Alpen, M Stolte, A Neubauer
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  ABSTRACT: The WHO separates marginal zone B-cell lymphomas (MZBL) of nodal and extranodal type. Both arise from memory B cells of the marginal zone. Extranodal MZBL of the mucosa-associated lymphatic tissue (MALT) have characteristic features such as homing in epithelial tissue, lymphoepithelial destruction, and a very indolent clinical course. They arise in epithelial tissues normally devoid of lymphatic cells, where the lymphatic tissue was acquired after, for instance, a chronic infection. The best example here is infection of the stomach with Helicobacter pylori ( Hp). Besides the classical association with gastric MALT lymphomas, there have been reports in which an association between Hp and diffuse large B-cell lymphoma (DLBCL) has been observed as well. Consequently, cure of Hp infection resulted in remission induction not only in gastric MALT lymphomas, but also in some patients with very limited stages of DLBCL of the stomach. In addition to the association with Hp, progress has been made with regard to MALT lymphoma biology. Translocation t(1;14) involving the Bcl-10 gene, and translocation t(11;18) involving a novel gene called MLT1, both result in activation of the crucial transcription factor NF-kappaB. These genetic events seem specific in that they have been observed only in MALT lymphomas. Once present, at least the more frequently observed translocation t(11;18) renders cells resistant to cure of Hp infection. Another clinically important question is that in many patients in complete remission after cure of Hp infection, detection of minimal residual disease is positive. Whether these cells are normal memory B cells (with the identical B-cell rearrangement as the original lymphoma clone), or dormant lymphoma cells, is unclear at present. In patients not responding to cure of Hp infection, several treatment options are discussed. MALT lymphomas have opened up a new discussion of lymphoma biology and have thus been called a model disease.
  Annals of Hematology 10/2003; 82(9):535-45. · 2.62 Impact Factor
• Article: Helicobacter and gastric MALT lymphoma.

  M Stolte, E Bayerdörffer, A Morgner, B Alpen, T Wündisch, C Thiede, A Neubauer
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  ABSTRACT: Helicobacter pylori infection is a pre-MALT lymphoma condition. H pylori eradication leads to complete remission in 80% of low grade stage E1 lymphomas, with a yearly recurrence rate of approximately 5%. The possibility for complete remission in high grade lymphomas needs to be investigated in prospective studies. In addition, the significance of persistent B cell monoclonality (stable disease? danger of relapse? regression of monoclonality?) needs to be investigated in follow up studies.
  Gut 06/2002; 50 Suppl 3:III19-24. · 10.11 Impact Factor
• Article: Long-term follow-up of gastric MALT lymphoma after H. pylori eradication.

  A Morgner, C Thiede, E Bayerdörffer, B Alpen, T Wündisch, A Neubauer, M Stolte
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  ABSTRACT: For almost 10 years, we have been familiar with the concept of mucosa-associated lymphoid tissue (MALT)-type lymphoma of the stomach caused by chronic Helicobacter pylori infection. Many epidemiologic, biologic, and molecular genetic studies have implicated H. pylori for its role in lymphoma genesis. Since the first reports on complete remission of gastric MALT lymphomas after cure of bacterial infection, many clinical studies have investigated the effect of eradicating H. pylori on the course of MALT lymphoma, and indeed were able to confirm remission of the lymphoma. To date, more than 650 patients worldwide have been treated for gastric MALT lymphoma with antibiotics, and we have gained many new insights concerning the biologic behavior of this disease, especially from the deepened knowledge of cytogenetics. Furthermore, factors relevant for the prediction of treatment outcome have been identified, which has helped to stratify patients into risk groups.
  Current Gastroenterology Reports 01/2002; 3(6):516-22.
• Article: Molecular diagnostics in low-grade gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type after Helicobacter pylori eradication therapy.

  B Alpen, C Thiede, T Wündisch, E Bayerdörffer, M Stolte, A Neubauer
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  ABSTRACT: The primary gastric lymphomas are extranodal non-Hodgkin's lymphomas that likely originate from the mucosa-associated lymphoid tissue (MALT). Data suggest that chronic infection with Helicobacter pylori (H pylori) is significantly associated with the pathogenesis of low-grade gastric MALT lymphomas. This is in keeping with the observation that many patients with early low-grade MALT lymphomas have complete remissions after H pylori eradication therapy. However, the stability of these remissions remains unclear and relapses have been reported. It can be difficult to distinguish between early malignant and benign disorders of the gastric mucosa. A polymerase chain reaction (PCR) assay can detect rearrangements of the variable region of immunoglobulin heavy chains. This assay can be used to distinguish the clonality of B lymphocytes and has been investigated as a test for differential diagnosis of MALT lymphomas. Monoclonality is observed in the majority of MALT-lymphoma samples at diagnosis but has been found in gastritis samples as well. Whether the presence of monoclonal B cells is associated with the risk of lymphoma progression remains unclear. As many as 50% of patients who have complete histologic remissions of MALT lymphoma after H pylori eradication therapy have persisting monoclonal bands in follow-up PCR monitoring. Although it is unclear as to whether monoclonality indicates the presence of minimal residual disease, patients who have persistent monoclonal bands during follow-up should be considered at risk for relapse. The PCR assay for rearrangements of the variable region of the immunoglobulin heavy-chain gene appears to be of low value in the diagnosis of B-cell malignancies but could provide a useful tool in the follow-up of patients who achieve remissions after H pylori eradication.
  Clinical lymphoma 10/2001; 2(2):103-8. · 3.11 Impact Factor
• Article: Are lymphocytic monoclonality and immunoglobulin heavy chain (IgH) rearrangement premalignant conditions in chronic gastritis?

  T Wündisch, C Thiede, B Alpen, M Stolte, A Neubauer
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  ABSTRACT: Normal gastric mucosa is devoid of lymphoid cells. Any increase of lymphocytes suggests chronic inflammation. Infection with Helicobacter pylori (Hp) is the major cause for nonautoimmune chronic gastritis and induces a mixed cellular response resulting in an acquired lymphoid tissue, or MALT (mucosa-associated lymphoid tissue). Hp has also been implicated in the genesis of gastric MALT-lymphoma. Polymerase chain reaction-based assays to detect the expansion of monoclonal B-cells have also been used to corroborate the diagnosis. In a considerable number of cases monoclonal B-cells remain detectable in follow-up biopsies, with the lymphoma being in complete histological remission. The clinical relevance of this finding is not clear yet. However, there also exist different reports that monoclonal B-cells can be found in gastric biopsies of patients with neither a histological sign nor a present or past history of lymphoma. In the light of these findings we address the question whether B-cell monoclonality can be seen as a premalignant condition in chronic gastritis and conclude that as of now the relevance of the finding of B-cell monoclonality remains unclear. As of now the only and gold standard for the diagnosis of gastric MALT-lymphoma is histopathology.
  Microscopy Research and Technique 07/2001; 53(6):414-8. · 1.79 Impact Factor
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  Available from: wjgnet.com

  Article: Development of early gastric cancer 4 and 5 years after complete remission of Helicobacter pylori associated gastric low grade marginal zone B cell lymphoma of MALT type.

  A Morgner, S Miehlke, M Stolte, A Neubauer, B Alpen, C Thiede, H Klann, F X Hierlmeier, C Ell, G Ehninger, E Bayerdörffer
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  ABSTRACT: To report 3 of 120 patients on the German MALT lymphoma trial with H. pylori associated gastric MALT lymphoma who developed early gastric cancer 4 and 5 years, after complete lymphoma remission following cure of H. pylori infection. Three patients (two men, 74 and 70 years; one women, 77 years) with H. pylori-associated low-grade MALT lymphoma achieved complete lymphoma remission after being cured. Surveillance endoscopies were performed twice a year in accordance to the protocol. Four years after complete lymphoma remission in two patients, and after 5 years in the other, early gastric adenocarcinoma of the mucosa-type, type IIa and type IIc, respectively, was detected, which were completely removed by endoscopic mucosa resection. In one patient, the gastric cancer was diagnosed at the same location as the previous MALT lymphoma, in the other patients it was detected at different sites of the stomach distant from location of the previous MALT lymphoma. The patients were H. pylori negative during the whole follow-up time. These findings strengthen the importance of regular Long-term follow-up endoscopies in patients with complete remission of gastric MALT lymphoma after cure of H. pylori infection. Furthermore, gastric adenocarcinoma may develop despite eradication of H. pylori.
  World Journal of Gastroenterology 05/2001; 7(2):248-53. · 2.47 Impact Factor
• Article: Long-term persistence of monoclonal B cells after cure of Helicobacter pylori infection and complete histologic remission in gastric mucosa-associated lymphoid tissue B-cell lymphoma.

  C Thiede, T Wündisch, B Alpen, B Neubauer, A Morgner, M Schmitz, G Ehninger, M Stolte, E Bayerdörffer, A Neubauer
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  ABSTRACT: 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. 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. 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. 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.
  Journal of Clinical Oncology 04/2001; 19(6):1600-9. · 18.37 Impact Factor
• Article: Helicobacter pylori eradication therapy in gastric high grade non Hodgkin's lymphoma (NHL).

  B Alpen, J Röbbecke, T Wündisch, M Stolte, A Neubauer
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  ABSTRACT: Primary gastric low-grade lymphoma of the mucosa associated lymphoid tissue (MALT) develops on the background of a chronic Helicobacter pylori (H. pylori) infection. Stable remissions can be induced by H. pylori eradication therapy as shown in clinical trials. In 8 cases of high-grade gastric lymphomas remissions after H. pylori eradication were observed retrospectively. We started a pilot-trial to investigate the value of H. pylori eradication therapy in early gastric high-grade B-cell lymphoma prospectively. So far, two H. pylori positive patients with high-grade B-cell lymphoma of the stomach stage Ann Arbor I E are included. They received a triple eradication-therapy (Clarithromycin 500 mg/d, Metronidazol 800 mg/d and Omeprazol 40 mg/d) for 7 days. Endoscopic controls are preformed every 4 weeks. Both patients became H. pylori negative after eradication therapy. One patient achieved complete remission (CR) 38 days after eradication. The continuous complete remission lasts now for 170 days. The second patient received only a partial remission (PR) 4 weeks after eradication and showed a slight progress 4 weeks later. He presently receives chemotherapy (CHOP). Patients with early high-grade gastric B-cell lymphomas should receive H. pylori eradication only within clinical trials. It seems to be possible to induce remissions of early high-grade gastric B-cell lymphomas with exclusive H. pylori eradication therapy. The stability of remission remains to be unclear and should be evaluated by following up the patients closely.
  Annals of Hematology 02/2001; 80 Suppl 3:B106-7. · 2.62 Impact Factor
• Article: Somatic hypermutation and B-cell lymphoma.

  D Dunn-Walters, C Thiede, B Alpen, J Spencer
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  ABSTRACT: During the B-cell response to T-cell-dependent antigens, the B cells undergo a rapid proliferative phase in the germinal centre. This is accompanied by the introduction of mutations into the immunoglobulin (Ig) variable region (V) genes. The B cells are then selected according to the affinity of the encoded immunoglobulin for antigen, resulting in affinity maturation of the response. Analysis of mutations in IgV genes has given insight into the history of individual B cells and their malignancies. In most cases, analysis of mutations confirms classifications of B-cell lineage designated by studies of cellular morphology and surface antigen expression. However, of particular interest is the subdivision of groups of malignancies by analysis of somatic hypermutation. It is now apparent that there are two subsets of chronic lymphocytic leukaemia (CLL), one with a low load of mutations and poor prognosis. and one with a heavy load of mutations with a much more favourable prognosis. In addition, in Burkitt's lymphoma, sporadic and endemic subtypes are now considered possibly to have a different pathogenesis, reflected in differences in the numbers of mutations. Hodgkin's disease, which was a mystery for many years, has now been shown to be a B-cell tumour. Although in many cases the Ig genes are crippled by somatic hypermutation, it is thought that failure to express Ig is more likely to be associated with problems of transcription. It has been proposed that the distribution of mutations in a B-cell lymphoma can be used to determine whether a lymphoma is selected. We have investigated the load and distribution of mutations in one group of lymphomas--marginal zone B-cell lymphomas of mucosa-associated lymphoid tissues (MALT-type lymphoma), which are dependent on Helicobacter pylori for disease progression, to investigate the limits of information that can be derived from such studies. Comparison of the load of mutations demonstrates that these tumours have approximately the same load of mutations as normal mucosal marginal zone B cells from the Peyer's patches and mucosal plasma cells. This is consistent with the origin of these cells from mucosal marginal zone B cells with plasma cell differentiation. To investigate selection in MALT lymphomas we compared a region of the framework region three in ten MALT lymphomas which use the V(H4) family, with the same codons in groups of V(H4) genes that are out of frame between V and J. The latter accumulate mutations but are not used and are not selected. A group of V(H4) genes are in-frame between V and J were also included for comparison. There were no obvious differences in the distribution of mutations between the groups of genes; the same hot spots and cold spots were apparent in each. In the MALT lymphomas, selection was apparent in the framework regions only and the tendency was to conserve. We therefore feel that there is selection to conserve antibody structure and that this does not reflect selection for antigen. We do not believe that antigen selection can be deduced reliably from sequence information alone. It is possible that somatic hypermutation could be a cause of malignancy since it has been shown that the process may generate DNA strand breaks and is known to be able to generate insertions and deletions. Such events may mediate the translocation of genes--a process that is pivotal in the evolution of many lymphomas.
  Philosophical Transactions of The Royal Society B Biological Sciences 02/2001; 356(1405):73-82. · 6.40 Impact Factor
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  Available from: hematologylibrary.org

  Article: Translocation t(11;18) absent in early gastric marginal zone B-cell lymphoma of MALT type responding to eradication of Helicobacter pylori infection.

  B Alpen, A Neubauer, J Dierlamm, P Marynen, C Thiede, E Bayerdörfer, M Stolte
  Blood 07/2000; 95(12):4014-5. · 9.90 Impact Factor
• Article: Frequency of TPR-MET rearrangement in patients with gastric carcinoma and in first-degree relatives.

  J Yu, S Miehlke, M P Ebert, J Hoffmann, M Breidert, B Alpen, T Starzynska, M Stolte Prof, P Malfertheiner, E Bayerdörffer
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  ABSTRACT: The activation of the c-met protooncogene through a rearrangement has been detected previously in gastric carcinoma tissue and precancerous lesions. In the current study the authors analyzed the rearrangement of TPR-MET in gastric carcinoma patients and in first-degree relatives to evaluate the potential role and timepoint of this genetic alteration in the process of gastric carcinogenesis and its potential value in identifying those individuals with an increased risk of developing gastric carcinoma. The presence of TPR-MET mRNA was determined in gastric tissue from 19 patients with gastric carcinoma and in the gastric mucosa of 18 first-degree relatives without gastric carcinoma and in the gastric mucosa of 18 first-degree relatives without gastric carcinoma using a nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. A 205-base pair (bp) cDNA fragment and a 70-bp cDNA fragment spanning the breakpoint were amplified by nested PCR. Amplification products were hybridized with an oligonucleotide labeled at the 3'-end with DIG-11-dUTP spanning the breakpoint using Southern blot analysis. The MNNG-HOS cell line served as a positive control. TPR-MET mRNA was detected in nine gastric carcinoma patients (47%). Among these patients, TPR-MET mRNA was present in the both tumor and tumor free tissues in 5 patients (26%), in the tumor tissue only in 2 patients (11%), and in the tumor free gastric mucosa only in 2 patients (11%). It is interesting to note that TPR-MET rearrangement also was detected in the gastric corpus mucosa of 1 first-degree relative (6%), but in none of the control subjects. The data from the current study indicate that TPR-MET activation may be an early event in gastric carcinogenesis and may be useful for the identification of individuals with an increased risk of developing gastric carcinoma.
  Cancer 05/2000; 88(8):1801-6. · 4.77 Impact Factor
• Article: Eradication of Helicobacter pylori and stability of remissions in low-grade gastric B-cell lymphomas of the mucosa-associated lymphoid tissue: results of an ongoing multicenter trial.

  C Thiede, T Wündisch, B Neubauer, B Alpen, A Morgner, M Ritter, G Ehninger, M Stolte, E Bayerdörffer, A Neubauer
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  ABSTRACT: The normal human stomach is devoid of any organized lymphatic tissue. Acquisition of mucosa-associated lymphatoid tissue (MALT) in the stomach is considered to be a direct consequence of chronic infection with Helicobacter pylori. Thus, MALT appears to be part of the host defense against the pathogen H. pylori. Consequently, lymphomas arising from gastric MALT may be seen as an end point of a clonal evolution starting from the infection. Cumulative data from several studies show that eradication of H. pylori induces complete histologic remissions in about 70%-80% of the patients. Here we present data of an extended analysis of an ongoing multicenter trial. Eighty-four patients with low-grade gastric MALT lymphoma in stage EI were treated using a dual regimen to eradicate H. pylori. Complete remission was observed in 68 (81%) patients; a partial remission was found in seven (8%) patients. In contrast, nine (11%) patients revealed "no change" and were referred for alternative treatment strategies. The majority of these cases were found to harbor high-grade lymphomas in deeper mucosal areas. Polymerase chain reaction (PCR) performed on the VDJ rearrangements of the immunoglobulin heavy chain yielded monoclonal bands in 50 of 65 analyzed patients (77%) at diagnosis. Interestingly, in patients analyzed during follow up after achieving complete histologic remission, ongoing PCR monoclonality was found in 19 of 39 eligible patients (49%). Several patients who developed local relapse of the lymphoma were found in the group with ongoing PCR monoclonality. Together with data from the literature, these results suggest that the majority of low-grade gastric MALT lymphomas in stage EI respond to eradication of H. pylori. Longer follow-up investigations are necessary to determine whether remissions really indicate a cure from the disease and to elucidate whether PCR monoclonality after complete histological remission is predictive of increased relapse rate.
  Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer 02/2000; 156:125-33.
• Article: Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma.

  C Thiede, B Alpen, A Morgner, M Schmidt, M Ritter, G Ehninger, M Stolte, E Bayerdörffer, A Neubauer
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  ABSTRACT: Although most patients with primary gastric low-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma experience complete endoscopic and histologic remission after the cure of Helicobacter pylori infection, in many patients, the polymerase chain reaction (PCR) still detects monoclonal B cells in the gastric mucosa. The present study asked whether the lymphoma immunoglobulin VH (IgVH) sequences remained stable in patients with gastric MALT lymphoma after H pylori eradication. Eight patients with stage EI disease treated with H pylori eradication were analyzed before and at different time points after the cure of the infection. After the amplification of IgVH genes from DNA extracted from gastric biopsy specimens, monoclonal PCR products were cloned and multiple clones (43 to 105) were sequenced per patient. Mutations were detected in all lymphoma VH sequences, which suggested germinal center or postgerminal center origin of the lymphoma B cells. In five of the eight patients, clonal heterogeneity was observed at diagnosis or during follow-up. Genealogical analysis of shared and unshared mutations showed that the process of somatic mutations was ongoing after H pylori eradication in four of the five patients who showed clonal instability. Ongoing mutations were observed in three of the four patients who completely responded to H pylori eradication, but in only one of the four patients who did not respond or who partially responded. In low-grade gastric MALT lymphomas, an ongoing process of somatic hypermutation and antigen selection can be detected after the therapeutic removal of the underlying stimulus H pylori. These data point to the relevance of yet unknown antigens that drive this disease. In addition, they challenge the view that these lymphomas may be cured solely by the eradication of H pylori.
  Journal of Clinical Oncology 01/1999; 16(12):3822-31. · 18.37 Impact Factor
• Article: What role does Helicobacter pylori eradication play in gastric MALT and gastric MALT lymphoma?

  C Thiede, A Morgner, B Alpen, T Wündisch, J Herrmann, M Ritter, G Ehninger, M Stolte, E Bayerdörffer, A Neubauer
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  ABSTRACT: The concept of mucosa-associated lymphoid tissue (MALT) has been introduced to differentiate biological functions from behavior of nonnodal vs. nodal lymphoid tissues. Lymphomas arising from MALT also behave differently than typical nodal lymphomas. In contrast to other tissues, MALT in the stomach is almost exclusively a result of Helicobacter pylori infection. Thus, MALT is part of the host defense against the pathogen H. pylori. Consequently, lymphomas arising from gastric MALT may be a clonal evolution starting from the infection. In low-grade gastric MALT lymphoma, cure of the infection may induce complete histological remission in the majority of patients. Investigators have recently reported that complete remission rate is between 70% and 80%. In an extended analysis, we have treated 84 patients with low-grade gastric MALT lymphoma in stage El, using a dual regimen to eradicate H. pylori. Complete remission was observed in 68 (80%) patients; a partial remission was found in 4 patients. In contrast, 12 patients showed no change and were referred to alternative treatment. In patients in complete remission, a polymerase chain reaction assay for the rearranged immunoglobulin heavy-chain gene remained positive in many cases. Together with data from the literature, these data suggest that the majority of patients with low-grade gastric MALT lymphomas in stage El respond to eradication of H. pylori. Longer follow-up investigations are necessary to determine if remissions indicate a cure from the disease.
  Gastroenterology 01/1998; 113(6 Suppl):S61-4. · 11.68 Impact Factor
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  Available from: oxfordjournals.org

  Article: Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma.

  A Neubauer, C Thiede, A Morgner, B Alpen, M Ritter, B Neubauer, T Wündisch, G Ehninger, M Stolte, E Bayerdörffer
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  ABSTRACT: 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.
  JNCI Journal of the National Cancer Institute 10/1997; 89(18):1350-5. · 13.76 Impact Factor
• Article: Underestimation of inversion (16) in acute myeloid leukaemia using standard cytogenetics as compared with polymerase chain reaction: results of a prospective investigation.

  M Ritter, C Thiede, U Schäkel, M Schmidt, B Alpen, U Pascheberg, B Mohr, G Ehninger, A Neubauer
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  ABSTRACT: In order to determine whether the polymerase chain reaction (PCR) is more suitable for the detection of inversion (16) as compared with standard cytogenetics, we prospectively investigated a total of 132 cases of de novo acute myeloid leukaemia (AML) (n = 121) and secondary AML after myelodysplastic syndromes (MDS) (n = 11) using a sensitive and nested PCR procedure to detect the fusion transcripts CBFbeta-MYH11. All patients were recruited within 10 months in an ongoing multicentre AML-trial. In addition, several cases from a retrospective molecular analysis were included. The data were compared with standard cytogenetics performed in a central laboratory. Of the 132 prospective AML cases, five patients (3.7%) harboured inv(16) upon conventional cytogenetics. In all cases fusion transcripts CBFbeta-MYH11 were detected using PCR. In addition in two patients fusion transcripts were detected, although cytogenetics revealed a normal karyotype. In the group of patients analysed retrospectively, four patients harboured fusion transcripts specific for CBFbeta-MYH11; cytogenetics were normal in one case, and could not be evaluated in two cases. These data show that PCR may be a better means to detect inv(16) in AML. Since inv(16) may have prognostic impact in AML, detection of this aberration seems important in the clinical management of AML patients.
  British Journal of Haematology 10/1997; 98(4):969-72. · 4.94 Impact Factor