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10. A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma

Author

Einsele, H, Bamberg, M, Budach, W, Schmidberger, H, Hess, C F, Wörmann, B, Meisner, C, Straka, C, Hebart, H, Trümper, L, Kröger, N, Zander, A R, Hegewisch-Becker, S, Hossfeld, D K, Schmidt, H, Müller, P, Schlimok, G, Hertenstein, B, Peest, D, Metzner, B, Frickhofen, N, Kanz, L, and Bensinger, W I

Published
2003
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37. Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells.

Author

Pantel, Klaus, Schlimok, Günter, Braun, Stephan, Kutter, Dominik, Lindemann, Fritz, Schaller, Gerhard, Funke, Ilona, Izbicki, Jakob R., Riethmuller, Gert, Pantel, K, Schlimok, G, Braun, S, Kutter, D, Lindemann, F, Schaller, G, Funke, I, Izbicki, J R, and Riethmüller, G

Abstract

Background: The development of monoclonal antibodies (MAbs) to cytokeratins, which are integral components of the epithelial cytoskeleton, has made possible immunocytochemical detection of epithelial tumor cells. Importantly, this technique allows the detection of epithelial tumor cells that have metastasized from primary adenocarcinomas to secondary sites such as the bone marrow.Purpose: The aim of the study was not only to detect micrometastatic cells in bone marrow, but also to assess the expression of nuclear proliferation markers (Ki-67 and p120) and the erbB2 oncogene (also known as ERBB2) in these cells and, thus, hopefully improve prognostic precision.Methods: Bone marrow aspirates were obtained from both sides of the upper iliac crest of 532 patients having definitive diagnoses of either breast or gastrointestinal cancer. The presence of micrometastatic epithelial tumor cells in bone marrow was assayed using the MAb cytokeratin 2 (CK2) to cytokeratin component 18 (CK18), in combination with the alkaline phosphatase-anti-alkaline phosphatase immunostaining technique. After primary screening of all marrow samples with MAb CK2, representative subgroups of CK18+ samples were selected for co-labeling with MAbs either to ErbB (n = 16), ErbB2 (n = 121), Ki-67 (n = 33), or p120 (n = 36) protein. An alternative labeling protocol based on the combination of immunogold and immunoenzymatic techniques was utilized to confirm the results derived from immunoenzymatic double staining.Results: In total, single CK18-positive tumor cells were detected in 180 (33.8%) of 532 bone marrow aspirates, with few differences among patients with breast or gastrointestinal cancer in TNM stage M0 (i.e., no distant metastasis). In patients with overt metastasis (stage M1), however, the incidence of metastatic cells in marrow increased to 73.7% in breast cancer, 52.5% in gastric cancer, and 39.0% in colon cancer. Whereas expression of Ki-67 or p120 on micrometastatic cells was observed only in 11 (15.9%) of 69 cancer patients analyzed, ErbB2+/CK18+ cells were found in 48 (67.6%) of 71 breast cancer patients and 14 (28.0%) of 50 patients with gastrointestinal cancer (P = .0001). The incidence of ErbB2+/CK18+ cells was positively correlated with the clinical stage of tumor progression.Conclusions: The high incidence of ErbB2 expression on micrometastatic breast cancer cells in the bone marrow suggests that these cells might have been positively selected during early stages of metastasis. The majority of these cells appear to be in a dormant state of cell growth.Implications: Although support from clinical follow-up is still needed, this study demonstrates that, beyond the mere presence of micrometastatic cells in bone marrow, useful prognostic information can be obtained by analysis of additional cell growth markers. [ABSTRACT FROM AUTHOR]

Published
1993

43. Mitoxantrone/high-dose Ara-C and recombinant human GM-CSF in the treatment of refractory non-Hodgkin's lymphoma. A pilot study.

Author

Ho, Anthony D., Valle, Francesco Del, Engelhard, Marianne, Hiddemann, Wolfgang, Rückle, Heide, Schlimok, GüNter, Haas, Rainer, Thiel, Ekhard, Andreesen, Reinhard, Fiedler, Walter, Frisch, Jürgen, Schulz, Gregor, Hunstein, Werner, Ho, A D, Del Valle, F, Engelhard, M, Hiddemann, W, Rückle, H, Schlimok, G, and Haas, R

Published
1990
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47. Treatment results of the thioether lipid ilmofosine in patients with malignant tumours.

Author

Winkelmann, M., Ebeling, K., Strohmeyer, G., Hottenrott, G., Mechl, Z., Berges, W., Scholten, T., Westerhausen, M., Schlimok, G., and Sterz, R.

Abstract

In a multicentre study patients with liver metastases stratified to the histology of the primary tumour were investigated. A total of 102 patients with colorectal adenocarcinoma, non-small-cell lung cancer, pancreatic cancer, primary liver carcinoma and malignant melanoma were treated with the thioether lipid ilmofosine. The drug was administered orally as a tablet at a dosage of 150-300 mg/day (75 mg/tablet). The tolerability of ilmofosine was poor. There was a dose-limiting gastrointestinal toxicity with nausea, vomiting and loss of appetite (WHO grade II-IV) in 67% of patients. During the period of therapy (1-29 weeks, 8.5 weeks mean) no complete remission and no partial response were observed. We thus conclude that treatment with oral ilmofosine is not effective in patients with liver metastases due to various malignancies. [ABSTRACT FROM AUTHOR]

Published
1992
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50. Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advanced Hodgkin's disease

Author

Diehl, V., Loeffler, M., Pfreundschuh, M., Ruehl, U., Hasenclever, D., Nisters-Backes, H., Sieber, M., Smith, K., Tesch, H., Geilen, W., Adler, M., Bartels, H., Brandenburg, U., Diezler, P., Doelken, G., Enzian, J., Fuchs, R., Gassmann, W., Gerhartz, H., Hagenaukamp, U., Hecht, T., Hiller, E., Hinkelbein, H., Lathan, B., Kirchner, H., Kuehn, G., Kuerten, H., Loos, U., Makoski, B., Oertel, W., Petsch, S., Pfab, R., Pflueger, H., Planker, M., Rohioff, R., Sack, H., Samandari, S., Sauer, R., Schalk, K., Schmitz, G., Schoppe, W., Schwieder, G., Szepesi, S., Teichmann, J., Wilhelmy, W., Worst, P., Fischer, R., Georgii, A., Huebner, K., Schwarze, E.W., Rohloff, R., Hagen-Aukamp, U., Kürten, H., Westerhausen, M., Pflüger, H., Entzian, J., Dölken, G., Ernst, H., König, J., Hellriegel, H., Kühn, G., Rühl, U., Szepesi, Schulz, U., Theml, S., Staiger, R., Haase, W., Wagner, T., Brandenburg, Boldt, I., Schmoll, H.J., Emminger, H., Gaβmann, W., Brix, T., Mödder, B., Hennekeuser, H., Schlimok, G., Doukas, Voss, A.-C., Krüger, B., Kutzner, K., Hinrichs, F., Temmesfeld, A., Luska, T., Schick, H.D., Preiβ, J., Gärtner, W., Mende, W., Alberti, W., Hoffmann, U., Urbanitz, D., Heide, Siebner, H., van de Weyer, K.H., Dornoff, D., Renner, E., Cohen, M., Czygan, P., Scheja, H.W., Schoenemann, J., Rochell, M., Peters, U., Koniczek, K., Mitrenga, D., Cammerer, U., Mantel, W., Hübner, K., and Diehl, Volker

Published
1995
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