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1. Midostaurin added to 10-day decitabine, for patients unfit for intensive chemotherapy with AML and higher risk MDS, irrespective of FLT3 mutational status, does not improve outcome

Author

Huls, Gerwin, Chitu, Dana A., Tick, Lidwine, Boersma, Rinske, Breems, Dimitri, Herbers, Alexandra, Klein, Saskia K., de Jonge, Suzan, Westerweel, Peter E., Cruijsen, Marjan, Hoogendoorn, Mels, Cuijpers, Marlous, Deeren, Dries, Bailly, Benjamin, Visser, Otto, van Rhenen, Anna, Posthuma, Eduard F. M., Valk, Peter J. M., Cloos, Jacqueline, Ammatuna, Emanuele, Refos, Jeannine M., Fakkert, R., Löwenberg, Bob, and Ossenkoppele, Gert J.

Published
2024
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2. Bayesian interim analysis for prospective randomized studies: reanalysis of the acute myeloid leukemia HOVON 132 clinical trial

Author

van der Maas, Niek G., Versluis, Jurjen, Nasserinejad, Kazem, van Rosmalen, Joost, Pabst, Thomas, Maertens, Johan, Breems, Dimitri, Manz, Markus, Cloos, Jacqueline, Ossenkoppele, Gert J., Floisand, Yngvar, Gradowska, Patrycja, Löwenberg, Bob, Huls, Gerwin, Postmus, Douwe, Pignatti, Francesco, and Cornelissen, Jan J.

Published
2024
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3. Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Author

Hilberink, Jacobien R., van Zeventer, Isabelle A., Chitu, Dana A., Pabst, Thomas, Klein, Saskia K., Stussi, Georg, Griskevicius, Laimonas, Valk, Peter J. M., Cloos, Jacqueline, van de Loosdrecht, Arjan A., Breems, Dimitri, van Lammeren-Venema, Danielle, Boersma, Rinske, Jongen-Lavrencic, Mojca, Fehr, Martin, Hoogendoorn, Mels, Manz, Markus G., Söhne, Maaike, van Marwijk Kooy, Rien, Deeren, Dries, van der Poel, Marjolein W. M., Legdeur, Marie Cecile, Tick, Lidwine, Chalandon, Yves, Ammatuna, Emanuele, Blum, Sabine, Löwenberg, Bob, Ossenkoppele, Gert J., and Huls, Gerwin

Published
2023
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4. A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes

Author

Sekeres, Mikkael A., Schuster, Michael, Joris, Magalie, Krauter, Jürgen, Maertens, Johan, Breems, Dimitri, Gyan, Emmanuel, Kovacsovics, Tibor, Verma, Amit, Vyas, Paresh, Wang, Eunice S., Ching, Keith, O’Brien, Thomas, Gallo Stampino, Corrado, Ma, Weidong Wendy, Kudla, Arthur, Chan, Geoffrey, and Zeidan, Amer M.

Published
2022
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5. Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome

Author

Grob, Tim, Al Hinai, Adil S.A., Sanders, Mathijs A., Kavelaars, François G., Rijken, Melissa, Gradowska, Patrycja L., Biemond, Bart J., Breems, Dimitri A., Maertens, Johan, van Marwijk Kooy, Marinus, Pabst, Thomas, de Weerdt, Okke, Ossenkoppele, Gert J., van de Loosdrecht, Arjan A., Huls, Gerwin A., Cornelissen, Jan J., Beverloo, H. Berna, Löwenberg, Bob, Jongen-Lavrencic, Mojca, and Valk, Peter J.M.

Published
2022
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6. Clofarabine added to intensive treatment in adult patients with newly diagnosed ALL: the HOVON-100 trial

Author

Rijneveld, Anita W., van der Holt, Bronno, de Weerdt, Okke, Biemond, Bart J., van de Loosdrecht, Arjen A., van der Wagen, Lotte E., Bellido, Mar, van Gelder, Michel, van der Velden, Walter J.F.M., Selleslag, Dominik, van Lammeren-Venema, Daniëlle, Halkes, Constantijn J.M., Fijnheer, Rob, Havelange, Violaine, van Sluis, Geerte L., Legdeur, Marie-Cecile, Deeren, Dries, Gadisseur, Alain, Sinnige, Harm A.M., Breems, Dimitri A., Jaspers, Aurélie, Legrand, Ollivier, Terpstra, Wim E., Boersma, Rinske S., Mazure, Dominiek, Triffet, Agnes, Tick, Lidwine W., Beel, Karolien, Maertens, Johan A., Beverloo, H. Berna, Bakkus, Marleen, Homburg, Christa H.E., de Haas, Valerie, van der Velden, Vincent H.J., and Cornelissen, Jan J.

Published
2022
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7. 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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9. CD34+CD38− leukemic stem cell frequency to predict outcome in acute myeloid leukemia

Author

Zeijlemaker, Wendelien, Grob, Tim, Meijer, Rosa, Hanekamp, Diana, Kelder, Angèle, Carbaat-Ham, Jannemieke C., Oussoren-Brockhoff, Yvonne J. M., Snel, Alexander N., Veldhuizen, Dennis, Scholten, Willemijn J., Maertens, Johan, Breems, Dimitri A., Pabst, Thomas, Manz, Markus G., van der Velden, Vincent H. J., Slomp, Jennichjen, Preijers, Frank, Cloos, Jacqueline, van de Loosdrecht, Arjan A., Löwenberg, Bob, Valk, Peter J. M., Jongen-Lavrencic, Mojca, Ossenkoppele, Gert J., and Schuurhuis, Gerrit J.

Published
2019
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10. 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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11. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia

Author

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

Published
2018
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12. Adequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients with lower risk myelodysplastic syndromes

Author

Delforge, Michel, Selleslag, Dominik, Beguin, Yves, Triffet, Agnès, Mineur, Philippe, Theunissen, Koen, Graux, Carlos, Trullemans, Fabienne, Boulet, Dominique, Van Eygen, Koen, Noens, Lucien, Van Steenweghen, Steven, Lemmens, Jan, Pierre, Pascal, D’hondt, Randal, Ferrant, Augustin, Deeren, Dries, Van De Velde, Ann, Wynendaele, Wim, André, Marc, De Bock, Robrecht, Efira, André, Breems, Dimitri, Deweweire, Anne, Geldhof, Kurt, Pluymers, Wim, Harrington, Amanda, MacDonald, Karen, Abraham, Ivo, and Ravoet, Christophe

Published
2014
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13. Disease Perception Is Correlated with Health-Related Quality of Life in Patients Suffering from Myelodysplastic Syndromes: Results of the Belgian Be-QUALMS Study.

Author

Heyrman, Bert, Meers, Stef, De Becker, Ann, Wouters, Kristien, Van Hoof, Achiel, Van De Velde, Ann, Graux, Carlos, Mazure, Dominiek, Selleslag, Dominik, Maes, Helena, Lemmens, Jan, Beckers, Marielle, Breems, Dimitri, Sid, Sélim, Berneman, Zwi, and Anguille, Sébastien

Subjects
MYELODYSPLASTIC syndromes treatment, MYELODYSPLASTIC syndromes, SCIENTIFIC observation, HEMOGLOBINS, HEALTH outcome assessment, ATTITUDES toward illness, PATIENTS' attitudes, BELGIANS, QUALITY of life, RESEARCH funding, QUESTIONNAIRES, LONGITUDINAL method
Abstract

Simple Summary: Myelodysplastic syndromes are a heterogenous group of bone-marrow cancers that prelude a possible evolution to acute myeloid leukemia. Most treatments aim at reinstalling bone marrow function and delay evolution to acute leukemia. The disease has a negative impact on health-related quality of life and amelioration is an independent treatment goal. In order to capture the impact of current treatments outside clinical trials we aimed to monitor quality of life during the course of treatment. Another key element in our study was to prospectively assess disease perception and the impact on quality of life. Not reaching our inclusion goal, we cannot make any conclusions or assumptions on our first objective. We can, however, demonstrate a clear significant relation between disease perception and health related quality of life in this patient population that may lead to a positive impact for future patients. Patients with myelodysplastic syndromes suffer from an impaired quality of life that is only partially explained by physical symptoms. In an observational study, we aimed to investigate the impact of current MDS treatments and the influence of disease perception on quality of life. Serial measurement of health-related quality of life was performed by 'the QUALMS', a validated MDS-specific patient reported outcome tool. Disease perception was evaluated by means of the Brief Illness Perception Questionnaire (B-IPQ). We prospectively collected data on 75 patients that started on a new treatment and could not demonstrate a significant change in QUALMS score or B-IPQ score during treatment. Six out of eight items evaluated in the B-IPQ correlated significantly with QUALMS score. In this small sample, no significant difference in QUALMS score was found between lower vs. higher risk MDS patients or other studied variables, e.g., targeted hemoglobin showed no correlation with QUALMS score. In daily practice attention must be paid to initial formation of disease perception as it correlates independently with health-related quality of life and does not change during treatment (clinicaltrials.gov identifier: NCT04053933). [ABSTRACT FROM AUTHOR]

Published
2023
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14. Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK)

Author

Ossenkoppele, Gert J., Stussi, Georg, Maertens, Johan, van Montfort, Kees, Biemond, Bart J., Breems, Dimitri, Ferrant, August, Graux, Carlos, de Greef, Georgine E., Halkes, C. J.M., Hoogendoorn, Mels, Hollestein, Rene M., Jongen-Lavrencic, Mojca, Levin, Mark D., van de Loosdrecht, Arjan A., van Marwijk Kooij, Marinus, van Norden, Yvette, Pabst, Thomas, Schouten, Harry C., Vellenga, Edo, Verhoef, Gregor E.G., de Weerdt, Okke, Wijermans, Pierre, Passweg, Jakob R., and Löwenberg, Bob

Published
2012
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16. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study

Author

Löwenberg, Bob, Beck, Joachim, Graux, Carlos, van Putten, Wim, Schouten, Harry C., Verdonck, Leo F., Ferrant, Augustin, Sonneveld, Pieter, Jongen-Lavrencic, Mojca, von Lilienfeld-Toal, Marie, Biemond, Bart J., Vellenga, Edo, Breems, Dimitri, de Muijnck, Hilde, Schaafsma, Ron, Verhoef, Gregor, Döhner, Hartmut, Gratwohl, Alois, Pabst, Thomas, Ossenkoppele, Gert J., Maertens, Johan, for the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), German Austrian AML Study Group (AMLSG), and Swiss Group for Clinical Cancer Research Collaborative Group (SAKK)

Published
2010
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17. 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., Al-Badri, Waleed K. W., Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A., van Elssen, Catharina H. M. J., Fischer, Thomas, Gjertsen, Bjorn T., van Gorkom, Gwendolyn N. Y., Gradowska, Patrycja, Greuter, Marjolein J. E., Griskevicius, Laimonas, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G., Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Löwenberg, Bob, and Ossenkoppele, Gert J.

Subjects
ACUTE myeloid leukemia, STEM cell transplantation, STEM cell treatment, INDUCTION chemotherapy, COST control
Abstract

Measurable residual disease (MRD) measured using multiparameter flowcytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non-allogenic stem cell transplantation treatment for MRD-negative patients in the ELN-2017 intermediate risk group. Currently, measurement of MFC-MRD in bone marrow is used for clinical decision making after 2 cycles of induction chemotherapy. However, measurement after 1 cycle has also been shown to have prognostic value, so the optimal time point remains a question of debate. We assessed the independent prognostic value of MRD results at either time point and concordance between these for 273 AML patients treated within and according to the HOVON-SAKK 92, 102, 103 and 132 trials. Cumulative incidence of relapse, event free survival and overall survival were significantly better for MRD-negative (<0.1%) patients compared to MRD-positive patients after cycle 1 and cycle 2 (p ≤ 0.002, for all comparisons). A total of 196 patients (71.8%) were MRD-negative after cycle 1, of which the vast majority remained negative after cycle 2 (180 patients; 91.8%). In contrast, of the 77 MRD-positive patients after cycle 1, only 41 patients (53.2%) remained positive. A cost reduction of –€571,751 per 100 patients could be achieved by initiating the donor search based on the MRD-result after cycle 1. This equals to a 50.7% cost reduction compared to the current care strategy in which the donor search is initiated for all patients. These results show that MRD after cycle 1 has prognostic value and is highly concordant with MRD status after cycle 2. When MRD-MFC is used to guide consolidation treatment (allo vs non-allo) in intermediate risk patients, allogeneic donor search may be postponed or omitted after cycle 1. Since the majority of MRD-negative patients remain negative after cycle 2, this could safely reduce the number of allogeneic donor searches and reduce costs. [ABSTRACT FROM AUTHOR]

Published
2022
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18. A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1–risk myelodysplastic syndrome

Author

Garcia-Manero, Guillermo, Gartenberg, Gary, Steensma, David P., Schipperus, Martin R., Breems, Dimitri A., de Paz, Raquel, Valcárcel, David, Kranenburg, Britte, Reddy, Manjula, and Komrokji, Rami S.

Published
2014
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20. Viral Evolution and Immunology of SARS-CoV-2 in a Persistent Infection after Treatment with Rituximab.

Author

Van der Moeren, Nathalie, Selhorst, Philippe, Ha, My, Heireman, Laura, Van Gaal, Pieter-Jan, Breems, Dimitri, Meysman, Pieter, Laukens, Kris, Verstrepen, Walter, Van Gasse, Natasja, Ogunjimi, Benson, Arien, Kevin K., and Naesens, Reinout

Subjects
SARS-CoV-2, CD20 antigen, WHOLE genome sequencing, LYMPHOCYTE count, INFECTION prevention, VIRUS diseases, IMMUNOCOMPROMISED patients
Abstract

Background. Prolonged shedding of SARS-CoV-2 in immunocompromised patients has been described. Furthermore, an accumulation of mutations of the SARS-CoV-2 genome in these patients has been observed. Methods. We describe the viral evolution, immunologic response and clinical course of a patient with a lymphoma in complete remission who had received therapy with rituximab and remained SARS-CoV-2 RT-qPCR positive for 161 days. Results. The patient remained hospitalised for 10 days, after which he fully recovered and remained asymptomatic. A progressive increase in Ct-value, coinciding with a progressive rise in lymphocyte count, was seen from day 137 onward. Culture of a nasopharyngeal swab on day 67 showed growth of SARS-CoV-2. Whole genome sequencing (WGS) demonstrated that the virus belonged to the wildtype SARS-CoV-2 clade 20B/GR, but rapidly accumulated a high number of mutations as well as deletions in the N-terminal domain of its spike protein. Conclusion. SARS-CoV-2 persistence in immunocompromised individuals has important clinical implications, but halting immunosuppressive therapy might result in a favourable clinical course. The long-term shedding of viable virus necessitates customized infection prevention measures in these individuals. The observed accelerated accumulation of mutations of the SARS-CoV-2 genome in these patients might facilitate the origin of new VOCs that might subsequently spread in the general community. [ABSTRACT FROM AUTHOR]

Published
2022
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21. The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed.

Author

Bakunina, Katerina, Putter, Hein, Versluis, Jurjen, Koster, Eva A. S., van der Holt, Bronno, Manz, Markus G., Breems, Dimitri A., Gjertsen, Bjorn T., Cloos, Jacqueline, Valk, Peter J. M., Passweg, Jakob, Pabst, Thomas, Ossenkoppele, Gert J., Löwenberg, Bob, Cornelissen, Jan J., and de Wreede, Liesbeth C.

Subjects
RANDOMIZED controlled trials, HEMATOPOIETIC stem cell transplantation, STEM cell transplantation, ACUTE myeloid leukemia, STEM cell treatment, INDUCTION chemotherapy, TREATMENT effectiveness
Abstract

Clofarabine is an active antileukemic drug for subgroups of patients with acute myeloid leukemia (AML). Multi‐state models can provide additional insights to supplement the original intention‐to‐treat analysis of randomized controlled trials (RCT). We re‐analyzed the HOVON102/SAKK30/09 phase III RCT for newly diagnosed AML patients, which randomized between standard induction chemotherapy with or without clofarabine. Using multi‐state models, we evaluated the effects of induction chemotherapy outcomes (complete remission [CR], measurable residual disease [MRD]), and post‐remission therapy with allogeneic stem cell transplantation [alloSCT] on relapse and death. Through the latter a consistent reduction in the hazard of relapse in the clofarabine arm compared to the standard arm was found, which occurred irrespective of MRD status or post‐remission treatment with alloSCT, demonstrating a strong and persistent antileukemic effect of clofarabine. During the time period between achieving CR and possible post‐remission treatment with alloSCT, non‐relapse mortality was higher in patients receiving clofarabine. An overall net benefit of treatment with clofarabine was identified using the composite endpoint current leukemia‐free survival (CLFS). In conclusion, these results enforce and extend the earlier reported beneficial effect of clofarabine in AML and show that multi‐state models further detail the effect of treatment on competing and series of events. [ABSTRACT FROM AUTHOR]

Published
2022
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25. Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch–Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial

Author

Breems, Dimitri A., Boogaerts, Marc A., Dekker, Adriaan W., Van Putten, Wim L. J., Sonneveld, Pieter, Huijgens, Peter C., Van der Lelie, Johannes, Vellenga, Edo, Gratwohl, Alois, Verhoef, Gregor E. G., Verdonck, Leo F., and Löwenberg, Bob

Published
2005

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

Author

Lam Ngai, Lok, Hanekamp, Diana, Kelder, Angèle, Scholten, Willemijn J., Carbaat ‐ Ham, Jannemieke, Snel, Alexander N., Bachas, Costa, Tettero, Jesse, van der Velden, Vincent, Slomp, Jennichjen, Hobo, Willemijn, Breems, Dimitri, Fischer, Thomas, Tore Gjertsen, Bjorn, Griškevičius, Laimonas, Juliusson, Gunnar, Maertens, Johan, Manz, Markus, Pabst, Thomas, and Passweg, Jakob

Published
2023
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31. Comparative Analysis of the Value of Allogeneic Hematopoietic Stem-Cell Transplantation in Acute Myeloid Leukemia With Monosomal Karyotype Versus Other Cytogenetic Risk Categories.

Author

Cornelissen, Jan J., Breems, Dimitri, van Putten, Wim L. J., Gratwohl, Alois A., Passweg, Jakob R., Pabst, Thomas, Maertens, Johan, Beverloo, H. Berna, Kooy, Marinus van Marwijk, Wijermans, Pierre W., Biemond, Bart J., Vellenga, Edo, Verdonck, Leo F., Ossenkoppele, Gert J., and Löwenberg, Bob

Published
2012
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33. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS.

Author

Janssen, Jeroen, Löwenberg, Bob, Manz, Markus, Bargetzi, Mario, Biemond, Bart, Borne, Peter von dem, Breems, Dimitri, Brouwer, Rolf, Chalandon, Yves, Deeren, Dries, Efthymiou, Anna, Gjertsen, Bjørn-Tore, Graux, Carlos, Gregor, Michael, Heim, Dominik, Hess, Urs, Hoogendoorn, Mels, Jaspers, Aurelie, Jie, Asiong, and Jongen-Lavrencic, Mojca

Subjects
THERAPEUTIC use of antineoplastic agents, MYELODYSPLASTIC syndromes, DRUG efficacy, GLYCINE, CONFIDENCE intervals, CANCER chemotherapy, ACUTE myeloid leukemia, PROTEOLYTIC enzymes, ANTINEOPLASTIC agents, ATRIAL fibrillation, CANCER patients, RANDOMIZED controlled trials, COMPARATIVE studies, INFECTION, SURVIVAL analysis (Biometry), DESCRIPTIVE statistics, STATISTICAL sampling, CYTARABINE, HYDROXY acids, LONGITUDINAL method, CHEMICAL inhibitors, EVALUATION, OLD age
Abstract

Simple Summary: Treatment results of acute myeloid leukemia (AML) in elderly patients are unsatisfactory. We investigated in an open label randomized phase II study whether addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy would improve outcome in this population. 231 AML patients > 65 years of age were randomly assigned to receive standard chemotherapy with or without tosedostat for two cycles. We found that complete bone marrow leukemia clearance was not significantly different between both arms. After two years, survival was 33% for the standard arm versus 18% for the tosedostat arm. More patients died due to infectious complications in the tosedostat arm than after standard treatment. Also, a cardiac rhythm abnormality called atrial fibrillation was more often seen in the tosedostat arm. We conclude that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly patients with acute myeloid leukemia. Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. [ABSTRACT FROM AUTHOR]

Published
2021
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35. Diphtheria Toxin Fused to Granulocyte-Macrophage Colony-Stimulating Factor Eliminates Acute Myeloid Leukemia Cells With the Potential to Initiate Leukemia in Immunodeficient Mice, But Spares Normal Hemopoietic Stem Cells

Author

Terpstra, Wim, Rozemuller, Henk, Breems, Dimitri A., Rombouts, Elwin J.C., Prins, Arie, FitzGerald, David J.P., Kreitman, Robert J., Wielenga, Jenne J., Ploemacher, Rob E., Löwenberg, Bob, Hagenbeek, Anton, and Martens, Anton C.M.

Published
1997
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