ABSTRACT
Teclistamab, a B-cell maturation antigen (BCMA) × CD3 directed bispecific antibody, has shown high response rates and durable remissions in the MAJESTEC-1 trial in patients with relapsed and refractory multiple myeloma (RRMM). We retrospectively assessed efficacy and tolerability in 123 patients treated at 18 different German centers to determine whether outcome is comparable in the real-world setting. Most patients had triple-class (93%) or penta-drug (60%) refractory disease, 37% of patients had received BCMA-directed pretreatment including idecabtagene vicleucel (ide-cel) CAR-T cell therapy (21/123, 17.1%). With a follow-up of 5.5 months, we observed an overall response rate (ORR) of 59.3% and a median progression-free survival (PFS) of 8.7 months. In subgroup analyses, we found significantly lower ORR and median PFS in patients with extramedullary disease (37%/2.1 months), and/or an ISS of 3 (37%/1.3 months), and ide-cel pretreated patients (33%/1.8 months). Nonetheless, the duration of response in ide-cel pretreated patients was comparable to that of anti-BCMA naive patients. Infections and grade ≥3 cytopenias were the most frequent adverse events. In summary, we found that teclistamab exhibited a comparable efficacy and safety profile in the real-world setting as in the pivotal trial.
Subject(s)
Antibodies, Bispecific , Antineoplastic Agents , Multiple Myeloma , Neoplasms, Plasma Cell , Humans , Multiple Myeloma/drug therapy , B-Cell Maturation Antigen , Retrospective Studies , Germany , Immunotherapy, AdoptiveABSTRACT
To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 days 2, 16, 30), procarbazine (60 mg/m2 days 2-11) and lomustine (110 mg/m2, day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/drug therapy , Lymphoma/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/mortality , Female , Humans , Immunologic Factors/administration & dosage , Lymphoma/diagnosis , Male , Methotrexate/administration & dosage , Neoplasm Staging , Proportional Hazards Models , Quality of Life , Remission Induction , Treatment Outcome , Tumor BurdenABSTRACT
In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to-transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m(2) and cytarabine 1 g/m(2), days 1-5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 × 30 mg/m(2)) and melphalan (140 mg/m(2)). The median patient age was 61 years (range 40-75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia-free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32-54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40-69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML.
Subject(s)
Adenine Nucleotides/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use , Arabinonucleosides/therapeutic use , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Salvage Therapy , Adult , Aged , Clofarabine , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Prospective Studies , Recurrence , Transplantation, HomologousABSTRACT
BACKGROUND: For patients with primary refractory or relapsed acute myeloid leukemia (AML), no treatment of choice has until now been defined to date. Cytarabine (Ara-C) is a key drug in the treatment of AML patients, there is still uncertainly regarding its optimal dose and infusion schedule. The aim of this study is to examine the impact of the Ara-C infusion schedule used as part of an intensive salvage regimen, in patients with relapsed or refractory AML. PATIENTS AND METHODS: A total of 252 adult patients (median age 59 years) with relapsed or refractory AML were randomly allocated to receive either Mito-FLAG with Ara-C as bolus (B) (1000 mg/m(2) over 1 h, every 12 h, days 1-5), or continuous infusion (CI) (150 mg/m(2) over 24 h, days 1-5) in combination with mitoxantrone, fludarabine, and granulocyte colony-stimulating factor (G-CSF). Autologous or allogeneic hematopoietic stem-cell transplantation was offered as consolidation therapy. Primary end point was the rate of complete remissions (CRs) after the first cycle of Mito-FLAG. RESULTS: The CR rates after Mito-FLAG (B) and Mito-FLAG (CI) were 54% and 43%, respectively (P = 0.1). There was no statistical difference between rates of grade 3/4 neutropenia, thrombocytopenia, mucositis, renal, and liver toxicity. More infections occurred, however, after Mito-FLAG (B) compared with Mito-FLAG (CI) (80% versus 69%, P = 0.01). The early death rate by day 42 was 13% in both arms. Median disease-free survival was comparable in the two arms (7.8 versus 7.1 months, P = 0.53) as was overall survival (7.1 versus 6.6 months, P = 0.53). CONCLUSION: A 5-day course of Ara-C 2 × 1000 mg/m(2) administered as bolus versus Ara-C 150 mg/m(2) administered by CI (in combination with mitoxantrone, fludarabine, and G-CSF), resulted in a nonsignificant trend in response rates in favor of Mito-FLAG (B) at the selected dose levels, but no differences in the survival outcome in relapsed or refractory AML. CLINICAL TRIAL NUMBER: LN_NN_2004_39/EudraCT number 2014-000083-18.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm/drug effects , Leukemia, Myeloid, Acute/drug therapy , Neoplasm Recurrence, Local/drug therapy , Salvage Therapy , Adolescent , Adult , Aged , Cytarabine/administration & dosage , Drug Administration Routes , Female , Follow-Up Studies , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Mitoxantrone/administration & dosage , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Prospective Studies , Survival Rate , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives , Young AdultABSTRACT
BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) allows in-vivo assessment of the gastrointestinal mucosal architecture during ongoing endoscopy. We investigated the feasibility and safety of pCLE during double balloon enteroscopy (DBE). METHODS: DBE was performed using the Fujinon EN-450P5. pCLE (Cellvizio-GI®, Mauna Kea Technologies) was performed after intravenous injection of 5-10 âmL fluorescein 1â% using a 1.8-mm probe (GastroFlex/ColoFlex Z-probe) at the deepest point of DBE insertion and in case of any pathological lesion. Primary outcome measure was technical success, defined as (i) successful advancement of the probe at the deepest DBE insertion and (ii) successful pCLE imaging of the intestinal mucosa. Secondary outcome was safety of the pCLE procedure. RESULTS: 27 DBE procedures (14 antegrade) were performed in 16 patients. The mean depth of small bowel insertion was 255 âcm for antegrade and 130â cm for retrograde DBE. Technical success of pCLE was achieved in 96.3â% (antegrade 92.8â%, retrograde 100â%). One technical failure occurred (incomplete probe advancement). There were no adverse events related to the pCLE procedure. pCLE imaging of the small bowel mucosal architecture was possible in all cases. Pathological conditions within the small bowel such as loss of villi, crypt hyperplasia, advanced neoplasia, or increased blood flow due to inflammation tissue could be successful visualized. CONCLUSION: This study is the first to demonstrate successful and safe application of pCLE in the deep small bowel during double balloon enteroscopy. Further studies are needed to determine the clinical benefit of pCLE in the management of patients with small bowel diseases.
Subject(s)
Double-Balloon Enteroscopy/methods , Intestinal Diseases/pathology , Intestinal Diseases/surgery , Intestine, Small/pathology , Intestine, Small/surgery , Microscopy, Confocal/methods , Surgery, Computer-Assisted/methods , Adult , Aged , Double-Balloon Enteroscopy/instrumentation , Female , Humans , Male , Microscopy, Confocal/instrumentation , Middle Aged , Surgery, Computer-Assisted/instrumentation , Transducers , Treatment OutcomeABSTRACT
Eradication rates in first-line Helicobacter pylori therapy have been declining over the last decades, mainly due to increasing resistance against the recommended antibiotics clarithromycin and metronidazole. Thus, there is a need to evaluate novel regimens and substances to offer effective alternative treatment strategies. New generation quinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against various Gram-positive and Gram-negative strains and are mostly well tolerated. Based on a large number of studies, quinolones have been introduced in second-line and rescue treatment and are recommended for these indications in current guidelines. Various studies have investigated alternative strategies for first-line treatment including quinolone-based regimens. In the context of increasing resistance rates of Helicobacter pylori against quinolones some risks and benefits have to be considered when using quinolones as a first-line strategy. Besides numerous studies investigating levofloxacin and moxifloxacin there are some promising results for the new substance sitafloxacin, which might overcome primary resistance of Helicobacter pylori against conventional quinolones.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Fluoroquinolones/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter pylori , Anti-Bacterial Agents/adverse effects , Aza Compounds/adverse effects , Aza Compounds/therapeutic use , Drug Resistance, Bacterial , Drug Therapy, Combination , Fluoroquinolones/adverse effects , Humans , Levofloxacin , Microbial Sensitivity Tests , Moxifloxacin , Ofloxacin/adverse effects , Ofloxacin/therapeutic use , Quinolines/adverse effects , Quinolines/therapeutic useABSTRACT
BACKGROUND: Generic omeprazole has been approved in many countries for the treatment of acid-related gastrointestinal disorders. However, clinical studies comparing generic to original proton pump inhibitors are limited. AIMS: To compare the effect of generic omeprazole 20 mg/day with esomeprazole 20 mg/day on intragastric acidity and to investigate the influence of the CYP2C19 metabolizer status. METHODS: In this randomised, single-blinded, two-way crossover study, 24 healthy Helicobacter pylori-negative subjects, received generic omeprazole (Omep; Hexal AG, Holzkirchen, Germany) 20 mg once daily or esomeprazole 20 mg once daily for five consecutive days. Twenty-four-hour intragastric pH was recorded on day 5 of each treatment. CYP2C19 status was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Over all, there were no statistically significant differences between generic omeprazole and esomeprazole with respect to median intragastric pH (3.5 and 3.9, P = 0.07), the total hours with intragastric pH >4 (10.4 and 11.3, P = 0.29), and during upright (9.6 and 9.1, P = 0.77) or supine (2.2 and 2.2, P = 0.94) position. However, in CYP2C19 rapid metabolizers, esomeprazole was superior to omeprazole, with the percentage of time with intragastric pH >3.0 and pH >3.5 being higher with esomeprazole than with generic omeprazole [Δ = 9% (P = 0.026) and Δ = 8% (P = 0.046), respectively]. CONCLUSIONS: Overall, generic omeprazole 20 mg appears to provide a similar intragastric acid control when compared with esomeprazole 20 mg. However, esomeprazole might be advantageous in subjects with a rapid CYP2C19 metabolizer status.
Subject(s)
Anti-Ulcer Agents/therapeutic use , Enzyme Inhibitors/therapeutic use , Gastroesophageal Reflux/drug therapy , Omeprazole/therapeutic use , Adolescent , Adult , Aryl Hydrocarbon Hydroxylases/genetics , Cross-Over Studies , Cytochrome P-450 CYP2C19 , Drugs, Generic/therapeutic use , Esomeprazole , Female , Gastric Acid , Gastric Acidity Determination , Gastroesophageal Reflux/genetics , Humans , Hydrogen-Ion Concentration/drug effects , Male , Middle Aged , Statistics as Topic , White People , Young AdultABSTRACT
This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.
Subject(s)
Gastroenteritis/diagnosis , Gastroenteritis/therapy , Gastroenterology/standards , Helicobacter Infections/diagnosis , Helicobacter Infections/therapy , Helicobacter pylori , Peptic Ulcer/diagnosis , Peptic Ulcer/therapy , Germany , HumansABSTRACT
This guideline updates a prior concensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE) and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based consensus guideline of S 3 level and has also implemented grading criteria according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics and therapy were taken into account.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Evidence-Based Medicine , Helicobacter Infections/drug therapy , Helicobacter pylori , Peptic Ulcer/drug therapy , Adolescent , Adult , Child , Cross-Sectional Studies , Drug Therapy, Combination , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastroscopy , Helicobacter Infections/diagnosis , Helicobacter Infections/epidemiology , Humans , Lymphoma, B-Cell/pathology , Lymphoma, B-Cell/prevention & control , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, B-Cell, Marginal Zone/prevention & control , Neoplasm Staging , Peptic Ulcer/diagnosis , Peptic Ulcer/epidemiology , Randomized Controlled Trials as Topic , Stomach Neoplasms/pathology , Stomach Neoplasms/prevention & controlSubject(s)
Anastomosis, Surgical , Capsule Endoscopy/adverse effects , Catheterization , Endoscopy, Gastrointestinal , Foreign Bodies/therapy , Intestinal Obstruction/complications , Intestine, Small , Meckel Diverticulum/surgery , Postoperative Complications/therapy , Adult , Colon/surgery , Humans , Intestinal Obstruction/diagnosis , Jejunum/surgery , Male , Postoperative Complications/diagnosisABSTRACT
BACKGROUND: The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge. AIM: To investigate the efficacy of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of H. pylori, and the correlation between cytochrome P450 2C19 (CYP2C19) polymorphisms and treatment outcome. METHODS: Patients infected with H. pylori resistant to both metronidazole and clarithromycin (n = 145) were randomized to either esomeprazole 20 mg, rifabutin 150 mg and amoxicillin 1 g, each given b.d. for 7 days (ERA), or to omeprazole 40 mg and amoxicillin 1000 mg, each given t.d.s. for 14 days (OA). Crossover therapy was offered in cases of persistent infection. CYP2C19 polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: Intention-to-treat and per-protocol eradication rates were: ERA 74% (62.4-83.6) and 78% (66.7-87.3); high-dose OA 70% (57.5-79.7) and 75% (62.5-84.5). Crossover therapy was successful in seven of 10 patients with ERA and in eight of 10 patients with OA. Premature discontinuation of treatment occurred in 2% and 5% of patients, respectively. There was only a non-significant trend to lower eradication rates in homozygous extensive metabolizers. CONCLUSIONS: Triple therapy with esomeprazole, rifabutin and amoxicillin and high-dose omeprazole/amoxicillin are comparable and effective and safe for rescue therapy of H. pylori regardless of the patient's CYP2C19 genotype.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter pylori , Rifabutin/therapeutic use , Adolescent , Adult , Aged , Amoxicillin/therapeutic use , Anti-Ulcer Agents/therapeutic use , Clarithromycin/therapeutic use , Cross-Over Studies , Drug Resistance, Bacterial , Drug Therapy, Combination , Esomeprazole , Female , Humans , Male , Metronidazole/therapeutic use , Middle Aged , Omeprazole/therapeutic use , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: An association between Helicobacter pylori infection and lymphocytic gastritis has been postulated. AIM: To assess the long-term effect of H. pylori eradication therapy on lymphocytic gastritis in a double-blind, placebo-controlled, multicentre trial. METHODS: Patients with lymphocytic gastritis were randomized to receive either 1-week triple therapy for eradication of H. pylori or omeprazole plus placebo. Endoscopy and histology was performed at baseline and after 3 and 12 months. Patients of the omeprazole/placebo group with persistent lymphocytic gastritis after 12 months received crossover open-label triple therapy. RESULTS: Fifty-one patients were randomized. Intention-to-treat analysis revealed a trend to a higher healing rate of lymphocytic gastritis 3 months after triple therapy compared with omeprazole/placebo (83.3% vs. 57.7%, 95% CI for RR: 0.8-2.8, P = 0.06). After 12 months, the healing rate of lymphocytic gastritis was significantly higher after triple therapy compared with omeprazole/placebo (intention-to-treat 95.8% vs. 53.8%, 95% CI for RR: 1.1-3.5, P = 0.01). All patients (n = 5) who received crossover triple therapy, showed healing of lymphocytic gastritis after further 12 months. CONCLUSION: Our study demonstrates that 1-week triple therapy aiming at eradication of H. pylori leads to a complete and long-lasting resolution of lymphocytic gastritis in the majority of patients.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Gastritis/drug therapy , Helicobacter Infections/drug therapy , Adult , Aged , Amoxicillin/therapeutic use , Anti-Ulcer Agents/therapeutic use , Clarithromycin/therapeutic use , Drug Therapy, Combination , Female , Gastritis/microbiology , Helicobacter pylori/drug effects , Humans , Lymphocyte Count , Lymphocytes/drug effects , Male , Middle Aged , Omeprazole/therapeutic use , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Budesonide (Entocort) is effective for the treatment of collagenous colitis. AIM: To assess the long-term outcome of patients after induction of clinical remission by budesonide treatment. METHODS: Fifty-one patients with chronic diarrhoea and histologically proven collagenous colitis were enrolled in randomized, placebo-controlled crossover trial using budesonide 9 mg daily for 6 weeks. Patients in clinical remission after either initial or crossover budesonide treatment were followed using standardized questionnaires. Clinical relapse was defined as five or more loose stools/day for at least 4 consecutive days. RESULTS: A total of 33 patients achieved clinical remission (85% per-protocol). During a median follow-up of 16 months, clinical relapse occurred in 20 patients (61%), after a median time of 2 weeks (range: 1-104, mean: 10 weeks). Patient age <60 years was identified as a significant risk factor for clinical relapse (OR = 7.4, P = 0.048). Budesonide was used for treatment of clinical relapse in 80% of patients achieving clinical response in all of them. CONCLUSIONS: Budesonide is effective in the treatment of collagenous colitis. Clinical relapses may occur in a considerable number of patients, particularly in those <60 years. Treatment of clinical relapse with budesonide appears to be an effective option.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Budesonide/therapeutic use , Colitis, Collagenous/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Over Studies , Diarrhea/drug therapy , Diarrhea/etiology , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: Patients with severe or complicated reflux disease may require higher than standard doses of a proton pump inhibitor for sufficient acid suppression. AIM: To test the hypothesis that esomeprazole 40 mg twice daily is superior to pantoprazole 40 mg twice daily in lowering intragastric acidity. METHODS: In a randomized, single-blinded, two-way crossover study, healthy subjects received esomeprazole 40 mg twice daily or pantoprazole 40 mg twice daily orally for five consecutive days. Continuous ambulatory 24-h intragastric pH was recorded on day 5 of each treatment. RESULTS: Thirty subjects were analysed. Esomeprazole provided significantly higher intragastric pH-values over the 24-h period [median intragastric pH 6.4 for esomeprazole and 5.1 for pantoprazole (P < 0.00005)]. Intragastric pH > 4 was maintained for 21.1 h with esomeprazole and 16.8 h with pantoprazole (P < 0.0001). An intragastric pH > 4 for more than 16 h was achieved in 96.7 and 56.7% of subjects, respectively (P = 0.0002). During night-time the proportion of time with intragastric pH > 4 was 85.4% with esomeprazole and 63.6% with pantoprazole (P = 0.0001). Nocturnal acid break through occurred less frequently on esomeprazole. CONCLUSIONS: Esomeprazole 40 mg twice daily provides better and more consistent intragastric acid control than pantoprazole 40 mg twice daily.
Subject(s)
Anti-Ulcer Agents/administration & dosage , Benzimidazoles/administration & dosage , Esomeprazole/analogs & derivatives , Esomeprazole/administration & dosage , Gastric Acid/metabolism , Proton Pump Inhibitors , Sulfoxides/administration & dosage , 2-Pyridinylmethylsulfinylbenzimidazoles , Adult , Anti-Ulcer Agents/adverse effects , Benzimidazoles/adverse effects , Cross-Over Studies , Esomeprazole/adverse effects , Female , Gastric Acidity Determination , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Pantoprazole , Single-Blind Method , Sulfoxides/adverse effectsABSTRACT
Gastric lymphoma and gastrointestinal stromal tumours (GISTs) are rare malignancies of the upper gastrointestinal tract. The most common gastric lymphoma are low-grade marginal zone B-cell lymphoma (MZBCL) of MALT type. They develop as a consequence of chronic Helicobacter pylori infection, the histological hallmark are lymphoepithelial lesions. In early stages of disease, H. pylori eradication alone may lead to complete lymphoma remission in up to 75% of cases. Nonresponder or locally advanced lymphoma should be treated with radiation therapy. Advanced lymphoma may be treated with the nucleoside analogon cladribine within clinical trials. Based on clinical and novel molecular markers a risk stratification and a prediction of response to therapy might be possible in the future. GISTs are mesenchymal tumours that characteristically express CD-117 (c-kit). They are mostly localized in the upper gastrointestinal tract and are frequently diagnosed in an advanced stage. Conventional chemotherapy is ineffective. For resectable non-metastasized tumours surgical therapy is the treatment of choice. Imatinib is the first and so far only effective systemic therapy which is presently indicated in irresectable or metastasized GISTs. More than 80% of patients respond to imatinib therapy either with partial remission or stable disease. FDG-PET plays an important role in the early prediction of response to imatinib therapy. The optimal dosage and duration of treatment and the role of imatinib as adjuvant or neo-adjuvant therapy for GISTs remains to be defined.
Subject(s)
Gastrointestinal Stromal Tumors/diagnosis , Lymphoma, B-Cell, Marginal Zone/diagnosis , Stomach Neoplasms/diagnosis , Gastric Mucosa/pathology , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/therapy , Helicobacter Infections/diagnosis , Helicobacter Infections/pathology , Helicobacter Infections/surgery , Helicobacter pylori , Humans , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, B-Cell, Marginal Zone/therapy , Neoplasm Staging , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Treatment OutcomeABSTRACT
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.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Lymphoma, B-Cell/microbiology , Lymphoma, B-Cell/therapy , Stomach Neoplasms/microbiology , Stomach Neoplasms/therapy , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 18 , Humans , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/genetics , Lymphoma, B-Cell, Marginal Zone/genetics , Lymphoma, B-Cell, Marginal Zone/microbiology , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/microbiology , Lymphoma, Large B-Cell, Diffuse/therapy , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Translocation, GeneticABSTRACT
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.
Subject(s)
Gastritis/microbiology , Helicobacter Infections/complications , Helicobacter pylori , Lymphoma, B-Cell, Marginal Zone/microbiology , Stomach Neoplasms/microbiology , Animals , Biopsy , Disease Progression , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastritis/drug therapy , Helicobacter Infections/drug therapy , Humans , Lymphoma, B-Cell, Marginal Zone/drug therapy , Lymphoma, B-Cell, Marginal Zone/pathology , Remission Induction , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathologyABSTRACT
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.