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Biomedical subjects

M Raderer

Publications and source records attributed to M Raderer.

At least 19 recordsLinked to original sources

Influence of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone on serologic parameters and clinical course in lymphoma patients with autoimmune diseases.

BACKGROUND: As patients with B-cell lymphomas suffering from an underlying autoimmune condition undergoing therapy with the CD20 antibody rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) offer the unique possibility of monitoring effects of therapy on various rheumatologic parameters, we have evaluated serologic autoimmune markers and the clinical outcome of patients with autoimmune diseases (ADs) who received lymphoma treatment with R-CHOP during the course of their disease. PATIENTS AND METHODS: We have retrospectively analysed 13 patients with non-Hodgkin's lymphoma who concurrently suffered from ADs and were treated with the R-CHOP regimen. Subjective parameters along with rheumatoid factor (RF) and antinuclear antibodies (ANA) were serially measured. RESULTS: The median levels of RF were 901 IU/ml [inter-quartile-range (IQR) 189-2520] before and 75 IU/ml (IQR 45-644) after therapy (P = 0.028). The median levels of ANA were 800 (IQR 140-2560) before and 100 (40-1280) after therapy (P = 0.027). Ten (77%) patients showed clinical improvement of their autoimmune symptoms, two (15%) reported no difference and one (7%) patient with rheumatoid arthritis-related worsening symptoms during therapy with R-CHOP. The autoimmune-related symptoms recurred after a median time of 7 weeks (IQR 6-8) in seven patients. In terms of lymphoma response, 11 patients achieved a complete remission and two a partial remission. CONCLUSIONS: This analysis indicates that R-CHOP given for lymphoma treatment is also effective for therapy of concurrent rheumatoid diseases. Both rheumatoid parameters as well as clinical symptoms showed a significant decrease during treatment with this immunochemotherapy. The effects on the rheumatic diseases, however, seem to be of limited duration.

Aged↗

18F-Fluoro-deoxy-glucose positron emission tomography in lymphoma of mucosa-associated lymphoid tissue: histology makes the difference.

BACKGROUND: The usefulness of 2-[fluorine-18]fluoro-2-deoxy-D-glucose Positron emission tomography (18F-FDG-PET) in lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is still a matter of debate, and conflicting results have been reported. We have evaluated whether the histological feature of plasmacytic differentiation (PD) might explain the heterogeneous behavior of MALT lymphoma regarding 18F-FDG uptake. PATIENTS AND METHODS: A total of 35 patients with a diagnosis of MALT lymphoma referred to our PET unit were studied. Whole-body 18F-FDG-PET scans were carried out on a General Electrics advanced PET scanner 40 min after i.v. injection of 300-380 MBq 18F-FDG. Images were reconstructed iteratively. In areas with focally elevated FDG uptake, standard uptake values (SUVs) were calculated. RESULTS: A total of 19 patients had MALT lymphoma with plasmacytic differentiation (pMALT), while MALT lymphoma without plasmacytic features was diagnosed in 16 patients. Sixteen of 19 patients with PD showed significant 18F-FDG uptake in involved sites (SUV: 3.5-11.7). By contrast, 13 of 16 patients with normal MALT lymphoma showed a false-negative 18F-FDG-PET result. Two of these patients disclosed no tracer uptake in the majority of involved sites apart from one single lesions, while three had a true-positive 18F-FDG-PET scan (SUV: 3.4-6.0). CONCLUSIONS: 18F-FDG-PET visualizes pMALT in a high proportion of patients, whereas FDG-PET results are significantly less reliable in typical MALT (P = 0.001). This finding may partly account for the heterogeneous results of 18F-FDG-PET-studies in MALT lymphoma.

Adult↗

MALT lymphoma associated genetic aberrations occur at different frequencies in primary and secondary intestinal MALT lymphomas.

BACKGROUND AND AIMS: Limited data are available on intestinal MALT lymphoma owing to its relatively rare occurrence. The frequency of associated genetic changes was therefore analysed in intestinal MALT lymphoma to determine whether primary and secondary examples may be distinguished by their genetic profile. METHODS: Patients diagnosed with MALT lymphoma involving the intestine were evaluated and compared with 71 cases with localised gastric MALT lymphoma. Paraffin embedded samples were evaluated for t(11;18)(q21;q21) by reverse transcription polymerase chain reaction, and by fluorescence in situ hybridisation for t(14;18)(q32;q21), t(1;14)(p22;q32), and trisomies 3 and 18. RESULTS: 30 consecutive patients with MALT lymphoma involving the intestine were identified: 16 had primary intestinal lymphoma and 14 had secondary MALT lymphoma. t(11;18)(q21;q21) was found in one third of the patients, but there was a significant difference between the secondary MALT lymphomas and the primary intestinal and gastric MALT lymphoma groups (57% v 12.5%, p = 0.019, and 57% v 24%, p = 0.022). Two patients with primary intestinal MALT lymphomas were positive for t(1;14)(p22;q32) and none was positive for t(14;18)(q32;q21). Primary intestinal MALT lymphoma had a significantly higher frequency of trisomies 3 or 18 (81% v 36%, p = 0.024; 81% v 14%, p<0.001), in contrast to secondary intestinal MALT lymphomas and localised gastric MALT lymphomas. CONCLUSIONS: The genetic profile of primary intestinal MALT lymphomas appears to be different from that of secondary intestinal or local gastric MALT lymphomas. Because of the high prevalence of trisomy 3 or 18, or both, in primary intestinal lymphoma, these numerical aberrations might be regarded as a genetic hallmark of the disease.

Adult↗

18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) visualizes follicular lymphoma irrespective of grading.

BACKGROUND: 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) has become a routine measure for staging and follow-up of patients with aggressive lymphoma. By contrast, its usefulness to visualize indolent lymphomas characterized by a lower cellular turnover has not clearly been defined. We have investigated accuracy and clinical usefulness of 18F-FDG-PET in patients with follicular lymphoma (FL). PATIENTS AND METHODS: A total of 64 patients with FL WHO grade I - III (48, 5, and 11 patients) were imaged at our institution to assess the value of 18F-FDG-PET for imaging of FL of different gradings. A total of 115 scans (48 before therapy and 67 for response assessment after treatment) were performed, and findings were compared to conventional staging including CT-scan of thorax and abdomen, sonography of lymph nodes and bone marrow biopsy. RESULTS: Overall, 18F-FDG-PET had a sensitivity of 98%, a specificity of 94%, a positive predictive value of 95% and a negative predictive value of 98%. These results were significantly more accurate (P = 0.023) than the conventional radiology studies. There was no significant difference (P = 0.093) in the accuracy between patients with indolent (WHO grade I and II) versus aggressive FL (WHO grade III). CONCLUSION: 18F-FDG-PET scan is a reliable method for staging and follow up of patients with nodal FL irrespective of tumor grading.

Adult↗

Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma.

Among peripheral T-cell lymphomas (PTCL), the heterogeneous category of unspecified PTCL represents the most common subtype. Nevertheless, recurrent chromosomal translocations are unknown in this aggressive type of lymphoma. Here we describe a novel t(5;9)(q33;q22) in unspecified PTCL. Molecular analyses delineated the breakpoints to ITK and SYK resulting in a previously undescribed expression of the Syk tyrosine kinase by Itk. ITK-SYK transcripts were detected in five of 30 (17%) unspecified PTCL, but not in cases of angioimmunoblastic T-cell lymphoma (n=9) and anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma (n=7). In all five translocation-positive cases, the breakpoints were identical fusing the N-terminal pleckstrin homology domain and proline-rich region of ITK to the tyrosine kinase domain of SYK. Three of the five t(5;9)(q33;q22)+ unspecified PTCL shared a very similar histological pattern with predominant involvement of lymphoid follicles and the same CD3+CD5+CD4+bcl-6+CD10+ immunophenotype. These results demonstrate the presence of a recurrent t(5;9)(q33;q22) in a subset of unspecified PTCL, which may represent a novel distinct subgroup of PTCL.

Aged↗

'Blind' antibiotic treatment targeting Chlamydia is not effective in patients with MALT lymphoma of the ocular adnexa.

BACKGROUND: Recent results have implicated Chlamydia, especially Chlamydia psittaci, in the development of ocular adnexal lymphoma in the large majority of patients. We present our experience with ex-juvantibus antibiotic treatment in patients diagnosed with MALT lymphoma of the ocular adnexa. PATIENTS AND METHODS: A retrospective analysis identified a total of 11 patients (six female, five male) with MALT-lymphoma of the ocular adnexa who were given doxycyclin 200 mg p.o. daily over 3 weeks. Patients were tested also for autoimmune conditions, Helicobacter status and hepatitis along with assessment of MALT-lymphoma specific genetic changes. RESULTS: After a median follow-up of 9 months, none of the patients responded to 'blind' antibiotic treatment with doxycyclin. Only one patient with bilateral conjunctival lymphoma related a short lasting subjective improvement, but was referred to alternative therapy due to progression and worsening symptoms after 6 months. CONCLUSIONS: In this uncontrolled series, no effect of 'blind' antibiotic treatment with doxycyclin could be found in our patients with MALT lymphoma of the ocular adnexa. These results are in contrast to other series and suggest a potential geographic difference in the role of Chlamydia in ocular adnexal lymphoma. Thus, antibiotic therapy without prior testing for Chlamydia should be discouraged.

Adult↗

Successful antibiotic treatment of Helicobacter pylori negative gastric mucosa associated lymphoid tissue lymphomas.

BACKGROUND AND AIMS: The role of antibiotic treatment in early stage gastric mucosa associated lymphoid tissue (MALT) lymphoma not associated with Helicobacter pylori infection has not been investigated. PATIENTS AND METHODS: Six patients with localised gastric MALT lymphoma underwent antibiotic treatment with clarithromycin, metronidazole, and pantoprazole. Staging, including endosonography plus gastroscopy, computed tomography of the thorax and abdomen, colonoscopy, magnetic resonance imaging of the salivary glands, and bone marrow biopsy were performed to rule out distant spread of the disease. In addition, MALT specific genetic changes, including reverse transcriptase-polymerase chain reaction for t(11;18)(q21;q21), were tested in all patients. H pylori infection was ruled out by histology, urease breath test, serology, and stool antigen testing. RESULTS: All six patients had MALT lymphoma restricted to the stomach, and no evidence of infection with H pylori was found. Only one patient tested positive for t(11;18)(q21;q21) while the remaining five displayed no genetic aberrations. Following antibiotic treatment, endoscopic controls were performed every three months. Five patients responded with lymphoma regression between three and nine months following antibiotic treatment (one partial remission and four complete responses). One patient had stable disease for 12 months and was then referred for chemotherapy. CONCLUSIONS: Patients with early stage gastric MALT lymphoma negative for H pylori might still benefit from antibiotic treatment as the sole treatment modality.

Anti-Bacterial Agents↗

T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma.

The three chromosomal translocations t(11;18)(q21;q21), t(14;18)(q32;q21), and t(1;14)(p22;q32) are associated with MALT lymphoma. In a case of MALT lymphoma of the thyroid, we observed t(3;14)(p14.1;q32) by cytogenetic analysis. Fluorescence in situ hybridization studies showed that the immunoglobulin heavy chain locus (IGH) was rearranged on chromosome 14. Long-distance inverse polymerase chain reaction identified FOXP1 as the partner gene on chromosome 3. To determine the frequency of the t(3;14)(p14.1;q32), two fluorescence in situ hybridization assays were established to screen 91 MALT lymphomas, all of which were negative for the above-mentioned three translocations, and eight splenic and six nodal marginal zone lymphomas. Overall, nine MALT lymphomas (10%) harbored t(3;14)(p14.1;q32) comprising tumors of the thyroid (three of six), ocular adnexa (four of 20), and skin (two of 20), whereas those of the stomach (n = 20), salivary gland (n = 20), and lung (n = 5) were negative as well as the splenic and nodal marginal zone lymphomas. Most t(3;14)(p14.1;q32) + MALT lymphomas harbored additional genetic abnormalities, such as trisomy 3. Further studies revealed that the three known translocations and t(3;14)(p14.1;q32) are mutually exclusive. Real-time quantitative reverse transcriptase polymerase chain reaction showed upregulation of FOXP1 in cases with t(3;14)(p14.1;q32) or trisomy 3. This study identifies FOXP1 as a new translocation partner of IGH in a site-dependent subset of MALT lymphomas.

Adaptor Proteins, Signal Transducing↗

[Neoadjuvant therapy for resectable esophageal cancer].

BACKGROUND: Surgical excision remains the only therapeutic approach with curative potential in patients with localized esophageal cancer. Due to the presence of lymph node metastases upon diagnosis in a large percentage of patients with locally advanced tumors and/or the presence of considerable co-morbidity, only a limited number of patients are amenable to surgery. These facts have prompted us to evaluate approaches including perioperative therapy modalities. METHODS: By means of a computer-supported search (MEDLINE, ASCO Proceedings) as well as a manual literature search, randomized clinical trials and meta-analyses evaluating preoperative therapy plus surgery in patients with resectable esophageal cancer were identified. RESULTS: Twenty-three randomized clinical studies and five meta-analyses were identified. Interpretation--especially of the older studies--however, is hampered by the lack of a stringent application of modern examination techniques allowing for exact specification of tumor stage (resectable/locally advanced) as well as the inclusion of patients with different histological entities (squamous cell/adenocarcinoma), different surgical techniques and the low number of patients. There were no significant differences for the following perioperative therapy modalities regarding tumor-related mortality: preoperative radiotherapy versus postoperative radiotherapy, preoperative and postoperative radiotherapy versus postoperative radiotherapy (higher mortality in preoperative and postoperative radiotherapy arm), preoperative radiotherapy versus surgery, preoperative chemotherapy versus surgery, preoperative and postoperative chemotherapy versus surgery. In terms of 3-year mortality, statistically significant differences could be found for the following therapy modalities: preoperative radiochemotherapy versus surgery (preoperative therapy superior), preoperative chemotherapy versus preoperative radiotherapy (preoperative radiotherapy superior). CONCLUSION: Judging from these data, no clear recommendation for a standard multimodality approach outside clinical studies can be given for patients with resectable esophageal cancer. Neoadjuvant therapy, therefore, can only be recommended in centers with a maximum surgical expertise and in the context of multidisciplinary study protocols.

Antibiotics, Antineoplastic↗

Effective treatment of a peripheral T-cell lymphoma/lymphoepitheloid cell variant (Lennert's lymphoma) refractory to chemotherapy with the CD-52 antibody alemtuzumab.

Lymphoepitheloid cell lymphoma (Lennert's lymphoma) is a rare malignant disease usually affecting patients at advanced age. Although classified as a "low-grade" lymphoma in the past, the clinical course is highly unfavorable and currently available chemotherapeutic regimens have given disappointing results. We present the case of a 74-year-old male suffering from disseminated Lennert's lymphoma. The patient underwent standard treatment approaches including chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); fludarabin and cyclophosphamide; and ifosfamide, carboplatin and etoposide (ICE). Due to progressive disease with all these regimens, chemotherapy was discontinued. As cells stained highly positive for CD52, immunotherapy with alemtuzumab (Campath-1H) was started using a standard dosing regime of 30 mg every third day. Although the patient received prophylactic anti-infective medication, leucocytopenia with reactivation of cytomegalovirus (CMV) infection was observed and the administration of alemtuzumab had to be stopped temporarily. Re-assessment of disease 5 weeks after the start of alemtuzumab disclosed a significant reduction of all thoracic and abdominal lesions, and therapy with alemtuzumab was continued after normalization of the number of CMV copies and is currently ongoing. Our observations indicate clinical activity of alemtuzumab in the treatment of Lennert's lymphoma, including even bulky nodal disease, particularly for patients who have failed conventional therapies.

Aged↗

Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of different sites.

Although several recurrent genetic aberrations are known to occur in MALT lymphoma, no comprehensive study on the most prevalent MALT lymphoma-associated genetic aberrations is available. We therefore screened 252 primary MALT lymphomas for translocations t(11;18)(q21;q21), t(14;18)(q32;q21), and t(1;14)(p22;q32), and trisomies 3 and 18. The above-listed translocations occurred mutually exclusively and were detected overall in 13.5, 10.8, and 1.6% of the cases; trisomy 3 and/or 18 occurred in 42.1%. The frequency at which the translocations occurred varied markedly with the primary site of disease. The t(11;18)(q21;q21) was mainly detected in pulmonary and gastric tumors, whereas the t(14;18)(q32;q21) was most commonly found in lesions of the ocular adnexa/orbit, skin, and salivary glands. Trisomies 3 and 18 each occurred most frequently in intestinal and salivary gland MALT lymphomas. Our results demonstrate that the three translocations and trisomies 3 and 18 occur at markedly variable frequencies in MALT lymphoma of different sites.

Chromosome Aberrations↗

Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) for treatment of early-stage gastric diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) of the stomach is a relatively common disease. Recently, chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine and prednisone (CHOP) has been reported as effective treatment for early-stage gastric DLBCL. Given the fact that the application of the CD20 antibody rituximab (R) in addition to CHOP has improved outcomes in nodal DLBCL, we have analysed our experience with application of R-CHOP in patients with early-stage gastric DLBCL. PATIENTS AND METHODS: Patients with histologically verified early-stage gastric DLBCL undergoing treatment with R-CHOP for initial management were analysed. RESULTS: Fifteen patients received a total of 79 cycles, with a median of six cycles per patient. All patients responded to therapy, 13 had a complete remission (CR) (87%) and two (13%) a partial remission. All patients in CR, except one who died unrelated to lymphoma, have remained so with a median follow-up of 15 months (range 4-42) after treatment. Subjective tolerance was moderate, and toxicities were mainly haematological, including leukocytopenia WHO grade 3 and 4 in 10 and five patients each. The addition of rituximab to the standard CHOP regimen did not appear to significantly increase toxicity. CONCLUSIONS: Our data indicate that R-CHOP is an effective regimen for management of early-stage gastric DLBCL. However, given the excellent results with CHOP alone in such patients, the value of adding rituximab to standard CHOP remains to be determined in a randomised trial.

Aged↗

Palliative chemotherapy for advanced gastric cancer.

BACKGROUND: More than two-thirds of patients diagnosed with gastric cancer will have unresectable disease. They present a difficult problem to clinicians as to whether to choose a strictly supportive approach or expose patients to the side-effects of a potentially ineffective treatment. The objective of this article is to review the clinical trials utilizing cytotoxic chemotherapy in patients with advanced gastric cancer. METHODS: A computerized (Medline) search was carried out to identify papers published on this topic between 1966 and 2003. Only articles with an English abstract were reviewed, and studies only presented in abstract form were not included in the analysis. RESULTS: A total of 101 trials were subsequently identified. Four randomized trials compared palliative chemotherapy with best supportive care in 174 patients with advanced gastric cancer. Effectiveness and side-effects were evaluated in 73 phase II studies and 24 randomized phase III trials. CONCLUSION: Analysis of results shows chemotherapy to be superior to best supportive care alone. Combination chemotherapy compared with monochemotherapy is associated with significantly higher overall (complete plus partial) response rates but nevertheless results in similar survival. ECF (epirubicin, cisplatin and 5-fluorouracil) currently represents one of the most effective regimens for advanced gastric cancer, whereas among the newer combinations, irinotecan- or taxane-based regimens have also given promising results. In patients with a poor performance status, consideration could be given to leucovorin-modulated 5-fluorouracil alone. Prognosis for the majority of patients, however, remains poor, as increases in survival were moderate at best.

Antineoplastic Combined Chemotherapy Protocols↗

Chemotherapy with cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone (CHOEP) is not effective in patients with enteropathy-type intestinal T-cell lymphoma.

BACKGROUND: Enteropathy-type intestinal T-cell lymphoma (ETCL) is a highly aggressive disease with poor response to conventional CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. According to promising data with the addition of etoposide (E) to the CHOP regimen (CHOEP) in aggressive lymphomas including T-cell lymphomas, we have treated patients with ETCL with CHOEP chemotherapy. PATIENTS AND METHODS: Ten consecutive patients (six female, four male) suffering from ETCL were given CHOEP at our institution. Four patients had advanced disease (stage III/IV), while five patients were rated to be in stage II and one in stage I. Treatment consisted of doxorubicin 50 mg/m2, cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 by intravenous infusion on day 1, etoposide 100 mg/m2 intravenously days 1-3 and oral prednisone days 1-5. Cycles were repeated every 3 weeks for a maximum of six courses. Assessment of response was done by means of conventional computed tomography scanning, endoscopy and also [18F]fluorodeoxyglucose positron emission tomography (FDG PET) in seven patients. RESULTS: A total of 41 cycles (median six, range one to six) were administered to our patients. Leukocytopenia/neutropenia WHO grade IV necessitating granulocyte colony-stimulating factor support occurred in all patients evaluable for toxicity, and febrile neutropenia was seen in two patients. Two patients had to undergo emergency surgery due to intestinal perforation after one and three courses of treatment, respectively. Therapeutic results, however, were disappointing: two patients had complete remission (CR), three had partial remissions and five patients progressed during treatment. Remissions, however, where only short-lasting, as only two patients are alive at a median follow-up of 7 months (range 2-16). One patient is in ongoing CR 10 months after initiation of chemotherapy and the other is currently undergoing second-line treatment for progressive disease as judged by follow-up investigations after three cycles of CHOEP. CONCLUSIONS: Our data demonstrate that CHOEP chemotherapy results in a high rate of hematotoxicity in patients with ETCL. In spite of this, therapeutic results were disappointing and do not appear to be superior to conventional CHOP chemotherapy. We conclude that CHOEP cannot be recommended for routine use in patients with ETCL.

Administration, Oral↗