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Biomedical subjects

F Schüler

Publications and source records attributed to F Schüler.

12 recordsLinked to original sources

Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study.

BACKGROUND: We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma. PATIENTS AND METHODS: Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. RESULTS: Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached", respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively. CONCLUSION: MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.

Adolescent↗

The modification of high-dose therapy shortens the duration of neutropaenia by delay of leucocyte nadir.

Infections during neutropaenia contribute still significantly to mortality and morbidity after high-dose therapy and autologous stem cell transplantation. Further acceleration of haemopoietic recovery seems impossible for biological reasons. Another approach to shorten neutropaenia could be to remove drugs from high-dose therapy protocols with strong contribution to immunosuppression and neutropaenia and unproven antineoplastic activity. In this retrospective matched-pair analysis, conventional busulphan/cyclophosphamide (Bu/Cy) high-dose therapy was compared to single-agent busulphan conditioning before autologous stem cell transplantation. This modification led to a significant shorter neutropaenic interval by protraction of cell decrease and to a significant mitigation of neutropaenia. After single-agent busulphan conditioning, leucocytes dropped below 1/nl at median 1.5 days later when compared to the patients from the busulphanBu/Cy control group (P=0.001). In a significant percentage of patients (n=6, 60%) leucocytes did not fall below 0.5 cells/nl at any time. In contrast, all patients from the Bu/Cy control group experienced deep neutropaenia (P=0.004). Thrombocytopaenia and requirement for transfusions of platelets or red cells were not influenced. Antineoplastic activity seemed to be preserved as determined by survival analysis. In conclusion, modification of high-dose regimen with the intention to shorten neutropaenia with preserved antitumour activity could be an approach to reduce infection-related morbidity and mortality and to consider economic necessities.

Adolescent↗

[Minimal residual disease in follicular and mantle cell lymphoma. Detection using quantitative molecular monitoring of circulating lymphoma cells].

BACKGROUND AND OBJECTIVE: In patients with follicular lymphoma and mantle cell lymphoma circulating lymphoma cells can be detected by quantitative real-time PCR with a high sensitivity and reproducibility. With this study we wanted to ascertain whether a continuous molecular remission achieved in patients with mantle cell lymphoma and follicular lymphoma has an impact on survival of these patients. PATIENT AND METHODS: We conducted these investigations in 32 patients (24 with follicular lymphoma and 8 with mantle cell lymphoma) who were treated in a randomized trial with chemotherapy plus/minus rituximab (MCP, R-MCP). A further ten patients had follicular lymphoma (stage I and II) in long-term complete remission after radiation therapy. RESULTS: Up to 18 years after initial diagnoses of a stage I or II follicular lymphoma circulating t(14;18) positive cells could be detected in the peripheral blood. In advanced stage follicular lymphoma patients molecular remissions could only be achieved when they were treated with combined chemo-immunotherapy (MCP+R). A significantly higher relapse-free survival correlates with sustained molecular remission. In contrast, the frustrating clinical results obtained from the treatment of patients with mantle cell lymphoma corresponded to an achievement of only short molecular remissions in very few patients. CONCLUSIONS: The consequent application of quantitative real-time PCR will further improve current treatment strategies in lymphoma patients. Especially, individual treatment options can be developed for patients who do not respond to a standard chemotherapy or progression of disease is recognized, if results of molecular monitoring will be confirmed in large prospective studies.

Humans↗

Quality assurance in RT-PCR-based BCR/ABL diagnostics--results of an interlaboratory test and a standardization approach.

Here we describe the results of an interlaboratory test for RT-PCR-based BCR/ABL analysis. The test was organized in two parts. The number of participating laboratories in the first and second part was 27 and 20, respectively. In the first part samples containing various concentrations of plasmids with the ela2, b2a2 or b3a2 BCR/ABL transcripts were analyzed by PCR. In the second part of the test, cell samples containing various concentrations of BCR/ABL-positive cells were analyzed by RT-PCR. Overall PCR sensitivity was sufficient in approximately 90% of the tests, but a significant number of false positive results were obtained. There were significant differences in sensitivity in the cell-based analysis between the various participants. The results are discussed, and proposals are made regarding the choice of primers, controls, conditions for RNA extraction and reverse transcription.

Base Sequence↗

Quantitative detection of t(14;18)-positive cells by real-time quantitative PCR using fluorogenic probes.

To detect t(14;18)-positive cells present in human lymphoma tissue, bone marrow aspirates and peripheral blood mononuclear cells (PBMNC), we have established an automated, real-time quantitative PCR using double-labeled fluorogenic probes. In relation to t(14;18)-positive genomic DNA or a cloned t(14;18)-DNA fragment, highly reproducible results can be obtained with initial copy numbers between 10 to 10(5). The detection of single copies has been verified by the stochastic multiple-tube approach. PBMNC cells obtained during clinical follow-up of patients with follicular lymphoma were analyzed by the one-step, real-time quantitative PCR and a two-step, semi-nested PCR combined with a limiting dilution assay. The quantitative results obtained by both assays correlate very well. Real-time quantitative PCR has several advantages: (i) it involves less critical pipetting steps, (ii) is less time-consuming and (iii) UTP, in combination with uracil-N-glycosylase, can be used to control carryover contamination. The higher specificity is due to optimized primer annealing conditions and MgCl2 concentration and the use of AmpliTaq Gold. The sensitivity is at least as high as by the two-step PCR. Real-time quantitative PCR will be very helpful in large epidemiological studies and in research for molecular staging and the detection of minimal residual tumor cells, including the analysis of blood stem-cell preparations to be used for transplantation after myelo-ablative therapy.

Cloning, Molecular↗

[The effect of ionic and nonionic x-ray contrast media on myocardial perfusion and myocardial function].

The influence of injections of Amidotrizoate and Iopromide into the left coronary artery on global myocardial perfusion and function (pressures in the left ventricle, heart rate) as well as excitation formation and transmission was studied in 16 patients with ischaemic heart disease. No statistically significant differences in myocardial perfusion measured were found with xenon-133 in this small group between rest and dipyridamole load for ionic and non-ionic contrast media.

Adult↗

[Vascular sling].

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Airway Obstruction↗