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3. Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies

Author

Langerbeins, Petra, Giza, Adam, Robrecht, Sandra, Cramer, Paula, von Tresckow, Julia, Al-Sawaf, Othman, Fink, Anna Maria, Fürstenau, Moritz, Kutsch, Nadine, Simon, Florian, Goede, Valentin, Hoechstetter, Manuela, Niemann, Carsten Utoft, da Cunha-Bang, Caspar, Kater, Arnon, Dubois, Julie, Gregor, Michael, Staber, Philipp Bernhard, Tausch, Eugen, Schneider, Christof, Stilgenbauer, Stephan, Eichhorst, Barbara, Fischer, Kirsten, and Hallek, Michael

Published
2024
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4. First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial

Author

Fürstenau, Moritz, Kater, Arnon P, Robrecht, Sandra, von Tresckow, Julia, Zhang, Can, Gregor, Michael, Thornton, Patrick, Staber, Philipp B, Tadmor, Tamar, Lindström, Vesa, Juliusson, Gunnar, Janssens, Ann, Levin, Mark-David, da Cunha-Bang, Caspar, Schneider, Christof, Goldschmidt, Neta, Vandenberghe, Elisabeth, Rossi, Davide, Benz, Rudolf, Nösslinger, Thomas, Heintel, Daniel, Poulsen, Christian B, Christiansen, Ilse, Frederiksen, Henrik, Enggaard, Lisbeth, Posthuma, Eduardus F M, Issa, Djamila E, Visser, Hein P J, Bellido, Mar, Kutsch, Nadine, Dürig, Jan, Stehle, Alexander, Vöhringer, Matthias, Böttcher, Sebastian, Schulte, Clemens, Simon, Florian, Fink, Anna-Maria, Fischer, Kirsten, Holmes, Emily E, Kreuzer, Karl-Anton, Ritgen, Matthias, Brüggemann, Monika, Tausch, Eugen, Stilgenbauer, Stephan, Hallek, Michael, Niemann, Carsten U, and Eichhorst, Barbara

Published
2024
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5. Author Correction: Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients

Author

Svanberg, Rebecka, MacPherson, Cameron, Zucco, Adrian, Agius, Rudi, Faitova, Tereza, Andersen, Michael Asger, da Cunha-Bang, Caspar, Gjærde, Lars Klingen, Møller, Maria Elizabeth Engel, Brooks, Patrick Terrence, Lindegaard, Birgitte, Sejdic, Adin, Harboe, Zitta Barrella, Gang, Anne Ortved, Hersby, Ditte Stampe, Brieghel, Christian, Nielsen, Susanne Dam, Podlekareva, Daria, Hald, Annemette, Bay, Jakob Thaning, Marquart, Hanne, Lundgren, Jens, Lebech, Anne-Mette, Helleberg, Marie, Niemann, Carsten Utoft, and Ostrowski, Sisse Rye

Published
2023
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6. High karyotypic complexity is an independent prognostic factor in patients with CLL treated with venetoclax combinations

Author

Fürstenau, Moritz, Thus, Yvonne J., Robrecht, Sandra, Mellink, Clemens H. M., van der Kevie-Kersemaekers, Anne-Marie, Dubois, Julie, von Tresckow, Julia, Patz, Michaela, Gregor, Michael, Thornton, Patrick, Staber, Philipp B., Tadmor, Tamar, Levin, Mark-David, da Cunha-Bang, Caspar, Schneider, Christof, Poulsen, Christian Bjoern, Illmer, Thomas, Schöttker, Björn, Janssens, Ann, Christiansen, Ilse, Nösslinger, Thomas, Baumann, Michael, Hebart, Holger, Gaska, Tobias, Regelink, Josien C., Dompeling, Ellen C., Lindström, Vesa, Juliusson, Gunnar, Widmer, Anouk, Goede, Jeroen, Goldschmidt, Neta, Simon, Florian, De Silva, Nisha, Fink, Anna-Maria, Fischer, Kirsten, Wendtner, Clemens-Martin, Ritgen, Matthias, Brüggemann, Monika, Tausch, Eugen, Spaargaren, Marcel, Eldering, Eric, Stilgenbauer, Stephan, Niemann, Carsten U., Hallek, Michael, Eichhorst, Barbara, Kreuzer, Karl-Anton, and Kater, Arnon P.

Published
2023
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8. Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients

Author

Svanberg, Rebecka, MacPherson, Cameron, Zucco, Adrian, Agius, Rudi, Faitova, Tereza, Andersen, Michael Asger, da Cunha-Bang, Caspar, Gjærde, Lars Klingen, Møller, Maria Elizabeth Engel, Brooks, Patrick Terrence, Lindegaard, Birgitte, Sejdic, Adin, Gang, Anne Ortved, Hersby, Ditte Stampe, Brieghel, Christian, Nielsen, Susanne Dam, Podlekareva, Daria, Hald, Annemette, Bay, Jakob Thaning, Marquart, Hanne, Lundgren, Jens, Lebech, Anne-Mette, Helleberg, Marie, Niemann, Carsten Utoft, and Ostrowski, Sisse Rye

Published
2022
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11. Supplementary Figure S6 from Improved Innate Immune Function in Patients with Chronic Lymphocytic Leukemia Treated with Targeted Therapy in Clinical Trials

Author

Svanberg Teglgaard, Rebecca, primary, Marquart, Hanne Vibeke, primary, Hartling, Hans Jakob, primary, Bay, Jakob Thaning, primary, da Cunha-Bang, Caspar, primary, Brieghel, Christian, primary, Faitová, Tereza, primary, Enggaard, Lisbeth, primary, Kater, Arnon P., primary, Levin, Mark-David, primary, Kersting, Sabina, primary, Ostrowski, Sisse Rye, primary, and Niemann, Carsten U., primary

Published
2024
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12. Data from Improved Innate Immune Function in Patients with Chronic Lymphocytic Leukemia Treated with Targeted Therapy in Clinical Trials

Author

Svanberg Teglgaard, Rebecca, primary, Marquart, Hanne Vibeke, primary, Hartling, Hans Jakob, primary, Bay, Jakob Thaning, primary, da Cunha-Bang, Caspar, primary, Brieghel, Christian, primary, Faitová, Tereza, primary, Enggaard, Lisbeth, primary, Kater, Arnon P., primary, Levin, Mark-David, primary, Kersting, Sabina, primary, Ostrowski, Sisse Rye, primary, and Niemann, Carsten U., primary

Published
2024
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13. Supplementary Table S2 from Improved Innate Immune Function in Patients with Chronic Lymphocytic Leukemia Treated with Targeted Therapy in Clinical Trials

Author

Svanberg Teglgaard, Rebecca, primary, Marquart, Hanne Vibeke, primary, Hartling, Hans Jakob, primary, Bay, Jakob Thaning, primary, da Cunha-Bang, Caspar, primary, Brieghel, Christian, primary, Faitová, Tereza, primary, Enggaard, Lisbeth, primary, Kater, Arnon P., primary, Levin, Mark-David, primary, Kersting, Sabina, primary, Ostrowski, Sisse Rye, primary, and Niemann, Carsten U., primary

Published
2024
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14. The Danish Lymphoid Cancer Research (DALY-CARE) data resource: the basis for developing data-driven hematology

Author

Brieghel, Christian, primary, Werling, Mikkel, additional, Frederiksen, Casper Moller, additional, Parviz, Mehdi, additional, da Cunha-Bang, Caspar, additional, Faitova, Tereza, additional, Teglgaard, Rebecca Svanberg, additional, Vainer, Noomi, additional, Lacoppidan, Thomas, additional, Rotbain, Emelie, additional, Agius, Rudi, additional, and Niemann, Carsten Utoft, additional

Published
2024
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15. Improved Innate Immune Function in Patients with Chronic Lymphocytic Leukemia Treated with Targeted Therapy in Clinical Trials

Author

Svanberg Teglgaard, Rebecca, Marquart, Hanne Vibeke, Hartling, Hans Jakob, Bay, Jakob Thaning, da Cunha-Bang, Caspar, Brieghel, Christian, Faitová, Tereza, Enggaard, Lisbeth, Kater, Arnon P., Levin, Mark David, Kersting, Sabina, Ostrowski, Sisse Rye, Niemann, Carsten U., Svanberg Teglgaard, Rebecca, Marquart, Hanne Vibeke, Hartling, Hans Jakob, Bay, Jakob Thaning, da Cunha-Bang, Caspar, Brieghel, Christian, Faitová, Tereza, Enggaard, Lisbeth, Kater, Arnon P., Levin, Mark David, Kersting, Sabina, Ostrowski, Sisse Rye, and Niemann, Carsten U.

Abstract

Purpose: Patients with chronic lymphocytic leukemia (CLL) have increased risk of severe infections. Although adaptive immune dysfunction is well described, clinical tools for identifying patients at risk are lacking, warranting investigation of additional immune components. In contrast to chemotherapy, targeted agents could spare or even improve innate immune function. Therefore, we investigated innate immune phenotypes and function in patients with CLL before and during targeted treatment. Experimental Design: Baseline and consecutive blood samples were collected from patients with CLL treated with acalabrutinib (n = 17) or ibrutinib+venetoclax (n = 18) in clinical trials. Innate immune function was assessed by TruCulture, a whole-blood ligand-stimulation assay quantifying cytokine release in response to standardized stimuli. Innate immune phenotypes were characterized by flow cytometry. As a proxy for infections, we mapped antimicrobial use before and during treatment. Results: At baseline, patients with CLL displayed impaired stimulated cytokine responses to the endotoxin lipopolysaccharide (LPS) along with deactivated monocytes, enrichment of myeloid-derived suppressor cells and metamyelocytes, and elevated (unstimulated) proinflammatory cytokines. Two/three cycles of acalabrutinib or ibrutinib normalized LPS-stimulated responses, in parallel with decreased duration of infections. Innate immune profiles and elevated proinflammatory cytokines further normalized during longer-term acalabrutinib or ibrutinib+venetoclax, paralleled by decreased infection frequency. Conclusions: Innate immune impairment and infection susceptibility in patients with CLL were restored in parallel during targeted therapy. Thus, targeted treatment may reduce the risk of infections in CLL, as currently under investigation in the PreVent-ACaLL phase 2 trial of acalabrutinib+venetoclax for high-risk CLL (NCT03868722)., PURPOSE: Patients with chronic lymphocytic leukemia (CLL) have increased risk of severe infections. Although adaptive immune dysfunction is well described, clinical tools for identifying patients at risk are lacking, warranting investigation of additional immune components. In contrast to chemotherapy, targeted agents could spare or even improve innate immune function. Therefore, we investigated innate immune phenotypes and function in patients with CLL before and during targeted treatment. EXPERIMENTAL DESIGN: Baseline and consecutive blood samples were collected from patients with CLL treated with acalabrutinib (n = 17) or ibrutinib+venetoclax (n = 18) in clinical trials. Innate immune function was assessed by TruCulture, a whole-blood ligand-stimulation assay quantifying cytokine release in response to standardized stimuli. Innate immune phenotypes were characterized by flow cytometry. As a proxy for infections, we mapped antimicrobial use before and during treatment. RESULTS: At baseline, patients with CLL displayed impaired stimulated cytokine responses to the endotoxin lipopolysaccharide (LPS) along with deactivated monocytes, enrichment of myeloid-derived suppressor cells and metamyelocytes, and elevated (unstimulated) proinflammatory cytokines. Two/three cycles of acalabrutinib or ibrutinib normalized LPS-stimulated responses, in parallel with decreased duration of infections. Innate immune profiles and elevated proinflammatory cytokines further normalized during longer-term acalabrutinib or ibrutinib+venetoclax, paralleled by decreased infection frequency. CONCLUSIONS: Innate immune impairment and infection susceptibility in patients with CLL were restored in parallel during targeted therapy. Thus, targeted treatment may reduce the risk of infections in CLL, as currently under investigation in the PreVent-ACaLL phase 2 trial of acalabrutinib+venetoclax for high-risk CLL (NCT03868722).

Published
2024

16. Trends in underlying causes of death in allogeneic hematopoietic cell transplant recipients over the last decade

Author

Søborg, Andreas, primary, Reekie, Joanne, additional, Sengeløv, Henrik, additional, Da Cunha‐Bang, Caspar, additional, Lund, Thomas Kromann, additional, Ekenberg, Christina, additional, Lodding, Isabelle Paula, additional, Moestrup, Kasper Sommerlund, additional, Lundgren, Louise, additional, Lundgren, Jens D., additional, and Wareham, Neval Ete, additional

Published
2024
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17. Infections in patients with chronic lymphocytic leukemia treated with time limited targeted drug combinations.

Author

Langerbeins, Petra, Giza, Adam, Robrecht, Sandra, Cramer, Paula, von Tresckow, Julia, Al‐Sawaf, Othman, Fink, Anna Maria, Fürstenau, Moritz, Kater, Arnon P., van der Spek, Ellen, Niemann, Carsten Utoft, da Cunha‐Bang, Caspar, Tausch, Eugen, Schneider, Christof, Stilgenbauer, Stephan, Fischer, Kirsten, Hallek, Michael, and Eichhorst, Barbara

Published
2024
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21. P619: TRACKING DISEASE PARAMETERS BY MRD, CT AND PET IN FIRST LINE CLL PATIENTS TREATED WITH FIXED DURATION IBRUTINIB-VENETOCLAX; INTERIM ANALYSIS OF THE FIRST 30 PATIENTS IN HOVON 158/NEXT STEP TRIAL.

Author

Kersting, Sabina, primary, Levin, Mark-David, additional, Dubois, Julie, additional, van Norden, Yvette, additional, Dobber, Johan, additional, Jauw, Yvonne, additional, van der Kevie-Kersemaekers, Anne-Marie, additional, Mellink, Clemens, additional, Da Cunha-Bang, Caspar, additional, Van Desr Burg, Leonie, additional, Te Raa, Doreen, additional, de Boer, Fransien, additional, Droogendijk, Jolanda, additional, Idink, Cecile, additional, De Heer, Koen, additional, Nijziel, Marten, additional, Tick, Lidwine, additional, Ludwig, Inge, additional, Silbermann, Mathijs, additional, Beeker, Aart, additional, Bellido, Mar, additional, Evers, Ludo, additional, Zwezerijnen, Gerben, additional, Zijlstra, Josée, additional, Kap, Marcel, additional, Niemann, Carsten, additional, and Kater, Arnon, additional

Published
2023
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22. S144: BTK AND BCL-2 ACTIVITY AT BASELINE PREDICTS MRD STATUS FOR CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS TREATED WITH IBRUTINIB + VENETOCLAX IN THE HOVON 141/VISION TRIAL

Author

Urban, Aleksandra, primary, Hermansen, Johanne, additional, Yin, Yanping, additional, Kong, Weikaixin, additional, Teglgaard, Rebecca, additional, Brieghel, Christian, additional, Kersting, Sabina, additional, Tjønnfjord, Geir E., additional, Levin, Mark-David, additional, Tran, Hoa T. T., additional, Mattsson, Mattias, additional, Ranti, Juha, additional, Veldhuis, Gerrit-Jan, additional, Da Cunha-Bang, Caspar, additional, Mous, Rogier, additional, Dubois, Julie, additional, Kater, Arnon, additional, Niemann, Carsten, additional, Aittokallio, Tero, additional, and Skånland, Sigrid, additional

Published
2023
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23. P629: THE CLL TREATMENT INFECTION MODEL – CLINICAL PROSPECTIVE VALIDATION AS PART OF THE PREVENT-ACALL TRIAL

Author

Niemann, Carsten, primary, Levin, Mark-David, additional, Österborg, Anders, additional, Lundin, Jeanette, additional, Kättström, Magdalena, additional, Vollerup, Jeanette, additional, Da Cunha-Bang, Caspar, additional, Foraux, Michael, additional, Brieghel, Christian, additional, de Boer, Fransien, additional, Enggaard, Lisbeth, additional, Bjorn Poulsen, Christian, additional, Reekie, Joanne, additional, and Agius, Rudi, additional

Published
2023
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24. S148: TIME-LIMITED VENETOCLAX AND IBRUTINIB FOR PATIENTS WITH RELAPSED/REFRACTORY CLL WHO HAVE UNDETECTABLE MRD – 4-YEAR FOLLOW UP FROM THE RANDOMIZED PHASE II VISION/HO141 TRIAL

Author

Kater, Arnon, primary, Dubois, Julie, additional, Brieghel, Christian, additional, Kersting, Sabina, additional, Enggaard, Lisbeth, additional, Veldhuis, Gerrit, additional, Mous, Rogier, additional, Mellink, Clemens, additional, Dobber, Johan, additional, Poulsen, Christian, additional, Da Cunha-Bang, Caspar, additional, Fredriksen, Hendrik, additional, Janssens, Ann, additional, Schjodt, Ida, additional, Dompeling, Ellen, additional, Ranti, Juha, additional, Mattsson, Mattias, additional, Bellido, Mar, additional, Tran, Hoa, additional, Nasserinejad, Kazem, additional, Levin, Mark-David, additional, and Niemann, Carsten, additional

Published
2023
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26. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia

Author

Eichhorst, Barbara, Niemann, Carsten U., Kater, Arnon P., Fuerstenau, Moritz, von Tresckow, Julia, Zhang, Can, Robrecht, Sandra, Gregor, Michael, Juliusson, Gunnar, Thornton, Patrick, Staber, Philipp B., Tadmor, Tamar, Lindstrom, Vesa, da Cunha-Bang, Caspar, Schneider, Christof, Poulsen, Christian B., Illmer, Thomas, Schoettker, Bjoern, Noesslinger, Thomas, Janssens, Ann, Christiansen, Ilse, Baumann, Michael, Frederiksen, Henrik, van der Klift, Marjolein, Jaeger, Ulrich, Leys, Maria B. L., Hoogendoorn, Mels, Lotfi, Kourosh, Hebart, Holger, Gaska, Tobias, Koene, Harry, Enggaard, Lisbeth, Goede, Jereon, Regelink, Josien C., Widmer, Anouk, Simon, Florian, De Silva, Nisha, Fink, Anna-Maria, Bahlo, Jasmin, Fischer, Kirsten, Wendtner, Clemens-Martin, Kreuzer, Karl A., Ritgen, Matthias, Brueggemann, Monika, Tausch, Eugen, Levin, Mark-David, van Oers, Marinus, Geisler, Christian, Stilgenbauer, Stephan, Hallek, Michael, Eichhorst, Barbara, Niemann, Carsten U., Kater, Arnon P., Fuerstenau, Moritz, von Tresckow, Julia, Zhang, Can, Robrecht, Sandra, Gregor, Michael, Juliusson, Gunnar, Thornton, Patrick, Staber, Philipp B., Tadmor, Tamar, Lindstrom, Vesa, da Cunha-Bang, Caspar, Schneider, Christof, Poulsen, Christian B., Illmer, Thomas, Schoettker, Bjoern, Noesslinger, Thomas, Janssens, Ann, Christiansen, Ilse, Baumann, Michael, Frederiksen, Henrik, van der Klift, Marjolein, Jaeger, Ulrich, Leys, Maria B. L., Hoogendoorn, Mels, Lotfi, Kourosh, Hebart, Holger, Gaska, Tobias, Koene, Harry, Enggaard, Lisbeth, Goede, Jereon, Regelink, Josien C., Widmer, Anouk, Simon, Florian, De Silva, Nisha, Fink, Anna-Maria, Bahlo, Jasmin, Fischer, Kirsten, Wendtner, Clemens-Martin, Kreuzer, Karl A., Ritgen, Matthias, Brueggemann, Monika, Tausch, Eugen, Levin, Mark-David, van Oers, Marinus, Geisler, Christian, Stilgenbauer, Stephan, and Hallek, Michael

Abstract

Background Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. Methods In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10(-4) [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival. Results A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax-rituximab, 229 to venetoclax-obinutuzumab, and 231 to venetoclax-obinutuzumab-ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax-obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax-rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P=0.32). Three-year progression-free survival was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax-obinutuzumab (87.7%; hazard ratio for, Funding Agencies|AbbVie

Published
2023
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27. Impact of type 2 diabetes on mortality, cause of death, and treatment in chronic lymphocytic leukemia

Author

Rotbain, Emelie Curovic, Allmer, Cristine, Rostgaard, Klaus, Andersen, Michael Asger, Vainer, Noomi, da Cunha-Bang, Caspar, Parikh, Sameer A., Rabe, Kari G., Hjalgrim, Henrik, Frederiksen, Henrik, Slager, Susan L., Niemann, Carsten Utoft, Rotbain, Emelie Curovic, Allmer, Cristine, Rostgaard, Klaus, Andersen, Michael Asger, Vainer, Noomi, da Cunha-Bang, Caspar, Parikh, Sameer A., Rabe, Kari G., Hjalgrim, Henrik, Frederiksen, Henrik, Slager, Susan L., and Niemann, Carsten Utoft

Abstract

Age-related comorbid conditions are exceedingly common in patients with chronic lymphocytic leukemia (CLL). As the prevalence of type 2 diabetes (T2D) is predicted to double during the next two decades, a better understanding of the interplay between CLL and T2D is of increasing importance. In this study, analyses were performed in parallel in two separate cohorts, based on Danish national registers and the Mayo Clinic CLL Resource. The primary outcomes were overall survival (OS) from time of CLL diagnosis, OS from time of treatment, and time to first treatment (TTFT), studied using Cox proportional hazard regression analysis and Fine-Gray regression analysis. In the Danish CLL cohort, the prevalence of T2D was 11%, in the Mayo CLL cohort, it was 12%. Patients with CLL and T2D had shorter OS both from time of diagnosis and from first-line treatment for were less likely to receive treatment for CLL compared with patients with CLL and without T2D. The increased mortality was largely driven by an increased risk of death due to infections, especially in the Danish cohort. The findings of this study emphasize a substantial subgroup of CLL patients with co-occurring T2D with an inferior prognosis and a possible unmet treatment need requiring additional interventions and further research.

Published
2023

28. Impact of type 2 diabetes on mortality, cause of death, and treatment in chronic lymphocytic leukemia

Author

Rotbain, Emelie Curovic, primary, Allmer, Cristine, additional, Rostgaard, Klaus, additional, Andersen, Michael Asger, additional, Vainer, Noomi, additional, da Cunha‐Bang, Caspar, additional, Parikh, Sameer A., additional, Rabe, Kari G., additional, Hjalgrim, Henrik, additional, Frederiksen, Henrik, additional, Slager, Susan L., additional, and Niemann, Carsten Utoft, additional

Published
2023
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29. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia

Author

Eichhorst, Barbara, primary, Niemann, Carsten U., additional, Kater, Arnon P., additional, Fürstenau, Moritz, additional, von Tresckow, Julia, additional, Zhang, Can, additional, Robrecht, Sandra, additional, Gregor, Michael, additional, Juliusson, Gunnar, additional, Thornton, Patrick, additional, Staber, Philipp B., additional, Tadmor, Tamar, additional, Lindström, Vesa, additional, da Cunha-Bang, Caspar, additional, Schneider, Christof, additional, Poulsen, Christian B., additional, Illmer, Thomas, additional, Schöttker, Björn, additional, Nösslinger, Thomas, additional, Janssens, Ann, additional, Christiansen, Ilse, additional, Baumann, Michael, additional, Frederiksen, Henrik, additional, van der Klift, Marjolein, additional, Jäger, Ulrich, additional, Leys, Maria B.L., additional, Hoogendoorn, Mels, additional, Lotfi, Kourosh, additional, Hebart, Holger, additional, Gaska, Tobias, additional, Koene, Harry, additional, Enggaard, Lisbeth, additional, Goede, Jereon, additional, Regelink, Josien C., additional, Widmer, Anouk, additional, Simon, Florian, additional, De Silva, Nisha, additional, Fink, Anna-Maria, additional, Bahlo, Jasmin, additional, Fischer, Kirsten, additional, Wendtner, Clemens-Martin, additional, Kreuzer, Karl A., additional, Ritgen, Matthias, additional, Brüggemann, Monika, additional, Tausch, Eugen, additional, Levin, Mark-David, additional, van Oers, Marinus, additional, Geisler, Christian, additional, Stilgenbauer, Stephan, additional, and Hallek, Michael, additional

Published
2023
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30. Implementation of the CLL Treatment Infection Model Adjoined to an Electronic Health Record System - Guidelines for Practical Implementation of Data-Driven Models

Author

Agius, Rudi, primary, Riis-Jensen, Anders C., additional, Wimmer, Bettina, additional, da Cunha-Bang, Caspar, additional, Murray, Daniel D., additional, Poulsen, Christian, additional, Bertelsen, Marianne B., additional, Schwartz, Berit, additional, Lundgren, Jens, additional, Langberg, Henning, additional, and Utoft Niemann, Carsten, additional

Published
2023
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31. High Karyotypic Complexity and Translocations Are Adverse Prognostic Features in Patients with Chronic Lymphocytic Leukemia without TP53 Aberrations Treated with Venetoclax-Based Time-Limited Combinations

Author

Furstenau, Moritz, Thus, Yvonne, Robrecht, Sandra, Mellink, Clemens, der Kevie-Kersemaekers, Anne-Marie, Dubois, Julie M. N., Von Tresckow, Julia, Patz, Michaela, Gregor, Michael, Thornton, Patrick, Staber, Philipp B., Tadmor, Tamar, Levin, Mark-David, da Cunha-Bang, Caspar, Schneider, Christof, Poulsen, Christian Bjørn, Illmer, Thomas, Schöttker, Björn, Janssens, Ann, Christiansen, Ilse, Baumann, Michael, Noesslinger, Thomas, Regelink, Josien, Dompeling, Ellen C, Lindström, Vesa, Juliusson, Gunnar, Widmer, Anouk, Goede, Jeroen Simon, Goldschmidt, Neta, Simon, Florian, De Silva, Nisha, Fink, Anna-Maria, Fischer, Kirsten, Wendtner, Clemens-Martin, Ritgen, Matthias, Brüggemann, Monika, Tausch, Eugen, Stilgenbauer, Stephan, Eldering, Eric, Niemann, Carsten Utoft, Hallek, Michael, Eichhorst, Barbara, Kreuzer, Karl-Anton, and Kater, Arnon P.

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022
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32. High Karyotypic Complexity and Translocations Are Adverse Prognostic Features in Patients with Chronic Lymphocytic Leukemia without TP53 Aberrations Treated with Venetoclax-Based Time-Limited Combinations

Author

Furstenau, Moritz, primary, Thus, Yvonne, additional, Robrecht, Sandra, additional, Mellink, Clemens, additional, Van Der Kevie-Kersemaekers, Anne-Marie, additional, Dubois, Julie M.N., additional, Von Tresckow, Julia, additional, Patz, Michaela, additional, Gregor, Michael, additional, Thornton, Patrick, additional, Staber, Philipp B., additional, Tadmor, Tamar, additional, Levin, Mark-David, additional, Da Cunha-Bang, Caspar, additional, Schneider, Christof, additional, Poulsen, Christian Bjørn, additional, Illmer, Thomas, additional, Schöttker, Björn, additional, Janssens, Ann, additional, Christiansen, Ilse, additional, Baumann, Michael, additional, Noesslinger, Thomas, additional, Regelink, Josien, additional, Dompeling, Ellen C, additional, Lindström, Vesa, additional, Juliusson, Gunnar, additional, Widmer, Anouk, additional, Goede, Jeroen Simon, additional, Goldschmidt, Neta, additional, Simon, Florian, additional, De Silva, Nisha, additional, Fink, Anna-Maria, additional, Fischer, Kirsten, additional, Wendtner, Clemens-Martin, additional, Ritgen, Matthias, additional, Brüggemann, Monika, additional, Tausch, Eugen, additional, Stilgenbauer, Stephan, additional, Eldering, Eric, additional, Niemann, Carsten Utoft, additional, Hallek, Michael, additional, Eichhorst, Barbara, additional, Kreuzer, Karl-Anton, additional, and Kater, Arnon P., additional

Published
2022
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33. Genetic Markers and Front Line FCR/BR Vs. Rve, Gve and Give Treatment - Outcome Results from the CLL13/GAIA Trial

Author

Tausch, Eugen, primary, Schneider, Christof, additional, Furstenau, Moritz, additional, Robrecht, Sandra, additional, Yosifov, Deyan Yordanov, additional, Mertens, Daniel, additional, Gregor, Michael, additional, Thornton, Patrick, additional, Staber, Philipp B., additional, Tadmor, Tamar, additional, Levin, Mark-David, additional, da Cunha-Bang, Caspar, additional, Poulsen, Christian Bjørn, additional, Illmer, Thomas, additional, Schöttker, Björn, additional, Janssens, Ann, additional, Christiansen, Ilse, additional, Noesslinger, Thomas, additional, Baumann, Michael, additional, Wendtner, Clemens-Martin, additional, Eldering, Eric, additional, Kreuzer, Karl-Anton, additional, Ritgen, Matthias, additional, Fink, Anna-Maria, additional, Fischer, Kirsten, additional, Kater, Arnon P., additional, Niemann, Carsten Utoft, additional, Hallek, Michael, additional, Eichhorst, Barbara, additional, and Stilgenbauer, Stephan, additional

Published
2022
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35. Identifying patients with chronic lymphocytic leukemia without need of treatment : End of endless watch and wait?

Author

Brieghel, Christian, Galle, Veerle, Agius, Rudi, Da Cunha-Bang, Caspar, Andersen, Michael A., Vlummens, Philip, Mattsson, Mattias, Rosenquist, Richard, Smedby, Karin E., Herling, Carmen D., Bahlo, Jasmin, Hallek, Michael, Lundgren, Jens D., Offner, Fritz, Niemann, Carsten U., Brieghel, Christian, Galle, Veerle, Agius, Rudi, Da Cunha-Bang, Caspar, Andersen, Michael A., Vlummens, Philip, Mattsson, Mattias, Rosenquist, Richard, Smedby, Karin E., Herling, Carmen D., Bahlo, Jasmin, Hallek, Michael, Lundgren, Jens D., Offner, Fritz, and Niemann, Carsten U.

Abstract

Introduction Early-stage chronic lymphocytic leukemia (CLL) challenges specialized management and follow-up. Methods We developed and validated a prognostic index to identify newly diagnosed patients without need of treatment (CLL-WONT) by a training/validation approach using data on 4708 patients. Composite scores derived from weighted hazards by multivariable analysis defined CLL-WONT risk groups. Results Age (>65 years: 1 point), Binet stage (B: 2 points), lactate dehydrogenase (LDH) (>205 U/L: 1 point), absolute lymphocyte count (15-30 x 10(9)/L: 1 point; >30 x 10(9)/L; 2 points), beta 2-microglobulin (>4 mg/L: 1 point), IGHV mutation status (unmutated: 1 point), and 11q or 17p deletion (1 point) were independently associated with shorter time to first treatment (TTFT). Low-risk patients demonstrated 5-year TTFT of 2% by internal validation, but 7-19% by external validation. Including all patients with complete scores, the 5-year TTFT was 10% for the 756 (39%) CLL-WONT low-risk patients, and the 704 (37%) patients who were both CLL-WONT and CLL-IPI low risk demonstrated even lower 5-year TTFT (8%). Conclusion We have adopted the CLL-WONT at an institution covering 1 800 000 individuals to allow patients with both low-risk CLL-WONT and CLL-IPI to be managed by primary healthcare providers, thereby prioritizing specialized hematology services for patients in dire need.

Published
2022
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36. Genetic Markers and Front Line FCR/BR Vs. Rve, Gve and Give Treatment - Outcome Results from the CLL13/GAIA Trial

Author

Tausch, Eugen, Schneider, Christof, Furstenau, Moritz, Robrecht, Sandra, Yosifov, Deyan Yordanov, Mertens, Daniel, Gregor, Michael, Thornton, Patrick, Staber, Philipp B., Tadmor, Tamar, Levin, Mark-David, Da Cunha-Bang, Caspar, Poulsen, Christian Bjorn, Illmer, Thomas, Schoettker, Bjoern, Janssens, Ann, Christiansen, Ilse, Noesslinger, Thomas, Baumann, Michael, Wendtner, Clemens-Martin, Eldering, Eric, Kreuzer, Karl-Anton, Ritgen, Matthias, Fink, Anna-Maria, Fischer, Kirsten, Kater, Arnon P., Niemann, Carsten Utoft, Hallek, Michael, Eichhorst, Barbara, Stilgenbauer, Stephan, Tausch, Eugen, Schneider, Christof, Furstenau, Moritz, Robrecht, Sandra, Yosifov, Deyan Yordanov, Mertens, Daniel, Gregor, Michael, Thornton, Patrick, Staber, Philipp B., Tadmor, Tamar, Levin, Mark-David, Da Cunha-Bang, Caspar, Poulsen, Christian Bjorn, Illmer, Thomas, Schoettker, Bjoern, Janssens, Ann, Christiansen, Ilse, Noesslinger, Thomas, Baumann, Michael, Wendtner, Clemens-Martin, Eldering, Eric, Kreuzer, Karl-Anton, Ritgen, Matthias, Fink, Anna-Maria, Fischer, Kirsten, Kater, Arnon P., Niemann, Carsten Utoft, Hallek, Michael, Eichhorst, Barbara, and Stilgenbauer, Stephan

Published
2022

38. The gut microbiome in patients with chronic lymphocytic leukemia

Author

Faitová, Tereza, Svanberg, Rebecka, Da Cunha-Bang, Caspar, Ilett, Emma E., Jørgensen, Mette, Noguera-Julian, Marc, Paredes, Roger, MacPherson, Cameron R., Niemann, Carsten U., Faitová, Tereza, Svanberg, Rebecka, Da Cunha-Bang, Caspar, Ilett, Emma E., Jørgensen, Mette, Noguera-Julian, Marc, Paredes, Roger, MacPherson, Cameron R., and Niemann, Carsten U.

Published
2022

40. The gut microbiome in patients with chronic lymphocytic leukemia

Author

Faitová, Tereza, primary, Svanberg, Rebecka, additional, Da Cunha-Bang, Caspar, additional, Ilett, Emma E., additional, Jørgensen, Mette, additional, Noguera-Julian, Marc, additional, Paredes, Roger, additional, MacPherson, Cameron R., additional, and Niemann, Carsten U., additional

Published
2022
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41. Identifying patients with chronic lymphocytic leukemia without need of treatment: End of endless watch and wait?

Author

Brieghel, Christian, primary, Galle, Veerle, additional, Agius, Rudi, additional, da Cunha‐Bang, Caspar, additional, Andersen, Michael A., additional, Vlummens, Philip, additional, Mattsson, Mattias, additional, Rosenquist, Richard, additional, Smedby, Karin E., additional, Herling, Carmen D., additional, Bahlo, Jasmin, additional, Hallek, Michael, additional, Lundgren, Jens D., additional, Offner, Fritz, additional, and Niemann, Carsten U., additional

Published
2022
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43. A Randomized Phase III Study of Venetoclax-Based Time-Limited Combination Treatments (RVe, GVe, GIVe) Vs Standard Chemoimmunotherapy (CIT: FCR/BR) in Frontline Chronic Lymphocytic Leukemia (CLL) of Fit Patients: First Co-Primary Endpoint Analysis of the International Intergroup GAIA (CLL13) Trial

Author

Eichhorst, Barbara, primary, Niemann, Carsten, additional, Kater, Arnon P., additional, Fürstenau, Moritz, additional, Von Tresckow, Julia, additional, Zhang, Can, additional, Robrecht, Sandra, additional, Gregor, Michael, additional, Juliusson, Gunnar, additional, Thornton, Patrick, additional, Staber, Philipp B., additional, Tadmor, Tamar, additional, Lindström, Vesa, additional, Da Cunha-Bang, Caspar, additional, Schneider, Christof, additional, Poulsen, Christian Bjørn, additional, Illmer, Thomas, additional, Schöttker, Björn, additional, Janssens, Ann, additional, Christiansen, Ilse, additional, Noesslinger, Thomas, additional, Baumann, Michael, additional, van der Klift, Marjolein, additional, Jaeger, Ulrich, additional, Frederiksen, Henrik, additional, Leijs, Maria B.L., additional, Hoogendoorn, Mels, additional, Lotfi, Kourosh, additional, Hebart, Holger, additional, Gaska, Tobias, additional, Koene, Harry R., additional, Simon, Florian, additional, De Silva, Nisha, additional, Fink, Anna-Maria, additional, Fischer, Kirsten, additional, Wendtner, Clemens-Martin, additional, Kreuzer, Karl-Anton, additional, Ritgen, Matthias, additional, Brüggemann, Monika, additional, Tausch, Eugen, additional, Levin, Mark-David, additional, Van Oers, Marinus H.J., additional, Geisler, Christian H., additional, Stilgenbauer, Stephan, additional, and Hallek, Michael, additional

Published
2021
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44. High Resolution Assessment of Minimal Residual Disease (MRD) By Next-Generation Sequencing (NGS) and High-Sensitivity Flow Cytometry (hsFCM) in the Phase 3 GAIA (CLL13) Trial

Author

Fürstenau, Moritz, primary, Schilhabel, Anke, additional, Robrecht, Sandra, additional, Zhang, Can, additional, Von Tresckow, Julia, additional, Niemann, Carsten Utoft, additional, Kater, Arnon P., additional, Tausch, Eugen, additional, Simon, Florian, additional, De Silva, Nisha, additional, Fink, Anna-Maria, additional, Fischer, Kirsten, additional, Wendtner, Clemens-Martin, additional, Gregor, Michael, additional, Thornton, Patrick, additional, Staber, Philipp B., additional, Tadmor, Tamar, additional, Levin, Mark-David, additional, Van Oers, Marinus H.J., additional, Da Cunha-Bang, Caspar, additional, Geisler, Christian H., additional, Stilgenbauer, Stephan, additional, Brüggemann, Monika, additional, Hallek, Michael, additional, Ritgen, Matthias, additional, and Eichhorst, Barbara, additional

Published
2021
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45. Comparison of Tumor Lysis Syndrome (TLS) Risk Reduction and Incidence in Different Venetoclax-Based Combinations within the Randomized Phase 3 GAIA (CLL13) Trial

Author

Fürstenau, Moritz, primary, Robrecht, Sandra, additional, Zhang, Can, additional, Von Tresckow, Julia, additional, Niemann, Carsten Utoft, additional, Kater, Arnon P., additional, Gregor, Michael, additional, Thornton, Patrick, additional, Staber, Philipp B., additional, Tadmor, Tamar, additional, Levin, Mark-David, additional, Da Cunha-Bang, Caspar, additional, Schneider, Christof, additional, Poulsen, Christian Bjørn, additional, Illmer, Thomas, additional, Schöttker, Björn, additional, Janssens, Ann, additional, Christiansen, Ilse, additional, Noesslinger, Thomas, additional, Baumann, Michael, additional, Simon, Florian, additional, De Silva, Nisha, additional, Fink, Anna-Maria, additional, Fischer, Kirsten, additional, Wendtner, Clemens-Martin, additional, Ritgen, Matthias, additional, Brüggemann, Monika, additional, Tausch, Eugen, additional, Van Oers, Marinus H.J., additional, Geisler, Christian H., additional, Stilgenbauer, Stephan, additional, Hallek, Michael, additional, and Eichhorst, Barbara, additional

Published
2021
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47. The Impact of Fitness and Dose Intensity on Safety and Efficacy Outcomes after Venetoclax-Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia

Author

Al-Sawaf, Othman, Fürstenau, Moritz, Giza, Adam, Robrecht, Sandra, Von Tresckow, Julia, Fink, Anna Maria, Simon, Florian, Tausch, Eugen, Schneider, Christof, Sivcheva, Liliya, Schwarer, Anthony, Loscertales, Javier, Weinkove, Robert, Strumberg, Dirk, Kilfoyle, Allanah R., Juliusson, Gunnar, Da Cunha-Bang, Caspar, Illmer, Thomas, Gregor, Michael, Thornton, Patrick, Janssens, Ann, Tadmor, Tamar, Lindström, Vesa, Staber, Philipp Bernhard, Levin, Mark-David, Wendtner, Clemens-Martin, Kreuzer, Karl-Anton, Ritgen, Matthias, Stilgenbauer, Stephan, Kater, Arnon P., Niemann, Carsten Utoft, Fischer, Kirsten, Eichhorst, Barbara F., and Hallek, Michael

Published
2023
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49. First-Line Venetoclax Combinations in Fit Patients with CLL: 4-Year Follow-up and NGS-Based MRD Analysis from the Phase 3 GAIA/CLL13 Trial

Author

Fürstenau, Moritz, Ritgen, Matthias, Robrecht, Sandra, Von Tresckow, Julia, Zhang, Can, Schilhabel, Anke, Gregor, Michael, Thornton, Patrick, Staber, Philipp Bernhard, Tadmor, Tamar, Lindström, Vesa, Juliusson, Gunnar, Janssens, Ann, Levin, Mark-David, Da Cunha-Bang, Caspar, Schneider, Christof, Goldschmidt, Neta, Vandenberghe, Elisabeth, Rossi, Davide, Benz, Rudolf A., Heintel, Daniel, Poulsen, Christian Bjørn, Christiansen, Ilse, Frederiksen, Henrik, Enggaard, Lisbeth, Posthuma, Eduardus, Issa, Djamila, Visser, Hein, Bellido, Mar, Kutsch, Nadine, Dürig, Jan, Stehle, Alexander, Voehringer, Matthias C., Böttcher, Sebastian, Schulte, Clemens, Simon, Florian, Fink, Anna-Maria, Fischer, Kirsten, Holmes, Emily, Kreuzer, Karl-Anton, Brüggemann, Monika, Tausch, Eugen, Stilgenbauer, Stephan, Hallek, Michael, Kater, Arnon P., Niemann, Carsten Utoft, and Eichhorst, Barbara F.

Published
2023
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50. Mapping comorbidity in chronic lymphocytic leukemia:impact of individual comorbidities on treatment, mortality, and causes of death

Author

Rotbain, Emelie Curovic, Niemann, Carsten Utoft, Rostgaard, Klaus, da Cunha-Bang, Caspar, Hjalgrim, Henrik, Frederiksen, Henrik, Rotbain, Emelie Curovic, Niemann, Carsten Utoft, Rostgaard, Klaus, da Cunha-Bang, Caspar, Hjalgrim, Henrik, and Frederiksen, Henrik

Abstract

Comorbid conditions are highly prevalent in chronic lymphocytic leukemia (CLL), nevertheless, detailed information on the association of specific comorbidities with CLL prognosis is missing. Using Danish, nation-wide registers, we followed consecutive patients from CLL-diagnosis in 1997–2018, until death or end of follow-up. Sub-grouping of comorbidities was defined using a modified Charlson comorbidity index. Patients were matched on sex, date of birth (±1 month), and region of residency with up to ten comparators from the general population. In total, 9170 patients with CLL were included in the study, with a median of 5.0 years of follow-up. All comorbid conditions studied were individually associated with increased mortality, and many also with increased cause-specific mortality, related or unrelated to CLL. Comorbidity correlated with increased mortality from infections and cardiovascular disease. CLL patients, particularly older, had a significant loss of lifetime compared with the general population. This study highlights a large subgroup of comorbid CLL patients with an unmet treatment-need and missing efficacy and safety data on treatment, who are under-prioritized in clinical trials. Also, studies assessing interventions that may provide better tolerability of treatment in older or comorbid patients, with cancer in general, and CLL in particular, are warranted.

Published
2021

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