Search Results - (Author, Cooperation:M. Kneba)

2015-10-16

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Cell Transformation, Neoplastic/genetics ; Clone Cells/metabolism/pathology ; DNA Copy Number Variations/genetics ; *Disease Progression ; *Evolution, Molecular ; Exome/genetics ; Genes, myc/genetics ; Humans ; Ikaros Transcription Factor/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis/*genetics/pathology/therapy ; MAP Kinase Signaling System/genetics ; Mutation/*genetics ; Neoplasm Recurrence, Local/*genetics ; Prognosis ; RNA Processing, Post-Transcriptional/genetics ; RNA Transport/genetics ; Ribosomal Proteins/genetics ; Treatment Outcome

2018-03-06

American Society of Hematology (ASH)

0006-4971

1528-0020

Biology

Medicine

Lymphoid Neoplasia, Clinical Trials and Observations

2018-11-23

American Society of Hematology (ASH)

0006-4971

1528-0020

Biology

Medicine

Lymphoid Neoplasia, Brief Reports

0006-291X

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Chemistry and Pharmacology

Physics

Electronic Resource

0022-2860

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Chemistry and Pharmacology

Physics

Electronic Resource

1365-3083

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The aim of the present study was to isolate and characterize the immune complexes detected by the Raji cell assay in metastatic breast cancer. However, the Raji cell binding material could not be separated from monomeric IgG by Sephacryl S-300 gel chromatography in any of the 16 sera investigated. The parallel elution profile of monomeric IgG and the Raji cell binding activity suggested that anti-Raji cell antibodies, rather than immune complexes of low molecular weight, were present in these sera. This was further substantiated by pepsin digestion of the Raji cell binding IgG fractions. The binding of F(ab')2 fragments was quantitatively comparable to the binding of undigested IgG, and the bound F(ab')2 fragments could be visualized by immunofluorescence at the cell membrane. The presence of antibodies against Raji cells was further confirmed by the complement-dependent cytotoxicity assay. These antibodies did not react with untransformed lymphocytes and there was no correlation with anti-Epstein-Barr virus antibodies. The incidence of cytotoxic anti-Raji cell antibodies in breast cancer was 12% compared to 20% in malignant lymphoma, to 0% in normals and patients with degenerative cardiovascular diseases, and to 5% in patients with auto-immune diseases.

Electronic Resource

1432-1440

Breast cancer ; Immune complexes

Springer Online Journal Archives 1860-2000

Medicine

Summary In 68 patients with metastatic breast cancer a follow-up study was performed to correlate circulating immune complexes (CIC) as detected by the C1q binding assay and the Raji cell radio immunoassay with the state of disease. Clinical examinations and determinations of CIC were carried out all four to eight weeks over at least six months. 19 patients were positive for CIC in the C1q binding assay and 12 in the Raji cell radio-immunoassay. There was no correlation between the results of both tests. In comparison 26 patients out of 68 with rheumatoid arthritis were positive in the C1q binding assay and 32 in the Raji cell assay. In these patients the results of both tests correlated significantly. There was only in a few cases of metastatic breast cancer a positive correlation between levels of CIC and changes of tumor burden. Furthermore, CIC did not prove to be of prognostic value.

Electronic Resource

1432-1440

Carcinoembryonic antigen ; CEA ; Breast cancer

Springer Online Journal Archives 1860-2000

Medicine

Summary The diagnostic validity of serial CEA determinations in metastatic breast cancer was investigated. First, the CEA values within 8 weeks after start of therapy were correlated with the response to therapy. Second, the CEA levels were used to predict progression after remission or stable disease. These investigations were performed in 150 patients with advanced breast cancer who had clinical follow-ups and serial CEA determinations every one to three months. CEA was not useful for monitoring response to therapy (sensitivity 63%, specifity 58%) or prediction of relapse (sensitivity 61%, specifity 82%) if CEA levels were correlated with clinical course in all patients. However, diagnostic validity of CEA was achieved if the patients were selected and appropriate definitions of significant changes in CEA used. Thus, 83% of the responders (sensitivity) could be identified by a significant decrease of CEA titers in patients with CEA levels of ≧10 ng/ml. A decrease of more than 10% of pretreatment levels during the first 4–8 weeks after start of therapy proved to be the appropriate definition of a significant decrease of CEA titers. However, 32% of the non-responders were misclassified as responders (unspecifity) using these criteria. The positive predictive value of a significant decrease of CEA for response to therapy was 72% (prevalence 45%), the negative predictive value 82% (prevalence 55%). Rising CEA titers specifically predicted progression of disease in patients with remission or stable disease. However, an appropriate sensitivity (86%) was achieved only in patients with baseline CEA levels of ≧5 ng/ml. The selection criteria described applied to one-third of the patients in the present study. Prospective studies based on these results have to show whether the definitions used can be generalized and are to be recommended for clinical practice.

Electronic Resource

1433-0415

Springer Online Journal Archives 1860-2000

Medicine

In den letzten Jahren wurden wesentliche Fortschritte in dem Verständnis der Biologie und Pathogenese der Non-Hodgkin-Lymphome (NHL) erzielt. Diese Fortschritte wurden insbesondere durch die Anwendung moderner Methoden der Zytogenetik und Molekularbiologie zum Studium der physiologischen B- und T-Zell-Entwicklung und der Lymphome erreicht: So konnte für viele Lymphomentitäten gezeigt werden, daß ihnen spezifische, genetische und molekulare Veränderungen zugrunde liegen, denen eine Schlüsselrolle in der Entwicklung dieser Erkrankungen zukommt. Die im Rahmen dieser Untersuchungen entwickelten experimentellen Methoden und gewonnenen Einblicke in die physiologische und maligne Lymphopoese sind nicht nur Grundlage neuartiger diagnostischer Methoden, sondern eröffnen zusätzlich auch neue Perspektiven für therapeutische Weiterentwicklungen.

Electronic Resource

1432-0584

Granulocyte-macrophage colony-stimulating factor ; Neutropenia ; Thrombocytopenia ; Testicular cancer

Springer Online Journal Archives 1860-2000

Medicine

Summary Despite the increasing use of granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of chemotherapy-induced neutropenia, few studies have focused on the activity and toxicity of the different clinically used dosages of GM-CSF. Forty-four patients with “poor-risk” (advanced disease, according to the Indiana University classification) testicular cancer were treated with a dose-intensified chemotherapy regimen of cisplatin (30 mg/m2), etoposide (200 mg/m2), and ifosfamide (1.6 g/m2), given on days 1–5 for a total of four cycles at planned intervals of 21 days. Patients (pts) received GM-CSF, either 10 (22 pts; 70 cycles evaluable) or 5 μg/kg body wt. daily s.c. (22 pts; 72 cycles evaluable), starting the first day after chemotherapy for 10 consecutive days. Overall, 34 patients (78%) achieved a favorable response (CR or PR with negative tumor markers), six patients (14%) failed this chemotherapy regimen, and four patients (9%) died of therapy-related complications. The durations of both neutropenia and thrombocytopenia increased with the number of treatment cycles given. The duration of granulocytopenia after the fourth PEI cycle was significantly shorter for patients receiving 10 μg/kg than for those with 5 μg/kg per day of GM-CSF (9 vs 13 days;p〈0.05). The median duration of thrombocytopenia 〈20000/μl after the fourth cycle of PEI was also significantly reduced in favor of patients receiving 10 μg/kg of GM-CSF (4 vs 9 days;p〈 0.02). However, there were no differences in the frequency of severe infections or in the achieved dose intensity. Five patients (11%) discontinued GM-CSF due to side effects (three anaphylactoid-type reactions, one myalgia and fever, one cutaneous toxicity). No difference in the frequency of side effects was seen between patients receiving 5 and those receiving 10 μg/kg per day of GM-CSF. The dose of 5 μg/kg per day of GM-CSF may be sufficient to ameliorate neutropenia following standard-dose chemotherapy, while higher dosages of GM-CSF may be advantageous in patients receiving repetitive cycles of dose-intensified chemotherapy.

Electronic Resource

1432-0584

Key words Chloroma ; Acute myeloblastic leukemia ; Chemotherapy ; Autologous stem cell transplantation

Springer Online Journal Archives 1860-2000

Medicine

Abstract Isolated chloromas (granulocytic sarcomas) are rare tumors, most of them progressing to acute myeloblastic leukemia within months. There are still no conclusive treatment strategies for this entity; however, early antileukemic chemotherapy seems to lower the probability of developing systemic disease and prolong survival. We report on a patient with isolated meningeal chloroma, primarily misdiagnosed as a high-grade Non-Hodgkin's lymphoma. Two cycles of antileukemic induction chemotherapy were administered, followed by local irradiation and intensified consolidation therapy with autologous stem cell transplantation. After 20 months, he is still in complete remission.

Electronic Resource

1432-0584

Key words Rituximab ; Anti-CD20 antibody treatment ; Follicular lymphomas ; Phase-II study

Springer Online Journal Archives 1860-2000

Medicine

Abstract Purpose: The current study was initiated to assess the clinical efficacy and side effects of rituximab in patients with relapsed advanced stage follicular lymphoma. Patients and methods: The study was performed as an open-label non-randomized multicenter phase-II trial and included patients older than 18 years of age with relapsed advanced-stage follicular lymphomas (FL) grades I and II, according to the REAL classification, or with centroblastic/centrocytic (CB/CC lymphomas according to the Kiel classification. Four weekly doses of 375 mg/m2 rituximab were applied. Results: 38 patients from eight centers were included between January 1997 and January 1998 and were evaluable for response and toxicity on an intention to treat basis. The median age was 55 years (range 26–75 years). Thirteen patients (35%) were in first relapse, 11 patients (30%) in second, and 13 patients (35%) in third relapse. The median time between primary diagnosis and study entry was 4.6 years (range 0.9–14.7 years). Twenty-three patients tolerated the application of rituximab without adverse events; in 13 cases the infusion rate had to be reduced because of side effects; in two patients the application was stopped because of pharyngeal edema and anaphylactoid reaction. The most frequent side effects were fever (13 patients) and rigor (13 patients); 65% of the side effects were observed after the first infusion. Twenty grade-III/IV side effects were considered to be related to treatment: lymphocytopenia (3), granalocytopenia (1), thrombocytopenia (2), fever (1), hyperglycermia (1), venous thrombosis (1), syncope (1), plasmatic coagulation disorder (1), shortness of breath (2), photosensitivity (1), cardiac failure (1), chills (1), sepsis (1), tumor lysis (1), anemia (1), and pharyngeal edema (1). Eight patients were not eligible for assessment of response because of non-follicular subtypes of low-grade lymphomas (n=6) or early termination of therapy at the first infusion because of severe side effects (n=2). From the 30 evaluable cases with follicular lymphomas, five patients achieved a complete remission (CR) (17%), nine patients a partial remission (PR) (30%), and two patients a minor response (MR) (7%). The overall response rate was 47%. The median time to treatment progression (TTP) was 201 days (range 64–293 days), with five patients experiencing long-lasting remissions of 214–293 days duration. In three patients, the rituximab-induced remission exceeded the preceding progression-free interval substantially. Bulky disease (P=0.058) and/or bone-marrow involvement (P=0.046) were associated with poor response. Conclusion: This study confirms the moderate treatment-related toxicity and the high antilymphoma activity of rituximab in patients with relapsed follicular lymphoma. Further studies are needed to determine the role of rituximab in the first-line treatment of these disorders and its combination with conventional chemotherapy.

Electronic Resource

1432-1335

CEA ; Breast cancer ; Prognosis

Springer Online Journal Archives 1860-2000

Medicine

Summary The capability of breast cancer to secrete CEA might have biological significance. In 105 patients with metastatic breast cancer serial CEA determinations and clinical follow-up data were available during progression of disease up to death. In this series, 39 patients (37%) had constantly low CEA levels (〈10 ng/ml), whereas 66 patients (63%) showed CEA values exceeding 10 ng/ml with progression. The patients with low CEA levels had significantly shorter median survival times (P=0.001) after mastectomy (39 versus 65 months) and after recurrence (18 versus 28 months) than the patients with high CEA levels. This difference was due first to a poor-risk group of 13 patients with rapidly disseminating tumors, very short survival (〈12 months), and low CEA levels. Secondly, there were more patients with pulmonary involvement and unfavorable prognosis and fewer patients with osseous metastases and long survival in the low-CEA group. In conclusion, there might be a subtype of breast cancer with rapid progression and low CEA secretion. This clinical observation has to be confirmed by histological grading and CEA staining of these tumors.

Electronic Resource

1569-8041

lymphoma ; minimal residual disease ; molecular diagnosis ; polymerase chain reaction

Springer Online Journal Archives 1860-2000

Medicine

Abstract Background: The capacity of the polymerase chain reaction (PCR) to detect very low numbers of cells bearing a t(14;18) translocation has led to its application in assessment of the results of treatment for follicular lymphoma, and suggestions that therapy might be guided by molecular studies. To test the reliability of PCR a collaborative study was undertaken to compare results from different laboratories in Europe and North America. Methods: Twenty laboratories with records of publication in molecular diagnostics were sent blood from normal donors with varying numbers of t(14;18)-bearing cells added from a cell line with a translocation in the major breakpoint region (MBR) of the bcl-2 gene. Samples contained 1000, 100, 10, 1 or 0 cells per ml of whole blood and were sent blinded in duplicate. PCR methodology varied widely, with the total number of amplification cycles between 30 and 70, and 13 different primers used for the MBR region. Twelve laboratories used nested PCR and eight single round amplification. Results: The sensitivity of nested and single round PCR was similar at 100 cells/ml but below this the nested method proved significantly more sensitive. The false positive rate was 28%, with 11 samples from 9 laboratories reported as positive when no t(14;18) cells were added. PCR product size and sequence analysis showed that false positives were due to contamination from cell-line DNA rather than background translocations in the donors. There was no significant difference in false positive rates between nested and single round techniques. Conclusion: The polymerase chain reaction to detectbcl-2–IgH rearrangements is presently carried out with widely disparate results. Further effort is required to bring forward a standard PCR protocol which can be re-tested in different laboratories to improve accuracy and reproducibility. The application of quantitative techniques such as real-time PCR may resolve many of the problems presently encountered.

Electronic Resource

1435-1536

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics

Electronic Resource