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1. Combined inhibition of EZH2 and CDK4/6 perturbs endoplasmic reticulum-mitochondrial homeostasis and increases antitumor activity against glioblastoma

Author

Freitag, Thomas, Kaps, Philipp, Ramtke, Justus, Bertels, Sarah, Zunke, Emily, Schneider, Björn, Becker, Anne-Sophie, Koczan, Dirk, Dubinski, Daniel, Freiman, Thomas M., Wittig, Felix, Hinz, Burkhard, Westhoff, Mike-Andrew, Strobel, Hannah, Meiners, Franziska, Wolter, Daniel, Engel, Nadja, Troschke-Meurer, Sascha, Bergmann-Ewert, Wendy, Staehlke, Susanne, Wolff, Annabell, Gessler, Florian, Junghanss, Christian, and Maletzki, Claudia

Published
2024
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3. Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315)

Author

Ababei, Juliana, Alt, Jürgen, Ammon, Andreas, Anhuf, Jürgen, Azeh, Ivo, Bauer, Stefan, Behringer, Dirk, Berger, Winfried, Bernhardt, Christiane, Bertram, Mathias, Boesche, Michael, Bohnet, Sabine, Bruch, Harald-Robert, Brückl, Wolfgang, Burkhard-Meier, Ulrike, Christopoulos, Petros, Däßler, Klaus-Ulrich, de Wit, Maike, Dechow, Tobias, Depenbusch, Reinhard, Dietze, Lutz, Dommach, Markus, Dörfel, Steffen, Eberhardt, Wilfried, Elender, Corinna, Elsel, Wolfgang, Emde, Till-Oliver, Faehling, Martin, Fietz, Thomas, Fischer, Jürgen R., Flieger, Dimitri, Freidt, Anke, Freier, Werner, Frenzel, Christian, Fuchs, Florian, Fuchs, Roswitha, Gaska, Tobias, Gleiber, Wolfgang, Grah, Christian, Griesinger, Frank, Grohé, Christian, Groschek, Matthias, Güldenzoph, Björn, Günther, Andreas, Haas, Siegfried, Hackenthal, Matthias, Hagen, Volker, Hahn, Lars, Hannig Carla, Verena, Hansen, Richard, Harich, Hanns-Detlev, Heilmann, Monika, Heinrich, Kathrin, Hering-Schubert, Christiane, Heßling, Jörg, Hoffknecht, Petra, Hortig, Patricia, Hübner, Gerdt, Hummel, Horst-Dieter, Hutzschenreuter, Ulrich, Illmer, Thomas, Innig, Georg, Jaeschke, Bastian, Junghanß, Christian, Kaiser, Ulrich, Kamal, Haytham, Kambartel, Kato, Kern, Jens, Kimmich, Martin, Kingreen, Dorothea, Kirchen, Heinz, Klausmann, Martine, Klein, Ortwin, Kokowski, Konrad, Körber, Wolfgang, Kortsik, Cornelius, Koschel, Dirk, Krämer, Benoit, Krammer-Steiner, Beate, Laack, Eckart, Lamberti, Christof, Leistner, Rumo David, Losem, Christoph, Lück, Andreas, Maintz, Christoph, Martin, Kerstin, Medgenberg, Dirk, Metzenmacher, Martin, Meyer zum Büschenfelde, Christian, Meyn, Philipp, Moorahrend, Enno, Müller, Annette, Müller, Lothar, Neise, Michael, Nückel, Holger, Nusch, Arnd, Overbeck, Tobias, Pelz, Henning, Petersen, Volker, Peuser, Bettina, Plath, Margarete, Randerath, Winfried J., Rauh, Jacqueline, Reck, Martin, Reichert, Dietmar, Reinmuth, Niels, Reiser, Marcel, Repp, Roland, Reschke, Daniel, Rittmeyer, Achim, Rodemer, Yolanda, Sackmann, Sandra, Sadjadian, Parvis, Sandner, Reiner, Sauer, Annette, Schäfer, Harald, Schaudt, Christoph, Schlag, Rudolf, Schmidt, Burkhard, Schmitz, Stephan, Schröder, Jan, Schroeder, Michael, Schulze, Mathias, Schumann, Christian, Schütte, Wolfgang, Schwaiblmair, Martin, Schwindt Peter, Florian, Sebastian, Martin, Seese, Bernd, Seipelt, Gernot, Sorgenfrei, Thomas, Steiff, Johannes, Steiniger, Heike, Trarbach, Tanja, Tufman, Amanda, Uhlig, Jens, Vehling-Kaiser, Ursula, von der Heyde, Eyck, von Verschuer, Ulla, Waller, Cornelius, Wehler, Thomas, Weißenborn, Georg, Weißinger, Florian, Wermke, Martin, Wesseler, Claas, Wiegand, Jörg, Wilhelm, Stefan, Wilke, Jochen, Zahn, Mark-Oliver, Zaiss, Matthias, Zeth, Matthias, Eberhardt, Wilfried E.E., Brueckl, Wolfgang M., Jänicke, Martina, Fleitz, Annette, Zacharias, Stefan, Hipper, Annette, Groth, Annika, Weichert, Wilko, and Thomas, Michael

Published
2024
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5. Hope for motherhood: pregnancy after allogeneic hematopoietic cell transplantation (a national multicenter study)

Author

Jost, Edgar, Schmid, Christoph, Baurmann, Herrad, Blau, Igor, Holderried, Tobias, Hertenstein, Bernd, Hänel, Mathias, Bornhäuser, Martin, Neidlinger, Helga, Kobbe, Guido, Winkler, Julia, Schroeder, Thomas, Bug, Gesine, Hopfer, Olaf, Finke, Jürgen, Hasenkamp, Justin, Krüger, William, Müller, Lutz, Kröger, Nikolaus, Eder, Matthias, Luft, Thomas, Hilgendorf, Inken, Ringhoffer, Mark, Stölzel, Friedrich, Scheid, Christoph, Platzbecker, Uwe, Wortmann, Friederike, Heinicke, Thomas, Wagner, Eva, Klein, Stefan, Burchert, Andreas, Tischer, Johanna, Stelljes, Matthias, Schäfer-Eckart, Kerstin, Wolff, Daniel, Junghanss, Christian, Ritter, Markus, Kaufmann, Martin, Bethge, Wolfgang, Mytilineos, Joannis, Einsel, Hermann, Sockel, Katja, Neu, Annika, Goeckenjan, Maren, Ditschkowski, Markus, Kröger, Nicolaus, Ayuk, Francis A., Stoelzel, Friedrich, Middeke, Jan Moritz, Bertz, Hartmut, Beverungen, David, von Bonin, Malte, Egger-Heidrich, Katharina, Heberling, Lisa, Trautmann-Grill, Karolin, Teipel, Raphael, Fraccaroli, Alessia, Fante, Matthias, Scheid, Christof, Holtick, Udo, Blau, Igor Wolfgang, Wulf, Gerald, Schwerdtfeger, Rainer, Kaun, Stephan, Winter, Susann, Theuser, Catrin, Beyersmann, Jan, Bornhaeuser, Martin, Schmeller, Sandra, and Schetelig, Johannes

Published
2024
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6. Different treatment strategies versus a common standard arm (CSA) in patients with newly diagnosed AML over the age of 60 years: a randomized German inter-group study

Author

Niederwieser, Dietger, Lang, Thomas, Krahl, Rainer, Heinicke, Thomas, Maschmeyer, Georg, Al-Ali, Haifa Kathrin, Schwind, Sebastian, Jentzsch, Madlen, Cross, Michael, Kahl, Christoph, Wolf, Hans-Heinrich, Sayer, Herbert, Schulze, Antje, Dreger, Peter, Hegenbart, Ute, Krämer, Alwin, Junghanss, Christian, Mügge, Lars-Olof, Hähling, Detlev, Hirt, Carsten, Späth, Christian, Peter, Norma, Opitz, Bernhard, Florschütz, Axel, Reifenrath, Kolja, Zojer, Niklas, Scholl, Sebastian, Pönisch, Wolfram, Heyn, Simone, Vucinic, Vladan, Hochhaus, Andreas, Aul, Carlo, Giagounidis, Aristoteles, Balleisen, Leopold, Oldenkott, Bernd, Staib, Peter, Kiehl, Michael, Schütte, Wolfgang, Naumann, Ralph, Eimermacher, Hartmut, Dörken, Bernd, Sauerland, Cristina, Lengfelder, Eva, Hiddemann, Wolfgang, Wörmann, Bernhard, Müller-Tidow, Carsten, Serve, Hubert, Schliemann, Christoph, Hehlmann, Rüdiger, Berdel, Wolfgang E., Pfirrmann, Markus, Krug, Utz, and Hoffmann, Verena S.

Published
2023
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7. 10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial

Author

Finke, Jürgen, Schaap, Nicolaas Petrus Michael, Zucenka, Andrius, Metzelder, Stephan, Jost, Edgar, Perić, Zinaida, Forghieri, Fabio, Allione, Bernadino, Martelli, Maurizio, Iori, Anna Paola, Wittnebel, Sebastian, Mengarelli, Andrea, Imovilli, Annalisa, Olivieri, Attilio, De Prijck, Bernard José Marie, van der Poel, Marjolein W.M., Junghanß, Christian, Salih, Helmut Rainer, Tafuri, Agostino, Guimarães, José Eduardo, Musso, Maurizio, De Fabritiis, Paolo, Chevallier, Patrice, Selleslag, Dominik Luc, Cascavilla, Nicola, Berneman, Zwi, Jaspers, Aurélie, Zuffa, Eliana, Vanstraelen, Gaëtan, Visani, Giuseppe, Cuijpers, Maria Louisa Henriëtte, De Becker, Ann, Mianulli, Anna Maria, Hackanson, Björn, Mihaylov, Georgi Georgiev, Martinelli, Giovanni, Paolini, Stefania, Zinzani, Pier Luigi, Henkes, Martin, Al-Ali, Haifa Kathrin, La Rosée, Paul, Chierichini, Anna, Cudillo, Laura, Specchia, Giorgina, Šimec, Njetočka Gredelj, Capalbo, Silvana Franca, Spinosa, Giuseppina, Molica, Stefano, de Jonge-Peeters, Susan Dorothé, Lübbert, Michael, Wijermans, Pierre W, Kicinski, Michal, Chantepie, Sylvain, Van der Velden, Walter J F M, Noppeney, Richard, Griškevičius, Laimonas, Neubauer, Andreas, Crysandt, Martina, Vrhovac, Radovan, Luppi, Mario, Fuhrmann, Stephan, Audisio, Ernesta, Candoni, Anna, Legrand, Olivier, Foà, Robin, Gaidano, Gianluca, van Lammeren-Venema, Danielle, Posthuma, Eduardus F M, Hoogendoorn, Mels, Giraut, Anne, Stevens-Kroef, Marian, Jansen, Joop H, de Graaf, Aniek O, Efficace, Fabio, Ammatuna, Emanuele, Vilque, Jean-Pierre, Wäsch, Ralph, Becker, Heiko, Blijlevens, Nicole, Dührsen, Ulrich, Baron, Frédéric, Suciu, Stefan, Amadori, Sergio, Venditti, Adriano, and Huls, Gerwin

Published
2023
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10. FOLFOX plus panitumumab or FOLFOX alone as additive therapy following R0/1 resection of RAS wild-type colorectal cancer liver metastases – The PARLIM trial (AIO KRK 0314)

Author

Modest, Dominik Paul, Karthaus, Meinolf, Kasper, Stefan, Moosmann, Nicolas, Keitel, Verena, Kiani, Alexander, Uhlig, Jens, Jacobasch, Lutz, Fischer v. Weikersthal, Ludwig, Fuchs, Martin, Kaiser, Florian, Lerchenmüller, Christian, Sent, Dagmar, Junghanß, Christian, Held, Swantje, Lorenzen, Sylvie, Kaczirek, Klaus, Jung, Andreas, Stintzing, Sebastian, and Heinemann, Volker

Published
2022
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12. Feasibility of individualized home exercise programs for patients with head and neck cancer–study protocol and first results of a multicentre single-arm intervention trial (OSHO #94).

Author

Felser, Sabine, Rogahn, Julia, Glass, Änne, Bonke, Lars Arne, Strüder, Daniel Fabian, Stolle, Jana, Schulze, Susann, Blaurock, Markus, Kriesen, Ursula, Junghanss, Christian, and Grosse-Thie, Christina

Abstract

Introduction: Patients with head and neck cancer (PwHNC) benefit from targeted exercise interventions: symptom relief, compensation for dysfunction, improvement in quality of life (QoL). Data on acceptance physical interventions in PwHNC are rare. The 'OSHO #94' trial investigates the short- and medium-term effects of individualized home exercise in PwHNC on QoL, physical activity and functionality. The study includes a feasibility phase (proof of concept) in order to evaluate the acceptance. Here we present the study protocol as well as the feasibility results. Methods and analysis: This prospective, multicentre, single-arm intervention study includes PwHNC ≥18 years of age in aftercare or palliative care with stable remission under immunotherapy. The study opened in January 01, 2021, with estimated completion by December 31, 2024. The PwHNC receive an individualized home exercise program consisting of mobilization, coordination, strengthening and stretching exercises. This should be carried out at least three times a week over 12 weeks for 15 to 30 minutes, supplemented by aerobic training two to three times a week for 30 minutes (intervention). Once weekly telephone calls with a physiotherapist are performed. Subsequently, there is a 12-week follow-up (FU) without exercise specifications/contact. Outcomes are measured before and after the intervention and following the FU. Primary outcome of the feasibility phase (n = 25) was the determination of the dropout rate during the intervention with a termination cut off if more than 30% PwHNC withdrew premature. The primary outcome of the OSHO #94' trial (N = 53) is the change in global QoL score from pre- to post-intervention (EORTC QLQ-C30). Secondary outcomes include clinical and patient-reported measures, training details as well as functional diagnostic data (e.g. level of physical activity, training frequency, flexibility, fall risk and aerobic performance). Results: 25 PwHNC were enrolled onto the feasibility cohort. Only16% (4/25 patients) did not complete the study. Therefore, recruitment of PwHNC was continued. The dropout rate was adjusted from 30% (N = 60) to 20% (N = 53, calculated sample size n = 42 PwHNC and 20% (n = 11) to dropout). Conclusions: Individualized home exercise programs in PwHNC in aftercare seem feasible. Consequently, the aim is now to evaluate the short and medium-term effects of individualized home exercise. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Allogeneic hematopoietic stem cell transplantation improves long-term outcome for relapsed AML patients across all ages: results from two East German Study Group Hematology and Oncology (OSHO) trials

Author

Heinicke, Thomas, Krahl, Rainer, Kahl, Christoph, Cross, Michael, Scholl, Sebastian, Wolf, Hans-Heinrich, Hähling, Detlev, Hegenbart, Ute, Peter, Norma, Schulze, Antje, Florschütz, Axel, Schmidt, Volker, Reifenrath, Kolja, Zojer, Niklas, Junghanss, Christian, Sayer, Herbert G., Maschmeyer, Georg, Späth, Christian, Hochhaus, Andreas, Fischer, Thomas, Al-Ali, Haifa Kathrin, and Niederwieser, Dietger

Published
2021
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15. Use of letermovir in off-label indications: Infectious Diseases Working Party of European Society of Blood and Marrow Transplantation retrospective study

Author

Styczyński, Jan, Tridello, Gloria, Xhaard, Alienor, Medinger, Michael, Mielke, Stephan, Taskinen, Mervi, Blijlevens, Nicole, Rodriguez, M. Aranzazu Bermudez, Solano, Carlos, Nikolousis, Emmanouil, Biffi, Alessandra, Groll, Andreas H., Junghanss, Christian, Tsirigotis, Panagiotis, Lioure, Bruno, Šrámek, Jiří, Holler, Ernst, Galaverna, Federica, Fagioli, Franca, Knelange, Nina, Wendel, Lotus, Gil, Lidia, de la Camara, Rafael, Mikulska, Malgorzata, and Ljungman, Per

Published
2021
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18. Addendum to the German Consensus Recommendations on Ponatinib in the Treatment of Chronic Myeloid Leukemia.

Author

Saussele, Susanne, La Rosée, Paul, Kiani, Alexander, Haverkamp, Wilhelm, Jentsch-Ullrich, Kathleen, Stegelmann, Frank, Rieger, Christina, Waller, Cornelius F., Franke, Georg-Nikolaus, Junghanss, Christian, Kirchmair, Rudolf, Theurl, Markus, and le Coutre, Philipp

Subjects
CHRONIC myeloid leukemia, DECISION trees, CARDIOVASCULAR diseases
Abstract

Background: Based on the new data from the primary analysis of the OPTIC (Optimizing Ponatinib Treatment in CP-CML) trial on dose optimization of ponatinib in patients with chronic phase (CP)-CML, the German consensus paper on ponatinib published in 2020 (Saussele S et al., Acta Haematol. 2020) has been updated in this addendum. Summary: Focus is on the update of efficacy and safety of ponatinib, reflecting the new data set, as well as the update of the benefit-risk assessment and recommendations for ponatinib starting dose in CP-CML – provided that the decision to use ponatinib has already been made. Furthermore, based on OPTIC and additional empirical data, the expert panel collaborated to develop a decision tree for ponatinib dosing, specifically for intolerant and resistant patients. The recommendations on cardiovascular management have also been updated based on the most recent 2021 guidelines of the European Society of Cardiology (ESC) on cardiovascular disease prevention in clinical practice. Key Messages: The OPTIC data confirm the high efficacy of ponatinib in patients with CP-CML and provide the basis for individualized dose adjustment during the course of treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial

Author

Beelen, Dietrich Wilhelm, Trenschel, Rudolf, Stelljes, Matthias, Groth, Christoph, Masszi, Tamás, Reményi, Péter, Wagner-Drouet, Eva-Maria, Hauptrock, Beate, Dreger, Peter, Luft, Thomas, Bethge, Wolfgang, Vogel, Wichard, Ciceri, Fabio, Peccatori, Jacopo, Stölzel, Friedrich, Schetelig, Johannes, Junghanß, Christian, Grosse-Thie, Christina, Michallet, Mauricette, Labussiere-Wallet, Hélène, Schaefer-Eckart, Kerstin, Dressler, Sabine, Grigoleit, Goetz Ulrich, Mielke, Stephan, Scheid, Christof, Holtick, Udo, Patriarca, Francesca, Medeot, Marta, Rambaldi, Alessandro, Micò, Maria Caterina, Niederwieser, Dietger, Franke, Georg-Nikolaus, Hilgendorf, Inken, Winkelmann, Nils Rudolf, Russo, Domenico, Socié, Gérard, Peffault de Latour, Régis, Holler, Ernst, Wolff, Daniel, Glass, Bertram, Casper, Jochen, Wulf, Gerald, Menzel, Helge, Basara, Nadezda, Bieniaszewska, Maria, Stuhler, Gernot, Verbeek, Mareike, Grass, Sandra, Iori, Anna Paola, Finke, Juergen, Benedetti, Fabio, Pichlmeier, Uwe, Hemmelmann, Claudia, Tribanek, Michael, Klein, Anja, Mylius, Heidrun Anke, Baumgart, Joachim, Dzierzak-Mietla, Monika, and Markiewicz, Miroslaw

Published
2020
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21. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study

Author

Bekadja, Mohamed, Hamladji, Rose-Marie, Ali, Hocine Ait, Hamdi, Selma, Touhami, Hadj, Mansour, Nourredine Sidi, Willenbacher, Wolfgang, Linkesch, Werner, Nemet, Damir, Pedersen, Robert Shou, Abildgaard, Niels, Laane, Edward, Hein, Marju, Mohty, Mohamad, Eveillard, Jean Richard, Yamani, Abderrazak el, Moreau, Philippe, Sanhes, Laurence, Lepeu, Gérard, Laribi, Kamel, Jourdan, Eric, Fitoussi, Olivier, Allangba, Olivier, Fleury, Joël, Escoffre, Martine, Benramdane, Riad, Cartron, Guillaume, Dine, Gérard, Legouffe, Eric, Harich, Hanns-Detlev, Illmer, Thomas, Dörfel, Steffen, Hannig, Carla Verena, Koenigsmann, Michael, Prange-Krex, Gabriele, Salwender, Hans, Tamm, Ingo, Zeller, Wolfgang, Maasberg, Michael, Schlag, Rudolf, Klausmann, Martine, Uhlig, Jens, Alkemper, Burkhard, Schütz, Stefan, Tessen, Hans-Werner, Mohr, Benno, Schmidt, Peter, Heinrich, Bernhard, Hebart, Holger, Seipelt, Gernot, Zoeller, Thomas, Heits, Frank, Müller-Naendrup, Clemens, Hansen, Richard, Repp, Roland, Von Weikersthal, Ludwig Fischer, Schmits, Rudolf, Heßling, Jörg, Krammer-Steiner, B., Janzen, Viktor, Schauer, Michael, Grüner, Marcus W., Kisro, Jens, Denzlinger, Claudio, Freier, Werner, Junghanss, Christian, Görner, Martin, Laichinger, Katharina, Ostermann, Helmut, Dürk, Heinz, Hess, Georg, Reich, Gernot, Terpos, Evangelos, Dimopoulos, Meletios, Matsouka, Panagiota, Pouli, Anastasia, Anagnostopoulos, Achilles, Masszi, Tamas, Borbényi, Zita, Ivanyi, Janos, Szomor, Arpad, Abadi, Uri, Nagler, Arnon, Magen, Hila, Avivi, Irit, Quitt, Miriam, Palumbo, Antonio, Boccadoro, Mario, De Stefano, Valerio, Za, Tommaso, Vallisa, Daniele, Foa, Roberto, Corso, Alessandro, Bosi, Alberto, Vacca, Angelo, Lanza, Francesco, Palazzo, Giulia, Avvisati, Giuseppe, Cavo, Michele, Ferrara, Felicetto, Consoli, Ugo, Cantonetti, Maria, Angelucci, Emanuele, Califano, Catello, Di Raimondo, Francesco, Guarini, Attilio, Musso, Maurizio, Pizzuti, Michele, Giuliani, Nicola, Ardizzoia, Antonio, Di Renzo, Nicola, Gaidano, Gianluca, Gozzetti, Alessandro, Pitini, Vincenzo, Farina, Gabriella, Centurioni, Riccardo, De Fabritiis, Paolo, Iuliano, Francesco, La Nasa, Giorgio, La Verde, Giacinto, Pane, Fabrizio, Recine, Umberto, La Targia, Maria, Mineo, Giuseppe, Cangialosi, Clotilde, Fagnani, Daniele, Federici, Augusto, Romano, Atelda, Specchia, Giorgina, Storti, Sergio, Bongarzoni, Velia, Bacigalupo, Andrea, Gobbi, Marco, Latte, Giancarlo, Mannina, Donato, Capalbo, Silvana, Lejniece, Sandra, Pečeliūnas, Valdas, Jurgutis, Mindaugas, Stankovic, Svetlana, Legiec, Wojciech, Woszczyk, Dariusz, Hołojda, Jadwiga, Gornik, Slawomir, Pluta, Andrzej, Morawiec-Szymonik, Elzbieta, Kyrcz-Krzemien, Slawomira, Homenda, Wojciech, Grosicki, Sebastian, Sulek, Kazimierz, Lange, Andrzej, Kloczko, Janusz, Starzak-Gwozdz, Jolanta, Hellmann, Andrzej, Komarnicki, Mieczyslaw, Kuliczkowski, Kazimierz, Viveiros, Carolina, Gonçalves, Cristina, Esefyeva, Natalia, Kochkareva, Julia, Kaplanov, Kamil, Volodicheva, Elena, Laricheva, Elena, Dergacheva, Valentina, Chukavina, Marina, Volchenko, Natalia, Nazarova, Irina, Anchukova, Ludmila, Ovanesova, Elena, Gritsenko, Taras, Salogub, Galina, Magomedova, Ludmila, Kuznetsova, Irina, Osyunikhina, Svetlana, Serdyuk, Olga, Karyagina, Elena, Ivanova, Valentina, Černelč, Slovenia Peter, Louw, Vernon, Coetzee, Corlia, Gunther, Karen, Moodley, Dhayanithi, Duran, Soledad, Gutiérrez, Asunción Echeveste, De Oteyza, Jaime Perez, Capote, Francisco Javier, Casanova, Maria, Sanchez, Jesus Martin, Rios-Herranz, Eduardo, Ibañez-Garcia, Jeronima, Herranz, Maria Jose, Hernandez, Belen, Sanchez, Sara Sanchez, Escalante, Fernando, Carnicero, Fernando, Lleonart, Joan Bargay, Gironella, Mercedes, Martínez, Rafael, De La Guia, Ana Lopez, Palomera, Luis, Iglesias, Rebeca, Ramos, Fernando Solano, De La Serna, Javier, Sanchez, Pedro Garcia, Vidal, Juan Besalduch, Mateos, Maria-Victoria, Morfa, Miguel Diaz, Beksac, Turkey – Meral, Vural, Filiz, Aydin, Yildiz, Unal, Ali, Goker, Hakan, Bilgir, Oktay, Guvenc, Birol, Turgut, Mehmet, Ozet, Gulsum Gulistan, Ali, Ridvan, Masliak, Zvenyslava, Kyselyova, Maryna, Glushko, Nataliia, Vybyrana, Renata, Skrypnyk, Igor, Tretyak, Natalya, Kharchevska, Tetiana, Dyagil, Iryna, Popovs'ka, Tetiana, Shimanskiy, Vadim, Lysa, Tamila, Oliynyk, Hanna, Vilchevskaya, Kateryna, Kryachok, Iryna, Popovych, Yuriy, Romanyuk, Natalia, Yushchenko, Natalia, Kaplan, Polina, Rekhtman, Grygoriy, Pylypenko, Halyna, Kozlov, Viktor, Drach, Johannes, Harousseau, Jean-Luc, Einsele, Hermann, Goldschmidt, Hartmut, Facon, Thierry, Michalet, Mauricette, Savchenko, Valery G., De la Rubia, Javier, Cook, Gordon, Mellqvist, Ulf-Henrik, Ludwig, Heinz, Beksac, Meral, Bekadja, Mohamed Amine, Durán, Maria Soledad, Kochkareva, Yulia, Berthou, Christian, Silva, João, Pedersen, Robert Schou, Černelč, Peter, Potamianou, Anna, Couturier, Catherine, Feys, Caroline, and Thoret-Bauchet, Florence

Published
2018
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22. Correction to: Allogeneic hematopoietic stem cell transplantation improves long‑term outcome for relapsed AML patients across all ages: results from two East German Study Group Hematology and Oncology (OSHO) trials

Author

Heinicke, Thomas, Krahl, Rainer, Kahl, Christoph, Cross, Michael, Scholl, Sebastian, Wolf, Hans‑Heinrich, Hähling, Detlev, Hegenbart, Ute, Peter, Norma, Schulze, Antje, Florschütz, Axel, Schmidt, Volker, Reifenrath, Kolja, Zojer, Niklas, Junghanss, Christian, Sayer, Herbert G., Maschmeyer, Georg, Späth, Christian, Hochhaus, Andreas, Fischer, Thomas, Al‑Ali, Haifa Kathrin, and Niederwieser, Dietger

Published
2021
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23. Comparative Analyses of Targeted Myeloid Cancer Next-Generation Sequencing Panel in Fresh Blood, Bone Marrow and FFPE Material.

Author

Hobeck, Andrea Daniela, Wendt, Sophia, Krohn, Saskia, Knuebel, Gudrun, Bartels, Stephan, Schipper, Elisa, Junghanss, Christian, and Murua Escobar, Hugo

Subjects
NUCLEOTIDE sequencing, SOMATIC mutation, COMPARATIVE studies, HEMATOLOGIC malignancies, BONE marrow, DATABASES
Abstract

Next-generation sequencing is a vital tool for personalized diagnostics and therapies in cancer. Despite numerous advantages, the method depends on multiple parameters regarding the sample material, e.g., sample fixation. A panel's ability to ensure balanced pre-amplification of the regions of interest is challenging, especially in targeted sequencing approaches, but of significant importance to its applicability across hematological malignancies and solid tumors. This study comparatively evaluated the technical performance of the commercially available OncomineTM Myeloid Panel in fresh and Formalin-fixed paraffin-embedded (FFPE) material by using an Ion Torrent™ Personal Genome Machine™ System and Ion GeneStudio S5 System platform. In total, 114 samples were analyzed, including 55 fresh materials and 59 FFPE samples. Samples were sequenced with a minimum of one million reads. Amplicons with coverage below 400 reads were classified as underperforming. In fresh material, 49/526 amplicons were identified as performing insufficiently, corresponding with 18 genes. Using FFPE material, 103/526 amplicons underperformed. Independent of input material, regions in 27 genes, including ASXL1, BCOR and BRAF, did not match quality parameters. Subsequently, exemplary mutations were extracted from the Catalogue of Somatic Mutations in Cancer database. This technical evaluation of the OncomineTM Myeloid Panel identified amplicons that do not achieve adequate coverage levels and which need to be considered when interpreting sequencing. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Physical exercise recommendations for patients with chronic myeloid leukemia based on individual preferences identified in a large international patient survey study of the East German Study Group for Hematology and Oncology (OSHO #97).

Author

Hollenbach, Lina, Rogahn, Julia, le Coutre, Philipp, Schulze, Susann, Muegge, Lars-Olof, Geissler, Jan, Gruen, Julia, Junghanss, Christian, and Felser, Sabine

Subjects
CHRONIC myeloid leukemia, SUNBURN, SKIN cancer, PATIENT surveys, SWIMMING pools, MYELOPROLIFERATIVE neoplasms, PROTEIN-tyrosine kinase inhibitors
Abstract

Background: Tyrosine kinase inhibitors (TKIs) have significantly lowered mortality of chronic myeloid leukemia (CML) patients adjusting life expectancy to that of the standard population. However, CML and its treatment with TKIs causes a high disease burden. Physical exercise (PE) could be a non-pharmacological approach to reducing these and improving quality of life. Purpose: The aim of this study was to determine the individual disease burden as well as PE preferences of CML patients and to deduce thereof specific PE recommendations. Methods: This multicenter survey was conducted in cooperation with the LeukaNET/Leukemia-patient network including CML patients aged =18 years (German Registry of Clinical Trials, DRKS00023698). The severity of selected symptoms was assessed using the adapted Myeloproliferative Neoplasms Symptom Assessment Form: 0 (absent), 1-30 (mild), 31-70 (moderate), or 71-100 (severe). Information about patients' PE needs and preferences depending on their motivation was recorded. Results: A total of 212 questionnaires were analyzed (52% female, median age 54 years). The prevalence of moderate-to-severe symptoms was 49% for fatigue, 40% for musculoskeletal pain, and 37% for concentration problems. Other commonly reported symptoms included skin reactions (42%) and weight gain (24%). The proportion of overweight/obese patients was 52%. Half of all respondents requested more information regarding PE. Patients with CML preferred individual training (82%), located outdoors (71%), at home (47%), or in an indoor swimming pool (31%). Regarding the training frequency, sportsinactive patients preferred a frequency of 1-2 training sessions per week, whereas sports-active patients preferred 3-4 sessions per week (p <0.001). Sports-inactive patients preferred a training time of 15-45 minutes, while sports-active patients preferred 30-60 minutes (p = 0.002). Subsequently, PE recommendations were developed for patients with CML. Combined resistance and endurance training (moderate intensity twice per week for 30 minutes) was recommended for beginners. Obese patients should prioritize joint-relieving sports. To reduce the risk of skin reactions, direct sunlight and possibly water sports should be avoided, and UV protection should be used. Conclusion: Counseling and motivation of CML patients to be physically active should be part of the standard of care as well as support for implementation. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Cross-Species Comparison of the Pan-RAF Inhibitor LY3009120's Anti-Tumor Effects in Equine, Canine, and Human Malignant Melanoma Cell Lines.

Author

Gao, Yu, Packeiser, Eva-Maria, Wendt, Sophia, Sekora, Anett, Cavalleri, Jessika-Maximiliane V., Pratscher, Barbara, Alammar, Moosheer, Hühns, Maja, Brenig, Bertram, Junghanss, Christian, Nolte, Ingo, and Murua Escobar, Hugo

Subjects
MELANOMA, CANCER cells, CELL lines, SKIN cancer, COMPARATIVE method, BRAF genes
Abstract

Malignant melanomas (MMs) are the abnormal proliferation of melanocytes and are one of the lethal skin cancers in humans, equines, and canines. Accordingly, MMs in companion animals can serve as naturally occurring animal models, completing conventional cancer models. The common constitutive activation of the MAPK and PI3K pathways in MMs has been described in all three species. Targeting the related pathways is considered a potential option in comparative oncologic approaches. Herein, we present a cross-species comparative analysis exposing a set of ten melanoma cell lines (one human, three equine, and six canine) derived from primary tumors or metastasis to a pan-RAF and RAF dimer inhibitor (LY3009120). Cellular response (proliferation, biomass, metabolism, early and late apoptosis/necrosis, and morphology) and the presence of pathogenic single-nucleotide variants (SNVs) within the mutational hotspot genes BRAF exon 11 and 15, NRAS exon 2 and 3, KRAS exon 2, and KIT exon 11 were analyzed. This study showed that equine malignant melanoma (EMM) cells (MelDuWi) harbor the KRAS p.Q61H mutation, while canine malignant melanoma (CMM) cells (cRGO1 and cRGO1.2) carry NRAS p.G13R. Except for EMM metastasis cells eRGO6 (wild type of the above-mentioned hotspot genes), all melanoma cell lines exhibited a decrease in dose dependence after 48 and 72 h of exposure to LY3009120, independent of the mutation hotspot landscape. Furthermore, LY3009120 caused significant early apoptosis and late apoptosis/necrosis in all melanoma cell lines except for eRGO6. The anti-tumor effects of LY3009120 were observed in nine melanoma cell lines, indicating the potential feasibility of experimental trials with LY3009120. The present study reveals that the irradiation-resistant canine metastasis cells (cRGO1.2) harboring the NRAS p.G13R mutation are significantly LY3009120-sensitive, while the equine metastases-derived eRGO6 cells show significant resistance to LY3009120, which make them both valuable tools for studying resistance mechanisms in comparative oncology. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Exploring Thiazolopyridine AV25R: Unraveling of Biological Activities, Selective Anti-Cancer Properties and In Silico Target and Binding Prediction in Hematological Neoplasms.

Author

Ladwig, Annika, Gupta, Shailendra, Ehlers, Peter, Sekora, Anett, Alammar, Moosheer, Koczan, Dirk, Wolkenhauer, Olaf, Junghanss, Christian, Langer, Peter, and Murua Escobar, Hugo

Subjects
SMALL molecules, BIOMOLECULES, GENE expression, MOLECULAR docking, TUMORS
Abstract

Thiazolopyridines are a highly relevant class of small molecules, which have previously shown a wide range of biological activities. Besides their anti-tubercular, anti-microbial and anti-viral activities, they also show anti-cancerogenic properties, and play a role as inhibitors of cancer-related proteins. Herein, the biological effects of the thiazolopyridine AV25R, a novel small molecule with unknown biological effects, were characterized. Screening of a set of lymphoma (SUP-T1, SU-DHL-4) and B- acute leukemia cell lines (RS4;11, SEM) revealed highly selective effects of AV25R. The selective anti-proliferative and metabolism-modulating effects were observed in vitro for the B-ALL cell line RS4;11. Further, we were able to detect severe morphological changes and the induction of apoptosis. Gene expression analysis identified a large number of differentially expressed genes after AV25R exposure and significant differentially regulated cancer-related signaling pathways, such as VEGFA-VEGFR2 signaling and the EGF/EGFR pathway. Structure-based pharmacophore screening approaches using in silico modeling identified potential biological AV25R targets. Our results indicate that AV25R binds with several proteins known to regulate cell proliferation and tumor progression, such as FECH, MAP11, EGFR, TGFBR1 and MDM2. The molecular docking analyses indicates that AV25R has a higher binding affinity compared to many of the experimentally validated small molecule inhibitors of these targets. Thus, here we present in vitro and in silico analyses which characterize, for the first time, the molecular acting mechanism of AV25R, including cellular and molecular biologic effects. Additionally, this predicted the target binding of the molecule, revealing a high affinity to cancer-related proteins and, thus, classified AVR25 for targeted intervention approaches. [ABSTRACT FROM AUTHOR]

Published
2023
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35. Basic ctDNA Panel Promises Affordable Clinical Validity in Colon Cancer Patients but Not in Pancreas Cancer Patients.

Author

Radefeldt, Mandy, Stellmacher-Kaiser, Silke, Krake, Susann, Kragl, Brigitte, Lemke, Sabrina, Beetz, Christian, Bauer, Peter, Junghanß, Christian, and Al-Ali, Ruslan

Subjects
PANCREATIC cancer, CIRCULATING tumor DNA, COLON cancer, CANCER patients, SOMATIC mutation, COLON (Anatomy)
Abstract

The potential of circulating tumor DNA (ctDNA) as a biomarker to assess the progression of various solid tumors has been explored extensively. In this study, we investigated the feasibility of utilizing a ctDNA sequencing panel specifically designed to target the most frequently mutated genomic regions in colon and pancreas cancers. Through somatic analysis of colon and pancreas tumors, we targeted 27 regions within eight genes. By employing PCR amplification and Illumina NGS, we ensured that each region was adequately covered with a minimum of 5000 reads (with an average of 12,000 reads). Our method exhibited reproducibility with repetition and dilutions. The positive detection threshold for ctDNA was set at a cutoff value of 0.5% ctDNA of the total reads using IGV. Among the samples analyzed, 71% of colon cancer cases displayed somatic mutations covered by the targeted regions. Within this group, detectable ctDNA was observed in 34% of the cases. Conversely, in pancreatic cancer, 55% of mutations were covered by the panel's regions, but only 13% of these cases exhibited detectable ctDNA. In follow-ups with the patients, changes in ctDNA percentages demonstrated complete concordance with changes in the clinical condition in 88% of the cases. Our findings suggest that employing a basic ctDNA-targeted panel can serve as a cost-effective and reliable approach for repeated monitoring of the efficacy of colon cancer therapy. However, in the case of pancreatic cancer, ctDNA showed limited utility, and alternative biomarkers may offer superior diagnostic value. Additionally, we found that a negative ctDNA test is not a guarantee for a relapse-free recovery; thus, we recommend a continuous follow-up with the patient on a long-term basis. [ABSTRACT FROM AUTHOR]

Published
2023
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36. Efficacy and safety of keratinocyte growth factor (palifermin) for prevention of oral mucositis in TBI-based allogeneic hematopoietic stem cell transplantation

Author

Schmidt, Volker, Niederwieser, Dietger, Schenk, Thomas, Behre, Gerhard, Klink, Anne, Pfrepper, Christian, Hinke, Axel, Beelen, Dietrich W., Junghanss, Christian, Uharek, Lutz, Krüger, William H., Hochhaus, Andreas, Sayer, Herbert G., and for the East German Study Group for Hematology and Oncology (OSHO)

Published
2018
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39. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial

Author

Röllig, Christoph, Serve, Hubert, Hüttmann, Andreas, Noppeney, Richard, Müller-Tidow, Carsten, Krug, Utz, Baldus, Claudia D, Brandts, Christian H, Kunzmann, Volker, Einsele, Hermann, Krämer, Alwin, Schäfer-Eckart, Kerstin, Neubauer, Andreas, Burchert, Andreas, Giagounidis, Aristoteles, Krause, Stefan W, Mackensen, Andreas, Aulitzky, Walter, Herbst, Regina, Hänel, Mathias, Kiani, Alexander, Frickhofen, Norbert, Kullmer, Johannes, Kaiser, Ulrich, Link, Hartmut, Geer, Thomas, Reichle, Albert, Junghanß, Christian, Repp, Roland, Heits, Frank, Dürk, Heinz, Hase, Jana, Klut, Ina-Maria, Illmer, Thomas, Bornhäuser, Martin, Schaich, Markus, Parmentier, Stefani, Görner, Martin, Thiede, Christian, von Bonin, Malte, Schetelig, Johannes, Kramer, Michael, Berdel, Wolfgang E, and Ehninger, Gerhard

Published
2015
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41. Physical exercise recommendations for patients with polycythemia vera based on preferences identified in a large international patient survey study of the East German Study Group for Hematology and Oncology (OSHO #97).

Author

Felser, Sabine, Rogahn, Julia, Hollenbach, Lina, Gruen, Julia, le Coutre, Philipp, Al‐Ali, Haifa Kathrin, Schulze, Susann, Muegge, Lars‐Olof, Kraze‐Kliebhahn, Veronika, and Junghanss, Christian

Subjects
POLYCYTHEMIA vera, PATIENT surveys, EXERCISE therapy, MYELOPROLIFERATIVE neoplasms, HEMATOLOGY, MYELOFIBROSIS, POSTPOLIOMYELITIS syndrome
Abstract

Background: Exercise therapy during cancer treatment reduces symptom burden and improves quality of life (QoL). Polycythemia vera (PV) is a myeloproliferative neoplasia associated with good overall survival (up to decades) but a significant symptom burden, including thromboembolic events and dysesthesias. There are no specific exercise recommendations for patients with PV. Thus, we aimed to determine the exercise preferences of patients with PV and to derive specific recommendations based on the most commonly reported symptoms. Methods: This multicenter survey included patients with PV ≥18 years old. Demographic, clinical, and disease burden data were collected. The severity of selected symptoms was assessed using the adapted Myeloproliferative Neoplasms Symptom Assessment Form: 0 (absent), 1–30 (mild), 31–70 (moderate), or 71–100 (severe). The patients' information needs about physical activity (PA) and exercise preferences were recorded depending on their motivation and analyzed with regard to demographic aspects. Results: The sample comprised 182 patients (68% female, 61 ± 12 years). The prevalence of moderate‐to‐severe symptoms was 60% for fatigue, 44% for concentration problems, and 35% for bone/muscle pain. Other commonly reported symptoms included skin reactions (49%), splenomegaly (35%), and increased bleeding tendency (28%). Overall, 67% of respondents requested more information regarding PA. Patients with PV preferred individual training (79%) located outdoors (79%) or at home (56%). Regarding the amount of training, sports‐inactive patients preferred a frequency of 1–2 times/week and session durations of 15–45 min, whereas sports‐active patients preferred 3–4 times/week and 30–60 min (p < 0.001). Higher sport‐inactiveness was observed in patients with lower educational level compared to patients with higher educational level (69% vs. 50%, p = 0.021). For beginners, combined resistance‐endurance (circuit) training two times/week, which can be performed outdoors or at home, should be recommended. In the case of splenomegaly or bleeding symptoms, exercises with a low injury risk should be chosen. Conclusion: PA is important for patients with PV; therefore, counseling should be integrated into the treatment plan. Specifically, patients with low educational level should be addressed. Prospective studies are warranted to evaluate the effects of the novel exercise recommendations. [ABSTRACT FROM AUTHOR]

Published
2023
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42. Questions arising on phlebotomy in polycythemia vera: prophylactic measures to reduce thromboembolic events require patient-focused decisions

Author

Heidel, Florian H., Al-Ali, Haifa-Kathrin, Hirt, Carsten, Kämpfe, Dietrich, Jentsch-Ullrich, Kathleen, Junghanss, Christian, Nowak, Ralf, Schwarzer, Andreas, Spohn, Claudia, Vucinic, Vladan, Hochhaus, Andreas, Lange, Thoralf, and For the Working Party Myeloproliferative Neoplasms of the East German Study Group Hematology/Oncology (OSHO)

Published
2018
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44. Double-Blind, Placebo Controlled, Randomized, Multicenter, Phase II Study to Assess the Efficacy of the High Affinity CXCR4 Inhibitor BL-8040 As Addition to Consolidation Therapy in AML By the SAL and OSHO Leukemia Study Groups

Author

Jaramillo Segura, Sonia, Wass, Maxi, Schaffrath, Judith, Rieger, Kathrin, Nogai, Axel, Haenel, Mathias, Herbst, Regina, Stoelzel, Friedrich, Röllig, Christoph, Jost, Edgar, Schlenk, Richard F., Noppeney, Richard, Brandts, Christian H., Krug, Utz, Goetze, Katharina S., Buske, Sebastian, Florschütz, Axel, Schubert, Jörg, Opitz, Bernhard, Mohren, Martin, Eßeling, Eva, von Witzendorff, Stephan, Subklewe, Marion, Kaufmann, Martin, Frickhofen, Norbert, Scholz, Christian W, Schäfer-Eckart, Kerstin, Kunzmann, Volker, Schmidt-Hieber, Martin, Sayer, Herbert G., Rank, Andreas, Hemmati, Philipp, Schueler, Frank, Kowoll, Simone, Scheller, Marina, Steighardt, Jörg, Edemir, Bayram, Mueller, Lutz Peter, Gliko-Kabir, Irit, Ludwig-Kraus, Beatrice, Edemir, Sabine, Sorani, Ella, Binder, Mascha, Vainstein, Abi, Kadosh, Shaul, Gromann, Cora, Wienke, Andreas, Baldus, Claudia D., Platzbecker, Uwe, Serve, Hubert, Bornhaeuser, Martin, Junghanss, Christian, and Mueller-Tidow, Carsten

Published
2022
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45. Increased LFS Following Hematopoietic Cell Transplantation As Compared to Conventional Consolidation Therapy in Patients >60 Years with AML in First Complete Remission and a Matched Donor: Results of a Randomized Phase III Study

Author

Niederwieser, Dietger, Hasenclever, Dirk, Berdel, Wolfgang E., Biemond, Bart J., Al-Ali, Haifa Kathrin, Chalandon, Yves, Van Gelder, Michel, Junghanss, Christian, Gahrton, Goesta, Haenel, Mathias, Hehlmann, Rüdiger, Heinicke, Thomas, Hochhaus, Andreas, Iacobelli, Simona, Kooy, Rien van Marwijk, Kröger, Nicolaus, Janssen, Jeroen J.W.M., Jentzsch, Madlen, Breywisch, Frank, Mohty, Mohamad, Masouridi-Levrat, Stavroula, Ossenkoppele, Gert, Passweg, Jakob, Pönisch, Wolfram, Schetelig, Johannes, Schliemann, Christoph, Schwind, Sebastian, Stelljes, Matthias, Valk, Peter JM, Lowenberg, Bob, and Cornelissen, Jan J.

Published
2022
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46. Combined BCL-2 and PI3K/AKT Pathway Inhibition in KMT2A -Rearranged Acute B-Lymphoblastic Leukemia Cells.

Author

Holz, Clemens, Lange, Sandra, Sekora, Anett, Knuebel, Gudrun, Krohn, Saskia, Murua Escobar, Hugo, Junghanss, Christian, and Richter, Anna

Subjects
PI3K/AKT pathway, ACUTE leukemia, HEMATOLOGIC malignancies, CHRONIC lymphocytic leukemia, ACUTE myeloid leukemia
Abstract

Numerous hematologic neoplasms, including acute B-lymphoblastic leukemia (B-ALL), are characterized by overexpression of anti-apoptotic BCL-2 family proteins. Despite the high clinical efficacy of the specific BCL-2 inhibitor venetoclax in acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL), dose limitation and resistance argue for the early exploration of rational combination strategies. Recent data indicated that BCL-2 inhibition in B-ALL with KMT2A rearrangements is a promising intervention option; however, combinatorial approaches have not been in focus so far. The PI3K/AKT pathway has emerged as a possible target structure due to multiple interactions with the apoptosis cascade as well as relevant dysregulation in B-ALL. Herein, we demonstrate for the first time that combined BCL-2 and PI3K/AKT inhibition has synergistic anti-proliferative effects on B-ALL cell lines. Of note, all tested combinations (venetoclax + PI3K inhibitors idelalisib or BKM-120, as well as AKT inhibitors MK-2206 or perifosine) achieved comparable anti-leukemic effects. In a detailed analysis of apoptotic processes, among the PI3K/AKT inhibitors only perifosine resulted in an increased rate of apoptotic cells. Furthermore, the combination of venetoclax and perifosine synergistically enhanced the activity of the intrinsic apoptosis pathway. Subsequent gene expression studies identified the pro-apoptotic gene BBC3 as a possible player in synergistic action. All combinatorial approaches additionally modulated extrinsic apoptosis pathway genes. The present study provides rational combination strategies involving selective BCL-2 and PI3K/AKT inhibition in B-ALL cell lines. Furthermore, we identified a potential mechanistic background of the synergistic activity of combined venetoclax and perifosine application. [ABSTRACT FROM AUTHOR]

Published
2023
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47. X‐linked inhibitor of apoptosis protein represents a promising therapeutic target for relapsed/refractory ALL.

Author

Carlet, Michela, Schmelz, Karin, Vergalli, Jenny, Herold, Tobias, Senft, Daniela, Jurinovic, Vindi, Hoffmann, Thomas, Proba, Jutta, Weichert, Nina, Junghanß, Christian, Roth, Mareike, Eschenburg, Georg, Barz, Malwine, Henze, Günter, Eckert, Cornelia, Eggert, Angelika, Zuber, Johannes, Hundsdoerfer, Patrick, and Jeremias, Irmela

Abstract

Acute lymphoblastic leukemia (ALL) represents the most frequent malignancy in children, and relapse/refractory (r/r) disease is difficult to treat, both in children and adults. In search for novel treatment options against r/r ALL, we studied inhibitor of apoptosis proteins (IAP) and Smac mimetics (SM). SM‐sensitized r/r ALL cells towards conventional chemotherapy, even upon resistance against SM alone. The combination of SM and chemotherapy‐induced cell death via caspases and PARP, but independent from cIAP‐1/2, RIPK1, TNFα or NF‐κB. Instead, XIAP was identified to mediate SM effects. Molecular manipulation of XIAP in vivo using microRNA‐30 flanked shRNA expression in cell lines and patient‐derived xenograft (PDX) models of r/r ALL mimicked SM effects and intermediate XIAP knockdown‐sensitized r/r ALL cells towards chemotherapy‐induced apoptosis. Interestingly, upon strong XIAP knockdown, PDX r/r ALL cells were outcompeted in vivo, even in the absence of chemotherapy. Our results indicate a yet unknown essential function of XIAP in r/r ALL and reveal XIAP as a promising therapeutic target for r/r ALL. Synopsis: Smac mimetics sensitize relapsed/refractory acute leukemia (r/r ALL) cell lines towards chemotherapy, independently from TNFα, RIPK1, NFκB and cIAP1/2 signaling. Knockdown in PDX models shows that XIAP harbors an essential function in vivo and represents an important therapeutic target for r/r ALL. r/r ALL cell lines are sensitized to standard chemotherapy by co‐treatment with Smac mimetics (SM).TNFα, RIPK1, NFκB and cIAP1/2 are dispensable for apoptosis induced by the combination of SM and conventional chemotherapy in r/r ALL.To study the role of XIAP in vivo, a miR30‐based, fluorochrome‐guided system was established, with distinct promoters inducing different knockdown strengths.Moderate XIAP knockdown mimics the effects of SM and sensitizes r/r ALL to chemotherapy, making XIAP an interesting therapeutic target to enhance chemotherapy.In PDX models in vivo, strong XIAP knockdown alone reduces ALL growth, demonstrating that XIAP harbors an essential function and represents an interesting therapeutic target in r/r ALL. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Anxieties, age and motivation influence physical activity in patients with myeloproliferative neoplasms - a multicenter survey from the East German study group for hematology and oncology (OSHO #97).

Author

Felser, Sabine, Rogahn, Julia, le Coutre, Philipp, Kathrin Al-Ali, Haifa, Schulze, Susann, Muegge, Lars-Olof, Gruen, Julia, Geissler, Jan, Kraze-Kliebhahn, Veronika, and Junghanss, Christian

Subjects
MYELOPROLIFERATIVE neoplasms, PHYSICAL activity, QUALITY of life, ANXIETY, MOTIVATION (Psychology), PSYCHO-oncology
Abstract

Background: Physical activity (PA) is a non-pharmacological approach to alleviate symptom burden and improve health-related quality of life (HrQoL) in cancer patients (pts). Whether pts with myeloproliferative neoplasms (MPN) PA behavior changes due to symptom burden and/or knowledge of the putative beneficial effects of PA has not yet been investigated. Methods: We performed a large questionnaire study in MPN pts. Self-reported PA behavior and potential influencing factors of 634 MPN pts were analyzed. Questionnaires were used to assess demographics, anxiety, severity of symptoms, HrQoL, current level of everyday and sports activities, and the level of information regarding the importance/possibilities of PA. According to their PA, the pts were assigned to the three groups: "inactive", "non-targeted active", and "sporty active" and compared with each other. Results: Key findings are that in 73% of the pts, the disease had an impact on PA, with 30% of pts reducing their PA. The prevalence of anxieties (e.g., occurrence of thrombosis and bleeding) regarding PA was 45%. Sporty active pts had a lower symptom burden and better HrQoL (p ≤ 0.001) compared to the other groups. Inactive pts were significantly older and had a higher body mass index than sporty active pts. Inactive and non-targeted active pts felt less informed about the importance/possibilities of PA (p = 0.002). Conclusion: Our results suggest that especially older and non-sporty MPN pts could benefit from motivational as well as disease-specific PA information. This study was registered at the German Registry of Clinical Trials, DRKS00023698. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Short-term immune-checkpoint inhibition partially rescues perturbed bone marrow hematopoiesis in mismatch-repair deficient tumors.

Author

Krone, Paula, Wolff, Annabell, Teichmann, Julia, Maennicke, Johanna, Henne, Julia, Engster, Leonie, Salewski, Inken, Bergmann, Wendy, Junghanss, Christian, and Maletzki, Claudia

Subjects
IMMUNE checkpoint inhibitors, BONE marrow, HEMATOPOIESIS, MYELOID-derived suppressor cells, REGULATORY T cells, HEREDITARY nonpolyposis colorectal cancer
Abstract

Wide-spread cancer-related immunosuppression often curtails immune-mediated antitumoral responses. Immune-checkpoint inhibitors (ICIs) have become a state-of-the-art treatment modality for mismatch repair-deficient (dMMR) tumors. Still, the impact of ICI-treatment on bone marrow perturbations is largely unknown. Using anti-PD1 and anti-LAG-3 ICI treatments, we here investigated the effect of bone marrow hematopoiesis in tumor-bearing Msh2loxP/loxP;TgTg(Vil1-cre) mice. The OS under anti-PD1 antibody treatment was 7.0 weeks (vs. 3.3 weeks and 5.0 weeks, control and isotype, respectively). In the anti-LAG-3 antibody group, OS was 13.3 weeks and thus even longer than in the anti-PD1 group (p = 0.13). Both ICIs induced a stable disease and reduced circulating and splenic regulatory T cells. In the bone marrow, a perturbed hematopoiesis was identified in tumor-bearing control mice, which was partially rescued by ICI treatment. In particular, B cell precursors and innate lymphoid progenitors were significantly increased upon anti-LAG-3 therapy to levels seen in tumor-free control mice. Additional normalizing effects of ICI treatment were observed for lin−c-Kit+IRF8+ hematopoietic stem cells, which function as a "master" negative regulator of the formation of polymorphonuclear-myeloid-derived suppressor cell generation. Accompanying immunofluorescence on the TME revealed significantly reduced numbers of CD206+F4/80+ and CD163+ tumor-associated M2 macrophages and CD11b+Gr1+ myeloid-derived suppressor cells especially upon anti-LAG-3 treatment. This study confirms the perturbed hematopoiesis in solid cancer. Anti-LAG-3 treatment partially restores normal hematopoiesis. The interference of anti-LAG-3 with suppressor cell populations in otherwise inaccessible niches renders this ICI very promising for subsequent clinical application. [ABSTRACT FROM AUTHOR]

Published
2023
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