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1. Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome

Author

Janssen, J. J. W. M., Löwenberg, B., Manz, M., Biemond, B. J., Westerweel, P. E., Klein, S. K., Fehr, M., Sinnige, H. A. M., Efthymiou, A., Legdeur, M. C. J. C., Pabst, T., Gregor, M., van der Poel, M. W. M., Deeren, D., Tick, L. W., Jongen-Lavrencic, M., van Obbergh, F., Boersma, R. S., de Weerdt, O., Chalandon, Y., Heim, D., Spertini, O., van Sluis, G., Graux, C., Stüssi, G., van Norden, Y., and Ossenkoppele, G. J.

Published
2022
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4. Correction: Lenalidomide added to standard intensive treatment for older patients with AML and high-risk MDS

Author

Ossenkoppele, G. J., Breems, D. A., Stuessi, G., van Norden, Y., Bargetzi, M., Biemond, B. J., A von dem Borne, P., Chalandon, Y., Cloos, J., Deeren, D., Fehr, M., Gjertsen, B., Graux, C., Huls, G., Janssen, J. J. J. W., Jaspers, A., Jongen-Lavrencic, M., de Jongh, E., Klein, S. K., van der Klift, M., van Marwijk Kooy, M., Maertens, J., Michaux, L., van der Poel, M. W. M., van Rhenen, A., Tick, L., Valk, P., Vekemans, M. C., van der Velden, W. J. F. M., de Weerdt, O., Pabst, T., Manz, M., and Löwenberg, B.

Published
2020
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5. Human T Cell Development and HIV Infection in Human Hemato-Lymphoid System Mice

Author

Baenziger, S., Ziegler, P., Mazzucchelli, L., Bronz, L., Speck, R. F., Manz, M. G., Compans, Richard W., editor, Cooper, Max D., editor, Honjo, Tasuku, editor, Koprowski, Hilary, editor, Melchers, Fritz, editor, Oldstone, Michael B. A., editor, Olsnes, Sjur, editor, Vogt, Peter K., editor, Nomura, Tatsuji, editor, Watanabe, Takeshi, editor, and Habu, Sonoko, editor

Published
2008
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6. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio

Author

Versluis, J, in ‘t Hout, F E M, Devillier, R, van Putten, W L J, Manz, M G, Vekemans, M -C, Legdeur, M -C, Passweg, J R, Maertens, J, Kuball, J, Biemond, B J, Valk, P J M, van der Reijden, B A, Meloni, G, Schouten, H C, Vellenga, E, Pabst, T, Willemze, R, Löwenberg, B, Ossenkoppele, G, Baron, F, Huls, G, and Cornelissen, J J

Published
2017
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7. Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40–60 years

Author

Cornelissen, J J, Versluis, J, Passweg, J R, van Putten, W L J, Manz, M G, Maertens, J, Beverloo, H B, Valk, P J M, van Marwijk Kooy, M, Wijermans, P W, Schaafsma, M R, Biemond, B J, Vekemans, M-C, Breems, D A, Verdonck, L F, Fey, M F, Jongen-Lavrencic, M, Janssen, J J W M, Huls, G, Kuball, J, Pabst, T, Graux, C, Schouten, H C, Gratwohl, A, Vellenga, E, Ossenkoppele, G, and Löwenberg, B

Published
2015
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8. Lenalidomide added to standard intensive treatment for older patients with AML and high-risk MDS

Author

Ossenkoppele, G.J., Breems, D.A., Stuessi, G., Norden, Y. van, Bargetzi, M., Biemond, B.J., Borne, P.A. von dem, Chalandon, Y., Cloos, J., Deeren, D., Fehr, M., Gjertsen, B., Graux, C., Huls, G., Janssen, J.J.J.W., Jaspers, A., Jongen-Lavrencic, M., Jongh, E. de, Klein, S.K., Klift, M. van der, Kooy, M.V., Maertens, J., Micheaux, L., Poel, M.W.M. van der, Rhenen, A. van, Tick, L., Valk, P., Vekemans, M.C., Velden, W.J.F.M. van der, Weerdt, O. de, Pabst, T., Manz, M., Lowenberg, B., Havelange, Moors, I., Obberg, F. van, Maertens, J.A., Hodossy, B., Vansteenweghen, S., Lammertijn, L., Sonet, A., Triffet, A., Gjertsen, B.T., Passweg, J., Heim, D., Giovanni, S., Betticher, D., Spertini, O., Gregor, M., Hess, U., Manz, M.G., Loosdrecht, A. van de, Janssen, J.J.W.M., Esser, J.W.J. van, Brouwer, R.E., Lammeren-Venema, D. van, Levin, M.D., Tick, L.W., Legdeur, M.C.J.C., Vellenga, E., Hoogendoorn, M., Veelken, J.H., Schouten, H.C., Cornelissen, J., Wouters, B., Raaijmakers, H.G.M., Kuball, J., Dutch-Belgian Hemato-Oncology, Swiss Grp Clinical Canc Res SAKK, Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Haematology, CCA - Cancer Treatment and Quality of Life, CCA - Cancer Treatment and quality of life, Hematology laboratory, Hematology, Department of History, International Institute of Social Studies, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Hematologie (9), UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service d'hématologie, and UCL - (SLuc) Service d'hématologie

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Phases of clinical research, HIGH-DOSE LENALIDOMIDE, ACUTE MYELOID-LEUKEMIA, THERAPY, 03 medical and health sciences, 0302 clinical medicine, Older patients, SDG 3 - Good Health and Well-being, Internal medicine, medicine, 610 Medicine & health, Adverse effect, Lenalidomide, Chemotherapy, business.industry, Intensive treatment, Myeloid leukemia, Hematology, ADULTS, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Cytarabine, business, medicine.drug
Abstract

Contains fulltext : 225470.pdf (Publisher’s version ) (Closed access) More effective treatment modalities are urgently needed in patients with acute myeloid leukemia (AML) of older age. We hypothesized that adding lenalidomide to intensive standard chemotherapy might improve their outcome. After establishing a safe lenalidomide, dose elderly patients with AML were randomly assigned in this randomized Phase 2 study (n = 222) to receive standard chemotherapy ("3 + 7") with or without lenalidomide at a dose of 20 mg/day 1-21. In the second cycle, patients received cytarabine 1000 mg/m(2) twice daily on days 1-6 with or without lenalidomide (20 mg/day 1-21). The CR/CRi rates in the two arms were not different (69 vs. 66%). Event-free survival (EFS) at 36 months was 19% for the standard arm versus 21% for the lenalidomide arm and overall survival (OS) 35% vs. 30%, respectively. The frequencies and grade of adverse events were not significantly different between the treatment arms. Cardiovascular toxicities were rare and equally distributed between the arms. The results of the present study show that the addition of lenalidomide to standard remission induction chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR2294 in The NederlandsTrial Register (www.trialregister.nl).

Published
2020
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10. Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Janssen, J J W M, Löwenberg, B, Manz, M, Biemond, B J, Westerweel, P E, Klein, S K, Fehr, M, Sinnige, H A M, Efthymiou, A, Legdeur, M C J C, Pabst, T, Gregor, M, van der Poel, M W M, Deeren, D, Tick, L W, Jongen-Lavrencic, M, van Obbergh, F, Boersma, R S, de Weerdt, O, Chalandon, Y, Heim, D, Spertini, O, van Sluis, G, Graux, Carlos, Stüssi, G, van Norden, Y, Ossenkoppele, G J, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Janssen, J J W M, Löwenberg, B, Manz, M, Biemond, B J, Westerweel, P E, Klein, S K, Fehr, M, Sinnige, H A M, Efthymiou, A, Legdeur, M C J C, Pabst, T, Gregor, M, van der Poel, M W M, Deeren, D, Tick, L W, Jongen-Lavrencic, M, van Obbergh, F, Boersma, R S, de Weerdt, O, Chalandon, Y, Heim, D, Spertini, O, van Sluis, G, Graux, Carlos, Stüssi, G, van Norden, Y, and Ossenkoppele, G J

Abstract

Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).

Published
2022

13. P406: ENHANCED SIGNIFICANCE OF FLT3-ITD RESIDUAL DISEASE DETECTION ON TREATMENT OUTCOME IN ACUTE MYELOID LEUKEMIA

Author

Grob, T., primary, Sanders, M., additional, Vonk, C., additional, Kavelaars, F., additional, Rijken, M., additional, Hanekamp, D., additional, Gradowska, P., additional, Cloos, J., additional, Fløisand, Y., additional, Marwijk Kooy, M. V., additional, Manz, M., additional, Ossenkoppele, G., additional, Tick, L., additional, Havelange, V., additional, Löwenberg, B., additional, Jongen-Lavrencic, M., additional, and Valk, P., additional

Published
2022
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14. P856: A SINGLE-CELL FUNCTIONAL PRECISION MEDICINE LANDSCAPE OF MULTIPLE MYELOMA

Author

Kropivsek, K., primary, Kachel, P., additional, Goetze, S., additional, Wegmann, R., additional, Severin, Y., additional, Hale, B. D., additional, Festl, Y., additional, Mena, J., additional, van Drogen, A., additional, Dietliker, N., additional, Tchinda, J., additional, Wollscheid, B., additional, Manz, M. G., additional, and Snijder, B., additional

Published
2022
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27. Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Author

Camenzind, Edoardo, Boersma, Eric, Wijns, William, Mauri, Laura, Rademaker-Havinga, Tessa, Ordoubadi, Farzin Fath, Suttorp, Maarten J., Al Kurdi, Mohammad, Steg, Ph Gabriel, Camenzind, E, Mauri, L, OʼNeill, W, Serruys, P W, Steg, PhG, Wijns, W, Verheugt, FWA, Bertrand, ME, Califf, R, DeMets, D, Wallentin, L, Bocksch, W, Bosmans, J, Garcia, H, Garg, S, Hanet, C, Herrman, J-PR, Kelbaek, H, Mc Fadden, E, Radke, PW, Rutsch, W, Tilsted, HH, Wykrzykowska, J, Alvarez, C, Rodriguez, A, Meredith, I, Muller, D, Whitbourn, R, Worthley, S, Whelan, A, Walters, D, Shetty, S, New, G, Cox, S, Batra, R, van Gaal, W, Bellamy, G, Mayr, H, Heigert, M, Huber, K, Leisch, F, Wijns, W, Desmet, W, Boland, J, Schroeder, E, Chenu, P, Legrand, V, Labinaz, M, Teefy, P, Bertrand, O, Gao, R, Ge, J, Kala, P, Cervinka, P, Ureña, P, Hartikainen, J, Steg, G, Fajadet, J, Carrie, D, Gilard, M, Barragan, P, Lablanche, J-M, Koning, R, Eltchaninoff, H, Darremont, O, Leroy, F, Bertrand, B, Robert, G, Schiele, F, Chassaing, S, Bressollette, E, Brunel, P, Quilliet, L, Brunet, J, Pansieri, M, Sideris, G, Stratiev, V, Teiger, E, Lebreton, H, Bonnet, J-L, Karsenty, B, Delarche, N, Lusson, J-R, Cassagnes, J, Brachmann, J, Kurowski, V, Buerke, M, Schieffer, B, Scholtz, W, Wiemer, M, Fichtlscherer, S, Schächinger, V, Kupatt, C, Boekstegers, P, Genth-Zotz, S, Bode, C, Frey, N, Neumann, F-J, Witzenbichler, B, Pels, K, Strasser, R, Kuck, K-H, Hauptmann, K-E, Baldus, S, Heitzer, T, Haude, M, Hoffmann, E, Jung, W, Hoffmann, S, Schmitt, C, Dissmann, M, Pauschinger, M, Werner, G, Braun-Delleus, R, Burkhardt, D, Manz, M, Voudris, V, Sionis, D, Kang-Yin, M-L, Tse, T-S, Merkely, B, Mehta, A, Parikh, K, Kumar, V, Chandra, P, Rath, P, Hiremath, S, Crean, P, Daly, K, Kornowski, R, Kerner, A, Mosseri, M, Jafari, G, Giudice, P, Trani, C, Manari, A, Prati, F, Pangrazi, A, Bolognese, L, Jeong, M-H, Kim, M-Y, Kim, H-S, Park, S-J, Erglis, A, Kalnins, A, Wagner, D, Zambahari, R, Ong, T-K, Sim, K, den Heijer, P, Appelman, Y, Suttorp, M-J, de Smet, B, Koolen, J, Stella, P, Harding, S, Warwick, J, Maslowski, A, Abernethy, M, Devlin, G, Rotevatn, S, Myreng, Y, Ciecwierz, D, Peruga, J, Reczuch, K, Campante Teles, R, Farto, P, Abreu, E, Leitão-Marques, A, Pereira, H, Vinereanu, D, Alkasab, S, Mhish, H, Al Kurdi, M, Al Turki, F, Wong, P, Teo, S-G, Goicolea Ruigomez, F-J, Valdés Chávarri, M, Bethencourt Gonzalez, A, Iñiguez Romo, A, López Minguez, J, Hernández García, J-M, Diaz Fernández, J, Ruiz Salmeron, R, Martinez Elbal, L, Zueco, J, López-Palop, RF, Melgares, R, Diderholm, E, Kåregren, A, Herterich, O, Olivencrona, G, Fröbert, O, Roffi, M, Verin, V, Girod, G, Vuilliomenet, A, Hsieh, I-C, Wu, C-J, Gershlick, A, Densem, C, Doshi, S, Manoharan, G, McCarthy, P, De Belder, M, Mills, J, Fath-Ordoubadi, F, Simpson, I, Greenwood, J, Chamberlain-Webber, R, Khan, Z, Cotton, J, Gunning, M, Smith, D, Talwar, S, Holmberg, S, Purcell, I, Anderson, R, Alamgir, F, Beatt, K, Kelly, P, Moussavian, M, Aji, J, Prashad, R, Zankar, A, Banerjee, S, Lewis, S, McLaurin, B, Douglas, J, Brener, S, Gupta, A, Walters, L, Driesman, M, Aycock, R, Mego, C, Fisher, D, Frankel, R, and Satler, L

Published
2014
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29. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS

Author

Janssen, J., Lowenberg, B., Manz, M., Bargetzi, Mario, Biemond, Bart J., Borne, Peter von dem, Velden, W.J.F.M. van der, Norden, Yvette van, Ossenkoppele, G.J., Janssen, J., Lowenberg, B., Manz, M., Bargetzi, Mario, Biemond, Bart J., Borne, Peter von dem, Velden, W.J.F.M. van der, Norden, Yvette van, and Ossenkoppele, G.J.

Abstract

Contains fulltext : 231606.pdf (publisher's version ) (Open Access)

Published
2021

30. Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Author

Janssen, J. (Jeroen), Löwenberg, B. (Bob), Manz, M. (Markus), Bargetzi, M. (Mario), Biemond, B.J. (Bart), Borne, P.A.K. (Peter) von dem, Breems, D.A. (Dimitri), Brouwer, R.E. (Rolf), Chalandon, Y. (Yves), Deeren, D. (Dries), Efthymiou, A. (Anna), Gjertsen, B.-T. (Bjørn-Tore), Graux, C. (Carlos), Gregor, M. (Michael), Heim, D. (Dominik), Hess, U. (Urs), Hoogendoorn, M. (Mels), Jaspers, A. (Aurelie), Jie, A. (Asiong), Jongen-Lavrencic, M. (Mojca), Klein, S. (Saskia), Klift, M. (Marjolein) van der, Kuball, J. (Jürgen), van Lammeren - Venema, D. (Danielle), Legdeur, M.C.J.C. (M. C J C), Loosdrecht, A.A. (Arjan) van de, Maertens, J. (Johan), Kooy, M.M. (Marinus van Marwijk), Moors, I. (Ine), Nijziel, M.R. (Marten), van Obbergh, F. (Florence), Oosterveld, M. (Margriet), Pabst, T. (Thomas), van der Poel, M. (Marjolein), Sinnige, H. (Harm), Spertini, O. (Olivier), Terpstra, W. (Wim), Tick, L.W. (Lidwine), Velden, W.J.F.M. (Walter) van der, Vekemans, M.-C. (Marie-Christiane), Vellenga, E. (Edo), Weerdt, O. (Okke) de, Westerweel, P. (Peter), Stussi, G. (Georg), Norden, Y. (Yvette) van, Ossenkoppele, G.J. (Gert), Janssen, J. (Jeroen), Löwenberg, B. (Bob), Manz, M. (Markus), Bargetzi, M. (Mario), Biemond, B.J. (Bart), Borne, P.A.K. (Peter) von dem, Breems, D.A. (Dimitri), Brouwer, R.E. (Rolf), Chalandon, Y. (Yves), Deeren, D. (Dries), Efthymiou, A. (Anna), Gjertsen, B.-T. (Bjørn-Tore), Graux, C. (Carlos), Gregor, M. (Michael), Heim, D. (Dominik), Hess, U. (Urs), Hoogendoorn, M. (Mels), Jaspers, A. (Aurelie), Jie, A. (Asiong), Jongen-Lavrencic, M. (Mojca), Klein, S. (Saskia), Klift, M. (Marjolein) van der, Kuball, J. (Jürgen), van Lammeren - Venema, D. (Danielle), Legdeur, M.C.J.C. (M. C J C), Loosdrecht, A.A. (Arjan) van de, Maertens, J. (Johan), Kooy, M.M. (Marinus van Marwijk), Moors, I. (Ine), Nijziel, M.R. (Marten), van Obbergh, F. (Florence), Oosterveld, M. (Margriet), Pabst, T. (Thomas), van der Poel, M. (Marjolein), Sinnige, H. (Harm), Spertini, O. (Olivier), Terpstra, W. (Wim), Tick, L.W. (Lidwine), Velden, W.J.F.M. (Walter) van der, Vekemans, M.-C. (Marie-Christiane), Vellenga, E. (Edo), Weerdt, O. (Okke) de, Westerweel, P. (Peter), Stussi, G. (Georg), Norden, Y. (Yvette) van, and Ossenkoppele, G.J. (Gert)

Abstract

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 wa

Published
2021
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31. Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Author

Janssen, J, Löwenberg, Bob, Manz, M, Bargetzi, M, Biemond, B, van den Borne, P, Breems, D, Brouwer, R, Chalandon, Y, Deeren, D, Efthymiou, A, Gjertsen, BT, Graux, C, Gregor, M, Heim, D, Hess, U, Hoogendoorn, M, Jaspers, A, Jie, A, Jongen - Lavrencic, Mojca, Klein, S, van der Klift, Maarten, Kuball, J, van Lammeren-Venema, D, Legdeur, MC, van de Loosdrecht, A, Maertens, J, Kooy, MM, Moors, I, Nijziel, M, van Obbergh, F, Oosterveld, M, Pabst, T, Poel, M, Sinnige, H, Spertini, O, Terpstra, W, Tick, L, van der Velden, W, Vekemans, MC, Vellenga, E, de Weerdt, O, Westerweel, P, Stüssi, G, van Norden, Yvette, Ossenkoppele, G, Janssen, J, Löwenberg, Bob, Manz, M, Bargetzi, M, Biemond, B, van den Borne, P, Breems, D, Brouwer, R, Chalandon, Y, Deeren, D, Efthymiou, A, Gjertsen, BT, Graux, C, Gregor, M, Heim, D, Hess, U, Hoogendoorn, M, Jaspers, A, Jie, A, Jongen - Lavrencic, Mojca, Klein, S, van der Klift, Maarten, Kuball, J, van Lammeren-Venema, D, Legdeur, MC, van de Loosdrecht, A, Maertens, J, Kooy, MM, Moors, I, Nijziel, M, van Obbergh, F, Oosterveld, M, Pabst, T, Poel, M, Sinnige, H, Spertini, O, Terpstra, W, Tick, L, van der Velden, W, Vekemans, MC, Vellenga, E, de Weerdt, O, Westerweel, P, Stüssi, G, van Norden, Yvette, and Ossenkoppele, G

Abstract

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.

Published
2021

43. Correction: Lenalidomide added to standard intensive treatment for older patients with AML and high-risk MDS

Author

UCL - (SLuc) Centre du cancer, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Ossenkoppele, G. J., Breems, D. A., Stuessi, G., van Norden, Y., Bargetzi, M., Biemond, B. J., A von dem Borne, P., Chalandon, Y., Cloos, J., Deeren, D., Fehr, M., Gjertsen, B., Graux, Carlos, Huls, G., Janssen, J. J. J. W., Jaspers, A., Jongen-Lavrencic, M., de Jongh, E., Klein, S. K., van der Klift, M., van Marwijk Kooy, M., Maertens, J., Michaux, L., van der Poel, M. W. M., van Rhenen, A., Tick, L., Valk, P., Vekemans, Marie-Christiane, van der Velden, W. J. F. M., de Weerdt, O., Pabst, T., Manz, M., Löwenberg, B., Havelange, Violaine, Sonet, Anne, UCL - (SLuc) Centre du cancer, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Ossenkoppele, G. J., Breems, D. A., Stuessi, G., van Norden, Y., Bargetzi, M., Biemond, B. J., A von dem Borne, P., Chalandon, Y., Cloos, J., Deeren, D., Fehr, M., Gjertsen, B., Graux, Carlos, Huls, G., Janssen, J. J. J. W., Jaspers, A., Jongen-Lavrencic, M., de Jongh, E., Klein, S. K., van der Klift, M., van Marwijk Kooy, M., Maertens, J., Michaux, L., van der Poel, M. W. M., van Rhenen, A., Tick, L., Valk, P., Vekemans, Marie-Christiane, van der Velden, W. J. F. M., de Weerdt, O., Pabst, T., Manz, M., Löwenberg, B., Havelange, Violaine, and Sonet, Anne

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

44. Challenges in diagnosis and management of neutropenia upon exposure to immune-checkpoint inhibitors: meta-analysis of a rare immune-related adverse side effect

Author

Boegeholz, J, Brueggen, C S, Pauli, C, Dimitriou, F, Haralambieva, E, Dummer, R, Manz, M G, Widmer, C C, Boegeholz, J, Brueggen, C S, Pauli, C, Dimitriou, F, Haralambieva, E, Dummer, R, Manz, M G, and Widmer, C C

Abstract

BACKGROUND Cancer immunotherapy via immune-checkpoint inhibition (ICI) by antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and cell death protein 1 (PD-1) have significantly improved the outcome of metastasized melanoma and of a rapidly increasing number of other cancer types. The anti-tumor effect is often accompanied by immune-related adverse events (irAE). Hematological irAE, specifically neutropenia, are rarely observed. However, neutropenia is associated with high morbidity and mortality due to infection complications. Thus, early detection and treatment is crucial. METHODS We present the clinical course of two patients with severe neutropenia after ICI therapy and demonstrate the difficulty of the diagnosis when a comedication of metamizole, a well-known analgesic drug used to treat cancer pain, is present. Further, we provide a comprehensive descriptive and statistical analysis of published data on diagnostics, treatment and infection complication in patients with at least grade 4 neutropenia by a systematic database search. RESULTS Finally, 34 patients were analyzed, including the two case reports from our cohort. The median onset of neutropenia was 10.5 weeks after first ICI administration (interquartile range: 6 weeks). In 76% (N = 26), a normalization of the neutrophil count was achieved after a median duration of neutropenia of 13 days. In a subsample of 22 patients with detailed data, the infection rate was 13%, proven by positive blood culture in 3 cases, but 68% (N = 15) presented with fever > 38 °C. Treatment regime differed relevantly, but mainly included G-CSF and intravenous corticosteroids. Death was reported in 14 patients (41%), 3 of whom (9%) were associated with hematological irAE but only two directly associated with neutropenia. CONCLUSION With an increasing number of cancer patients eligible to ICI therapy, the incidence of severe hematological toxicities may rise substantially over the next years. Clinicians working

Published
2020

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