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3. CD37 is a safe chimeric antigen receptor target to treat acute myeloid leukemia

Author

Caulier, Benjamin, Joaquina, Sandy, Gelebart, Pascal, Dowling, Tara Helén, Kaveh, Fatemeh, Thomas, Moritz, Tandaric, Luka, Wernhoff, Patrik, Katyayini, Niveditha Umesh, Wogsland, Cara, Gjerstad, May Eriksen, Fløisand, Yngvar, Kvalheim, Gunnar, Marr, Carsten, Kobold, Sebastian, Enserink, Jorrit M., Gjertsen, Bjørn Tore, McCormack, Emmet, Inderberg, Else Marit, and Wälchli, Sébastien

Published
2024
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5. Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response: clinical and immunological effects

Author

Geelen, Inge G.P., Gullaksen, Stein-Erik, Ilander, Mette M., Olssen-Strömberg, Ulla, Mustjoki, Satu, Richter, Johan, Blijlevens, Nicole M.A., Smit, Willem M., Gjertsen, Bjorn T., Gedde-Dahl, Tobias, Markevärn, Berit, Koppes, Malika M.A., Westerweel, Peter E., Hjorth-Hansen, Henrik, and Janssen, Jeroen J.W.M.

Published
2023
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8. Overlapping features of therapy-related and de novo NPM1-mutated AML

Author

Othman, Jad, Meggendorfer, Manja, Tiacci, Enrico, Thiede, Christian, Schlenk, Richard, Dillon, Richard, Stasik, Sebastian, Venanzi, Alessandra, Bertoli, Sarah, Delabesse, Eric, Dumas, Pierre-Yves, Pigneux, Arnaud, Bidet, Audrey, Gilkes, Amanda F., Thomas, Ian, Voso, Maria Teresa, Rambaldi, Alessandro, Brunetti, Lorenzo, Perriello, Vincenzo M., Andresen, Vibeke, Gjertsen, Bjorn T., Martelli, Maria Paola, Récher, Christian, Röllig, Christoph, Bornhäuser, Martin, Serve, Hubert, Müller-Tidow, Carsten, Baldus, Claudia D., Haferlach, Tortsten, Russell, Nigel, and Falini, Brunangelo

Published
2023
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9. Rapid label expansion based on public-private collaboration in IMPRESS-Norway.

Author

Helland, Aslaug, primary, Tasken, Kjetil, additional, Blix, Egil Støre, additional, Lonning, Per Eystein, additional, Gjertsen, Bjorn T., additional, Hovland, Randi, additional, Randen, Ulla, additional, Gilje, Bjornar, additional, Kyte, Jon Amund, additional, Flobak, Åsmund, additional, Russnes, Hege, additional, Fagereng, Gro Live, additional, and Smeland, Sigbjørn, additional

Published
2024
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10. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia.

Author

Kreitman, Robert, Dearden, Claire, Zinzani, Pier, Delgado, Julio, Karlin, Lionel, Robak, Tadeusz, Gladstone, Douglas, le Coutre, Philipp, Dietrich, Sascha, Gotic, Mirjana, Larratt, Loree, Offner, Fritz, Schiller, Gary, Swords, Ronan, Bacon, Larry, Bocchia, Monica, Bouabdallah, Krimo, Breems, Dimitri, Cortelezzi, Agostino, Dinner, Shira, Doubek, Michael, Gjertsen, Bjorn, Gobbi, Marco, Hellmann, Andrzej, Lepretre, Stephane, Maloisel, Frederic, Ravandi, Farhad, Rousselot, Philippe, Rummel, Mathias, Siddiqi, Tanya, Tadmor, Tamar, Troussard, Xavier, Yi, Cecilia, Saglio, Giuseppe, Roboz, Gail, Balic, Kemal, Standifer, Nathan, He, Peng, Marshall, Shannon, Wilson, Wyndham, Pastan, Ira, Yao, Nai-Shun, and Giles, Francis

Subjects
Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Bacterial Toxins, Drug Resistance, Neoplasm, Exotoxins, Female, Follow-Up Studies, Humans, Leukemia, Hairy Cell, Male, Middle Aged, Neoplasm Recurrence, Local, Prognosis, Remission Induction, Salvage Therapy, Survival Rate
Abstract

This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability.

Published
2018

11. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial

Author

Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J., Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W., Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J.F.M., Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W.J., Bargetzi, Mario, Klein, Saskia K., Gadisseur, Alain, Westerweel, Peter E., Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A., Hoogendoorn, Mels, Legdeur, Marie-Cecile J.C., Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T., Janssen, Jeroen J.W.M., Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J.M., van Elssen, Catharina H.M.J., Manz, Markus G., Floisand, Yngvar, and Ossenkoppele, Gert J.

Published
2021
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12. Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib - interim results from the DAstop2 trial

Author

Flygt, Hjalmar, Soederlund, Stina, Richter, Johan, Saussele, Susanne, Koskenvesa, Perttu, Stenke, Leif, Mustjoki, Satu, Dimitrijevic, Andreja, Stentoft, Jesper, Majeed, Waleed, Roy, Lydia, Wolf, Dominik, Dreimane, Arta, Gjertsen, Bjorn Tore, Gedde-Dahl, Tobias, Ahlstrand, Erik, Markevaern, Berit, Hjorth-Hansen, Henrik, Janssen, Jeroen, Olsson-Stroemberg, Ulla, Flygt, Hjalmar, Soederlund, Stina, Richter, Johan, Saussele, Susanne, Koskenvesa, Perttu, Stenke, Leif, Mustjoki, Satu, Dimitrijevic, Andreja, Stentoft, Jesper, Majeed, Waleed, Roy, Lydia, Wolf, Dominik, Dreimane, Arta, Gjertsen, Bjorn Tore, Gedde-Dahl, Tobias, Ahlstrand, Erik, Markevaern, Berit, Hjorth-Hansen, Henrik, Janssen, Jeroen, and Olsson-Stroemberg, Ulla

Abstract

Tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML) has become part of routine care for patients with a sustained deep molecular response (DMR). Approximately 50% experience a molecular relapse upon TKI cessation. Most of them quickly regain DMR upon TKI resumption. Whether these patients can achieve a second treatment-free remission (TFR) remains unclear. DAstop2 (ClinicalTrials.gov ID: NCT03573596) is a prospective study including patients with a failed first TFR attempt re-treated with any TKI for >= one year. Upon entering the study, patients received the TKI dasatinib for additional two years. Patients with sustained DMR for >= 1 year qualified for a second TKI stop. Ninety-four patients were included between Oct 2017-Dec 2021. At the time of data analysis, 62 patients had attempted a 2(nd) stop. After a median follow-up of 27 months from 2(nd) stop, TFR rates were 61, 56 and 46% at 6, 12 and 24 months respectively. No progression to advanced stage disease was seen and 87% had re-achieved MR4 within a median of 3 months from TKI re-initiation. In summary, we show that a 2(nd) TFR attempt after dasatinib treatment is safe, feasible and TFR rates seem in the range of those reported in trials of a first TKI stop., Funding Agencies|Uppsala University

Published
2024
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13. IFN-[alpha] with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia

Author

Huuhtanen, Jani, Ilander, Mette, Yadav, Bhagwan, Dufva, Olli M.J., Lahteenmaki, Hanna, Kasanen, Tiina, Klievink, Jay, Olsson-Stromberg, Ulla, Stentoft, Jesper, Richter, Johan, Koskenvesa, Perttu, Hoglund, Martin, Soderlund, Stina, Dreimane, Arta, Porkka, Kimmo, Gedde-Dahl, Tobias, Gjertsen, Bjorn T., Stenke, Leif, Myhr-Eriksson, Kristina, Markevarn, Berit, Lubking, Anna, Dimitrijevic, Andreja, Udby, Lene, Bjerrum, Ole Weis, Hjorth-Hansen, Henrik, and Mustjoki, Satu

Subjects
Immune system -- Health aspects, Interferon alpha -- Dosage and administration -- Physiological aspects, Dasatinib -- Dosage and administration -- Physiological aspects, Chronic myeloid leukemia -- Drug therapy -- Physiological aspects, Chemotherapy, Combination -- Methods -- Physiological aspects, Health care industry
Abstract

In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-[alpha] is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-[alpha] in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCR[beta] sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and [CD8.sup.+] T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of [CD8.sup.+] recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-[alpha] reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-[alpha] had costimulatory effects on TCR signaling. Our work supports the combination of IFN-[alpha] with TKI therapy, as IFN-[alpha] broadens the immune repertoire and restores immunological function., Introduction Currently, the ultimate therapeutic goal in patients with chronic-phase chronic myeloid leukemia (CP-CML) is to achieve deep molecular remission, which would allow the discontinuation of tyrosine kinase inhibitor (TKI) [...]

Published
2022
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14. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial

Author

Nicol, Andrew, Grigoriadis, George, Catalano, John, LeBlanc, Richard, Elemary, Mohamed, Bahlis, Nizar, Facon, Thierry, Karlin, Lionel, Ribrag, Vincent, Attal, Michel, Goldschmidt, Hartmut, Engelhardt, Monika, Weisel, Katja, Mackensen, Andreas, Nagler, Arnon, Ben Yehuda, Dina, Avivi, Irit, Benyamini, Noam, Magen-Nativ, Hila, Palumbo, Antonio, Cavo, Michele, Tobinai, Kensei, Iida, Shinsuke, Chou, Takaai, Suzuki, Kenshi, Kosugi, Hiroshi, Taniwaki, Masafumi, Sunami, Kazutaka, Matsumoto, Morio, Ando, Kiyoshi, Ganly, Peter, Blacklock, Hilary, Simpson, David, George, Anupkumar, Schjesvold, Fredrik, Gjertsen, Bjorn, Lahuerta, Juan, Blade, Joan, Oriol Rocafiguera, Albert, Mateos, Maria, Rodriguez-Otero, Paula, Larson, Sarah, Atanackovic, Djordje, Devarakonda, Srinivas, Bitran, Jacob, Zonder, Jeffrey, Morganstein, Neil, Hay, Mohammad, Chanan-Khan, Asher, Saylors, Gene, Kio, Ebenezer, Oliff, Ira, Kirkel, Dean, Shtivelband, Mikhail, Yuen, Carrie, Yee, Andrew, Shah, Jatin, Htut, Myo, Raza, Shahzad, Chhabra, Saurabh, Stiff, Patrick, Hari, Parameswaran, Bank, Bruce, Malek, Ehsan, Gasparetto, Cristina, Faroun, Ycaoub, Sherbenou, Daniel, Kreisle, William, Singhal, Seema, Rosenblatt, Jacalyn, Usmani, Saad, Lee, Wes, Safah, Hana, Lutzky, Jose, Suh, Jason, Pan, Dorothy, Baron, Ari, Manges, Robert, Steis, Ronald, Oliveira, Moacyr, Moreb, Jan, Callander, Natalie, Anz, Bertrand, Raptis, Anastasios, Stampleman, Laura, Melear, Jason, Boyd, Thomas, Garbo, Lawrence, Klein, Leonard, Shao, Spencer, Lyons, Roger, McIntyre, Kristi, Tarantolo, Stefano, Yasenchak, Christopher, Yimer, Habte, Mateos, Maria-Victoria, Oriol, Albert, Larocca, Alessandra, Usmani, Saad Z, Jagannath, Sundar, Ocio, Enrique M, San Miguel, Jesus, Kher, Uma, Farooqui, Mohammed, Liao, Jason, Marinello, Patricia, and Lonial, Sagar

Published
2019
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15. Prognostic Significance of Measurable Residual Disease Detection by Flow Cytometry in Autologous Stem Cell Apheresis Products in AML

Author

Tettero, Jesse M., primary, Buisman, Yara, additional, Ngai, Lok Lam, additional, Bachas, Costa, additional, Gjertsen, Bjorn T., additional, Kelder, Angèle, additional, van de Loosdrecht, Arjan A., additional, Manz, Markus G., additional, Pabst, Thomas, additional, Scholten, Willemijn, additional, Ossenkoppele, Gert J., additional, Cloos, Jacqueline, additional, and de Leeuw, David C., additional

Published
2023
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16. Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib – interim results from the DAstop2 trial

Author

Flygt, Hjalmar, primary, Söderlund, Stina, additional, Richter, Johan, additional, Saussele, Susanne, additional, Koskenvesa, Perttu, additional, Stenke, Leif, additional, Mustjoki, Satu, additional, Dimitrijevic, Andreja, additional, Stentoft, Jesper, additional, Majeed, Waleed, additional, Roy, Lydia, additional, Wolf, Dominik, additional, Dreimane, Arta, additional, Gjertsen, Bjorn, additional, Gedde-Dahl, Tobias, additional, Ahlstrand, Erik, additional, Markevärn, Berit, additional, Hjorth-Hansen, Henrik, additional, Janssen, Jeroen, additional, and Olsson-Strömberg, Ulla, additional

Published
2023
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17. Prospective validation of the prognostic relevance of CD34+CD38– AML stem cell frequency in the HOVON-SAKK132 trial

Author

Ngai, Lok Lam, Hanekamp, Diana, Janssen, Fleur, Carbaat-Ham, Jannemieke, Hofland, Maaike A M, Fayed, Mona M H E, Kelder, Angèle, Oudshoorn-van Marsbergen, Laura, Scholten, Willemijn J, Snel, Alexander N, Bachas, Costa, Tettero, Jesse M, Breems, Dimitri A, Fischer, Thomas, Gjertsen, Bjorn T, Griskevicius, Laimonas, Juliusson, Gunnar, van de Loosdrecht, Arjan A, Maertens, Johan A, Manz, Markus G, Pabst, Thomas, Passweg, Jakob R, Porkka, Kimmo, Valk, Peter J M, Gradowska, Patrycja, Löwenberg, Bob, de Leeuw, David C, Janssen, Jeroen J W M, Ossenkoppele, Gert J, Cloos, Jacqueline, Hematology laboratory, VU University medical center, Hematology, AII - Cancer immunology, AII - Inflammatory diseases, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, and CCA - Cancer Treatment and quality of life

Subjects
All institutes and research themes of the Radboud University Medical Center, Immunology, Cell Biology, Hematology, 610 Medicine & health, Biochemistry, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Item does not contain fulltext

Published
2023

20. P409: BCL-2/BCL-XL INHIBITION INDUCES APOPTOSIS AND CIRCUMVENTS VENETOCLAX RESISTANCE IN TP53-MUTATED ACUTE MYELOID LEUKEMIA

Author

Vänttinen, Ida, primary, Kytölä, Sari, additional, Dufva, Olli, additional, Hellesøy, Monica, additional, Gullaksen, Stein-Erik, additional, Ruokoranta, Tanja, additional, Brück, Oscar, additional, Siitonen, Sanna, additional, Ettala, Pia, additional, Pyörälä, Marja, additional, Rimpilainen, Johanna, additional, Siitonen, Timo, additional, Tore Gjertsen, Bjorn, additional, Heckman, Caroline, additional, Kuusanmäki, Heikki, additional, and Kontro, Mika, additional

Published
2023
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21. PB1762: A NEW MONOCLONAL ANTIBODY PROVIDES INSIGHTS ON NPM1 MUTANT SUBCELLULAR EXPRESSION, INTRACLONAL CELL DIFFERENTIATION AND MRD IN NPM1-MUTATED AML

Author

Falini, Brunangelo, primary, Martelli, Maria Paola, additional, Rossi, Riccardo, additional, Facchetti, Fabio, additional, Zini, Stefania, additional, Borlenghi, Erica, additional, Sabbatini, Elena, additional, Brunetti, Lorenzo, additional, Sorcini, Daniele, additional, Perriello, Vincenzo, additional, Tiacci, Enrico, additional, Gjertsen, Bjorn, additional, and Andresen, Vibeke, additional

Published
2023
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22. P1387: TREATMENT WITH A LEUKEMIA-DERIVED DENDRITIC CELL VACCINE INDUCES INNATE AND ADAPTIVE IMMUNE RESPONSE CORRELATING WITH CLINICAL RESPONSE IN AML PATIENTS IN CR1 WITH MEASURABLE RESIDUAL DISEASE

Author

van Zeeburg, Hester, primary, Kaur Singh, Satwinder, additional, Wagner-Drouet, Eva, additional, Platzbecker, Uwe, additional, Holderried, Tobias, additional, VAN Elssen, Catharina, additional, Giagounidis, Aristoteles, additional, Tore Gjertsen, Bjorn, additional, van de Loosdrecht, Arjan, additional, and Rovers, Jeroen, additional

Published
2023
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23. P432: VALIDATION OF LIMIT OF QUANTIFICATION APPROACH BASED FLOW CYTOMETRY FOR MEASURABLE RESIDUAL DISEASE ASSESSMENT IN ACUTE MYELOID LEUKEMIA IN THE HOVON-SAKK-132 TRIAL

Author

Tettero, Jesse, primary, Palmieri, Raffaele, additional, Lam Ngai, Lok, additional, Bachas, Costa, additional, Arena, Valentina, additional, Breems, Dimitri, additional, Fischer, Thomas, additional, Tore Gjertsen, Bjorn, additional, Griškevičius, Laimonas, additional, Juliusson, Gunnar, additional, Maertens, Johan, additional, Manz, Markus, additional, Maurillo, Luca, additional, Pabst, Thomas, additional, Passweg, Jakob, additional, Piciocchi, Alfonso, additional, Porkka, Kimmo, additional, Löwenberg, Bob, additional, Venditti, Adriano, additional, Ossenkoppele, Gert, additional, Buccisano, Francesco, additional, and Cloos, Jacqueline, additional

Published
2023
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24. P475: EMERGING LEUKEMIA ASSOCIATED IMMUNOPHENOTYPES (LAIPS) IN BONE MARROW OF ACUTE MYELOID LEUKEMIA PATIENTS AFTER INTENSIVE CHEMOTHERAPY.

Author

Lam Ngai, Lok, primary, Hanekamp, Diana, additional, Kelder, Angèle, additional, Scholten, Willemijn J., additional, Carbaat - Ham, Jannemieke, additional, Snel, Alexander N., additional, Bachas, Costa, additional, Tettero, Jesse, additional, van der Velden, Vincent, additional, Slomp, Jennichjen, additional, Hobo, Willemijn, additional, Breems, Dimitri, additional, Fischer, Thomas, additional, Tore Gjertsen, Bjorn, additional, Griškevičius, Laimonas, additional, Juliusson, Gunnar, additional, Maertens, Johan, additional, Manz, Markus, additional, Pabst, Thomas, additional, Passweg, Jakob, additional, Porkka, Kimmo, additional, Valk, Peter, additional, Gradowska, Patrycja, additional, Löwenberg, Bob, additional, de Leeuw, David, additional, van de Loosdrecht, Arjan, additional, Ossenkoppele, Gert, additional, and Cloos, Jacqueline, additional

Published
2023
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25. P448: PROGNOSTIC SIGNIFICANCE OF MEASURABLE RESIDUAL DISEASE DETECTION BY FLOW CYTOMETRY IN AUTOLOGOUS STEM CELL APHERESIS PRODUCTS OF PATIENTS WITH AML

Author

Tettero, Jesse, primary, Buisman, Yara, additional, Lam Ngai, Lok, additional, Bachas, Costa, additional, Tore Gjertsen, Bjorn, additional, Kelder, Angèle, additional, van de Loosdrecht, Arjan, additional, Manz, Markus, additional, Pabst, Thomas, additional, Scholten, Willemijn, additional, Ossenkoppele, Gert, additional, Cloos, Jacqueline, additional, and de Leeuw, David, additional

Published
2023
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26. JAK1/2 and BCL2 inhibitors synergize to counteract bone marrow stromal cell–induced protection of AML

Author

Karjalainen, Riikka, Pemovska, Tea, Popa, Mihaela, Liu, Minxia, Javarappa, Komal K., Majumder, Muntasir M., Yadav, Bhagwan, Tamborero, David, Tang, Jing, Bychkov, Dmitrii, Kontro, Mika, Parsons, Alun, Suvela, Minna, Mayoral Safont, Mireia, Porkka, Kimmo, Aittokallio, Tero, Kallioniemi, Olli, McCormack, Emmet, Gjertsen, Bjørn T., Wennerberg, Krister, Knowles, Jonathan, and Heckman, Caroline A.

Published
2017
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27. Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML

Author

Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, van Norden, Yvette, Biemond, Bart J., Schouten, Harry C., Spertini, Olivier, Vellenga, Edo, Graux, Carlos, Havelange, Violaine, de Greef, Georgine E., de Weerdt, Okke, Legdeur, Marie-Cecile J.C., Kuball, Juergen, Kooy, Marinus van Marwijk, Gjertsen, Bjorn T., Jongen-Lavrencic, Mojca, van de Loosdrecht, Arjan A., van Lammeren-Venema, Daniëlle, Hodossy, Beata, Breems, Dimitri A., Chalandon, Yves, Passweg, Jakob, Valk, Peter J.M., Manz, Markus G., and Ossenkoppele, Gert J.

Published
2017
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31. Measurable residual disease-guided therapy in intermediate-risk acute myeloid leukemia patients is a valuable strategy in reducing allogeneic transplantation without negatively affecting survival

Author

Tettero, Jesse M., primary, Ngai, Lok Lam, additional, Bachas, Costa, additional, Breems, Dimitri A., additional, Fischer, Thomas, additional, Gjertsen, Bjorn T., additional, Gradowska, Patrycja, additional, Griskevicius, Laimonas, additional, Janssen, Jeroen J.W.M., additional, Juliusson, Gunnar, additional, Maertens, Johan, additional, Manz, Markus G., additional, Pabst, Thomas, additional, Passweg, Jakob, additional, Porkka, Kimmo, additional, Valk, Peter J.M., additional, Löwenberg, Bob, additional, Ossenkoppele, Gert J., additional, and Cloos, Jacqueline, additional

Published
2023
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32. Supplementary Data from Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia

Author

Malani, Disha, primary, Kumar, Ashwini, primary, Brück, Oscar, primary, Kontro, Mika, primary, Yadav, Bhagwan, primary, Hellesøy, Monica, primary, Kuusanmäki, Heikki, primary, Dufva, Olli, primary, Kankainen, Matti, primary, Eldfors, Samuli, primary, Potdar, Swapnil, primary, Saarela, Jani, primary, Turunen, Laura, primary, Parsons, Alun, primary, Västrik, Imre, primary, Kivinen, Katja, primary, Saarela, Janna, primary, Räty, Riikka, primary, Lehto, Minna, primary, Wolf, Maija, primary, Gjertsen, Bjorn Tore, primary, Mustjoki, Satu, primary, Aittokallio, Tero, primary, Wennerberg, Krister, primary, Heckman, Caroline A., primary, Kallioniemi, Olli, primary, and Porkka, Kimmo, primary

Published
2023
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33. Supplementary Tables from Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia

Author

Malani, Disha, primary, Kumar, Ashwini, primary, Brück, Oscar, primary, Kontro, Mika, primary, Yadav, Bhagwan, primary, Hellesøy, Monica, primary, Kuusanmäki, Heikki, primary, Dufva, Olli, primary, Kankainen, Matti, primary, Eldfors, Samuli, primary, Potdar, Swapnil, primary, Saarela, Jani, primary, Turunen, Laura, primary, Parsons, Alun, primary, Västrik, Imre, primary, Kivinen, Katja, primary, Saarela, Janna, primary, Räty, Riikka, primary, Lehto, Minna, primary, Wolf, Maija, primary, Gjertsen, Bjorn Tore, primary, Mustjoki, Satu, primary, Aittokallio, Tero, primary, Wennerberg, Krister, primary, Heckman, Caroline A., primary, Kallioniemi, Olli, primary, and Porkka, Kimmo, primary

Published
2023
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34. Data from Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia

Author

Malani, Disha, primary, Kumar, Ashwini, primary, Brück, Oscar, primary, Kontro, Mika, primary, Yadav, Bhagwan, primary, Hellesøy, Monica, primary, Kuusanmäki, Heikki, primary, Dufva, Olli, primary, Kankainen, Matti, primary, Eldfors, Samuli, primary, Potdar, Swapnil, primary, Saarela, Jani, primary, Turunen, Laura, primary, Parsons, Alun, primary, Västrik, Imre, primary, Kivinen, Katja, primary, Saarela, Janna, primary, Räty, Riikka, primary, Lehto, Minna, primary, Wolf, Maija, primary, Gjertsen, Bjorn Tore, primary, Mustjoki, Satu, primary, Aittokallio, Tero, primary, Wennerberg, Krister, primary, Heckman, Caroline A., primary, Kallioniemi, Olli, primary, and Porkka, Kimmo, primary

Published
2023
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35. Supplementary Figures from Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia

Author

Malani, Disha, primary, Kumar, Ashwini, primary, Brück, Oscar, primary, Kontro, Mika, primary, Yadav, Bhagwan, primary, Hellesøy, Monica, primary, Kuusanmäki, Heikki, primary, Dufva, Olli, primary, Kankainen, Matti, primary, Eldfors, Samuli, primary, Potdar, Swapnil, primary, Saarela, Jani, primary, Turunen, Laura, primary, Parsons, Alun, primary, Västrik, Imre, primary, Kivinen, Katja, primary, Saarela, Janna, primary, Räty, Riikka, primary, Lehto, Minna, primary, Wolf, Maija, primary, Gjertsen, Bjorn Tore, primary, Mustjoki, Satu, primary, Aittokallio, Tero, primary, Wennerberg, Krister, primary, Heckman, Caroline A., primary, Kallioniemi, Olli, primary, and Porkka, Kimmo, primary

Published
2023
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36. Early response evaluation by single cell signaling profiling in acute myeloid leukemia

Author

Tislevoll, Benedicte Sjo, Hellesoy, Monica, Fagerholt, Oda Helen Eck, Gullaksen, Stein-Erik, Srivastava, Aashish, Birkeland, Even, Kleftogiannis, Dimitrios, Ayuda-Duran, Pilar, Piechaczyk, Laure, Tadele, Dagim Shiferaw, Skavland, Jorn, Baliakas, Panagiotis, Hovland, Randi, Andresen, Vibeke, Seternes, Ole Morten, Tvedt, Tor Henrik Anderson, Aghaeepour, Nima, Gavasso, Sonia, Porkka, Kimmo, Jonassen, Inge, Floisand, Yngvar, Enserink, Jorrit, Blaser, Nello, Gjertsen, Bjorn Tore, Tislevoll, Benedicte Sjo, Hellesoy, Monica, Fagerholt, Oda Helen Eck, Gullaksen, Stein-Erik, Srivastava, Aashish, Birkeland, Even, Kleftogiannis, Dimitrios, Ayuda-Duran, Pilar, Piechaczyk, Laure, Tadele, Dagim Shiferaw, Skavland, Jorn, Baliakas, Panagiotis, Hovland, Randi, Andresen, Vibeke, Seternes, Ole Morten, Tvedt, Tor Henrik Anderson, Aghaeepour, Nima, Gavasso, Sonia, Porkka, Kimmo, Jonassen, Inge, Floisand, Yngvar, Enserink, Jorrit, Blaser, Nello, and Gjertsen, Bjorn Tore

Abstract

Aberrant pro-survival signaling is a hallmark of cancer cells, but the response to chemotherapy is poorly understood. In this study, we investigate the initial signaling response to standard induction chemotherapy in a cohort of 32 acute myeloid leukemia (AML) patients, using 36-dimensional mass cytometry. Through supervised and unsupervised machine learning approaches, we find that reduction of extracellular-signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the myeloid cell compartment 24 h post-chemotherapy is a significant predictor of patient 5-year overall survival in this cohort. Validation by RNA sequencing shows induction of MAPK target gene expression in patients with high phosphoERK1/2 24 h post-chemotherapy, while proteomics confirm an increase of the p38 prime target MAPK activated protein kinase 2 (MAPKAPK2). In this study, we demonstrate that mass cytometry can be a valuable tool for early response evaluation in AML and elucidate the potential of functional signaling analyses in precision oncology diagnostics.

Published
2023
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37. Measurable residual disease-guided therapy in intermediate-risk acute myeloid leukemia patients is a valuable strategy in reducing allogeneic transplantation without negatively affecting survival

Author

Tettero, Jesse M., Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A., Fischer, Thomas, Gjertsen, Bjorn T., Gradowska, Patrycja, Griskevicius, Laimonas, Janssen, Jeroen J.W.M., Juliusson, Gunnar, Maertens, Johan, Manz, Markus G., Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Valk, Peter J.M., Löwenberg, Bob, Ossenkoppele, Gert J., Cloos, Jacqueline, Tettero, Jesse M., Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A., Fischer, Thomas, Gjertsen, Bjorn T., Gradowska, Patrycja, Griskevicius, Laimonas, Janssen, Jeroen J.W.M., Juliusson, Gunnar, Maertens, Johan, Manz, Markus G., Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Valk, Peter J.M., Löwenberg, Bob, Ossenkoppele, Gert J., and Cloos, Jacqueline

Published
2023

38. Prognostic Significance of Measurable Residual Disease Detection by Flow Cytometry in Autologous Stem Cell Apheresis Products in AML

Author

Tettero, Jesse M; https://orcid.org/0000-0002-0811-0824, Buisman, Yara, Ngai, Lok Lam; https://orcid.org/0000-0003-0969-3766, Bachas, Costa; https://orcid.org/0000-0001-5983-6193, Gjertsen, Bjorn T; https://orcid.org/0000-0001-9358-9704, Kelder, Angèle, van de Loosdrecht, Arjan A; https://orcid.org/0000-0001-8311-983X, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas; https://orcid.org/0000-0002-6055-5257, Scholten, Willemijn, Ossenkoppele, Gert J, Cloos, Jacqueline; https://orcid.org/0000-0001-9150-8026, de Leeuw, David C; https://orcid.org/0000-0003-4591-8467, Tettero, Jesse M; https://orcid.org/0000-0002-0811-0824, Buisman, Yara, Ngai, Lok Lam; https://orcid.org/0000-0003-0969-3766, Bachas, Costa; https://orcid.org/0000-0001-5983-6193, Gjertsen, Bjorn T; https://orcid.org/0000-0001-9358-9704, Kelder, Angèle, van de Loosdrecht, Arjan A; https://orcid.org/0000-0001-8311-983X, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas; https://orcid.org/0000-0002-6055-5257, Scholten, Willemijn, Ossenkoppele, Gert J, Cloos, Jacqueline; https://orcid.org/0000-0001-9150-8026, and de Leeuw, David C; https://orcid.org/0000-0003-4591-8467

Published
2023

39. Measurable residual disease-guided therapy in intermediate-risk acute myeloid leukemia patients is a valuable strategy in reducing allogeneic transplantation without negatively affecting survival

Author

Tettero, Jesse M, Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A, Fischer, Thomas, Gjertsen, Bjorn T, Gradowska, Patrycja, Griskevicius, Laimonas, Janssen, Jeroen J W M, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Valk, Peter J M; https://orcid.org/0000-0002-8857-9461, Löwenberg, Bob; https://orcid.org/0000-0001-8982-5217, Ossenkoppele, Gert J, Cloos, Jacqueline, Tettero, Jesse M, Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A, Fischer, Thomas, Gjertsen, Bjorn T, Gradowska, Patrycja, Griskevicius, Laimonas, Janssen, Jeroen J W M, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Valk, Peter J M; https://orcid.org/0000-0002-8857-9461, Löwenberg, Bob; https://orcid.org/0000-0001-8982-5217, Ossenkoppele, Gert J, and Cloos, Jacqueline

Published
2023

42. Use of an Allogeneic Leukemia-Derived Dendritic Cell Vaccine in MRD+ AML-Patients Results in MRD Conversion, Improved Relapse-Free Survival and Vaccine Induced Immune Responses to Tumor Antigens

Author

Van de Loosdrecht, Arjan A., primary, Cloos, Jacqueline, additional, Wagner-Drouet, Eva-Maria, additional, Platzbecker, Uwe, additional, Holderried, Tobias A.W., additional, van Elssen, Catharina, additional, Giagounidis, Aristoteles, additional, Lehmann, Sören, additional, van Zeeburg, Hester J.T., additional, Rovers, Jeroen, additional, and Gjertsen, Bjorn T., additional

Published
2022
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43. Induction of a Systemic Immune Response during Use of an Allogenic Leukemia-Derived Dendritic Cell Vaccine in MRD+ AML Patients Correlates with Clinical Response and MRD Conversion

Author

Van de Loosdrecht, Arjan A., primary, Cloos, Jacqueline, additional, Wagner-Drouet, Eva-Maria, additional, Platzbecker, Uwe, additional, Holderried, Tobias A.W., additional, van Elssen, Catharina, additional, Giagounidis, Aristoteles, additional, Welters, Marij J.P., additional, van der Burg, Sjoerd H., additional, van Zeeburg, Hester J.T., additional, Rovers, Jeroen, additional, and Gjertsen, Bjorn T., additional

Published
2022
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44. Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis

Author

Tettero, Jesse M., primary, Al-Badri, Waleed K. W., additional, Ngai, Lok Lam, additional, Bachas, Costa, additional, Breems, Dimitri A., additional, van Elssen, Catharina H. M. J., additional, Fischer, Thomas, additional, Gjertsen, Bjorn T., additional, van Gorkom, Gwendolyn N. Y., additional, Gradowska, Patrycja, additional, Greuter, Marjolein J. E., additional, Griskevicius, Laimonas, additional, Juliusson, Gunnar, additional, Maertens, Johan, additional, Manz, Markus G., additional, Pabst, Thomas, additional, Passweg, Jakob, additional, Porkka, Kimmo, additional, Löwenberg, Bob, additional, Ossenkoppele, Gert J., additional, Janssen, Jeroen J. W. M., additional, and Cloos, Jacqueline, additional

Published
2022
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47. Prospective Validation of CD34+CD38- Leukemic Stem Cell Frequency in the HOVON-SAKK 132 Trial: Perspectives for Future Improvements

Author

Ngai, Lok Lam, Hanekamp, Diana, Janssen, Fleur, Carbaat-Ham, Jannemieke, Hofland, Maaike A.M., Fayed, Mona M.H.E, Kelder, Angèle, Oudshoorn-van Marsbergen, Laura, Scholten, Willemijn J., Snel, Alexander N., Bachas, Costa, Tettero, Jesse M., Breems, Dimitri A., Fischer, Thomas, Gjertsen, Bjørn Tore, Griškevičius, Laimonas, Juliusson, Gunnar, Maertens, Johan A., Manz, Markus G, Pabst, Thomas, Passweg, Jakob R., Porkka, Kimmo, Gradowska, Patrycja, Lowenberg, Bob, de Leeuw, David C., Janssen, Jeroen J.W.M., Ossenkoppele, Gert J., and Cloos, Jacqueline

Published
2022
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48. Measurable Residual Disease Guided Therapy in Intermediate-Risk AML Patients Compared to an Unguided Cohort Using Propensity Score Matching

Author

Tettero, Jesse M., Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A., Fischer, Thomas, Gjertsen, Bjørn Tore, Gradowska, Patrycja, Griskevicius, Laimonas, Janssen, Jeroen J.W.M., Juliusson, Gunnar, Maertens, Johan A., Manz, Markus G, Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Valk, Peter JM, Lowenberg, Bob, Ossenkoppele, Gert J., and Cloos, Jacqueline

Published
2022
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50. Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia

Author

Malani, Disha, Kumar, Ashwini, Brück, Oscar, Kontro, Mika, Yadav, Bhagwan, Hellesøy, Monica, Kuusanmäki, Heikki, Dufva, Olli, Kankainen, Matti, Eldfors, Samuli, Potdar, Swapnil, Saarela, Jani, Turunen, Laura, Parsons, Alun, Västrik, Imre, Kivinen, Katja, Saarela, Janna, Räty, Riikka, Lehto, Minna, Wolf, Maija, Gjertsen, Bjorn Tore, Mustjoki, Satu, Aittokallio, Tero, Wennerberg, Krister, Heckman, Caroline A., Kallioniemi, Olli, Porkka, Kimmo, Malani, Disha, Kumar, Ashwini, Brück, Oscar, Kontro, Mika, Yadav, Bhagwan, Hellesøy, Monica, Kuusanmäki, Heikki, Dufva, Olli, Kankainen, Matti, Eldfors, Samuli, Potdar, Swapnil, Saarela, Jani, Turunen, Laura, Parsons, Alun, Västrik, Imre, Kivinen, Katja, Saarela, Janna, Räty, Riikka, Lehto, Minna, Wolf, Maija, Gjertsen, Bjorn Tore, Mustjoki, Satu, Aittokallio, Tero, Wennerberg, Krister, Heckman, Caroline A., Kallioniemi, Olli, and Porkka, Kimmo

Abstract

We generated ex vivo drug-response and multiomics profiling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, and functional data for application in clinical treatment decisions. Actionable drugs were found for 97% of patients with AML, and the recommendations were clinically implemented in 37 relapsed or refractory patients. We report a 59% objective response rate for the individually tailored therapies, including 13 complete responses, as well as bridging five patients with AML to allogeneic hematopoietic stem cell transplantation. Data integration across all cases enabled the identification of drug response biomarkers, such as the association of IL15 overexpression with resistance to FLT3 inhibitors. Integration of molecular profiling and large-scale drug response data across many patients will enable continuous improvement of the FPMTB recommen-dations, providing a paradigm for individualized implementation of functional precision cancer medicine.

Published
2022

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