1,047 results on '"Kneba, Michael"'
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2. Obinutuzumab, acalabrutinib, and venetoclax, after an optional debulking with bendamustine in relapsed or refractory chronic lymphocytic leukaemia (CLL2-BAAG): a multicentre, open-label, phase 2 trial
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Cramer, Paula, Fürstenau, Moritz, Robrecht, Sandra, Giza, Adam, Zhang, Can, Fink, Anna-Maria, Fischer, Kirsten, Langerbeins, Petra, Al-Sawaf, Othman, Tausch, Eugen, Schneider, Christof, Schetelig, Johannes, Dreger, Peter, Böttcher, Sebastian, Kreuzer, Karl-Anton, Schilhabel, Anke, Ritgen, Matthias, Brüggemann, Monika, Kneba, Michael, Stilgenbauer, Stephan, Eichhorst, Barbara, and Hallek, Michael
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- 2022
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3. Obinutuzumab (GA-101), ibrutinib, and venetoclax (GIVe) frontline treatment for high-risk chronic lymphocytic leukemia
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Huber, Henriette, Edenhofer, Simone, von Tresckow, Julia, Robrecht, Sandra, Zhang, Can, Tausch, Eugen, Schneider, Christof, Bloehdorn, Johannes, Fürstenau, Moritz, Dreger, Peter, Ritgen, Matthias, Illmer, Thomas, Illert, Anna L., Dürig, Jan, Böttcher, Sebastian, Niemann, Carsten U., Kneba, Michael, Fink, Anna-Maria, Fischer, Kirsten, Döhner, Hartmut, Hallek, Michael, Eichhorst, Barbara, and Stilgenbauer, Stephan
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- 2022
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4. Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study
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Pott, Christiane, primary, Jurinovic, Vindi, additional, Trotman, Judith, additional, Kehden, Britta, additional, Unterhalt, Michael, additional, Herold, Michael, additional, Jagt, Richard van der, additional, Janssens, Ann, additional, Kneba, Michael, additional, Mayer, Jiri, additional, Young, Moya, additional, Schmidt, Christian, additional, Knapp, Andrea, additional, Nielsen, Tina, additional, Brown, Helen, additional, Spielewoy, Nathalie, additional, Harbron, Chris, additional, Bottos, Alessia, additional, Mundt, Kirsten, additional, Marcus, Robert, additional, Hiddemann, Wolfgang, additional, and Hoster, Eva, additional
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- 2024
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5. Marker für minimale Resterkrankung: Minimal Residual Disease
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Brüggemann, Monika, primary, Pott, Christiane, additional, Stübig, Thomas, additional, Kneba, Michael, additional, and Hochhaus, Andreas, additional
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- 2022
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6. Bendamustine, followed by obinutuzumab and idelalisib in chronic lymphocytic leukemia (CLL2‐BCG): Final analysis of a multicenter, open‐label phase‐II‐trial.
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Cramer, Paula, von Tresckow, Julia, Fink, Anna‐Maria, Robrecht, Sandra, Giza, Adam, Tausch, Eugen, Müller, Lothar, Knauf, Wolfgang, Zingerle, Matthias, Al‐Sawaf, Othman, Langerbeins, Petra, Fischer, Kirsten, Kreuzer, Karl‐Anton, Kneba, Michael, Wendtner, Clemens‐Martin, Stilgenbauer, Stephan, Eichhorst, Barbara, and Hallek, Michael
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- 2024
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7. Early treatment with FCR versus watch and wait in patients with stage Binet A high-risk chronic lymphocytic leukemia (CLL): a randomized phase 3 trial
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Herling, Carmen D., Cymbalista, Florence, Groß-Ophoff-Müller, Carolin, Bahlo, Jasmin, Robrecht, Sandra, Langerbeins, Petra, Fink, Anna-Maria, Al-Sawaf, Othman, Busch, Raymonde, Porcher, Raphael, Cazin, Bruno, Dreyfus, Brigitte, Ibach, Stefan, Leprêtre, Stéphane, Fischer, Kirsten, Kaiser, Florian, Eichhorst, Barbara, Wentner, Clemens-Martin, Hoechstetter, Manuela A., Döhner, Hartmut, Leblond, Veronique, Kneba, Michael, Letestu, Remi, Böttcher, Sebastian, Stilgenbauer, Stephan, Hallek, Michael, and Levy, Vincent
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- 2020
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8. Influence of obesity and gender on treatment outcomes in patients with chronic lymphocytic leukemia (CLL) undergoing rituximab-based chemoimmunotherapy
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Fürstenau, Moritz, Hopfinger, Georg, Robrecht, Sandra, Fink, Anna-Maria, Al-Sawaf, Othman, Langerbeins, Petra, Cramer, Paula, Tresckow, Julia Von, Maurer, Christian, Kutsch, Nadine, Hoechstetter, Manuela, Dreyling, Martin, Lange, Elisabeth, Kneba, Michael, Stilgenbauer, Stephan, Döhner, Hartmut, Hensel, Manfred, Kiehl, Michael G., Jaeger, Ulrich, Wendtner, Clemens-Martin, Goede, Valentin, Fischer, Kirsten, von Bergwelt-Baildon, Michael, Eichhorst, Barbara, Hallek, Michael, and Theurich, Sebastian
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- 2020
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9. A model for predicting effect of treatment on progression-free survival using MRD as a surrogate end point in CLL
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Dimier, Natalie, Delmar, Paul, Ward, Carol, Morariu-Zamfir, Rodica, Fingerle-Rowson, Günter, Bahlo, Jasmin, Fischer, Kirsten, Eichhorst, Barbara, Goede, Valentin, van Dongen, Jacques J.M., Ritgen, Matthias, Böttcher, Sebastian, Langerak, Anton W., Kneba, Michael, and Hallek, Michael
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- 2018
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10. Short telomeres are associated with inferior outcome, genomic complexity, and clonal evolution in chronic lymphocytic leukemia
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Jebaraj, Billy Michael Chelliah, Tausch, Eugen, Landau, Dan A., Bahlo, Jasmin, Robrecht, Sandra, Taylor-Weiner, Amaro N., Bloehdorn, Johannes, Scheffold, Annika, Mertens, Daniel, Böttcher, Sebastian, Kneba, Michael, Jäger, Ulrich, Zenz, Thorsten, Wenger, Michael K., Fingerle-Rowson, Guenter, Wendtner, Clemens, Fink, Anna-Maria, Wu, Catherine J., Eichhorst, Barbara, Fischer, Kirsten, Hallek, Michael, Döhner, Hartmut, and Stilgenbauer, Stephan
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- 2019
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11. Lenalidomide maintenance after first-line therapy for high-risk chronic lymphocytic leukaemia (CLLM1): final results from a randomised, double-blind, phase 3 study
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Fink, Anna Maria, Bahlo, Jasmin, Robrecht, Sandra, Al-Sawaf, Othman, Aldaoud, Ali, Hebart, Holger, Jentsch-Ullrich, Kathleen, Dörfel, Steffen, Fischer, Kirsten, Wendtner, Clemens-Martin, Nösslinger, Thomas, Ghia, Paolo, Bosch, Francesc, Kater, Arnon P, Döhner, Hartmut, Kneba, Michael, Kreuzer, Karl-Anton, Tausch, Eugen, Stilgenbauer, Stephan, Ritgen, Matthias, Böttcher, Sebastian, Eichhorst, Barbara, and Hallek, Michael
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- 2017
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12. MRD Detection in B-Cell Non-Hodgkin Lymphomas Using Ig Gene Rearrangements and Chromosomal Translocations as Targets for Real-Time Quantitative PCR
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Pott, Christiane, primary, Brüggemann, Monika, additional, Ritgen, Matthias, additional, van der Velden, Vincent H. J., additional, van Dongen, Jacques J. M., additional, and Kneba, Michael, additional
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- 2019
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13. Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
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Saussele, Susanne, Hehlmann, Rüdiger, Fabarius, Alice, Jeromin, Sabine, Proetel, Ulrike, Rinaldetti, Sebastien, Kohlbrenner, Katharina, Einsele, Hermann, Falge, Christiane, Kanz, Lothar, Neubauer, Andreas, Kneba, Michael, Stegelmann, Frank, Pfreundschuh, Michael, Waller, Cornelius F., Oppliger Leibundgut, Elisabeth, Heim, Dominik, Krause, Stefan W., Hofmann, Wolf-Karsten, Hasford, Joerg, Pfirrmann, Markus, Müller, Martin C., Hochhaus, Andreas, and Lauseker, Michael
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- 2018
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14. Supplementary Tables from Cellular Uptake of Imatinib into Leukemic Cells Is Independent of Human Organic Cation Transporter 1 (OCT1)
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Nies, Anne T., primary, Schaeffeler, Elke, primary, van der Kuip, Heiko, primary, Cascorbi, Ingolf, primary, Bruhn, Oliver, primary, Kneba, Michael, primary, Pott, Christiane, primary, Hofmann, Ute, primary, Volk, Christopher, primary, Hu, Shuiying, primary, Baker, Sharyn D., primary, Sparreboom, Alex, primary, Ruth, Peter, primary, Koepsell, Hermann, primary, and Schwab, Matthias, primary
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- 2023
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15. Supplementary Figures from Cellular Uptake of Imatinib into Leukemic Cells Is Independent of Human Organic Cation Transporter 1 (OCT1)
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Nies, Anne T., primary, Schaeffeler, Elke, primary, van der Kuip, Heiko, primary, Cascorbi, Ingolf, primary, Bruhn, Oliver, primary, Kneba, Michael, primary, Pott, Christiane, primary, Hofmann, Ute, primary, Volk, Christopher, primary, Hu, Shuiying, primary, Baker, Sharyn D., primary, Sparreboom, Alex, primary, Ruth, Peter, primary, Koepsell, Hermann, primary, and Schwab, Matthias, primary
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- 2023
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16. Data from Cellular Uptake of Imatinib into Leukemic Cells Is Independent of Human Organic Cation Transporter 1 (OCT1)
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Nies, Anne T., primary, Schaeffeler, Elke, primary, van der Kuip, Heiko, primary, Cascorbi, Ingolf, primary, Bruhn, Oliver, primary, Kneba, Michael, primary, Pott, Christiane, primary, Hofmann, Ute, primary, Volk, Christopher, primary, Hu, Shuiying, primary, Baker, Sharyn D., primary, Sparreboom, Alex, primary, Ruth, Peter, primary, Koepsell, Hermann, primary, and Schwab, Matthias, primary
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- 2023
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17. Supplementary Methods from Cellular Uptake of Imatinib into Leukemic Cells Is Independent of Human Organic Cation Transporter 1 (OCT1)
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Nies, Anne T., primary, Schaeffeler, Elke, primary, van der Kuip, Heiko, primary, Cascorbi, Ingolf, primary, Bruhn, Oliver, primary, Kneba, Michael, primary, Pott, Christiane, primary, Hofmann, Ute, primary, Volk, Christopher, primary, Hu, Shuiying, primary, Baker, Sharyn D., primary, Sparreboom, Alex, primary, Ruth, Peter, primary, Koepsell, Hermann, primary, and Schwab, Matthias, primary
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- 2023
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18. Patient specific real-time PCR in precision medicine – Validation of IG/TR based MRD assessment in lymphoid leukemia
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Schilhabel, Anke, Szczepanowski, Monika, van Gastel-Mol, Ellen J., Schillalies, Janina, Ray, Jill, Kim, Doris, Nováková, Michaela, Dombrink, Isabel, van der Velden, Vincent H.J., Boettcher, Sebastian, Brüggemann, Monika, Kneba, Michael, van Dongen, Jacques J.M., Langerak, Anton W., Ritgen, Matthias, Schilhabel, Anke, Szczepanowski, Monika, van Gastel-Mol, Ellen J., Schillalies, Janina, Ray, Jill, Kim, Doris, Nováková, Michaela, Dombrink, Isabel, van der Velden, Vincent H.J., Boettcher, Sebastian, Brüggemann, Monika, Kneba, Michael, van Dongen, Jacques J.M., Langerak, Anton W., and Ritgen, Matthias
- Abstract
Detection of patient- and tumor-specific clonally rearranged immune receptor genes using real-time quantitative (RQ)-PCR is an accepted method in the field of precision medicine for hematologic malignancies. As individual primers are needed for each patient and leukemic clone, establishing performance specifications for the method faces unique challenges. Results for series of diagnostic assays for CLL and ALL patients demonstrate that the analytic performance of the method is not dependent on patients’ disease characteristics. The calibration range is linear between 10-1 and 10-5 for 90% of all assays. The detection limit of the current standardized approach is between 1.8 and 4.8 cells among 100,000 leukocytes. RQ-PCR has about 90% overall agreement to flow cytometry and next generation sequencing as orthogonal methods. Accuracy and precision across different labs, and above and below the clinically applied cutoffs for minimal/measurable residual disease (MRD) demonstrate the robustness of the technique. The here reported comprehensive, IVD-guided analytical validation provides evidence that the personalized diagnostic methodology generates robust, reproducible and specific MRD data when standardized protocols for data generation and evaluation are used. Our approach may also serve as a guiding example of how to accomplish analytical validation of personalized in-house diagnostics under the European IVD Regulation.
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- 2023
19. Final analysis of the CLL2-GIVe trial:obinutuzumab, ibrutinib, and venetoclax for untreated CLL with del(17p)/TP53mut
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Huber, Henriette, Tausch, Eugen, Schneider, Christof, Edenhofer, Simone, von Tresckow, Julia, Robrecht, Sandra, Giza, Adam, Zhang, Can, Fürstenau, Moritz, Dreger, Peter, Ritgen, Matthias, Illmer, Thomas, Illert, Anna Lena, Dürig, Jan, Böttcher, Sebastian, Niemann, Carsten U., Kneba, Michael, Al-Sawaf, Othman, Kreuzer, Karl Anton, Fink, Anna Maria, Fischer, Kirsten, Döhner, Hartmut, Hallek, Michael, Eichhorst, Barbara, Stilgenbauer, Stephan, Huber, Henriette, Tausch, Eugen, Schneider, Christof, Edenhofer, Simone, von Tresckow, Julia, Robrecht, Sandra, Giza, Adam, Zhang, Can, Fürstenau, Moritz, Dreger, Peter, Ritgen, Matthias, Illmer, Thomas, Illert, Anna Lena, Dürig, Jan, Böttcher, Sebastian, Niemann, Carsten U., Kneba, Michael, Al-Sawaf, Othman, Kreuzer, Karl Anton, Fink, Anna Maria, Fischer, Kirsten, Döhner, Hartmut, Hallek, Michael, Eichhorst, Barbara, and Stilgenbauer, Stephan
- Abstract
The final analysis of the open-label, multicenter phase 2 CLL2-GIVe trial shows response and tolerability of the triple combination of obinutuzumab, ibrutinib, and venetoclax (GIVe regimen) in 41 previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) with del(17p) and/or TP53 mutation. Induction consisted of 6 cycles of GIVe; venetoclax and ibrutinib were continued up to cycle 12 as consolidation. Ibrutinib was given until cycle 15 or up to cycle 36 in patients not achieving a complete response and with detectable minimal residual disease. The primary end point was the complete remission rate at cycle 15, which was achieved at 58.5% (95% CI, 42.1-73.7; P < .001). The last patient reached the end of the study in January 2022. After a median observation time of 38.4 months (range, 3.7-44.9), the 36-month progression-free survival was 79.9%, and the 36-month overall survival was 92.6%. Only 6 patients continued ibrutinib maintenance. Adverse events of concern were neutropenia (48.8%, grade ≥3) and infections (19.5%, grade ≥3). Cardiovascular toxicity grade 3 occurred as atrial fibrillation at a rate of 2.4% between cycles 1 and 12, as well as hypertension (4.9%) between cycles 1 and 6. The incidence of adverse events of any grade and grade ≥3 was highest during induction and decreased over time. Progressive disease was observed in 7 patients between cycles 27 and 42. In conclusion, the CLL2-GIVe regimen is a promising fixed-duration, first-line treatment for patients with high-risk CLL with a manageable safety profile., The final analysis of the open-label, multicenter phase 2 CLL2-GIVe trial shows response and tolerability of the triple combination of obinutuzumab, ibrutinib, and venetoclax (GIVe regimen) in 41 previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) with del(17p) and/or TP53 mutation. Induction consisted of 6 cycles of GIVe; venetoclax and ibrutinib were continued up to cycle 12 as consolidation. Ibrutinib was given until cycle 15 or up to cycle 36 in patients not achieving a complete response and with detectable minimal residual disease. The primary end point was the complete remission rate at cycle 15, which was achieved at 58.5% (95% CI, 42.1-73.7; P <.001). The last patient reached the end of the study in January 2022. After a median observation time of 38.4 months (range, 3.7-44.9), the 36-month progression-free survival was 79.9%, and the 36-month overall survival was 92.6%. Only 6 patients continued ibrutinib maintenance. Adverse events of concern were neutropenia (48.8%, grade ≥3) and infections (19.5%, grade ≥3). Cardiovascular toxicity grade 3 occurred as atrial fibrillation at a rate of 2.4% between cycles 1 and 12, as well as hypertension (4.9%) between cycles 1 and 6. The incidence of adverse events of any grade and grade ≥3 was highest during induction and decreased over time. Progressive disease was observed in 7 patients between cycles 27 and 42. In conclusion, the CLL2-GIVe regimen is a promising fixed-duration, first-line treatment for patients with high-risk CLL with a manageable safety profile.
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- 2023
20. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network
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Hermine, Olivier, Hoster, Eva, Walewski, Jan, Bosly, André, Stilgenbauer, Stephan, Thieblemont, Catherine, Szymczyk, Michal, Bouabdallah, Reda, Kneba, Michael, Hallek, Michael, Salles, Gilles, Feugier, Pierre, Ribrag, Vincent, Birkmann, Josef, Forstpointner, Roswitha, Haioun, Corinne, Hänel, Mathias, Casasnovas, René Olivier, Finke, Jürgen, Peter, Norma, Bouabdallah, Kamal, Sebban, Catherine, Fischer, Thomas, Dührsen, Ulrich, Metzner, Bernd, Maschmeyer, Georg, Kanz, Lothar, Schmidt, Christian, Delarue, Richard, Brousse, Nicole, Klapper, Wolfram, Macintyre, Elizabeth, Delfau-Larue, Marie-Hélène, Pott, Christiane, Hiddemann, Wolfgang, Unterhalt, Michael, and Dreyling, Martin
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- 2016
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21. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial
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Eichhorst, Barbara, Fink, Anna-Maria, Bahlo, Jasmin, Busch, Raymonde, Kovacs, Gabor, Maurer, Christian, Lange, Elisabeth, Köppler, Hubert, Kiehl, Michael, Sökler, Martin, Schlag, Rudolf, Vehling-Kaiser, Ursula, Köchling, Georg, Plöger, Christoph, Gregor, Michael, Plesner, Torben, Trneny, Marek, Fischer, Kirsten, Döhner, Harmut, Kneba, Michael, Wendtner, Clemens-Martin, Klapper, Wolfram, Kreuzer, Karl-Anton, Stilgenbauer, Stephan, Böttcher, Sebastian, and Hallek, Michael
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- 2016
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22. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial
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Fischer, Kirsten, Bahlo, Jasmin, Fink, Anna Maria, Goede, Valentin, Herling, Carmen Diana, Cramer, Paula, Langerbeins, Petra, von Tresckow, Julia, Engelke, Anja, Maurer, Christian, Kovacs, Gabor, Herling, Marco, Tausch, Eugen, Kreuzer, Karl-Anton, Eichhorst, Barbara, Böttcher, Sebastian, Seymour, John F., Ghia, Paolo, Marlton, Paula, Kneba, Michael, Wendtner, Clemens-Martin, Döhner, Hartmut, Stilgenbauer, Stephan, and Hallek, Michael
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- 2016
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23. Patient specific real-time PCR in precision medicine – Validation of IG/TR based MRD assessment in lymphoid leukemia
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Schilhabel, Anke, primary, Szczepanowski, Monika, additional, van Gastel-Mol, Ellen J., additional, Schillalies, Janina, additional, Ray, Jill, additional, Kim, Doris, additional, Nováková, Michaela, additional, Dombrink, Isabel, additional, van der Velden, Vincent H. J., additional, Boettcher, Sebastian, additional, Brüggemann, Monika, additional, Kneba, Michael, additional, van Dongen, Jacques J. M., additional, Langerak, Anton W., additional, and Ritgen, Matthias, additional
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- 2023
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24. Effects on Survival of Non-Myeloablative Chemoimmunotherapy Compared to High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation (HDC-ASCT) As Consolidation Therapy in Patients with Primary CNS Lymphoma - Results of an International Randomized Phase III Trial (MATRix/IELSG43)
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Illerhaus, Gerald, primary, Ferreri, Andrés J.M., additional, Binder, Mascha, additional, Borchmann, Peter, additional, Hasenkamp, Justin, additional, Stilgenbauer, Stephan, additional, Roeth, Alexander, additional, Weber, Thomas, additional, Egerer, Gerlinde, additional, Ernst, Thomas, additional, Hertenstein, Bernd, additional, Lenz, Georg, additional, Kobbe, Guido, additional, Brunnberg, Uta, additional, Schmidt, Christian, additional, Kneba, Michael, additional, Dreyling, Martin, additional, Möhle, Robert, additional, Panse, Jens, additional, Heinicke, Thomas, additional, Schroll, Sebastian, additional, Larsen, Thomas S., additional, Salwender, Hans, additional, Naumann, Ralph, additional, Hess, Georg, additional, Thurner, Lorenz, additional, Pukrop, Tobias, additional, Keller, Ulrich, additional, Blystadt, Anne Kirsti, additional, Kroschinsky, Frank P., additional, Re, Francesca, additional, Pulczynski, Elisa, additional, Orsucci, Lorella, additional, Pospiech, Lisa, additional, Deckert, Martina, additional, Ponzoni, Maurilio, additional, Wendler, Julia, additional, Valk, Elke, additional, Calimeri, Teresa, additional, Kasenda, Benjamin, additional, Trepel, Martin, additional, Fricker, Heidi, additional, von Gottberg, Philipp, additional, Burger, Elvira, additional, Ihorst, Gabriele, additional, Grishina, Olga, additional, Hader, Claudia, additional, Zucca, Emanuele, additional, Finke, Jürgen, additional, and Schorb, Elisabeth, additional
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- 2022
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25. Final Analysis of the Prospective Multicenter CLL2-Give Trial of Obinutuzumab (GA101, G), Ibrutinib (I), and Venetoclax (Ve) in Untreated Patients with CLL with 17p Deletion/TP53 Mutation
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Huber, Henriette, primary, Tausch, Eugen, additional, Schneider, Christof, additional, Edenhofer, Simone, additional, Von Tresckow, Julia, additional, Robrecht, Sandra, additional, Giza, Adam, additional, Zhang, Can, additional, Furstenau, Moritz, additional, Dreger, Peter, additional, Ritgen, Matthias, additional, Illmer, Thomas, additional, Illert, Anna Lena, additional, Dürig, Jan, additional, Böttcher, Sebastian, additional, Niemann, Carsten Utoft, additional, Kneba, Michael, additional, Fink, Anna-Maria, additional, Fischer, Kirsten, additional, Döhner, Hartmut, additional, Hallek, Michael, additional, Eichhorst, Barbara, additional, and Stilgenbauer, Stephan, additional
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- 2022
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26. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns
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Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, 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Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
- Subjects
Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.
- Published
- 2023
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27. Combined burden and functional impact tests for cancer driver discovery using DriverPower
- Author
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- Subjects
Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
- Published
- 2023
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28. Integrative pathway enrichment analysis of multivariate omics data
- Author
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Vijver, Marc J, and Veer, L van’t
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
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- 2023
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29. Pathway and network analysis of more than 2500 whole cancer genomes
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
- Published
- 2023
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30. Divergent mutational processes distinguish hypoxic and normoxic tumours
- Author
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Bhandari, Vinayak, Li, Constance H, Bristow, Robert G, Boutros, Paul C, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, 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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
- Published
- 2023
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31. Genomic footprints of activated telomere maintenance mechanisms in cancer
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Catherine D, Muiños, Ferran, Mularoni, Loris, Mungall, Andrew J, Mungall, Karen, Musgrove, Elizabeth A, Mustonen, Ville, Mutch, David, Muyas, Francesc, Muzny, Donna M, Muñoz, Alfonso, Myers, Jerome, Myklebost, Ola, Möller, Peter, Nagae, Genta, Nagrial, Adnan M, Nahal-Bose, Hardeep K, Nakagama, Hitoshi, Nakamura, Hiromi, Nakamura, Toru, Nakano, Kaoru, Nandi, Tannistha, Nangalia, Jyoti, Nastic, Mia, Navarro, Arcadi, Neal, David E, Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J, Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, G Petur, Nielsen, Morten Muhlig, Nik-Zainal, Serena, Noble, Michael S, Nones, Katia, Northcott, Paul A, Notta, Faiyaz, O’Connor, Brian D, O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A, Ojesina, Akinyemi I, Ojima, Hidenori, Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, Prinz, Manuel, Pritchard, Antonia L, Prokopec, Stephenie D, Provenzano, Elena, Puente, Xose S, Puig, Sonia, Pulido-Tamayo, Sergio, Pupo, Gulietta M, Purdie, Colin A, Quinn, Michael C, Rabionet, Raquel, Rader, Janet S, Radlwimmer, Bernhard, Radovic, Petar, Raeder, Benjamin, Raine, Keiran M, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Raphael, Benjamin J, Rathmell, W Kimryn, Rausch, Tobias, Reifenberger, Guido, Reimand, Jüri, Reis-Filho, Jorge, Reuter, Victor, Reyes-Salazar, Iker, Reyna, Matthew A, Reynolds, Sheila M, Rheinbay, Esther, Riazalhosseini, Yasser, Richardson, Andrea L, Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Roach, Jeffrey, Roberts, Lewis R, Robertson, A Gordon, Robertson, Alan J, Rodriguez, Javier Bartolomé, Rodríguez-González, F Germán, Roehrl, Michael HA, Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C, Rosenwald, Andreas, Rowe, Edward W, Royo, Romina, Rozen, Steven G, Rubanova, Yulia, Rubin, Mark A, Rubio-Perez, Carlota, Rudneva, Vasilisa A, Rusev, Borislav C, Ruzzenente, Andrea, Rätsch, Gunnar, Sabarinathan, Radhakrishnan, Sabelnykova, Veronica Y, Sadeghi, Sara, Sahinalp, S Cenk, Saini, Natalie, Saito-Adachi, Mihoko, Saksena, Gordon, Salcedo, Adriana, Salgado, Roberto, Salichos, Leonidas, Sallari, Richard, Saller, Charles, Salvia, Roberto, Sam, Michelle, Samra, Jaswinder S, Sanchez-Vega, Francisco, Sander, Chris, Sanders, Grant, Sarin, Rajiv, Sarrafi, Iman, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn PM, Scardoni, Maria, Scarlett, Christopher J, Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E, Schilhabel, Markus B, Schlomm, Thorsten, Schmidt, Heather K, Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schwarz, Roland F, Scolyer, Richard A, Scott, David, Seethala, Raja, Segre, Ayellet V, Selander, Iris, Semple, Colin A, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shapira, Ofer, Shelton, Troy, Shen, Ciyue, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stein, Lincoln D, Stenhouse, Alasdair, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tiao, Grace, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, Tsunoda, Tatsuhiko, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Umer, Husen M, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Uusküla-Reimand, Liis, Valencia, Alfonso, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vazquez, Miguel, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Verbeke, Lieven PC, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wang, Jian, Wang, Jiayin, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warrell, Jonathan, Warren, Anne Y, Waszak, Sebastian M, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Wheeler, David A, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Derek W, Wright, Mark H, Wu, Chin-Lee, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Junjun, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
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- 2023
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32. Is Next-Generation Sequencing the way to go for Residual Disease Monitoring in Acute Lymphoblastic Leukemia?
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Kotrova, Michaela, Trka, Jan, Kneba, Michael, and Brüggemann, Monika
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- 2017
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33. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial
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Hoelzer, Dieter, Walewski, Jan, Döhner, Hartmut, Viardot, Andreas, Hiddemann, Wolfgang, Spiekermann, Karsten, Serve, Hubert, Dührsen, Ulrich, Hüttmann, Andreas, Thiel, Eckhard, Dengler, Jolanta, Kneba, Michael, Schaich, Markus, Schmidt-Wolf, IngoG. H., Beck, Joachim, Hertenstein, Bernd, Reichle, Albrecht, Domanska-Czyz, Katarzyna, Fietkau, Rainer, Horst, Heinz-August, Rieder, Harald, Schwartz, Stefan, Burmeister, Thomas, and Gökbuget, Nicola
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- 2014
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34. CD20 Expression as a Possible Novel Prognostic Marker in CLL: Application of EuroFlow Standardization Technique and Normalization Procedures in Flow Cytometric Expression Analysis
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Schilhabel, Anke, primary, Walter, Peter Jonas, additional, Cramer, Paula, additional, von Tresckow, Julia, additional, Kohlscheen, Saskia, additional, Szczepanowski, Monika, additional, Laqua, Anna, additional, Fischer, Kirsten, additional, Eichhorst, Barbara, additional, Böttcher, Sebastian, additional, Schneider, Christof, additional, Tausch, Eugen, additional, Brüggemann, Monika, additional, Kneba, Michael, additional, Hallek, Michael, additional, and Ritgen, Matthias, additional
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- 2022
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35. Treatment of Adult ALL According to Protocols of the German Multicenter Study Group for Adult ALL (GMALL)
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German Multicenter Study Group for Adult ALL (GMALL), Gökbuget, Nicola, Arnold, Renate, Böhme, Angelika, Fietkau, Rainer, Freund, Matthias, Ganser, Arnold, Kneba, Michael, Lipp, Thomas, Ludwig, Wolf-Dieter, Maschmeyer, Georg, Messerer, Dorle, Rieder, Harald, Thiel, Eckhard, Hoelzer, Dieter, Estey, E. H., Faderl, S. H., and Kantarjian, H. M.
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- 2008
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36. Allogeneic Stem Cell Transplantation with BEAM and Alemtuzumab Conditioning Immediately after Remission Induction Has Curative Potential in Advanced T-Cell Non-Hodgkin's Lymphoma
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Czajczynska, Anna, Günther, Andreas, Repp, Roland, Humpe, Andreas, Schub, Natalie, Raff, Thorsten, Nickelsen, Maike, Schrauder, André, Schrappe, Martin, Kneba, Michael, and Gramatzki, Martin
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- 2013
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37. The genomic and transcriptional landscape of primary central nervous system lymphoma
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Radke, Josefine, Ishaque, Naveed, Hostench, Xavier Pastor, Richter, Julia, Rosenstiel, Philip, Rosenwald, Andreas, Schilhabel, Markus, Schreiber, Stefanie, Vater, Inga, Wagener, Rabea, Siebert, Reiner, Bernhart, Stephan H, Binder, Hans, Borgoni, Simone, Doose, Gero, Eils, Roland, Hoffmann, Steve, Hopp, Lydia, Kleinheinz, Kortine, Kretzmer, Helene, Kreuz, Markus, Korbel, Jan, Langenberger, David, Loeffler, Markus, Juraeva, Dilafruz, Rosolowski, Maciej, Stadler, Peter F, Sungalee, Stephanie, Pritsch, Fabienne, Paramasivam, Nagarajan, Balasubramanian, Gnana Prakash, Schlesner, Matthias, Sahay, Shashwat, Weniger, Marc, Pehl, Debora, Koll, Randi, Radbruch, Helena, Osterloh, Anja, Korfel, Agnieszka, Misch, Martin, Onken, Julia, Faust, Katharina, Vajkoczy, Peter, Moskopp, Dag, Wang, Yawen, Jödicke, Andreas, Gu, Zuguang, Trümper, Lorenz, Anagnostopoulos, Ioannis, Lenze, Dido, Küppers, Ralf, Hummel, Michael, Schmitt, Clemens A, Wiestler, Otmar D, Wolf, Stephan, Unterberg, Andreas, Schumann, Elisa, Herold-Mende, Christel, Brors, Benedikt, Consortium, ICGC MMML-Seq, Wiemann, Stefan, Heppner, Frank, Wagner, Susanne, Haake, Andrea, Sieverling, Lina, Richter, Gesine, Lawerenz, Chris, Eils, Jürgen, Kerssemakers, Jules, Jaeger-Schmidt, Christina, Scholz, Ingrid, Bergmann, Anke K, Borst, Christoph, Braulke, Friederike, Uhrig, Sebastian, Burkhardt, Birgit, Claviez, Alexander, Dreyling, Martin, Eberth, Sonja, Einsele, Hermann, Frickhofen, Norbert, Haas, Siegfried, Hansmann, Martin-Leo, Karsch, Dennis, Klepl, Nicole, Hübschmann, Daniel, Kneba, Michael, Lisfeld, Jasmin, Mantovani-Löffler, Luisa, Rohde, Marius, Ott, German, Stadler, Christina, Staib, Peter, Stilgenbauer, Stephan, Zenz, Thorsten, Toprak, Umut H, Kube, Dieter, Klapper, Wolfram, Kostezka, Ulrike, Möller, Peter, Szczepanowski, Monika, Ammerpohl, Ole, Aukema, Sietse M, López, Cristina, Binder, Vera, Borkhardt, Arndt, Hoell, Jessica I, Leich, Ellen, Lichter, Peter, Nagel, Inga, Pischimariov, Jordan, Radlwimmer, Bernhard, Weniger, Marc (Beitragende*r), and Küppers, Ralf (Beitragende*r)
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Central Nervous System ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Cancer Research ,Multidisciplinary ,genetics [Central Nervous System Neoplasms] ,Medizin ,General Physics and Astronomy ,pathology [Central Nervous System Neoplasms] ,Genomics ,General Chemistry ,metabolism [Lymphoma, Large B-Cell, Diffuse] ,General Biochemistry, Genetics and Molecular Biology ,Central Nervous System Neoplasms ,hemic and lymphatic diseases ,metabolism [Central Nervous System] ,Humans ,ddc:610 ,Lymphoma, Large B-Cell, Diffuse ,ddc:500 - Abstract
Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations.
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- 2022
38. Impact of unbalanced minor route versus major route karyotypes at diagnosis on prognosis of CML
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Fabarius, Alice, Kalmanti, Lida, Dietz, Christian T., Lauseker, Michael, Rinaldetti, Sébastien, Haferlach, Claudia, Göhring, Gudrun, Schlegelberger, Brigitte, Jotterand, Martine, Hanfstein, Benjamin, Seifarth, Wolfgang, Hänel, Mathias, Köhne, Claus-Henning, Lindemann, Hans W., Berdel, Wolfgang E., Staib, Peter, Müller, Martin C., Proetel, Ulrike, Balleisen, Leopold, Goebeler, Maria-Elisabeth, Dengler, Jolanta, Falge, Christiane, Kanz, Lothar, Burchert, Andreas, Kneba, Michael, Stegelmann, Frank, Pfreundschuh, Michael, Waller, Cornelius F., Spiekermann, Karsten, Brümmendorf, Tim H., Edinger, Matthias, Hofmann, Wolf-Karsten, Pfirrmann, Markus, Hasford, Joerg, Krause, Stefan, Hochhaus, Andreas, Saußele, Susanne, Hehlmann, Rüdiger, and for the SAKK and the German CML Study Group
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- 2015
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39. Akute lymphatische Leukämie der Erwachsenen
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Rieder, Harald, Kneba, Michael, Ganten, Detlev, editor, Ruckpaul, Klaus, editor, Schlegelberger, Brigitte, editor, and Fonatsch, Christa, editor
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- 2003
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40. Effects on Survival of Non-Myeloablative Chemoimmunotherapy Compared to High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation (HDC-ASCT) As Consolidation Therapy in Patients with Primary CNS Lymphoma - Results of an International Randomized Phase III Trial (MATRix/IELSG43)
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Illerhaus, Gerald, Farreri, Andres J. M., Binder, Mascha, Borchmann, Peter, Hasenkamp, Justin, Stilgenbauer, Stephan, Roeth, Alexander, Webern, Thomas, Egerer, Gerlinde, Ernst, Thomas, Hertenstein, Bernd, Lenz, Georg, Kobbe, Guido, Brunnberg, Uta, Schmidt, Christian, Kneba, Michael, Dreyling, Martin, Moehle, Robert, Panse, Jens, Heinicke, Thomas, Schroll, Sebastian, Larsen, Thomas S., Salwender, Hans, Naumann, Ralph, Hess, Georg, Thurner, Lorenz, Pukrop, Tobias, Keller, Ulrich, Blystadt, Anne Kirsti, Kroschinsky, Frank P., Re, Francesca, Pulczynski, Elisa, Orsucci, Lorella, Pospiech, Lisa, Deckert, Martina, Ponzoni, Maurilio, Wendler, Julia, Valk, Elke, Calimeri, Teresa, Kasenda, Benjamin, Trepel, Martin, Fricker, Heidi, von Gottberg, Philipp, Burger, Elvira, Ihorst, Gabriele, Grishina, Olga, Hader, Claudia, Zucca, Emanuele, Finke, Juergen, Schorb, Elisabeth, Illerhaus, Gerald, Farreri, Andres J. M., Binder, Mascha, Borchmann, Peter, Hasenkamp, Justin, Stilgenbauer, Stephan, Roeth, Alexander, Webern, Thomas, Egerer, Gerlinde, Ernst, Thomas, Hertenstein, Bernd, Lenz, Georg, Kobbe, Guido, Brunnberg, Uta, Schmidt, Christian, Kneba, Michael, Dreyling, Martin, Moehle, Robert, Panse, Jens, Heinicke, Thomas, Schroll, Sebastian, Larsen, Thomas S., Salwender, Hans, Naumann, Ralph, Hess, Georg, Thurner, Lorenz, Pukrop, Tobias, Keller, Ulrich, Blystadt, Anne Kirsti, Kroschinsky, Frank P., Re, Francesca, Pulczynski, Elisa, Orsucci, Lorella, Pospiech, Lisa, Deckert, Martina, Ponzoni, Maurilio, Wendler, Julia, Valk, Elke, Calimeri, Teresa, Kasenda, Benjamin, Trepel, Martin, Fricker, Heidi, von Gottberg, Philipp, Burger, Elvira, Ihorst, Gabriele, Grishina, Olga, Hader, Claudia, Zucca, Emanuele, Finke, Juergen, and Schorb, Elisabeth
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- 2022
41. Final Analysis of the Prospective Multicenter CLL2-Give Trial of Obinutuzumab (GA101, G), Ibrutinib (I), and Venetoclax (Ve) in Untreated Patients with CLL with 17p Deletion/TP53 Mutation
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Huber, Henriette, Tausch, Eugen, Schneider, Christof, Edenhofer, Simone, Von Tresckow, Julia, Robrecht, Sandra, Giza, Adam, Zhang, Can, Furstenau, Moritz, Dreger, Peter, Ritgen, Matthias, Illmer, Thomas, Illert, Anna Lena, Duerig, Jan, Boettcher, Sebastian, Niemann, Carsten Utoft, Kneba, Michael, Fink, Anna-Maria, Fischer, Kirsten, Doehner, Hartmut, Hallek, Michael, Eichhorst, Barbara, Stilgenbauer, Stephan, Huber, Henriette, Tausch, Eugen, Schneider, Christof, Edenhofer, Simone, Von Tresckow, Julia, Robrecht, Sandra, Giza, Adam, Zhang, Can, Furstenau, Moritz, Dreger, Peter, Ritgen, Matthias, Illmer, Thomas, Illert, Anna Lena, Duerig, Jan, Boettcher, Sebastian, Niemann, Carsten Utoft, Kneba, Michael, Fink, Anna-Maria, Fischer, Kirsten, Doehner, Hartmut, Hallek, Michael, Eichhorst, Barbara, and Stilgenbauer, Stephan
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- 2022
42. CD20 Expression as a Possible Novel Prognostic Marker in CLL: Application of EuroFlow Standardization Technique and Normalization Procedures in Flow Cytometric Expression Analysis
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Schilhabel, Anke, Walter, Peter Jonas, Cramer, Paula, von Tresckow, Julia, Kohlscheen, Saskia, Szczepanowski, Monika, Laqua, Anna, Fischer, Kirsten, Eichhorst, Barbara, Boettcher, Sebastian, Schneider, Christof, Tausch, Eugen, Brueggemann, Monika, Kneba, Michael, Hallek, Michael, Ritgen, Matthias, Schilhabel, Anke, Walter, Peter Jonas, Cramer, Paula, von Tresckow, Julia, Kohlscheen, Saskia, Szczepanowski, Monika, Laqua, Anna, Fischer, Kirsten, Eichhorst, Barbara, Boettcher, Sebastian, Schneider, Christof, Tausch, Eugen, Brueggemann, Monika, Kneba, Michael, Hallek, Michael, and Ritgen, Matthias
- Abstract
Simple Summary Up to 50% of patients with chronic lymphocytic leukemia relapse within four years after anti-CD20-directed treatment with a need for a subsequent treatment, which can potentially include anti-CD20 agents again. To retrospectively study the influence of CD20 expression in CLL patients receiving anti-CD20 directed therapy on therapy response, we designed and evaluated a bead-based normalization approach for the analysis of CD20 expression levels to reduce variation of flow cytometric measurements due to technical issues. Normalization significantly reduced the variability of median fluorescence intensities of fluorochrome-conjugated beads without artificially rendering the instruments' performances, and longitudinal biological variations of marker expression based on MFI values could be robustly assessed. In a cross-trial comparison, strong MRD response correlated with the CD20 expression level before therapy started in patients receiving Ofatumumab, but not in patients receiving Obinutuzumab. Background: CD20 expression is a controversial issue regarding response prediction to anti-CD20 therapy in chronic lymphocytic leukemia (CLL). Methods: Median fluorescence intensities (MFIs) of standard fluorescence beads from the daily calibration of flow cytometers according to EuroFlow protocols were used to establish a normalization approach to study CD20 expression on CLL cells. CD20 MFI was retrospectively assessed prior to and during treatment from flow cytometric measurements of peripheral blood in patients with different depths of molecular response in the four phase-II CLL2-BXX trials (BIG; BAG; BIO; BCG; N = 194) administering either Obinutuzumab or Ofatumumab in combination with targeted agents. Results: No significant difference was observed between the normalized and measured MFIs of CD19 and CD20 on CLL cells. During treatment, CD20 expression levels on CLL cells did not significantly differ between the four investigated different treatment schemes
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- 2022
43. Impact of telomere length on the outcome of allogeneic stem cell transplantation for poor‐risk chronic lymphocytic leukaemia: results from the GCLLSG CLL3X trial
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Scheffold, Annika, Jebaraj, Billy Michael Chelliah, Jaramillo, Sonia, Tausch, Eugen, Steinbrecher, Daniela, Hahn, Michael, Böttcher, Sebastian, Ritgen, Matthias, Bunjes, Donald, Zeis, Matthias, Stadler, Michael, Uharek, Lutz, Scheid, Christoph, Hegenbart, Ute, Hallek, Michael, Kneba, Michael, Schmitz, Norbert, Döhner, Hartmut, Dreger, Peter, and Stilgenbauer, Stephan
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- 2017
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44. Alemtuzumab consolidation in chronic lymphocytic leukaemia: a phase I/II multicentre trial
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Al‐Sawaf, Othman, Fischer, Kirsten, Herling, Carmen D., Ritgen, Matthias, Böttcher, Sebastian, Bahlo, Jasmin, Elter, Thomas, Stilgenbauer, Stephan, Eichhorst, Barbara F., Busch, Raymonde, Elberskirch, Ute, Abenhardt, Wolfgang, Kneba, Michael, Hallek, Michael, and Wendtner, Clemens‐Martin
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- 2017
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45. Has MRD monitoring superseded other prognostic factors in adult ALL?
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Brüggemann, Monika, Raff, Thorsten, and Kneba, Michael
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- 2012
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46. Mutations driving CLL and their evolution in progression and relapse
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Landau, Dan A., Tausch, Eugen, Taylor-Weiner, Amaro N., Stewart, Chip, Reiter, Johannes G., Bahlo, Jasmin, Kluth, Sandra, Bozic, Ivana, Lawrence, Mike, Bottcher, Sebastian, Carter, Scott L., Cibulskis, Kristian, Mertens, Daniel, Sougnez, Carrie L., Rosenberg, Mara, Hess, Julian M., Edelmann, Jennifer, Kless, Sabrina, Kneba, Michael, Ritgen, Matthias, Fink, Anna, Fischer, Kirsten, Gabriel, Stacey, Lander, Eric S., Nowak, Martin A., Dohner, Hartmut, Hallek, Michael, Neuberg, Donna, Getz, Gad, Stilgenbauer, Stephan, and Wu, Catherine J.
- Subjects
Gene mutations -- Observations ,Metastasis -- Genetic aspects ,Chronic lymphocytic leukemia -- Genetic aspects -- Development and progression ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome., In recent years, unbiased massively parallel sequencing of whole exornes (WES) in chronic lymphocytic leukaemia (CLL) has yielded fresh insights into the genetic basis of this disease (1-4). Two important [...]
- Published
- 2015
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47. Ist NGS der bessere Spürhund bei Akuter Lymphatischer Leukämie?
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Knecht, Henrik, Füllgrabe, Marc, Trautmann, Heiko, Herrmann, Dietrich, Ritgen, Matthias, Kneba, Michael, Pott, Christiane, and Brüggemann, Monika
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- 2015
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48. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies
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Gökbuget, Nicola, Kneba, Michael, Raff, Thorsten, Trautmann, Heiko, Bartram, Claus-Rainer, Arnold, Renate, Fietkau, Rainer, Freund, Mathias, Ganser, Arnold, Ludwig, Wolf-Dieter, Maschmeyer, Georg, Rieder, Harald, Schwartz, Stefan, Serve, Hubert, Thiel, Eckhard, Brüggemann, Monika, and Hoelzer, Dieter
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- 2012
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49. Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial
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Dreger, Peter, Döhner, Hartmut, McClanahan, Fabienne, Busch, Raymonde, Ritgen, Matthias, Greinix, Hildegard, Fink, Anna-Maria, Knauf, Wolfgang, Stadler, Michael, Pfreundschuh, Michael, Dührsen, Ulrich, Brittinger, Günter, Hensel, Manfred, Schetelig, Johannes, Winkler, Dirk, Bühler, Andreas, Kneba, Michael, Schmitz, Norbert, Hallek, Michael, and Stilgenbauer, Stephan
- Published
- 2012
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50. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial
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Engert, Andreas, Haverkamp, Heinz, Kobe, Carsten, Markova, Jana, Renner, Christoph, Ho, Antony, Zijlstra, Josée, Král, Zdenek, Fuchs, Michael, Hallek, Michael, Kanz, Lothar, Döhner, Hartmut, Dörken, Bernd, Engel, Nicole, Topp, Max, Klutmann, Susanne, Amthauer, Holger, Bockisch, Andreas, Kluge, Regine, Kratochwil, Clemens, Schober, Otmar, Greil, Richard, Andreesen, Reinhard, Kneba, Michael, Pfreundschuh, Michael, Stein, Harald, Eich, Hans Theodor, Müller, Rolf-Peter, Dietlein, Markus, Borchmann, Peter, and Diehl, Volker
- Published
- 2012
- Full Text
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