45 results on '"Falge, C"'
Search Results
2. Kollaboratives Film-Making als Beispiel für Diversitäts- und Kultursensible Online-Gesundheitsinformationen
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Falge, C, Topalovic, M, Sparla, L, Stadtteilforscher*innen, Falge, C, Topalovic, M, Sparla, L, and Stadtteilforscher*innen
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- 2022
3. Transferprojekt Bochumer Stadtteilforscher*innen Ansatz im Wittener Marienviertel: Ergebnisse und Reflexionen zur Gesundheitsförderung vermeintlich schwer erreichbarer Communities
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Falge, C, Rutert, B, Kappel, R, Schlue, G, Prochowski, M, Falge, C, Rutert, B, Kappel, R, Schlue, G, and Prochowski, M
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- 2022
4. Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV
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Kalmanti, L, Saussele, S, Lauseker, M, Müller, M C, Dietz, C T, Heinrich, L, Hanfstein, B, Proetel, U, Fabarius, A, Krause, S W, Rinaldetti, S, Dengler, J, Falge, C, Oppliger-Leibundgut, E, Burchert, A, Neubauer, A, Kanz, L, Stegelmann, F, Pfreundschuh, M, Spiekermann, K, Scheid, C, Pfirrmann, M, Hochhaus, A, Hasford, J, and Hehlmann, R
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- 2015
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5. Kollaborative Online-Forschung in Zeiten von COVID-19: Eine Community-Forschung zu Online-Gesundheitsinformationen im Kontext diversitätssensibler Aspekte
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Falge, C, Betscher, S, Geldermann, A, and Jünger, S
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ddc: 610 ,Medicine and health - Abstract
Hintergrund/Fragestellung/Problem: Im Rahmen des Projekts „Orientierungshilfen im Umgang mit Online-Gesundheitsinformationen“ kooperierten das Stadtteillabor Bochum, die Hochschule für Gesundheit Bochum und ceres (Uni Köln), um Bedarfe an Orientierungsangebote zu Online-Gesundheitsinformationen [zum vollständigen Text gelangen Sie über die oben angegebene URL]
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- 2021
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6. Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib
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Hanfstein, B, Shlyakhto, V, Lauseker, M, Hehlmann, R, Saussele, S, Dietz, C, Erben, P, Fabarius, A, Proetel, U, Schnittger, S, Krause, S W, Schubert, J, Einsele, H, Hänel, M, Dengler, J, Falge, C, Kanz, L, Neubauer, A, Kneba, M, Stegelmann, F, Pfreundschuh, M, Waller, C F, Spiekermann, K, Baerlocher, G M, Pfirrmann, M, Hasford, J, Hofmann, W-K, Hochhaus, A, and Müller, M C
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- 2014
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7. Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment
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Gratwohl, A, Pfirrmann, M, Zander, A, Kröger, N, Beelen, D, Novotny, J, Nerl, C, Scheid, C, Spiekermann, K, Mayer, J, Sayer, H G, Falge, C, Bunjes, D, Döhner, H, Ganser, A, Schmidt-Wolf, I, Schwerdtfeger, R, Baurmann, H, Kuse, R, Schmitz, N, Wehmeier, A, Th Fischer, J, Ho, A D, Wilhelm, M, Goebeler, M-E, Lindemann, H W, Bormann, M, Hertenstein, B, Schlimok, G, Baerlocher, G M, Aul, C, Pfreundschuh, M, Fabian, M, Staib, P, Edinger, M, Schatz, M, Fauser, A, Arnold, R, Kindler, T, Wulf, G, Rosselet, A, Hellmann, A, Schäfer, E, Prümmer, O, Schenk, M, Hasford, J, Heimpel, H, Hossfeld, D K, Kolb, H-J, Büsche, G, Haferlach, C, Schnittger, S, Müller, M C, Reiter, A, Berger, U, Sauele, S, Hochhaus, A, and Hehlmann, R
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- 2016
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8. Orientierungshilfen zum Umgang mit Gesundheitsinformationen im Internet: Diversitätssensible Stärkung digitaler Gesundheitskompetenz
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Geldermann, A, Jünger, S, Falge, C, Woopen, C, Geldermann, A, Jünger, S, Falge, C, and Woopen, C
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- 2021
9. Correction:High-risk additional chromosomal abnormalities at low blast counts herald death by CML (Leukemia, (2020), 34, 8, (2074-2086), 10.1038/s41375-020-0826-9)
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Hehlmann, Rüdiger, Voskanyan, Astghik, Lauseker, Michael, Pfirrmann, Markus, Kalmanti, Lida, Rinaldetti, Sebastien, Kohlbrenner, Katharina, Haferlach, Claudia, Schlegelberger, Brigitte, Fabarius, Alice, Seifarth, Wolfgang, Spieß, Birgit, Wuchter, Patrick, Krause, Stefan, Kolb, Hans Jochem, Neubauer, Andreas, Hossfeld, Dieter K., Nerl, Christoph, Gratwohl, Alois, Baerlocher, Gabriela M., Burchert, Andreas, Brümmendorf, Tim H., Hasford, Jörg, Hochhaus, Andreas, Saußele, Susanne, Baccarani, Michele, von Weikersthal, L. Fischer, Hahn, M., Schlimok, G., Reichert, D., Janssen, J., Martens, U., Majunke, P., Reichert, Peter, Neben, K., Korsten, S., Scholz, Ch, Oldenkott, B., Heßling, J., Kingreen, D., Sperling, C., Schelenz, C., Blau, I., Urmersbach, A., Ludwig, W., Le Coutre, P., Arnold, R., de Wit, M., Pezzutto, A., Schäfer, E., Schroers, R., Lochter, A., Behringer, D., Ko, Y., Weidenhöfer, S., Verbeek, W., Brossart, P., Trenn, G., Pommerien, W., Krauter, J., Doering, G., Munzinger, H., Diekmann, C., Hertenstein, B., Stier, S., Möller-Faßbender, F., Hänel, M., Zöller, T., Lamberti, C., Koch, B., Henzel, A., Wagner, S., Schmalenbach, A., Hoffknecht, M., Ehninger, G., Kiani, A., Illmer, T., Aul, C., Flaßhove, M., Henneke, F., Simon, M., Müller, L., Becker, H., Janz, R., Eckart, M. J., Fuchs, R., Schlegel, F., Wattad, M., Rudolph, R., Beelen, D. W., Lindemann, A., Linck, D., Wassman, Jäger, E., Al-Batran, S., Reiber, T., Waller, C. F., Hoeffkes, H., Schulz, L., Tajrobehkar, K., Mittermüller, J., Pralle, H., Runde, V., Hoyer, A., Tessen, H., Trümper, L., Schmidt, C., Sieber, M., Eschenburg, H., Depenbusch, R., Rösel, S., Lindemann, H. W., Wolf, H., Spohn, C., Moeller, R., Hossfeld, D., Zander, A., Schafhausen, P., Köster, H., Hollburg, W., Schmitz, N., Dürk, H., Hemeier, M., Grote-Metke, A., Weischer, H., Bechtel, B., Balleisen, L., Sosada, M., Ho, A., Petersen, V., Dengler, J., Bildat, S., Hahn, L., Dietzfelbinger, H., Gröschel, W., Bartholomäus, A., Freier, W., Sievers, B., Pfreundschuh, I. M., Herrmann, T., Fauser, A., Menzel, J., Kemmerling, M., Hansen, R., Link, H., Schatz, M., Bentz, M., Prümmer, O., Kneba, M., Heymanns, J., Schmitz, S., Scheid, C., Lollert, A., Neise, M., Planker, M., Stauch, M., Schröder, M., Kempf, B., Vehling-Kaiser, U., Kremers, S., Köchling, G., Hartmann, F., Neuhaus, T., Fetscher, S., Kämpfe, D., Heil, G., Uppenkamp, M., Goldmann, B., Huber, T. Fischer, Hieber, U., Plöger, C., Griesshammer, M., Lange, C., Göttler, B., Lunscken, C., Schiel, X., Scheidegger, C., Stötzer, O., Hitz, H., Schick, H., Völkl, S., Spiekermann, K., Berdel, W., Hebart, H., Ladda, E., Schmidt, P., Burkhardt, U., Hentschke, S., Falge, C., Reschke, D., Köhne, C. A., Müller-Naendrup, C., Sauer, M., Frühauf, S., Ranft, K., Dencausse, Y., Sandritter, B., Baake, G., Hofknecht, M., Dengler, R., Edinger, M., Schenk, M., Wehmeier, A., Weidelich, H. P., Pihusch, R., Stahlhut, K., Baldus, M., Matzdorff, A., Geer, T., Schanz, S., Käfer, G., Gassmann, W., Priebe-Richter, C., Demandt, M., Springer, G., Fiechtner, H., Denzlinger, C., Schleicher, J., Assman, D., Gaeckler, R., Adam, G., Waladkhani, A., Rendenbach, B., Forstbauer, H., Kanz, L., Jacki, S., Stegelmann, F., Kalhori, N., Nusch, A., Langer, W., Müller, F., Brettner, S., Uebelmesser, B., Kamp, T., Schadeck-Gressel, C., Josten, K., Klein, O., Schwerdtfeger, R., Baurmann, H., Strotkötter, H., Fett, W., Raghavachar, A., Maintz, C., Goebler, M. C., Schlag, R., Elsel, W., Wernli, M., Heim, D., Wuillemin, W., Hess, U., Gmür, J., and Mayer, J.
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
10. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)
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Hanfstein, B, Müller, M C, Hehlmann, R, Erben, P, Lauseker, M, Fabarius, A, Schnittger, S, Haferlach, C, Göhring, G, Proetel, U, Kolb, H-J, Krause, S W, Hofmann, W-K, Schubert, J, Einsele, H, Dengler, J, Hänel, M, Falge, C, Kanz, L, Neubauer, A, Kneba, M, Stegelmann, F, Pfreundschuh, M, Waller, C F, Branford, S, Hughes, T P, Spiekermann, K, Baerlocher, G M, Pfirrmann, M, Hasford, J, Sauele, S, and Hochhaus, A
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- 2012
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11. Superior CMR-rates with tolerability-adapted imatinib 800 mg vs. 400 mg vs. 400 mg + IFN in CML: The randomized German CML-Study IV: V633
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Sauâele, S., Lauseker, M., Müller, M. C., Proetel, U., Hanfstein, B., Jung-Munkwitz, S., Leitner, A., Baerlocher, G. M., Heim, D., Ehninger, G., Hossfeld, D. K., Krause, S. W., Nerl, C., Pralle, H., Schubert, J., Einsele, H., Ho, A. D., Falge, C., Hänel, M., Pfreundschuh, M., Kanz, L., Stegelmann, F., Köhne, C.-H., Kremers, S., Burchert, A., Spiekermann, K., Koschmieder, S., Waller, C. F., Bentz, M., Haferlach, C., Schlegelberger, B., Schnittger, S., Pfirrmann, M., Hasford, J., Hochhaus, A., and Hehlmann, R.
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- 2011
12. Therapy with imatinib in elderly CML patients (≥65 years): Results of the German CML-Study IV: V632
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Proetel, U., Pletsch, N., Lauseker, M., Jung-Munkwitz, S., Müller, M. C., Hanfstein, B., Leitner, A., Haferlach, C., Schlegelberger, B., Schnittger, S., Ehninger, G., Hossfeld, D. K., Krause, S. W., Nerl, C., Pralle, H., Heim, D., Baerlocher, G. M., Balleisen, L., Einsele, H., Ho, A. D., Falge, C., Hänel, M., Pfreundschuh, M., Kanz, L., Stegelmann, F., Köhne, C.-H., Kremers, S., Spiekermann, K., Koschmieder, S., Waller, C. F., Bentz, M., Pfirrmann, M., Hochhaus, A., Hasford, J., Hehlmann, R., and Sauâele, S.
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- 2011
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13. Optimization of imatinib therapy by combination. Final results of the pilot phase of the randomized German CML Study IV: V279
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Leitner, A., Sauele, S., Pletsch, N., Lauseker, M., Jung-Munkwitz, S., Proetel, U., Müller, M. C., Haferlach, C., Schlegelberger, B., Schnittger, S., Hanfstein, B., Pfirrmann, M., Ehninger, G., Fischer, T., Hossfeld, D., Kolb, H.-J., Krause, S., Nerl, C., Pralle, H., Gratwohl, A., Baerlocher, G., Heimpel, H., Balleisen, L., Einsele, H., Falge, C., Haenel, M., Pfreundschuh, M., Kanz, L., Stegelmann, F., Köhne, C. H., Kremers, S., Spiekermann, K., Koschmieder, S., Waller, C. F., Bentz, M., Hochhaus, A., Hasford, J., and Hehlmann, R.
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- 2010
14. OPTIMIZATION OF IMATINIB THERAPY BY COMBINATION, DOSE ESCALATION AND TRANSPLANTATION. DESIGNED FIRST INTERIM ANALYSIS OF THE RANDOMIZED GERMAN CML STUDY IV: V54
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Hehlmann, R., Saussele, S., Lauseker, M., Leitner, A., Pletsch, N., Shazi, S., Haferlach, C., Schlegelberger, B., Müller, M., Schenk, T., Pfirrmann, M., Ehninger, G., Fischer, T., Hasford, J., Hochhaus, A., Hossfeld, D. K., Kolb, H.-J., Krause, S. W., Nerl, C., Pralle, H., Gratwohl, A., Tobler, A., Heimpel, H., Balleisen, L., Einsele, H., Ho, A., Falge, C., Hänel, M., Pfreundschuh, M., Kanz, L., Döhner, H., Köhne, C.-H., Kremers, S., Spiekermann, K., Berdel, W., Waller, C., and Bentz, M.
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- 2009
15. Allogeneic hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) in the imatinib era: Evaluation of its impact within a subgroup of the German CML Study IV: V56
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Sauele, S., Lauseker, M., Gratwohl, A., Beelen, D., Bunjes, D., Schwerdtfeger, R., Kolb, H.-J., Ho, A., Falge, C., Holler, E., Schlimok, G., Zander, A., Arnold, R., Kanz, L., Dengler, R., Haferlach, C., Schlegelberger, B., Pfirrmann, M., Müller, M. C., Schnittger, S., Leitner, A., Pletsch, N., Hochhaus, A., Hasford, J., and Hehlmann, R.
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- 2009
16. Treatment of Peripheral (Mature) T-Cell Lymphomas with Alemtuzumab, Fludarabine, Cyclophosphamide and Doxorubicin (Campath-FCD) - Preliminary Results of a Phase II Study: O116
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Weidmann, E., Krause, S. W., Hess, G., Dreyling, M., Hebart, H., Subklewe, M., Falge, C., Chow, K. U., Banat, G. A., Filipp, C., Al-Batran, S. E., Gramatzki, M., Hansmann, M. L., Jäger, E., and Mitrou, P. S.
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- 2004
17. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants
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Hehlmann, R., Lauseker, M., Baerlocher, G. M., Heim, D., Brümmendorf, T. H., Fabarius, A., Haferlach, C., Schlegelberger, B., Müller, M. C., Jeromin, S., Proetel, U., Kohlbrenner, K., Saußele, S., Voskanyan, A., Rinaldetti, S., Seifarth, W., Spieß, B., Balleisen, L., Goebeler, M. C., Hänel, M., Ho, A., Dengler, J., Falge, C., Pfirrmann, M., Kanz, L., Kremers, S., Burchert, A., Kneba, M., Stegelmann, F., Köhne, C. A., Lindemann, H. W., Waller, C. F., Pfreundschuh, M., Spiekermann, K., Krause, S., Berdel, W. E., Müller, L., Edinger, M., Mayer, J., Beelen, D. W., Bentz, M., Link, H., Hertenstein, B., Fuchs, Roland, Wernli, M., Kolb, H. J., Schlegel, F., Schlag, R., de Wit, M., Trümper, L., Hebart, H., Hahn, M., Thomalla, J., Scheid, C., Schafhausen, P., Verbeek, W., Neubauer, A., Eckart, M. J., Gassmann, W., Pezzutto, A., Schenk, M., Brossart, P., Geer, T., Bildat, S., Schäfer, E., Hochhaus, A., Hasford, J., Hossfeld, D. K., SAKK and the German CML Study Group, Nerl, C., and Gratwohl, A.
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Cancer Research ,Medizin ,Alpha interferon ,610 Medicine & health ,03 medical and health sciences ,0302 clinical medicine ,chronic myeloid leukemia ,Internal medicine ,medicine ,Survival analysis ,Relative survival ,business.industry ,Myeloid leukemia ,Imatinib ,Hematology ,medicine.disease ,3. Good health ,Surgery ,Leukemia ,030104 developmental biology ,Imatinib mesylate ,030220 oncology & carcinogenesis ,Cytarabine ,Original Article ,business ,medicine.drug - Abstract
Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival. peerReviewed
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- 2017
18. Final Evaluation of Randomized CML-Study IV: 10-Year Survival and Evolution of Terminal Phase
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Hehlmann, Rüdiger, primary, Lauseker, Michael, additional, Saussele, Susanne, additional, Pfirrmann, Markus, additional, Krause, Stefan W., additional, Kolb, Hans-Jochem, additional, Neubauer, Andreas, additional, Hossfeld, Dieter K., additional, Nerl, Christoph, additional, Gratwohl, Alois, additional, Baerlocher, Gabriela M., additional, Heim, Dominik, additional, Bruemmendorf, Tim Henrik, additional, Fabarius, Alice, additional, Haferlach, Claudia, additional, Schlegelberger, Brigitte, additional, Müller, Martin C., additional, Jeromin, Sabine, additional, Proetel, Ulrike, additional, Kohlbrenner, Katharina, additional, Voskanyan, Astghik, additional, Rinaldetti, Sébastien, additional, Seifarth, Wolfgang, additional, Spiess, Birgit, additional, Balleisen, Leopold, additional, Goebeler, Maria E, additional, Hänel, Mathias, additional, Ho, Anthony D., additional, Dengler, J, additional, Falge, C, additional, Kanz, Lothar, additional, Köhne, Claus-Henning, additional, Burchert, Andreas, additional, Kneba, Michael, additional, Stegelmann, Frank, additional, Köhne, C, additional, Lindemann, Hans-Walter, additional, Waller, C, additional, Pfreundschuh, Michael, additional, Spiekermann, Karsten, additional, Berdel, Wolfgang E, additional, Müller, L, additional, Edinger, Matthias, additional, Mayer, Jiri, additional, Beelen, Dietrich W, additional, Bentz, Martin, additional, Link, Hartmut, additional, Hertenstein, Bernd, additional, Fuchs, R, additional, Wernli, Martin, additional, Schlegel, F, additional, Schlag, Rudolph, additional, de Wit, M, additional, Trümper, Lorenz, additional, Hebarth, H, additional, Hahn, M, additional, Thomalla, Jörg, additional, Scheid, Christof, additional, Schafhausen, Philippe, additional, Verbeek, Walter, additional, Eckart, Michael J., additional, Gassmann, Winfried, additional, Pezzutto, Antonio, additional, Schenk, Michael, additional, Brossart, Peter, additional, Geer, Thomas, additional, Bildat, Stephan, additional, Schäfer, E, additional, Hochhaus, Andreas, additional, and Hasford, Joerg, additional
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- 2017
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19. ASSESSMENT OF IMATINIB 400MG AS FIRST LINE TREATMENT OF CHRONIC MYELOID LEUKEMIA: 10-YEAR SURVIVAL RESULTS OF THE RANDOMIZED CML STUDY IV
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Hehlmann, R., Lauseker, M., Saussele, S., Pfirrmann, M., Krause, S., Kolb, H-J, Neubauer, A., Hossfeld, D. K., Nerl, C., Gratwohl, A., Baerlocher, G. M., Heim, D., Fabarius, A., Haferlach, C., Schlegelberger, B., Mueller, M. C., Jeromin, S., Proetel, U., Kohlbrenner, K., Burchert, A., Voskanyan, A., Rinaldetti, S., Goebeler, M., Dengler, J., Ho, A., Falge, C., Kanz, L., Kneba, M., Stegelmann, F., Pfreundschuh, M., Waller, C. F., Spiekermann, K., Fuchs, R., Scheid, C., Haenel, M., Koehne, C-H, Bruemmendorf, H., Lindemann, H-W, Berdel, W. E., Staib, P., Balleisen, L., Brossart, P., Schenk, M., Zankovich, R., Geer, T., Hertenstein, B., Bildat, S., Hochhaus, A., Hasford, J., Hehlmann, R., Lauseker, M., Saussele, S., Pfirrmann, M., Krause, S., Kolb, H-J, Neubauer, A., Hossfeld, D. K., Nerl, C., Gratwohl, A., Baerlocher, G. M., Heim, D., Fabarius, A., Haferlach, C., Schlegelberger, B., Mueller, M. C., Jeromin, S., Proetel, U., Kohlbrenner, K., Burchert, A., Voskanyan, A., Rinaldetti, S., Goebeler, M., Dengler, J., Ho, A., Falge, C., Kanz, L., Kneba, M., Stegelmann, F., Pfreundschuh, M., Waller, C. F., Spiekermann, K., Fuchs, R., Scheid, C., Haenel, M., Koehne, C-H, Bruemmendorf, H., Lindemann, H-W, Berdel, W. E., Staib, P., Balleisen, L., Brossart, P., Schenk, M., Zankovich, R., Geer, T., Hertenstein, B., Bildat, S., Hochhaus, A., and Hasford, J.
- Published
- 2017
20. Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis
- Author
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Eichhorst, Barbara F, Fischer, Kirsten, Fink, Anna Maria, Elter, Thomas, Wendtner, Clemens M, Goede, Valentin, Bergmann, Manuela, Stilgenbauer, Stephan, Hopfinger, Georg, Ritgen, Matthias, Bahlo, Jasmin, Busch, Raymonde, Hallek, Michael, Oduncu, F, Dreyling, M, Forstpointner, R, Schneller, F, Bogner, C, Peschel, C, Ringshausen, I, Götze, K, Goebeler, Me, Rückle, Lanz, Ritgen, M, Schawitzke, A, Heydrich, B, Kern, K, Böttcher, S, Irmer, S, Strack, U, Borries, V, Klima, Km, Scholz, C, Herold, M, Härtwig, K, Dürig, J, Dührsen, U, Müller Beissenhirtz, H, Noppeney, R, Schüttrumpf, S, Hohloch, K, Binder, C, Hasenkamp, J, Trümper, L, Bäsecke, J, Rieger, M, Witzens Harig, M, Friedrichs, B, Rieger, K, Uharek, L, Kubuschok, B, Murawski, N, Held, G, Zwick, C, Pfreundschuh, M, Fingerle Rowson, G, Reiser, M, Elter, T, Eichhorst, B, Pallasch, C, Hallek, M, Borchmann, P, Hacker, U, Schinkel, S, Wieker, K, Sökler, M, Wolf, Hh, Eucker, J, Staib, P, Schlegel, F, Kropff, M, Kahl, C, Hess, G, Beck, J, Wölfel, T, Bokemeyer, C, Schilling, G, Dierlamm, J, Schüler, F, Busemann, C, Dölken, G, Trendelenburg, Tk, Bühler, A, Stilgenbauer, S, Viardot, A, Greiner, J, Zenz, T, Gaidzik, V, Langer, C, Döhner, H, Werner, I, Dienst, A, Habersang, K, Härtel, N, Leitner, A, Kehrer, G, Middeke, H, Heinisch, K, Adorf, D, Ismer, B, Hering Schubert, C, Jäckle, J, Aulmann, C, Söllner, S, Majunke, P, Fuss, H, Käfer, G, Potenberg, J, Dietrich, G, Hartung, E, Pronath, A, Riedhammer, Fj, Zehrfeld, T, Prümmer, O, Gatter, J, Meier, A, Wattad, M, Heit, W, Sauer, I, Hilgers, K, Geissler, M, Bauer, J, Stein, W, Voigtmann, R, Natt, F, Nickelsen, M, Zeis, M, Schmitz, N, Lange, E, Stoltefuss, A, Schubert, J, Dürk, Ha, Kloke, O, Fauser, A, Roemer, E, Kraut, L, Musch, E, Kohl, S, Link, H, Kirsch, Jf, Schatz, M, Mezger, J, Kempf, B, Heil, G, Derigs, Hg, Roll, C, Kettner, E, Dübbers, Hw, Lutz, L, Hentrich, M, Hoffmann, U, Ibe, M, Falge, C, Schäfer Eckart, K, Rothmann, F, Raghavachar, A, Beckmann, K, Behringer, D, Stauder, H, Hempfling, C, Matzdorff, A, Hähling, D, Kaesberger, Kj, Mück, R, Waladkhani, Ar, Clemens, M, Kraft, J, Ehlert, T, N. N., Schloen, A, Sandritter, B, Scholz, Diekmann, C, Pflüger, Kh, Hausner, G, Fetscher, S, Aulitzky, W, Brugger, W, Frickhofen, N, Fuhr, Lange, C, Lambertz, H, Schulz, L, Schmier, M, Bentz, M, Tauchmann, Gm, Schmidt, M, Meiler, J, Sandmann, M, Kürschner, D, Maier Bay, B, Lindemann, W, Diers, J, Riemeier Sievers, C, Daun, M, Mergenthaler, Hg, Hiller, S, Schirmer, V, Kirchner, H, Langer, W, Günther, B, Gassmann, W, Franke, K, Burghardt, F, Abele, U, Celikel Becker, D, von Weikersthal LF, Brög, G, Hauch, U, Heinrich, B, Brudler, O, Häcker, B, Eckart, Mj, Bolouri, H, Göttler, B, Kindler, M, Zuchold, K, Strohbach, F, Plingen, Ml, Seibt Jung, H, Kirsch, A, Herrenberger, J, Doering, G, von Grünhagen, U, Franke, H, Weniger, J, Kerzel, W, Schmalfeld, M, Rohrberg, R, Hurtz, Hj, Gehbauer, G, Hahnfeld, S, Vehling Kaiser, U, Abenhardt, W, Bosse, D, Böning, L, Schmidt, B, Schick, Hd, Jacobs, G, Stauch, M, Hoffmann, R, Müller, S, Hahn, M, Freier, W, Dietzfelbinger, H, Rassmann, I, Söling, U, Siehl, S, Rudolph, R, Weinert, R, Sauer, A, Meyer, B, Eschenburg, H, Schadeck Gressel, C, Grabenhorst, U, Perker, M, Otremba, B, Reschke, D, Hinrichs, Hf, Zirpel, I, Höring, E, Respondek, M, Köppler, H, Heymanns, J, Weide, R, Hünermund, K, Thiel, C, Reiber, T, Spohn, C, Springer, G, Fiechtner, H, Hübner, A, Kurschel, E, Weiss, J, Schlag, R, Schäfer, E, Hartwich, G, Schmitz, S, Steinmetz, T, Kim, Ts, Lerchenmüller, C, Wehmeyer, J, Laubenstein, Hp, Rendenbach, B, Lebahn, H, Kröning, H, Uhle, R, Balló, H, Gaede, B, Zumbrink, S, Eckert, R, Kamp, T, Reimann, B, Burkhard, O, Mittermüller, J, Hansen, R, Hitz, H, Schliesser, G, Schmitt, Hr, Forstbauer, H, Grundeis, M, Schulze, M, Baldus, M, Lakner, V, Haen, M, Müller, C, Dörfel, S, Göhler, T, Welslau, M, Achtzehn, V, Culmann, H, Gerhardt, S, Ulshöfer, T, Koschuth, A, Schmidt, P, Müller, L, Schneider, M, Koniczek, K, Porowski, P, Glados, M, Knoblich, J, Ben Yehuda, D, Jäger, U, Gaiger, A, Schwarzmeier, J, Nösslinger, T, Smith, M, Patton, N, Gibbons, S, Bouabdallah, R, Gandhi, M, Marlton, P, Mills, T, Angelucci, E, Sorano, Gg, Casula, P, Berneman, Z, Kohser, P, Hudcova Burgetova, A, Machová, R, Papajik, T, Kubová, Z, Fineman, R, Mayer, J, Doubek, M, Brychtova, Y, Ciceri, F, Caligaris Cappio, F, Crocchiolo, R, Dauriac, C, Bernard, M, Escoffre Barbe, M, Lamy, T, Zikesova, E, Karban, J, Salkova, J, Trnený, M, Pytlik, R, Tiley, C, Forsyth, C, Vokurka, S, Koza, V, Van Hoof, A, Selleslag, D, Sebban, C, Baker, B, Belada, D, Jebavy, L, Smolej, L, Pavel, Z, Di Ianni, M, Castaigne, S, Del Poeta, G, Amadori, S, Catalano, J, Ganju, V, Hertzberg, M, Laurenti, L, Dalseg, Am, Bron, D, Morton, J, Durrant, S, Casado, Lf, Theunissen, K, Atias, D, Berkhan, L, Seymour, J, Wolf, M, Bosly, A, Osma Cordoba MM, Portois, C, Jaubert, J, Ferrant, A, Lambert, C, Maerevoet, E, Van den Neste, E, Gadeberg, O, Carney, B, Cannell, P, Eghbali, H, Legouffe, E, Bordessoule, D, Chaury, M, Moreau, S, Pierri, I, Gobbi, M, Berrebi, A, Lishner, M, Yerushazim, R, Yermiaku, T, Kosolov, V, Ambrosetti, Achille, Andreoli, Al, Huguet, F, Laurent, G, Orsucci, L, Forconi, F, Musuraca, G, Zinzani, Pl, Loscertales, J, Mcquillan, A, Cordingley, F, Leahy, M, Cazin, B, Taylor, Mulligan, S, Herbrecht, Cull, G, Seldon, M, Rowlings, P, Ludwig, H, Zojer, N, Solal Céligny, P, Pomponi, F, Savdkova, L, Kozák, T, Christiansen, I, Pérez, I, Campbell, P, Canales Albendea, M, De Paz, R, Arthur, C, Gisselbrecht, C., Eichhorst B.F., Fischer K., Fink A.M., Elter T., Wendtner C.M., Goede V., Bergmann M., Stilgenbauer S., Hopfinger G., Ritgen M., Bahlo J., Busch R., Hallek M., and Zinzani P.L.
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Male ,medicine.medical_specialty ,Cyclophosphamide ,Chronic lymphocytic leukemia ,Immunology ,Medizin ,Antineoplastic Combined Chemotherapy Protocols ,Blood Cell Count ,Disease Progression ,Disease-Free Survival ,Female ,Follow-Up Studies ,Humans ,Leukemia, Lymphocytic, Chronic, B-Cell ,Middle Aged ,Prognosis ,Recurrence ,Remission Induction ,Tomography, X-Ray Computed ,Physical examination ,Biochemistry ,Chemoimmunotherapy ,medicine ,Chronic ,Tomography ,Leukemia ,medicine.diagnostic_test ,business.industry ,B-Cell ,Cancer ,Cell Biology ,Hematology ,medicine.disease ,Lymphocytic ,imaging techniques ,X-Ray Computed ,Fludarabine ,Surgery ,chronic lymphocytic leukemia ,Radiology ,business ,Progressive disease ,medicine.drug - Abstract
The clinical value of imaging is well established for the follow-up of many lymphoid malignancies but not for chronic lymphocytic leukemia (CLL). A meta-analysis was performed with the dataset of 3 German CLL Study Group phase 3 trials (CLL4, CLL5, and CLL8) that included 1372 patients receiving first-line therapy for CLL. Response as well as progression during follow-up was reassessed according to the National Cancer Institute Working Group1996 criteria. A total of 481 events were counted as progressive disease during treatment or follow-up. Of these, 372 progressions (77%) were detected by clinical symptoms or blood counts. Computed tomography (CT) scans or ultrasound were relevant in 44 and 29 cases (9% and 6%), respectively. The decision for relapse treatment was determined by CT scan or ultrasound results in only 2 of 176 patients (1%). CT scan results had an impact on the prognosis of patients in complete remission only after the administration of conventional chemotherapy but not after chemoimmunotherapy. In conclusion, physical examination and blood count remain the methods of choice for staging and clinical follow-up of patients with CLL as recommended by the International Workshop on Chronic Lymphocytic Leukemia 2008 guidelines. These trials are registered at http://www.isrctn.org as ISRCTN 75653261 and ISRCTN 36294212 and at http://www.clinicaltrials.gov as NCT00281918.
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- 2011
21. Long-term correction of neutropenia in Felty's syndrome with granulocyte colony-stimulating factor
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Wandt, H., Seifert, M., Falge, C., and Gallmeier, W. M.
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- 1993
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22. Clonal Evolution and Blast Crisis Correlate with Enhanced Proteolytic Activity of Separase in BCR-ABL b3a2 Fusion Type CML under Imatinib Therapy
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Haaß, Wiltrud, Kleiner, Helga, Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung, Morgner, A., Herbst, R., Matek, W., Lamberti, C., Zöller, T., Koch, B., Marth, T., Henzel, A., Wagner, S., Woska, E., German CML Study Group, Neumann, F., Hoffknecht, M. M., Illmer, T., Wolf, T., Ehninger, G., Kiani, A., Platzbecker, U., Aul, C., Badrakhan, C. D., Giagounidis, A., Wernli, M., Flaßhove, M., Henneke, F., Moritz, T., Simon, M., Müller, L. L., Janz, R., Eckart, M., Häcker, B., Rech, D., Mackensen, A., Bargetzi, M., Krause, S. W., Staib, P., Schlegel, F., Wätzig, K., Rudolph, R., Wattad, M., Baur, F. K., Heit, W., Beelen, D. W., Hüttmann, A., Fischer von Weikersthal, L., Novotny, J., Trenschel, R., Lindemann, A., Linck, D., Jäger, E., Al-Batran, Salah-Eddin, Ottmann, O. G., Serve, H., Reiber, T., Semsek, D., Gro, V., Waller, C., Kühnemund, A., Hoeffkes, H. G., Lambertz, H., Schulz, L., Tajrobehkar, K., Mittermüller, J., Rummel, M. J., Burchardt, A., Pralle, H., Müller, S., Runde, V., Klei, M., Westheider, J., Hoyer, A., Tessen, H. W., Hesse, A., Trümper, L., Binder, C., Schmidt, C. A., Hirt, C., Hahn, M., Sieber, M., Eschenburg, H., Wilhelm, S., Depenbusch, R., Rösel, S., Eimermacher, H., Spohn, C., Moeller, R., Schmitz, N., Nickelsen, M., Schlimok, G., Engel, E., Haatanen, T., Hollburg, W., Platz, D., Köster, H., Bokemeyer, C., Schafhausen, P., Grote-Metke, A., Bechtel, B., Hemeier, M., Reichert, D., Sosada, M., Ganser, A., Schlegelberger, B., Ho, A. D., Rohlfing, S., Dengler, J., Petersen, V., Porowski, P., Hahn, L., Dietzfelbinger, H., Weiß, Christel, Janssen, J., Gröschel, W., Bartholomäus, A., Pfreundschuh, M., Kemmerling, M., Hansen, R., Reeb, M., Link, H., Mahlmann, S., Mezger, J., Schatz, M., Furkert, J., Schmier, M., Gatter, J., Neumann, S., Heymanns, J., Steinmetz, H. T., Schmitz, S., Scheid, C., Planker, M., Frieling, T., Lollert, A., Mandel, T., Neise, M., Schröder, M., Greif, D., Kempf, B., März, W., Kremers, S., Müller, L., Hartmann, F., Heil, G., Goldmann, B., Majunke, P. J., Heinkele, P., Gregor, M., Theobald, M., Fischer, T., Thomas, S., Hensel, M., Plöger, C., Schuster, D., Brust, J., Hieber, U., Paliege, R., Hehlmann, R., Neubauer, A., Burchert, A., Graeven, U., Lange, C., Schmidt, G., Völkl, S., Schmidt, B., Hitz, H., Spiekermann, K., Reichert, P., Hiddemann, W., Haferlach, T., Haferlach, C., Schnittger, S., Stötzer, O., Scheidegger, C., Fischer, C., Berdel, W. E., Koppele, A., Hebart, H., Fuss, H., Snaga, A., Schmidt, P., Hoffmann, R., Reschke, D., Zirpel, I., Sauer, M., Lenk, G., Theilmann, L., Sandritter, B., Neben, K., Schenk, M., Dengler, R., Herr, W., Krause, S., Braun, B., Günther, E., Wacker, A., Pihusch, R., Baldus, M., Matzdorff, A., Staiger, H. J., Pollmeier, G., Grimminger, W., Geer, T., Schanz, S., Jür, C., Gassmann, W., Seitz, K., Kaesberger, J., Mück, R., Heim, D., Illerhaus, G., Denzlinger, C., Fiechtner, H., Springer, G., Hoffmann, D., Jacki, S. H., Kanz, L., Bross-Bach, U., Döhner, H., Stegelmann, F., Haferlach, Claudia, Gratwohl, A., Kalhori, N., Langer, W., Nusch, A., Wei, J., Kamp, T., Schadeck-Gressel, C., Schwerdtfeger, R., Josten, K. M., Klein, O., Fett, W., Tichelli, A., Strotkötter, H., Maintz, C., Groschek, M., Schlag, R., Elsel, W., Schüler, F., Dölken, G., Lindemann, H. W., Wolf, H. H., Schmoll, H. J., Korsten, S., Braumann, D., Hoelzer, P., Kleeberg, U., Hossfeld, D., Lange, E., Schubert, J., Weischer, H., Dürk, H. A., Kirchner, H. H., Bu, E C., Henesser, D., Sievers, B., Freier, W., Kaiser, U., Peest, D., Römer, E., Hermann, T., Fauser, A., Valverde, M. L., Menzel, J., Kemper, J., le Coutre, P., Hochhaus, A., La Rosée, P., Bentz, M., Prümmer, O., Kneba, M., Strack, U., Schoch, R., Severin, K., Stauch, M., Arnold, R., Karbach, U., Vehling-Kaiser, U., Köchling, G., Wei, U., Middeke, H., Neuhaus, T., Martin, H., Fetscher, S., Schmielau, J., Kämpfe, D., Ludwig, W. D., Uppenkamp, M., Wei, B., Thum, P., Wuillemin, W., Hofmann, W. K., Griesshammer, M., Tischler, H. J., Becker, M., Hanfstein, B., Müller, M., Ratei, R., Saußele, S., Lunscken, C., Kolb, H. J., Lutz, L., Hentrich, M., Nerl, C., Wendtner, C., Ladda, E., Gnad, M., Teutsch, C., Suna, H., Schmidt, E., Koschmieder, S., Falge, C., Wandt, H., Wilhelm, M., Köhne, C. H., Schweiger, C., Müller-Naendrup, C., Frühauf, S., Ludwig, F., Ranft, K., Dencausse, Y., Baake, G., Ritter, P. R., Kloke, O., Göttler, B., Schick, H. D., Schlegelberger, Brigitte, Urmersbach, A., Weidenhöfer, S., Weidinger, P., Wacker, D., Wehmeyer, J., Kreuser, E. D., Schlenska-Lange, A., Edinger, R., Andreesen, R., Wehmeier, A., Stahlhut, K., Blau, I., Käfer, G., Cerny, T., Hess, U., Priebe-Richter, C., Stange-Budumlu, O., Demandt, M., Freunek, G., Heidemann, E., Schleicher, J., Mergenthaler, H. G., Ihle, H., Boewer, C., Zeller, C., Laubenstein, H. P., Rendenbach, B., Clemens, M., Waladkhani, A. R., Forstbauer, H., Müller, F., Brettner, S., Raghavachar, A., Sperling, C., Kunzmann, V., Goebeler, M. E., Gmür, J., Schelenz, C., Koschuth, A., Kingreen, D., Heßling, J., Derwahl, K. M., Oldenkott, B., Müller, Martin C., Englisch, H. J., Thiel, E., Burmeister, T., Notter, M., de Wit, M., Rothaug, W., Büschel, G., Beyer, J., Dahmen, E., Hehlmann, Rüdiger, Biaggi, C., Lämmle, B., Friess, D., Baerlocher, G., Oppliger Leibundgut, E., Tobler, A., Just, M., Schäfer, E., Behringer, D., Brandt, M., Hofmann, Wolf-Karsten, Schmiegel, W., Vaupel, H. A., Verbeek, W., Ko, Y. D., Sauerbruch, T., Hahn-Ast, C., Janzen, V., Schmidt-Wolf, Ingo G. H., Trenn, G., Fabarius, Alice, van der Linde, M., Pommerien, W., Fritz, L., Krauter, J., Lordick, F., Fritsch, G., Pflüger, K. H., Diekmann, C., Kullmer, J., Doering, G., Seifarth, Wolfgang, Munzinger, H., Hertenstein, B., Peyn, A., Mayer, J., Zácková, D., Kujickova, J., Stier, S., Wejda, B., Möller-Faßbender, F., and Hänel, M.
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Adult ,Aged, 80 and over ,Chromosome Aberrations ,Adolescent ,Fusion Proteins, bcr-abl ,Antineoplastic Agents ,Chromosome Breakage ,Middle Aged ,Clonal Evolution ,Young Adult ,hemic and lymphatic diseases ,Cell Line, Tumor ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Proteolysis ,Imatinib Mesylate ,Humans ,Blast Crisis ,Separase ,Research Article ,Aged - Abstract
PLoS ONE 10(6), e0129648 (2015). doi:10.1371/journal.pone.0129648, Published by PLoS, Lawrence, Kan.
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- 2015
- Full Text
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23. Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment
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Gratwohl, A., Pfirrmann, M., Zander, A., Kroger, N., Beelen, D., Novotny, J., Nerl, C., Scheid, C., Spiekermann, K., Mayer, J., Sayer, H. G., Falge, C., Bunjes, D., Doehner, H., Ganser, A., Schmidt-Wolf, I., Schwerdtfeger, R., Baurmann, H., Kuse, R., Schmitz, N., Wehmeier, A., Fischer, J. Th, Ho, A. D., Wilhelm, M., Goebeler, M-E, Lindemann, H. W., Bormann, M., Hertenstein, B., Schlimok, G., Baerlocher, G. M., Aul, C., Pfreundschuh, M., Fabian, M., Staib, P., Edinger, M., Schatz, M., Fauser, A., Arnold, R., Kindler, T., Wulf, G., Rosselet, A., Hellmann, A., Schaefer, E., Pruemmer, O., Schenk, M., Hasford, J., Heimpel, H., Hossfeld, D. K., Kolb, H-J, Buesche, G., Haferlach, C., Schnittger, S., Mueller, M. C., Reiter, A., Berger, U., Saussele, S., Hochhaus, A., Hehlmann, R., Gratwohl, A., Pfirrmann, M., Zander, A., Kroger, N., Beelen, D., Novotny, J., Nerl, C., Scheid, C., Spiekermann, K., Mayer, J., Sayer, H. G., Falge, C., Bunjes, D., Doehner, H., Ganser, A., Schmidt-Wolf, I., Schwerdtfeger, R., Baurmann, H., Kuse, R., Schmitz, N., Wehmeier, A., Fischer, J. Th, Ho, A. D., Wilhelm, M., Goebeler, M-E, Lindemann, H. W., Bormann, M., Hertenstein, B., Schlimok, G., Baerlocher, G. M., Aul, C., Pfreundschuh, M., Fabian, M., Staib, P., Edinger, M., Schatz, M., Fauser, A., Arnold, R., Kindler, T., Wulf, G., Rosselet, A., Hellmann, A., Schaefer, E., Pruemmer, O., Schenk, M., Hasford, J., Heimpel, H., Hossfeld, D. K., Kolb, H-J, Buesche, G., Haferlach, C., Schnittger, S., Mueller, M. C., Reiter, A., Berger, U., Saussele, S., Hochhaus, A., and Hehlmann, R.
- Abstract
Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N = 166 patients) and best available drug treatment (group B; N = 261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high( P < 0.001) and non-high-risk disease (P = 0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P = 0.005) and free of drug treatment (56% vs 6%; P < 0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.
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- 2016
24. Classification and Ontology Maintenance in Agent-Based Knowledge Management Frameworks: A Prototypical Approach.
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Falge, C., Cobos, R., and Groh, G.
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- 2007
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25. Multizentrische prospektive kontrollierte Studie zur Therapie der chronisch myeloischen Leukämie. Vergleich von Busulfan, Hydroxyurea und Interferon alpha (Stand April 1990)
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Hehlmann, R., primary, Heimpel, H., additional, Heinze, B., additional, Georgii, A., additional, Kolb, H.J., additional, Hossfeld, D.K., additional, Wussow, P.v., additional, Hochhaus, A., additional, Grießhammer, M., additional, Diehl, V., additional, Wickramanayake, P.D., additional, Gallmeier, W., additional, Falge, C., additional, Essers, U., additional, Bergmann, L., additional, Meyer, P., additional, Walther, F., additional, Kanz, L., additional, Queißer, U., additional, Hohnloser, J., additional, Westerhausen, M., additional, Kleeberg, U.R., additional, Heilein, A., additional, Käbisch, A., additional, Heiss, F., additional, Zimmermann, R., additional, Meuret, G., additional, Tichelli, A., additional, Berdel, W.E., additional, Schmitz, N., additional, Tigges, F.-J., additional, Eimermacher, H., additional, Schmid, L., additional, Löffler, H., additional, Pralle, H., additional, Queißer, W., additional, Burkhardt, R., additional, Ansari, H., additional, and Hasford, J., additional
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- 1991
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26. The German CML Study, Comparison of Busulfan vs. Hydroxyurea vs. Interferon alpha and Establishment of Prognostic Score 1.
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Hehlmann, R., Heimpel, H., Kolb, H. J., Heinze, B., Hochhaus, A., Griesshammer, M., Pralle, H., Queisser, W. P. D., Essers, U., Falge, C., Bergmann, L., Queisser, U., Meyer, P., Schmitz, N., Wickramanayake, P. D., Walther, F., Westerhausen, M., Kleeberg, U. R., Heilein, A., and Käbisch, A.
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- 1993
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27. Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group
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Hehlmann, R, Heimpel, H, Hasford, J, Kolb, HJ, Pralle, H, Hossfeld, DK, Queiβer, W, Löffler, H, Heinze, B, Georgii, A, Wussow, P.v., Bartram, C., Grieβhammer, M., Bergmann, L., Essers, U., Falge, C., Hochhaus, A., Queiβer, U., Sick, C., Meyer, P., Schmitz, N., Verpoort, K., Eimermacher, H., Walther, F., Westerhausen, M., Kleeberg, U.R., Heilein, A., Käbisch, A., Barz, C., Zimmermann, R., Meuret, G., Tichelli, A., Berdel, W.E., Kanz, L., Anger, B., Tigges, F.J., Schmid, L., Brockhaus, W., Zankovich, R., Schlafer, U., Weiβenfels, I., Mainzer, K., Tobler, A., Perker, M., Hohnloser, J., Messener, D., Thiele, J., Buhr, T., and Ansah, H.
- Abstract
In a randomized multicenter study the influence of hydroxyurea versus busulfan on the duration of the chronic phase and on survival of chronic myelogenous leukemia (CML) was determined. In addition cross resistance and adverse reactions of the drugs were analyzed. From July 1983 to January 1991, 441 CML patients were randomized to receive hydroxyurea or busulfan. Of these, 90.7% were Philadelphia positive; 25.7% were low, 38.2% intermediate, and 36.2% high risk patients according to Sokal's score. The median survival of the busulfan treated Philadelphia-positive patients is 45.4 months and of the hydroxyurea group 58.2 months (P = .008). The survival advantage for the hydroxyurea treated patients is recognized in all risk groups. Sixty four patients reached therapy resistance before blast crisis and were crossed over to the alternative drug. The 23 patients with primary hydroxyurea had a median survival of 5.6 years, the 41 patients with primary busulfan therapy a median survival of 2.7 years (P = .02). Adverse reactions were less frequent with hydroxyurea with no severe adverse effects (lung fibrosis, long lasting bone marrow aplasia). The analysis of white blood cell counts in the course of treatment showed lower counts in the hydroxyurea patients. We conclude that hydroxyurea is superior to busulfan in therapy of CML in chronic phase and should be used as first line therapy. Busulfan may have a role as secondary therapy after hydroxyurea resistance or intolerance.
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- 1993
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28. Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment
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Schäfer, E, Schlimok, G, Falge, C, Schmidt-Wolf, I, Schnittger, S, Staib, P, Kröger, N, Hochhaus, A, Scheid, C, Prümmer, O, Arnold, R, Haferlach, C, Spiekermann, K, Wehmeier, A, Th Fischer, J, Berger, U, Mayer, J, Kolb, H-J, Baerlocher, Gabriela M., Gratwohl, A, Reiter, A, Pfreundschuh, M, Hasford, J, Hertenstein, B, Schatz, M, Nerl, C, Bunjes, D, Fauser, A, Ho, A D, Beelen, D, Müller, M C, Rosselet, A, Wilhelm, M, Zander, A, Edinger, M, Hellmann, A, Sayer, H G, Goebeler, M-E, Hossfeld, D K, Novotny, J, Wulf, G, Büsche, G, Heimpel, H, Fabian, M, Pfirrmann, M, Baurmann, H, Ganser, A, Hehlmann, R, Aul, C, Schenk, M, Bormann, M, Schwerdtfeger, R, Kindler, T, Lindemann, H W, Döhner, H, Saußele, S, Schmitz, N, and Kuse, R
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hemic and lymphatic diseases ,610 Medicine & health ,3. Good health - Abstract
Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P
29. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants
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Hehlmann, R., Lauseker, M., Saußele, S., Pfirrmann, M., Krause, S., Kolb, H. J., Neubauer, A., Hossfeld, D. K., Nerl, C., Gratwohl, A., Baerlocher, G. M., Heim, D., Brümmendorf, T. H., Fabarius, A., Haferlach, C., Schlegelberger, B., Müller, M. C., Jeromin, S., Proetel, U., Kohlbrenner, K., Voskanyan, A., Rinaldetti, S., Seifarth, W., Spieß, B., Balleisen, L., Goebeler, M. C., Hänel, M., Ho, A., Dengler, J., Falge, C., Kanz, L., Kremers, S., Burchert, A., Kneba, M., Stegelmann, F., Köhne, C. A., Lindemann, H. W., Waller, C. F., Pfreundschuh, M., Spiekermann, K., Berdel, W. E., Müller, L., Edinger, M., Mayer, J., Beelen, D. W., Bentz, M., Link, H., Hertenstein, B., Fuchs, Roland, Wernli, M., Schlegel, F., Schlag, R., De Wit, M., Trümper, L., Hebart, H., Hahn, M., Thomalla, J., Scheid, C., Schafhausen, P., Verbeek, W., Eckart, M. J., Gassmann, W., Pezzutto, A., Schenk, M., Brossart, P., Geer, T., Bildat, S., Schäfer, E., Hochhaus, A., Hasford, J., and SAKK And The German CML Study Group
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3. Good health - Abstract
Leukemia : normal and malignant hemopoiesis 31, 2398-2406 (2017). doi:10.1038/leu.2017.253, Published by Springer Nature, London
30. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants
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Hehlmann, R, Lauseker, M, Saußele, S, Pfirrmann, M, Krause, S, Kolb, H J, Neubauer, A, Hossfeld, D K, Nerl, C, Gratwohl, A, Baerlocher, Gabriela M., Heim, D, Brümmendorf, T H, Fabarius, A, Haferlach, C, Schlegelberger, B, Müller, M C, Jeromin, S, Proetel, U, Kohlbrenner, K, Voskanyan, A, Rinaldetti, S, Seifarth, W, Spieß, B, Balleisen, L, Goebeler, M C, Hänel, M, Ho, A, Dengler, J, Falge, C, Kanz, L, Kremers, S, Burchert, A, Kneba, M, Stegelmann, F, Köhne, C A, Lindemann, H W, Waller, C F, Pfreundschuh, M, Spiekermann, K, Berdel, W E, Müller, L, Edinger, M, Mayer, J, Beelen, D W, Bentz, M, Link, H, Hertenstein, B, Fuchs, R, Wernli, M, Schlegel, F, Schlag, R, De Wit, M, Trümper, L, Hebart, H, Hahn, M, Thomalla, J, Scheid, C, Schafhausen, P, Verbeek, W, Eckart, M J, Gassmann, W, Pezzutto, A, Schenk, M, Brossart, P, Geer, T, Bildat, S, Schäfer, E, Hochhaus, A, and Hasford, J
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610 Medicine & health ,3. Good health - Abstract
Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.
31. Migrants and health: Political and institutional responses to cultural diversity in health systems
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Falge, C., Ruzza, C., and Oliver Schmidtke
32. Synthesis of angiotensinogen by isolated rat liver cells and its regulation in comparison to serum albumin
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Weigand, K., primary, Wernze, H., additional, and Falge, C., additional
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- 1977
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33. Randomized Comparison of Interferon-α With Busulfan and Hydroxyurea in Chronic Myelogenous Leukemia
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Hehlmann, R., Heimpel, H., Hasford, J., Kolb, H.J., Pralle, H., Hossfeld, D.K., Queißer, W., Löffler, H., Hochhaus, A., Heinze, B., Georgii, A., Bartram, CR., Grießhammer, M., Bergmann, L., Essers, U., Falge, C., Queißer, U., Meyer, P., Schmitz, N., Eimermacher, H., Walther, F., Fett, W., Kleeberg, U.R., Käbisch, A., Nerl, C., Zimmermann, R., Meuret, G., Tichelli, A., Kanz, L., Tigges, F.-J., Schmid, L., Brockhaus, W., Tobler, A., Reiter, A., Perker, M., Emmerich, B., Verpoort, K., Zankovich, R., Wussow, P.v., Prümmer, O., Thiele, J., Buhr, T., Carbonell, F., and Ansari, H.
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- 1994
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34. Strategies for change among institutional and civil society actors
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Özçürümez, Saime, Wylie, L., Falge, C., Ruzza, C., and Schmidtke, O.
- Abstract
Chapter 5 This chapter will first provide background on the political and regulatory frameworks of Germany, Canada and Italy, as this is the legislation that qualifies access to health services. This allows us to highlight how the essential regulatory frameworks are both a considerable constraint and opportunity for civil society and migrant organizations. They also allow us to show the dynamic nature of the relation between state and civil society-more specifically, between state and organized civil society. In each of the countries we consider, civil society develops in ways that are in part isomorphic and in part complementary to the structure of the state. Each of the states we examine support civil society in different ways and for different purposes, and in doing so shape the way pro-migrant associations operate. The first section of this chapter will illustrate these processes. We will then move to examine how civil society actors have become engaged in the field of health care and what strategies they have adopted in our national contexts. Finally, we will examine what policy lessons can be learned from our case studies, both in terms of access and in terms of policy effectiveness in the service delivery and advocacy functions.
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- 2012
35. Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV.
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Michel C, Burchert A, Hochhaus A, Saussele S, Neubauer A, Lauseker M, Krause SW, Kolb HJ, Hossfeld DK, Nerl C, Baerlocher GM, Heim D, Brümmendorf TH, Fabarius A, Haferlach C, Schlegelberger B, Balleisen L, Goebeler ME, Hänel M, Ho A, Dengler J, Falge C, Möhle R, Kremers S, Kneba M, Stegelmann F, Köhne CH, Lindemann HW, Waller CF, Spiekermann K, Berdel WE, Müller L, Edinger M, Mayer J, Beelen DW, Bentz M, Link H, Hertenstein B, Fuchs R, Wernli M, Schlegel F, Schlag R, de Wit M, Trümper L, Hebart H, Hahn M, Thomalla J, Scheid C, Schafhausen P, Verbeek W, Eckart MJ, Gassmann W, Schenk M, Brossart P, Wündisch T, Geer T, Bildat S, Schäfer E, Hasford J, Hehlmann R, and Pfirrmann M
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- Aged, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Remission Induction, Retrospective Studies, Survival Rate, Time Factors, Treatment Outcome, Antineoplastic Agents therapeutic use, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Neoplasm Recurrence, Local drug therapy, Withholding Treatment statistics & numerical data
- Abstract
Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg ('high-dose') imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients. Study protocol registered at clinicaltrials.gov 00055874 ., (Copyright© 2019 Ferrata Storti Foundation.)
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- 2019
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36. Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV.
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Saussele S, Hehlmann R, Fabarius A, Jeromin S, Proetel U, Rinaldetti S, Kohlbrenner K, Einsele H, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Oppliger Leibundgut E, Heim D, Krause SW, Hofmann WK, Hasford J, Pfirrmann M, Müller MC, Hochhaus A, and Lauseker M
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- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Machine Learning, Male, Middle Aged, Progression-Free Survival, Treatment Failure, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Models, Theoretical, Remission Induction methods
- Abstract
Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1% BCR-ABL at about 12-15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later.
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- 2018
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37. Impact of unbalanced minor route versus major route karyotypes at diagnosis on prognosis of CML.
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Fabarius A, Kalmanti L, Dietz CT, Lauseker M, Rinaldetti S, Haferlach C, Göhring G, Schlegelberger B, Jotterand M, Hanfstein B, Seifarth W, Hänel M, Köhne CH, Lindemann HW, Berdel WE, Staib P, Müller MC, Proetel U, Balleisen L, Goebeler ME, Dengler J, Falge C, Kanz L, Burchert A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Brümmendorf TH, Edinger M, Hofmann WK, Pfirrmann M, Hasford J, Krause S, Hochhaus A, Saußele S, and Hehlmann R
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- Adolescent, Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Humans, Karyotyping, Male, Middle Aged, Survival Rate, Abnormal Karyotype, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Philadelphia Chromosome
- Abstract
Major route additional cytogenetic aberrations (ACA) at diagnosis of chronic myeloid leukaemia (CML) indicate an increased risk of progression and shorter survival. Since major route ACA are almost always unbalanced, it is unclear whether other unbalanced ACA at diagnosis also confer an unfavourable prognosis. On the basis of 1348 Philadelphia chromosome-positive chronic phase patients of the randomized CML study IV, we examined the impact of unbalanced minor route ACA at diagnosis versus major route ACA on prognosis. At diagnosis, 1175 patients (87.2 %) had a translocation t(9;22)(q34;q11) and 74 (5.5 %) a variant translocation t(v;22) only, while a loss of the Y chromosome (-Y) was present in addition in 44 (3.3 %), balanced or unbalanced minor route ACA each in 17 (1.3 %) and major route ACA in 21 (1.6 %) cases. Patients with unbalanced minor route ACA had no significantly different cumulative incidences of complete cytogenetic remission or major molecular remission and no significantly different progression-free survival (PFS) or overall survival (OS) than patients with t(9;22), t(v;22), -Y and balanced minor route karyotypes. In contrast, patients with major route ACA had a shorter OS and PFS than all other groups (all pairwise comparisons to each of the other groups: p ≤ 0.015). Five-year survival probabilities were for t(9;22) 91.4 % (95 % CI 89.5-93.1), t(v; 22) 87 % (77.2-94.3), -Y 89.0 % (76.7-97.0), balanced 100 %, unbalanced minor route 92.3 % (72.4-100) and major route 52.2 % (28.2-75.5). We conclude that only major route, but not balanced or unbalanced minor route ACA at diagnosis, has a negative impact on prognosis of CML.
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- 2015
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38. Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib.
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Hanfstein B, Lauseker M, Hehlmann R, Saussele S, Erben P, Dietz C, Fabarius A, Proetel U, Schnittger S, Haferlach C, Krause SW, Schubert J, Einsele H, Hänel M, Dengler J, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Pfirrmann M, Hasford J, Hofmann WK, Hochhaus A, and Müller MC
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- Adolescent, Adult, Aged, Aged, 80 and over, Alternative Splicing, Blood Platelets drug effects, Blood Platelets pathology, Drug Monitoring, Female, Fusion Proteins, bcr-abl metabolism, Genotype, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Leukocytes drug effects, Leukocytes pathology, Male, Middle Aged, Phenotype, RNA, Messenger metabolism, Remission Induction, Survival Analysis, Treatment Outcome, Antineoplastic Agents therapeutic use, Benzamides therapeutic use, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Piperazines therapeutic use, Pyrimidines therapeutic use, RNA, Messenger genetics
- Abstract
The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 × 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 × 10(9)/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier:00055874)., (Copyright© Ferrata Storti Foundation.)
- Published
- 2014
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39. Explaining survival differences between two consecutive studies with allogeneic stem cell transplantation in patients with chronic myeloid leukemia.
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Pfirrmann M, Saussele S, Hochhaus A, Reiter A, Berger U, Hossfeld DK, Nerl C, Scheid C, Spiekermann K, Mayer J, Hellmann A, Lechner K, Falge C, Sayer HG, Bunjes D, Ganser A, Beelen DW, Baldomero H, Schanz U, Heimpel H, Kolb HJ, Hasford J, Gratwohl A, and Hehlmann R
- Subjects
- Adolescent, Adult, Child, Female, Humans, Kaplan-Meier Estimate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive immunology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, Risk Factors, Transplantation Immunology, Transplantation, Homologous, Young Adult, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- Abstract
Purpose: In the two consecutive German studies III and IIIA on chronic myeloid leukemia, between 1995 and 2004, 781 patients were randomized to receive either allogeneic hematopoietic stem cell transplantation with a related donor or continued drug treatment. Despite comparable transplantation protocols and most centers participating in both studies, the post-transplant survival probabilities for patients transplanted in first chronic phase were significantly higher in study IIIA (144 patients) than in study III (113 patients). Prior to the decision on a combined analysis of both studies, reasons for this discrepancy had to be investigated., Methods: The Cox proportional hazard cure model was used to identify prognostic factors for post-transplant survival., Results: Donor-recipient matching for human leukocyte antigen, patient age, time between diagnosis and transplantation, and calendar time showed a significant influence on survival and/or the incidence of cure. Added as a further factor, affiliation to study IIIA had no significant impact any longer., Conclusions: Discrepancies in influential prognostic factors explained the different post-transplant survival probabilities between the studies. The significance of calendar time suggests a lack of consistency of transplantation practice over time. Accordingly, the prerequisite for a common assessment of overall survival in the two randomized transplantation arms was not met. Moreover, our analyses provide an independent validation of established prognostic factors and their cutoffs. The statistical approach in investigating and modeling potential prognostic factors for survival sets an example for the examination of studies with unexpected outcome differences in concurrent treatment arms.
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- 2014
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40. Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV.
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Hehlmann R, Müller MC, Lauseker M, Hanfstein B, Fabarius A, Schreiber A, Proetel U, Pletsch N, Pfirrmann M, Haferlach C, Schnittger S, Einsele H, Dengler J, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Ehninger G, Heim D, Heimpel H, Nerl C, Krause SW, Hossfeld DK, Kolb HJ, Hasford J, Saußele S, and Hochhaus A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Benzamides adverse effects, Cytarabine administration & dosage, Disease Progression, Disease-Free Survival, Female, Fusion Proteins, bcr-abl antagonists & inhibitors, Fusion Proteins, bcr-abl genetics, Fusion Proteins, bcr-abl metabolism, Humans, Imatinib Mesylate, Interferon-alpha administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive enzymology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Molecular Targeted Therapy, Piperazines adverse effects, Proportional Hazards Models, Protein Kinase Inhibitors adverse effects, Pyrimidines adverse effects, Remission Induction, Risk Factors, Time Factors, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Benzamides administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines administration & dosage, Protein Kinase Inhibitors administration & dosage, Pyrimidines administration & dosage
- Abstract
Purpose: Deep molecular response (MR(4.5)) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR(4.5) under different treatment modalities and whether MR(4.5) predicts survival., Patients and Methods: Patients from the randomized CML-Study IV were analyzed for confirmed MR(4.5) which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR(4.5) on survival., Results: Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70% (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR(4.5) at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR(4.5). No patient with confirmed MR(4.5) has experienced progression., Conclusion: MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.
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- 2014
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41. Younger patients with chronic myeloid leukemia do well in spite of poor prognostic indicators: results from the randomized CML study IV.
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Kalmanti L, Saussele S, Lauseker M, Proetel U, Müller MC, Hanfstein B, Schreiber A, Fabarius A, Pfirrmann M, Schnittger S, Dengler J, Falge C, Kanz L, Neubauer A, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Krause SW, Heim D, Nerl C, Hossfeld DK, Kolb HJ, Hochhaus A, Hasford J, and Hehlmann R
- Subjects
- Adolescent, Adult, Age Factors, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Benzamides administration & dosage, Benzamides therapeutic use, Cytarabine administration & dosage, Female, Follow-Up Studies, Fusion Proteins, bcr-abl blood, Fusion Proteins, bcr-abl genetics, Humans, Imatinib Mesylate, Interferon-alpha administration & dosage, Kaplan-Meier Estimate, Karnofsky Performance Status, Leukemia, Myeloid, Chronic-Phase blood, Leukemia, Myeloid, Chronic-Phase drug therapy, Leukemia, Myeloid, Chronic-Phase genetics, Male, Middle Aged, Piperazines administration & dosage, Piperazines therapeutic use, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors therapeutic use, Pyrimidines administration & dosage, Pyrimidines therapeutic use, RNA, Messenger blood, RNA, Neoplasm blood, Randomized Controlled Trials as Topic statistics & numerical data, Risk Factors, Splenomegaly etiology, Treatment Outcome, Young Adult, Leukemia, Myeloid, Chronic-Phase mortality
- Abstract
Since the advent of tyrosine kinase inhibitors, the impact of age on outcome of chronic myeloid leukemia (CML) patients has changed. We therefore analyzed patients from the randomized CML study IV to investigate disease manifestations and outcome in different age groups. One thousand five hundred twenty-four patients with BCR-ABL-positive chronic phase CML were divided into four age groups: (1) 16-29 years, n = 120; (2) 30-44 years, n = 383; (3) 45-59 years, n = 495; and (4) ≥60 years, n = 526. Group 1 (adolescents and young adults (AYAs)) presented with more aggressive disease features (larger spleen size, more frequent symptoms of organomegaly, higher white blood count, higher percentage of peripheral blasts and lower hemoglobin levels) than the other age groups. In addition, a higher rate of patients with BCR-ABL transcript levels >10 % on the international scale (IS) at 3 months was observed. After a median observation time of 67.5 months, no inferior survival and no differences in cytogenetic and molecular remissions or progression rates were observed. We conclude that AYAs show more aggressive features and poor prognostic indicators possibly indicating differences in disease biology. This, however, does not affect outcome.
- Published
- 2014
- Full Text
- View/download PDF
42. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV.
- Author
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Fabarius A, Leitner A, Hochhaus A, Müller MC, Hanfstein B, Haferlach C, Göhring G, Schlegelberger B, Jotterand M, Reiter A, Jung-Munkwitz S, Proetel U, Schwaab J, Hofmann WK, Schubert J, Einsele H, Ho AD, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Lauseker M, Pfirrmann M, Hasford J, Saussele S, and Hehlmann R
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Disease Progression, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Karyotyping, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Male, Middle Aged, Prognosis, Prospective Studies, Randomized Controlled Trials as Topic, Time Factors, Translocation, Genetic, Treatment Outcome, Trisomy, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chromosome Aberrations, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
- Abstract
The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph(+)) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (-Y) and 41 patients (3.6%) had ACAs except -Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), -Y, minor- and major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major-route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis.
- Published
- 2011
- Full Text
- View/download PDF
43. Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV.
- Author
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Saussele S, Lauseker M, Gratwohl A, Beelen DW, Bunjes D, Schwerdtfeger R, Kolb HJ, Ho AD, Falge C, Holler E, Schlimok G, Zander AR, Arnold R, Kanz L, Dengler R, Haferlach C, Schlegelberger B, Pfirrmann M, Müller MC, Schnittger S, Leitner A, Pletsch N, Hochhaus A, Hasford J, and Hehlmann R
- Subjects
- Adult, Algorithms, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Benzamides, Cytarabine administration & dosage, Dose-Response Relationship, Drug, Female, Germany, Humans, Imatinib Mesylate, Immunosuppressive Agents administration & dosage, Interferons administration & dosage, Male, Piperazines administration & dosage, Pyrimidines administration & dosage, Transplantation Conditioning methods, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Piperazines therapeutic use, Pyrimidines therapeutic use
- Abstract
The role of allogeneic stem cell transplantation in chronic myeloid leukemia is being reevaluated. Whereas drug treatment has been shown to be superior in first-line treatment, data on allogeneic hematopoietic stem cell transplantation (allo SCT) as second-line therapy after imatinib failure are scarce. Using an interim safety analysis of the randomized German CML Study IV designed to optimize imatinib therapy by combination, dose escalation, and transplantation, we here report on 84 patients who underwent consecutive transplantation according to predefined criteria (low European Group for Blood and Marrow Transplantation [EBMT] score, imatinib failure, and advanced disease). Three-year survival after transplantation of 56 patients in chronic phase was 91% (median follow-up: 30 months). Transplantation-related mortality was 8%. In a matched pair comparison of patients who received a transplant and those who did not, survival was not different. Three-year survival after transplantation of 28 patients in advanced phase was 59%. Eighty-eight percent of patients who received a transplant achieved complete molecular remissions. We conclude that allo SCT could become the preferred second-line option after imatinib failure for suitable patients with a donor. The study is registered at the National Institutes of Health, http://clinicaltrials.gov: NCT00055874.
- Published
- 2010
- Full Text
- View/download PDF
44. Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia.
- Author
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Hehlmann R, Berger U, Pfirrmann M, Heimpel H, Hochhaus A, Hasford J, Kolb HJ, Lahaye T, Maywald O, Reiter A, Hossfeld DK, Huber C, Löffler H, Pralle H, Queisser W, Tobler A, Nerl C, Solenthaler M, Goebeler ME, Griesshammer M, Fischer T, Kremers S, Eimermacher H, Pfreundschuh M, Hirschmann WD, Lechner K, Wassmann B, Falge C, Kirchner HH, and Gratwohl A
- Subjects
- Adolescent, Adult, Child, Cohort Studies, Female, Humans, Male, Middle Aged, Prognosis, Risk, Treatment Outcome, Antineoplastic Agents pharmacology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Transplantation, Homologous methods
- Abstract
Early allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as primary treatment modality for patients with chronic myeloid leukemia (CML). This concept has been challenged by transplantation mortality and improved drug therapy. In a randomized study, primary HSCT and best available drug treatment (IFN based) were compared in newly diagnosed chronic phase CML patients. Assignment to treatment strategy was by genetic randomization according to availability of a matched related donor. Evaluation followed the intention-to-treat principle. Six hundred and twenty one patients with chronic phase CML were stratified for eligibility for HSCT. Three hundred and fifty four patients (62% male; median age, 40 years; range, 11-59 years) were eligible and randomized. One hundred and thirty five patients (38%) had a matched related donor, of whom 123 (91%) received a transplant within a median of 10 months (range, 2-106 months) from diagnosis. Two hundred and nineteen patients (62%) had no related donor and received best available drug treatment. With an observation time up to 11.2 years (median, 8.9 years), survival was superior for patients with drug treatment (P = .049), superiority being most pronounced in low-risk patients (P = .032). The general recommendation of HSCT as first-line treatment option in chronic phase CML can no longer be maintained. It should be replaced by a trial with modern drug treatment first.
- Published
- 2007
- Full Text
- View/download PDF
45. Proceedings: Synthesis and secretion of albumin and angiotensinogen by isolated rat liver cells.
- Author
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Weigand K, Wernze H, and Falge C
- Subjects
- Albumins metabolism, Angiotensinogen metabolism, Animals, In Vitro Techniques, Rats, Albumins biosynthesis, Angiotensin II analogs & derivatives, Angiotensinogen biosynthesis, Liver metabolism
- Published
- 1974
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