Search

Your search keyword '"Ades, L"' showing total 487 results
Start Over Author "Ades, L"
487 results on '"Ades, L"'

1. Efficacy and safety of bemcentinib in patients with advanced myelodysplastic neoplasms or acute myeloid leukemia failing hypomethylating agents- the EMSCO phase II BERGAMO trial

Author

Kubasch, A. S., Peterlin, P., Cluzeau, T., Götze, K. S., Sockel, K., Teipel, R., Jentzsch, M., Attalah, H., Sebert, M., Chermat, F., Gloaguen, S., Puttrich, M., Cross, M., Schneider, M., Kayser, S., Schipp, D., Giagounidis, A., Tirado-Gonzalez, I., Descot, A., van de Loosdrecht, A., Weigert, A., Metzeler, K. H., Fenaux, P., Medyouf, H., Platzbecker, U., and Ades, L.

Published
2023
Full Text
View/download PDF

3. A multitiered analysis platform for genome sequencing: Design and initial findings of the Australian Genomics Cardiovascular Disorders Flagship

Author

Austin, R, Brown, JS, Casauria, S, Madelli, EO, Mattiske, T, Boughtwood, T, Metke, A, Davis, A, Horton, AE, Winlaw, D, Das, D, Soka, M, Giannoulatou, E, Rath, EM, Haan, E, Blue, GM, Vohra, J, Atherton, JJ, van Spaendonck-Zwarts, K, Cox, K, Burnett, L, Wallis, M, Haas, M, Quinn, MCJ, Pachter, N, Poplawski, NK, Stark, Z, Bagnall, RD, Weintraub, RG, Pantaleo, S-J, Lunke, S, De Fazio, P, Thompson, T, James, P, Chang, Y, Fatkin, D, Macciocca, I, Ingles, J, Dunwoodie, SL, Semsarian, C, McGaughran, J, Ades, L, Enriquez, A, McLean, A, Smyth, R, Alankarage, D, McNamara, J, Morgan almog, Fear, V, Medi, C, Al-Shinnag, M, Fine, M, Sy, R, Finlay, K, Milnes, D, Tang, D, Garza, D, Milward, M, Taylor, J, Morrish, A, Taylor, S, Barnett, C, Gongolidis, L, Morwood, J, Tchan, M, Gray, B, Mountain, H, Bodek, S, Greer, C, Mowat, D, Thorpe, J, Boggs, K, Ng, C-A, Trainer, A, Bogwitz, M, Nowak, N, Trivedi, G, Hanna, B, Martinez, NN, Valente, G, Bray, A, Harvey, R, Ohanian, M, Brion, M-J, Hayward, J, O’Sullivan, S, Vandenberg, J, Brown, J, Herrera, C, Overkov, A, Verma, K, Richardson, RB, Hill, A, Vidgen, M, Hollingsworth, G, Patel, C, Burns, C, Hollway, G, Perrin, M, Waddel-Smith, K, Cao, M, Perry, M, Carr, W, Howting, D, Pflaumer, A, Phillips, P, Wilson, M, Chalinor, H, Isbister, J, Phuong, T, Jackson, M, Pope-Couston, R, Worgan, L, Chapman, G, Wornham, L, Charitou, T, Jane-Pantaleo, S, Punni, P, Wu, K, Chong, B, Johnson, R, Yeates, L, Collins, F, Kelly, A, Quinn, M, Zentner, D, Correnti, G, King-Smith, S, Rajagopalan, S, Kirk, E, Raju, H, Cunningham, F, Kummerfeld, S, Lassman, T, Regan, M, Davis, J, Lipton, J, Rogers, J, Ryan, M, Sandaradura, S, de Silva, M, MacIntyre, P, Schonrock, N, Den Elzen, N, Scuffham, P, Devery, S, Mallawaarachchi, A, Dobbins, J, Mansour, J, Sherburn, I, Martin, E, Sherlock, M-C, Dwyer, N, Mathew, J, Singer, E, Elbracht-Leong, S, Smerdon, C, Elliott, D, Smith, J, Austin, R, Brown, JS, Casauria, S, Madelli, EO, Mattiske, T, Boughtwood, T, Metke, A, Davis, A, Horton, AE, Winlaw, D, Das, D, Soka, M, Giannoulatou, E, Rath, EM, Haan, E, Blue, GM, Vohra, J, Atherton, JJ, van Spaendonck-Zwarts, K, Cox, K, Burnett, L, Wallis, M, Haas, M, Quinn, MCJ, Pachter, N, Poplawski, NK, Stark, Z, Bagnall, RD, Weintraub, RG, Pantaleo, S-J, Lunke, S, De Fazio, P, Thompson, T, James, P, Chang, Y, Fatkin, D, Macciocca, I, Ingles, J, Dunwoodie, SL, Semsarian, C, McGaughran, J, Ades, L, Enriquez, A, McLean, A, Smyth, R, Alankarage, D, McNamara, J, Morgan almog, Fear, V, Medi, C, Al-Shinnag, M, Fine, M, Sy, R, Finlay, K, Milnes, D, Tang, D, Garza, D, Milward, M, Taylor, J, Morrish, A, Taylor, S, Barnett, C, Gongolidis, L, Morwood, J, Tchan, M, Gray, B, Mountain, H, Bodek, S, Greer, C, Mowat, D, Thorpe, J, Boggs, K, Ng, C-A, Trainer, A, Bogwitz, M, Nowak, N, Trivedi, G, Hanna, B, Martinez, NN, Valente, G, Bray, A, Harvey, R, Ohanian, M, Brion, M-J, Hayward, J, O’Sullivan, S, Vandenberg, J, Brown, J, Herrera, C, Overkov, A, Verma, K, Richardson, RB, Hill, A, Vidgen, M, Hollingsworth, G, Patel, C, Burns, C, Hollway, G, Perrin, M, Waddel-Smith, K, Cao, M, Perry, M, Carr, W, Howting, D, Pflaumer, A, Phillips, P, Wilson, M, Chalinor, H, Isbister, J, Phuong, T, Jackson, M, Pope-Couston, R, Worgan, L, Chapman, G, Wornham, L, Charitou, T, Jane-Pantaleo, S, Punni, P, Wu, K, Chong, B, Johnson, R, Yeates, L, Collins, F, Kelly, A, Quinn, M, Zentner, D, Correnti, G, King-Smith, S, Rajagopalan, S, Kirk, E, Raju, H, Cunningham, F, Kummerfeld, S, Lassman, T, Regan, M, Davis, J, Lipton, J, Rogers, J, Ryan, M, Sandaradura, S, de Silva, M, MacIntyre, P, Schonrock, N, Den Elzen, N, Scuffham, P, Devery, S, Mallawaarachchi, A, Dobbins, J, Mansour, J, Sherburn, I, Martin, E, Sherlock, M-C, Dwyer, N, Mathew, J, Singer, E, Elbracht-Leong, S, Smerdon, C, Elliott, D, and Smith, J

Published
2024

7. Topic: AS04-MDS Biology and Pathogenesis/AS04e-Spliceosome machinery: DNA REPLICATION STRESS DUE TO LOSS OF R-LOOPS IN MYELODYSPLASTIC SYNDROMES WITH SF3B1 MUTATION

Author

Rombaut, D., primary, Lefevre, C., additional, Farhat, B., additional, Bondu, S., additional, Letessier, A., additional, Lesieur-Pasquier, A., additional, Castillo-Guzman, D., additional, Leduc, M., additional, Hartono, S., additional, Chesnais, V., additional, Mangione, R., additional, Boussaid, I., additional, Houy, A., additional, Bouscary, D., additional, Willems, L., additional, Chapuis, N., additional, Kosmider, O., additional, Park, S., additional, Raynaud, S., additional, Cluzeau, T., additional, Clappier, E., additional, Fenaux, P., additional, Ades, L., additional, Margueron, R., additional, Wassef, M., additional, Alsafadi, S., additional, Solary, E., additional, Constantinou, A., additional, Stern, M.-H., additional, Palancade, B., additional, Droin, N., additional, Miotto, B., additional, Chédin, F., additional, and Fontenay, M., additional

Published
2023
Full Text
View/download PDF

9. GERMLINE CHEK2 MUTATED MDS PATIENTS

Author

Freiman, L., primary, Larcher, L., additional, Tueur, G., additional, Vasquez, N., additional, Da Costa, M., additional, Raffoux, E., additional, Ades, L., additional, Fenaux, P., additional, Jean, S., additional, Duployer, N., additional, Clappier, E., additional, and Sébert, M., additional

Published
2023
Full Text
View/download PDF

10. Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment: ACCELERATED FAILURE TIME MODELS AS A CLINICALLY PLAUSIBLE WAY TO DESCRIBE SURVIVAL IN MDS – AN ANALYSIS OF THE IWG-PM DATABASE

Author

Pfeilstöcker, M., primary, Tuechler, H., additional, Ades, L., additional, Cermak, J., additional, Chermat, F., additional, Della Porta, M., additional, Fenaux, P., additional, Garcia-Manero, G., additional, Germing, U., additional, Haase, D., additional, Kündgen, A., additional, Lübbert, M., additional, Magalhaes, S., additional, Malcovati, L., additional, Miyazaki, Y., additional, Sanz, G., additional, Santini, V., additional, Sekeres, M., additional, Walter, M., additional, Valent, P., additional, and Greenberg, P., additional

Published
2023
Full Text
View/download PDF

11. Topic: AS01-Diagnosis/AS01c-Molecular aberrations (cytogenetic, genetic, gene expression): GENOMIC CLASSIFICATION OF MYELODYSPLASTIC SYNDROMES

Author

Bernard, E., primary, Hasserjian, R., additional, Greenberg, P., additional, Ossa, J. Arango, additional, Creignou, M., additional, Nannya, Y., additional, Tuechler, H., additional, Medina-Martinez, J., additional, Levine, M., additional, Jädersten, M., additional, Germing, U., additional, Sanz, G., additional, Van De Loosdrecht, A., additional, Kosmider, O., additional, Follo, M., additional, Thol, F., additional, Zamora, L., additional, Pinheiro, R., additional, Pellagatti, A., additional, Elias, H., additional, Haase, D., additional, Ganster, C., additional, Ades, L., additional, Tobiasson, M., additional, Palomo, L., additional, Della Porta, M., additional, Fenaux, P., additional, Belickova, M., additional, Savona, M., additional, Klimek, V., additional, Santos, F., additional, Boultwood, J., additional, Kotsianidis, I., additional, Santini, V., additional, Solé, F., additional, Platzbecker, U., additional, Heuser, M., additional, Valent, P., additional, Finelli, C., additional, Voso, M.T., additional, Shih, L.-Y., additional, Fontenay, M., additional, Jansen, J., additional, Cervera-Zamora, J., additional, Gattermann, N., additional, Ebert, B., additional, Bejar, R., additional, Malcovati, L., additional, Cazzola, M., additional, Ogawa, S., additional, Hellstrom-Lindberg, E., additional, and Papaemmanuil, E., additional

Published
2023
Full Text
View/download PDF

12. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes

Author

Sauta, E, Robin, M, Bersanelli, M, Travaglino, E, Meggendorfer, M, Zhao, L, Caballero Berrocal, J, Sala, C, Maggioni, G, Bernardi, M, Di Grazia, C, Vago, L, Rivoli, G, Borin, L, D'Amico, S, Tentori, C, Ubezio, M, Campagna, A, Russo, A, Mannina, D, Lanino, L, Chiusolo, P, Giaccone, L, Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Nibourel, O, Bicchieri, M, Bolli, N, Rambaldi, A, Passamonti, F, Savevski, V, Santoro, A, Germing, U, Kordasti, S, Santini, V, Diez-Campelo, M, Sanz, G, Sole, F, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Della Porta, M, Sauta, Elisabetta, Robin, Marie, Bersanelli, Matteo, Travaglino, Erica, Meggendorfer, Manja, Zhao, Lin-Pierre, Caballero Berrocal, Juan Carlos, Sala, Claudia, Maggioni, Giulia, Bernardi, Massimo, Di Grazia, Carmen, Vago, Luca, Rivoli, Giulia, Borin, Lorenza, D'Amico, Saverio, Tentori, Cristina Astrid, Ubezio, Marta, Campagna, Alessia, Russo, Antonio, Mannina, Daniele, Lanino, Luca, Chiusolo, Patrizia, Giaccone, Luisa, Voso, Maria Teresa, Riva, Marta, Oliva, Esther Natalie, Zampini, Matteo, Riva, Elena, Nibourel, Olivier, Bicchieri, Marilena, Bolli, Niccolo', Rambaldi, Alessandro, Passamonti, Francesco, Savevski, Victor, Santoro, Armando, Germing, Ulrich, Kordasti, Shahram, Santini, Valeria, Diez-Campelo, Maria, Sanz, Guillermo, Sole, Francesc, Kern, Wolfgang, Platzbecker, Uwe, Ades, Lionel, Fenaux, Pierre, Haferlach, Torsten, Castellani, Gastone, Della Porta, Matteo Giovanni, Sauta, E, Robin, M, Bersanelli, M, Travaglino, E, Meggendorfer, M, Zhao, L, Caballero Berrocal, J, Sala, C, Maggioni, G, Bernardi, M, Di Grazia, C, Vago, L, Rivoli, G, Borin, L, D'Amico, S, Tentori, C, Ubezio, M, Campagna, A, Russo, A, Mannina, D, Lanino, L, Chiusolo, P, Giaccone, L, Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Nibourel, O, Bicchieri, M, Bolli, N, Rambaldi, A, Passamonti, F, Savevski, V, Santoro, A, Germing, U, Kordasti, S, Santini, V, Diez-Campelo, M, Sanz, G, Sole, F, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Della Porta, M, Sauta, Elisabetta, Robin, Marie, Bersanelli, Matteo, Travaglino, Erica, Meggendorfer, Manja, Zhao, Lin-Pierre, Caballero Berrocal, Juan Carlos, Sala, Claudia, Maggioni, Giulia, Bernardi, Massimo, Di Grazia, Carmen, Vago, Luca, Rivoli, Giulia, Borin, Lorenza, D'Amico, Saverio, Tentori, Cristina Astrid, Ubezio, Marta, Campagna, Alessia, Russo, Antonio, Mannina, Daniele, Lanino, Luca, Chiusolo, Patrizia, Giaccone, Luisa, Voso, Maria Teresa, Riva, Marta, Oliva, Esther Natalie, Zampini, Matteo, Riva, Elena, Nibourel, Olivier, Bicchieri, Marilena, Bolli, Niccolo', Rambaldi, Alessandro, Passamonti, Francesco, Savevski, Victor, Santoro, Armando, Germing, Ulrich, Kordasti, Shahram, Santini, Valeria, Diez-Campelo, Maria, Sanz, Guillermo, Sole, Francesc, Kern, Wolfgang, Platzbecker, Uwe, Ades, Lionel, Fenaux, Pierre, Haferlach, Torsten, Castellani, Gastone, and Della Porta, Matteo Giovanni

Abstract

Purpose: Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M. Methods: A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed. Results: IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score. Conclusion: IPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevan

Published
2023

13. A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes: a multicentre, observational cohort study

Author

Maggioni, G, Bersanelli, M, Travaglino, E, Alfonso Piérola, A, Kasprzak, A, Sangerman Montserrat, A, Sauta, E, Sala, C, Matteuzzi, T, Meggendorfer, M, Gnocchi, M, Zhao, L, Astrid Tentori, C, Nachtkamp, K, Dall'Olio, D, Mosca, E, Ubezio, M, Campagna, A, Russo, A, Rivoli, G, Bernardi, M, Borin, L, Teresa Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Saba, E, D'Amico, S, Lanino, L, Tinterri, B, Re, F, Bicchieri, M, Giordano, L, Angelotti, G, Morandini, P, Sophie Kubasch, A, Passamonti, F, Rambaldi, A, Savevski, V, Santoro, A, A van de Loosdrecht, A, Brogi, A, Santini, V, Kordasti, S, Sanz, G, Sole, F, Gattermann, N, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Germing, U, Diez-Campelo, M, G Della Porta, M, Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Piérola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin-Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez-Campelo, Matteo G Della Porta, Maggioni, G, Bersanelli, M, Travaglino, E, Alfonso Piérola, A, Kasprzak, A, Sangerman Montserrat, A, Sauta, E, Sala, C, Matteuzzi, T, Meggendorfer, M, Gnocchi, M, Zhao, L, Astrid Tentori, C, Nachtkamp, K, Dall'Olio, D, Mosca, E, Ubezio, M, Campagna, A, Russo, A, Rivoli, G, Bernardi, M, Borin, L, Teresa Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Saba, E, D'Amico, S, Lanino, L, Tinterri, B, Re, F, Bicchieri, M, Giordano, L, Angelotti, G, Morandini, P, Sophie Kubasch, A, Passamonti, F, Rambaldi, A, Savevski, V, Santoro, A, A van de Loosdrecht, A, Brogi, A, Santini, V, Kordasti, S, Sanz, G, Sole, F, Gattermann, N, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Germing, U, Diez-Campelo, M, G Della Porta, M, Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Piérola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin-Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez-Campelo, and Matteo G Della Porta

Abstract

BACKGROUND: Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. METHODS: In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Düsseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. FINDINGS: The study included 7792 (58·7%) men and 5492 (41·3%) women. 10 906 (82·1%) patients were White, and race was not reported for 2378 (17·9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p<0·0001 in both cohorts; DDX41 not available in the EuroMDS cohort vs p=0·0062 in the IWG-PM cohort; IDH2 p<0·0001 in EuroMDS vs p=0·042 in IWG-PM; TET2 p=0·031 vs p=0·035; U2AF1 p=0·033 vs p<0·0001) and mutations in two genes were enriched in women (DNMT3A p<0·000

Published
2023

14. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes

Author

Sauta, E., Robin, M., Bersanelli, M., Travaglino, E., Meggendorfer, M., Zhao, L. -P., Caballero Berrocal, J. C., Sala, C., Maggioni, G., Bernardi, M., Di Grazia, C., Vago, L., Rivoli, G., Borin, L., D'Amico, S., Tentori, C. A., Ubezio, M., Campagna, A., Russo, A., Mannina, D., Lanino, L., Chiusolo, Patrizia, Giaccone, L., Voso, Maria Teresa, Riva, M., Oliva, E. N., Zampini, M., Riva, E., Nibourel, O., Bicchieri, M., Bolli, N., Rambaldi, A., Passamonti, F., Savevski, V., Santoro, A., Germing, U., Kordasti, S., Santini, V., Diez-Campelo, M., Sanz, G., Sole, F., Kern, W., Platzbecker, U., Ades, L., Fenaux, P., Haferlach, T., Castellani, G., Della Porta, M. G., Chiusolo P. (ORCID:0000-0002-1355-1587), Voso M. T., Sauta, E., Robin, M., Bersanelli, M., Travaglino, E., Meggendorfer, M., Zhao, L. -P., Caballero Berrocal, J. C., Sala, C., Maggioni, G., Bernardi, M., Di Grazia, C., Vago, L., Rivoli, G., Borin, L., D'Amico, S., Tentori, C. A., Ubezio, M., Campagna, A., Russo, A., Mannina, D., Lanino, L., Chiusolo, Patrizia, Giaccone, L., Voso, Maria Teresa, Riva, M., Oliva, E. N., Zampini, M., Riva, E., Nibourel, O., Bicchieri, M., Bolli, N., Rambaldi, A., Passamonti, F., Savevski, V., Santoro, A., Germing, U., Kordasti, S., Santini, V., Diez-Campelo, M., Sanz, G., Sole, F., Kern, W., Platzbecker, U., Ades, L., Fenaux, P., Haferlach, T., Castellani, G., Della Porta, M. G., Chiusolo P. (ORCID:0000-0002-1355-1587), and Voso M. T.

Abstract

PURPOSEMyelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M.METHODSA total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed.RESULTSIPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score.CONCLUSIONIPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may

Published
2023

15. P095 - Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment: ACCELERATED FAILURE TIME MODELS AS A CLINICALLY PLAUSIBLE WAY TO DESCRIBE SURVIVAL IN MDS – AN ANALYSIS OF THE IWG-PM DATABASE

Author

Pfeilstöcker, M., Tuechler, H., Ades, L., Cermak, J., Chermat, F., Della Porta, M., Fenaux, P., Garcia-Manero, G., Germing, U., Haase, D., Kündgen, A., Lübbert, M., Magalhaes, S., Malcovati, L., Miyazaki, Y., Sanz, G., Santini, V., Sekeres, M., Walter, M., Valent, P., and Greenberg, P.

Published
2023
Full Text
View/download PDF

16. P057 - Topic: AS04-MDS Biology and Pathogenesis/AS04e-Spliceosome machinery: DNA REPLICATION STRESS DUE TO LOSS OF R-LOOPS IN MYELODYSPLASTIC SYNDROMES WITH SF3B1 MUTATION

Author

Rombaut, D., Lefevre, C., Farhat, B., Bondu, S., Letessier, A., Lesieur-Pasquier, A., Castillo-Guzman, D., Leduc, M., Hartono, S., Chesnais, V., Mangione, R., Boussaid, I., Houy, A., Bouscary, D., Willems, L., Chapuis, N., Kosmider, O., Park, S., Raynaud, S., Cluzeau, T., Clappier, E., Fenaux, P., Ades, L., Margueron, R., Wassef, M., Alsafadi, S., Solary, E., Constantinou, A., Stern, M.-H., Palancade, B., Droin, N., Miotto, B., Chédin, F., and Fontenay, M.

Published
2023
Full Text
View/download PDF

17. P011 - Topic: AS01-Diagnosis/AS01c-Molecular aberrations (cytogenetic, genetic, gene expression): GENOMIC CLASSIFICATION OF MYELODYSPLASTIC SYNDROMES

Author

Bernard, E., Hasserjian, R., Greenberg, P., Ossa, J. Arango, Creignou, M., Nannya, Y., Tuechler, H., Medina-Martinez, J., Levine, M., Jädersten, M., Germing, U., Sanz, G., Van De Loosdrecht, A., Kosmider, O., Follo, M., Thol, F., Zamora, L., Pinheiro, R., Pellagatti, A., Elias, H., Haase, D., Ganster, C., Ades, L., Tobiasson, M., Palomo, L., Della Porta, M., Fenaux, P., Belickova, M., Savona, M., Klimek, V., Santos, F., Boultwood, J., Kotsianidis, I., Santini, V., Solé, F., Platzbecker, U., Heuser, M., Valent, P., Finelli, C., Voso, M.T., Shih, L.-Y., Fontenay, M., Jansen, J., Cervera-Zamora, J., Gattermann, N., Ebert, B., Bejar, R., Malcovati, L., Cazzola, M., Ogawa, S., Hellstrom-Lindberg, E., and Papaemmanuil, E.

Published
2023
Full Text
View/download PDF

21. P374: BLINATUMOMAB AS CONSOLIDATION FOR ADULT B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA. A REAL-WORLD STUDY

Author

Urbino, I., primary, Lengline, E., additional, Cerrano, M., additional, Rabian, F., additional, Kim, R., additional, Sebert, M., additional, Itzykson, R., additional, Audisio, E., additional, Ades, L., additional, Dombret, H., additional, Raffoux, E., additional, Ferrero, D., additional, Clappier, E., additional, and Boissel, N., additional

Published
2022
Full Text
View/download PDF

22. PB1805: INSIGHTS FROM ORAL AZACITIDINE EARLY ACCESS PROGRAM IN FRANCE: PATIENT POPULATION WITH ACUTE MYELOID LEUKEMIA RECEIVING ORAL-AZA FOR MAINTENANCE OF COMPLETE REMISSION AFTER INDUCTION CHEMOTHERAPY

Author

Raffoux, E., primary, De Botton, S., additional, Ades, L., additional, Carré, M., additional, Cluzeau, T., additional, Saillard, C., additional, Heiblig, M., additional, Beckerich, F., additional, Gastaud, L., additional, Dupuis, A., additional, Richez, U., additional, and Dumas, P.-Y., additional

Published
2022
Full Text
View/download PDF

23. S169: CLINICAL AND MOLECULAR MARKERS FOR PREDICTING RESPONSE TO ROMIPLOSTIM TREATMENT IN LOWER-RISK MYELODYSPLASTIC SYNDROMES

Author

Kubasch, A. S., primary, Giagounidis, A., additional, Metzgeroth, G., additional, Jonasova, A., additional, Herbst, R., additional, Diaz, J. M. T., additional, De Renzis, B., additional, Götze, K. S., additional, Huetter-Kroenke, M.-L., additional, Gourin, M.-P., additional, Slama, B., additional, Dimicoli-Salazar, S., additional, Cony-Makhoul, P., additional, Laribi, K., additional, Park, S., additional, Jersemann, K., additional, Schipp, D., additional, Metzeler, K. H., additional, Tiebel, O., additional, Sockel, K., additional, Gloaguen, S., additional, Mies, A., additional, Chermat, F., additional, Thiede, C., additional, Sapena, R., additional, Schlenk, R. F., additional, Fenaux, P., additional, Platzbecker, U., additional, and Ades, L., additional

Published
2022
Full Text
View/download PDF

28. Caractéristiques phénotypiques et mutationnelles des maladies auto-immunes et inflammatoires (MAI) associées aux néoplasies myéloprolifératives (NMP)

Author

Elessa, D., primary, Zhao, L.P., additional, Daltro De Oliveira, R., additional, Maslah, N., additional, Soret-Dulphy, J., additional, Verger, E., additional, Marcault, C., additional, Parquet, N., additional, Fenaux, P., additional, Ades, L., additional, Raffoux, E., additional, Giraudier, S., additional, Fain, O., additional, Cassinat, B., additional, Kiladjian, J.J., additional, Mekinian, A., additional, and Benajiba, L., additional

Published
2021
Full Text
View/download PDF

29. Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies

Author

Iqbal, M, Maroofian, R, Çavdarlı, B, Riccardi, F, Field, M, Banka, S, Bubshait, DK, Li, Y, Hertecant, J, Baig, SM, Dyment, D, Efthymiou, S, Abdullah, U, Makhdoom, EUH, Ali, Z, Scherf de Almeida, T, Molinari, F, Mignon-Ravix, C, Chabrol, B, Antony, J, Ades, L, Pagnamenta, AT, Jackson, A, Douzgou, S, Genomics England Research Consortium, Beetz, C, Karageorgou, V, Vona, B, Rad, A, Baig, JM, Sultan, T, Alvi, JR, Maqbool, S, Rahman, F, Toosi, MB, Ashrafzadeh, F, Imannezhad, S, Karimiani, EG, Sarwar, Y, Khan, S, Jameel, M, Noegel, AA, Budde, B, Altmüller, J, Motameny, S, Höhne, W, Houlden, H, Nürnberg, P, Wollnik, B, Villard, L, Alkuraya, FS, Osmond, M, Hussain, MS, and Yigit, G

Abstract

PURPOSE: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. METHODS: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable. RESULTS: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were predicted to induce premature protein truncation leading to a loss of PCDHGC4 function. The three detected missense variants were located in extracellular cadherin (EC) domains EC5 and EC6 of PCDHGC4, and in silico analysis of the affected residues showed that two of these substitutions were predicted to influence the Ca2+-binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4. CONCLUSION: We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans.

Published
2021

31. Toxic iron species in lower-risk myelodysplastic syndrome patients : course of disease and effects on outcome

Author

Hoeks, Marlijn, Bagguley, Tim, van Marrewijk, Corine, Smith, Alex, Bowen, David, Culligan, Dominic, Kolade, Seye, Symeonidis, Argiris, Garelius, Hege, Spanoudakis, Michail, Langemeijer, Saskia, Roelofs, Rian, Wiegerinck, Erwin, Tatic, Aurelia, Killick, Sally, Panagiotidis, Panagiotis, Stanca, Oana, Hellström-Lindberg, Eva, Cermak, Jaroslav, van der Klauw, Melanie, Wouters, Hanneke, van Kraaij, Marian, Blijlevens, Nicole, Swinkels, Dorine W., de Witte, Theo, Stauder, R., Walder, A., Pfeilstöcker, M., Schoenmetzler-Makrai, A., Burgstaller, S., Thaler, J., Mandac Rogulj, I., Krejci, M., Voglova, J., Rohon, P., Jonasova, A., Cermak, J., Mikulenkova, D., Hochova, I., Jensen, P. D., Holm, M. S., Kjeldsen, L., Dufva, I. H., Vestergaard, H., Re, D., Slama, B., Fenaux, P., Choufi, B., Cheze, S., Klepping, D., Salles, B., de Renzis, B., Willems, L., De Prost, D., Gutnecht, J., Courby, S., Siguret, V., Tertian, G., Pascal, L., Chaury, M., Wattel, E., Guerci, A., Legros, L., Itzykson, R., Ades, L., Isnard, F., Sanhes, L., Benramdane, R., Stamatoullas, A., Amé, S., Beyne-Rauzy, O., Gyan, E., Platzbecker, U., Badrakan, C., Germing, U., Lübbert, M., Schlenk, R., Kotsianidis, I., Tsatalas, C., Pappa, V., Galanopoulos, A., Michali, E., Panagiotidis, P., Viniou, N., Katsigiannis, A., Roussou, P., Terpos, E., Kostourou, A., Kartasis, Z., Pouli, A., Palla, K., Briasoulis, V., Hatzimichael, E., Vassilopoulos, G., Symeonidis, A., Kourakli, A., Zikos, P., Anagnostopoulos, A., Kotsopoulou, M., Megalakaki, K., Protopapa, M., Vlachaki, E., Konstantinidou, P., Stemer, G., Nemetz, A., Gotwin, U., Cohen, O., Koren, M., Levy, E., Greenbaum, U., Gino-Moor, S., Price, M., Ofran, Y., Winder, A., Goldshmidt, N., Elias, S., Sabag, R., Hellman, I., Ellis, M., Braester, A., Rosenbaum, H., Berdichevsky, S., Itzhaki, G., Wolaj, O., Yeganeh, S., Katz, O., Filanovsky, K., Dali, N., Mittelman, M., Malcovati, L., Fianchi, L., vd Loosdrecht, A., Matthijssen, V., Herbers, A., Pruijt, H., Aboosy, N., de Vries, F., Velders, G., Jacobs, E., Langemeijer, S., MacKenzie, M., Lensen, C., Kuijper, P., Madry, K., Camara, M., Almeida, A., Vulkan, G., Stanca Ciocan, O., Tatic, A., Savic, A., Pedro, C., Xicoy, B., Leiva, P., Munoz, J., Betes, V., Benavente, C., Lozano, M., Martinez, M., Iniesta, P., Bernal, T., Diez Campelo, M., Tormo, D., Andreu Lapiedra, R., Sanz, G., Hesse Sundin, E., Garelius, H., Karlsson, C., Antunovic, P., Jönsson, A., Brandefors, L., Nilsson, L., Kozlowski, P., Hellstrom-Lindberg, E., Grövdal, M., Larsson, K., Wallvik, J., Lorenz, F., Ejerblad, E., Culligan, D., Craddock, C., Kolade, S., Cahalin, P., Killick, S., Ackroyd, S., Wong, C., Warren, A., Drummond, M., Hall, C., Rothwell, K., Green, S., Ali, S., Bowen, D., Karakantza, M., Dennis, M., Jones, G., Parker, J., Bowen, A., Radia, R., Das-Gupta, E., Vyas, P., Nga, E., Creagh, D., Ashcroft, J., Mills, J., Bond, L., Life Course Epidemiology (LCE), and VU University medical center

Subjects
Adult, Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Iron Overload, Iron, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Ferroportin, Lower risk, Gastroenterology, Article, Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], 03 medical and health sciences, 0302 clinical medicine, Hepcidin, Internal medicine, Humans, Medicine, Blood Transfusion, Prospective Studies, Aged, Soluble transferrin receptor, biology, business.industry, Transferrin saturation, Hematology, Middle Aged, Erythroferrone, Prognosis, 3. Good health, Survival Rate, Ferritin, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], 030104 developmental biology, Oncology, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, biology.protein, Erythropoiesis, Female, business, Myelodysplastic syndrome, Follow-Up Studies, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Red blood cell transfusions (RBCT) remain the cornerstone of supportive care in lower-risk myelodysplastic syndrome (LRMDS) [1]. Transfusion dependency in LRMDS patients is associated with inferior outcomes, mainly attributed to severe bone marrow failure [2]. However, iron toxicity, due to frequent RBCT or ineffective erythropoiesis, may be an additional negative prognostic factor [3,4,5,6]. Recently, much progress has been made in unraveling the iron metabolism. The peptide hormone hepcidin is the key regulator by inhibiting iron uptake through degradation of ferroportin, a cellular iron exporter [7]. Erythroferrone and GDF15, produced by erythroblasts, inhibit hepcidin production, which leads to increased uptake and cellular release of iron for the purpose of erythropoiesis [8]. The pathophysiology of iron metabolism in MDS is still not completely understood. Exceedingly high reactive oxygen species (ROS) levels are associated with iron toxicity, disease development, and progression in MDS patients [9,10,11,12]. Malondialdehyde (MDA), resulting from lipid peroxidation of polyunsaturated fatty acids, is a biomarker of oxidative stress [10, 12]. Currently, little is known about the prognostic impact of ROS in MDS patients. The aim of this study is twofold: (1) describe iron and oxidative stress parameters over time in LRMDS patients and (2) to assess their effect on overall and progression-free survival. The EUMDS registry prospectively collects observational data on newly diagnosed LRMDS patients from 148 centers in 16 countries in Europe and Israel as of January 2008. All patients provided informed consent. Clinical data were collected at baseline and at each six-monthly follow-up visit. Serum samples were collected prospectively at each visit from 256 patients included in six participating countries. Conventional iron parameters were measured with routine assays. We additionally analyzed hepcidin, growth differentiation factor 15 (GDF15), soluble transferrin receptor (sTfR), non-transferrin bound iron (NTBI), labile plasma iron (LPI), and MDA. Subjects were prospectively followed until death, loss to follow-up, or withdrawal of consent. All iron parameters were measured centrally at the department of Laboratory Medicine of the Radboudumc, Nijmegen, The Netherlands. Serum samples were collected just prior to transfusion in transfusion-dependent patients and stored at −80 °C. Details on the assays and reference ranges of hepcidin, GDF15, sTfR, NTBI, LPI, and MDA are provided in the supplement. The Spearman rank test was used to evaluate correlations between iron parameters. We stratified the results by transfusion dependency per visit and the presence of ring sideroblasts. When evaluating temporal changes in iron parameters, with linear quantile mixed models, we excluded patients from the timepoint they received iron chelation therapy. Overall survival (OS) was defined as the time from MDS diagnosis to death or, in case of progression-free survival, to date of progression or death; patients still alive at the end of follow-up were censored. Time-dependent Kaplan–Meier curves and cox proportional hazards models were used. In total, 256 consecutive patients, were included in this study. Over five six-monthly visits, 1040 samples were collected. Table 1 describes the patient characteristics. Most patients without ring sideroblasts were transfusion-independent at diagnosis (nonRS-TI; 55.9%), 18.8% with ring sideroblasts were transfusion-independent (RS-TI), 18.4% without ring sideroblasts were transfusion-dependent (nonRS-TD), and 7% with ring sideroblasts were transfusion-dependent patients (RS-TD). The median follow-up time was 6.6 years (95% CI 5.9–7.0). LPI was positively correlated with transferrin saturation (TSAT) (r = 0.15, p < 0.001, Fig. S1). LPI values increased exponentially at TSAT values above 80%. This effect was most pronounced in the transfusion-dependent groups, but also observed in the RS-TI group. MDA was weakly correlated with NTBI (r = 0.09, p = 0.069) and negatively correlated with hemoglobin level (r = −0.1, p = 0.033). GDF15 and hepcidin were negatively correlated in the RS-TI and nonRS-TD group and significantly negatively correlated in the RS-TD group (r = −0.34, p = 0.007, Fig. S2). Serum ferritin levels were elevated in all subgroups with a mean value of 858 µg/L at visit 5. The highest serum ferritin levels were observed in the RS-TD group (mean value at visit 5: 2092 µg/L, Table S1). Serum ferritin increased significantly per visit in the RS-TD group (beta 454.46 µg/L; 95% CI 334.65–574.27), but not in the other groups (Table S2). All subgroups, except for the nonRS-TI, had elevated TSAT levels. TSAT levels were most markedly increased in the RS-TD group with a mean TSAT of 88% at visit 5 (Table S1). In both transfusion-dependent groups the median increase per visit was significant (Table S2). LPI was elevated in the RS-TD group exclusively with a mean value of 0.59 µmol/L at visit 5 (Table S1). NTBI was elevated in all subgroups, with the highest values in the RS-TD group (Table S1). The increase in median NTBI level was significant in both transfusion-dependent groups (Table S2). Hepcidin levels were markedly elevated in the nonRS-TD group. Interestingly, hepcidin levels were lower in the RS-TD group, probably reflecting ineffective erythropoiesis, likewise supported by lower hepcidin/ferritin ratios in RS groups (Table S1). Median hepcidin levels increased over time in the transfusion-dependent subgroups only (Table S2). GDF15 levels, analyzed in the light of its potential role in hepcidin suppression, were increased in all subgroups (Table S1). The RS subgroups had higher GDF15 levels compared to the nonRS groups, reflecting increased erythropoiesis. Mean sTfR levels were within the reference range in all subgroups except for the RS-TI group, which showed elevated levels, reflecting...

Published
2021

32. Topic: AS08-Treatment/AS08g-Clinical trials - Phase II-III

Author

Cluzeau, T., primary, Sebert, M., additional, Rahmé, R., additional, Cuzzubbo, S., additional, Walter-Petrich, A., additional, Peterlin, P., additional, Recher, C., additional, Stamatoullas, A., additional, Willems, L., additional, Raffoux, E., additional, Berthon, C., additional, Sallman, D., additional, Ades, L., additional, and Fenaux, P., additional

Published
2021
Full Text
View/download PDF

35. Infiltrat myéloïde clonal identifié par next generation sequencing dans les lésions cutanées associées aux syndromes myélodysplasiques et leucémies myélomonocytaires chroniques

Author

Martin de Frémont, G., primary, Hirsch, P., additional, Gimenez De Mestral, S., additional, Moguelet, P., additional, Ditchi, Y., additional, Emile, J.F., additional, Senet, P., additional, Georgin-Lavialle, S., additional, Hanslik, T., additional, Maurier, F., additional, Adedjouma, A., additional, Abisror, N., additional, Mahevas, T., additional, Malard, F., additional, Ades, L., additional, Fenaux, P., additional, Fain, O., additional, and Mekinian, A., additional

Published
2021
Full Text
View/download PDF

37. Author Correction: Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Author

Bernard E, Nannya Y, Hasserjian RP, Devlin SM, Tuechler H, Medina-Martinez JS, Yoshizato T, Shiozawa Y, Saiki R, Malcovati L, Levine MF, Arango JE, Zhou Y, Solé F, Cargo CA, Haase D, Creignou M, Germing U, Zhang Y, Gundem G, Sarian A, van de Loosdrecht AA, Jädersten M, Tobiasson M, Kosmider O, Follo MY, Thol F, Pinheiro RF, Santini V, Kotsianidis I, Boultwood J, Santos FPS, Schanz J, Kasahara S, Ishikawa T, Tsurumi H, Takaori-Kondo A, Kiguchi T, Polprasert C, Bennett JM, Klimek VM, Savona MR, Belickova M, Ganster C, Palomo L, Sanz G, Ades L, Della Porta MG, Smith AG, Werner Y, Patel M, Viale A, Vanness K, Neuberg DS, Stevenson KE, Menghrajani K, Bolton KL, Fenaux P, Pellagatti A, Platzbecker U, Heuser M, Valent P, Chiba S, Miyazaki Y, Finelli C, Voso MT, Shih LY, Fontenay M, Jansen JH, Cervera J, Atsuta Y, Gattermann N, Ebert BL, Bejar R, Greenberg PL, Cazzola M, Hellström-Lindberg E, Ogawa S, and Papaemmanuil E

Published
2021

38. Toxic iron species in lower-risk myelodysplastic syndrome patients: course of disease and effects on outcome

Author

Hoeks, M. Bagguley, T. van Marrewijk, C. Smith, A. Bowen, D. Culligan, D. Kolade, S. Symeonidis, A. Garelius, H. Spanoudakis, M. Langemeijer, S. Roelofs, R. Wiegerinck, E. Tatic, A. Killick, S. Panagiotidis, P. Stanca, O. Hellström-Lindberg, E. Cermak, J. van der Klauw, M. Wouters, H. van Kraaij, M. Blijlevens, N. Swinkels, D.W. de Witte, T. Stauder, R. Walder, A. Pfeilstöcker, M. Schoenmetzler-Makrai, A. Burgstaller, S. Thaler, J. Mandac Rogulj, I. Krejci, M. Voglova, J. Rohon, P. Jonasova, A. Cermak, J. Mikulenkova, D. Hochova, I. Jensen, P.D. Holm, M.S. Kjeldsen, L. Dufva, I.H. Vestergaard, H. Re, D. Slama, B. Fenaux, P. Choufi, B. Cheze, S. Klepping, D. Salles, B. de Renzis, B. Willems, L. De Prost, D. Gutnecht, J. Courby, S. Siguret, V. Tertian, G. Pascal, L. Chaury, M. Wattel, E. Guerci, A. Legros, L. Itzykson, R. Ades, L. Isnard, F. Sanhes, L. Benramdane, R. Stamatoullas, A. Amé, S. Beyne-Rauzy, O. Gyan, E. Platzbecker, U. Badrakan, C. Germing, U. Lübbert, M. Schlenk, R. Kotsianidis, I. Tsatalas, C. Pappa, V. Galanopoulos, A. Michali, E. Panagiotidis, P. Viniou, N. Katsigiannis, A. Roussou, P. Terpos, E. Kostourou, A. Kartasis, Z. Pouli, A. Palla, K. Briasoulis, V. Hatzimichael, E. Vassilopoulos, G. Symeonidis, A. Kourakli, A. Zikos, P. Anagnostopoulos, A. Kotsopoulou, M. Megalakaki, K. Protopapa, M. Vlachaki, E. Konstantinidou, P. Stemer, G. Nemetz, A. Gotwin, U. Cohen, O. Koren, M. Levy, E. Greenbaum, U. Gino-Moor, S. Price, M. Ofran, Y. Winder, A. Goldshmidt, N. Elias, S. Sabag, R. Hellman, I. Ellis, M. Braester, A. Rosenbaum, H. Berdichevsky, S. Itzhaki, G. Wolaj, O. Yeganeh, S. Katz, O. Filanovsky, K. Dali, N. Mittelman, M. Malcovati, L. Fianchi, L. vd Loosdrecht, A. Matthijssen, V. Herbers, A. Pruijt, H. Aboosy, N. de Vries, F. Velders, G. Jacobs, E. Langemeijer, S. MacKenzie, M. Lensen, C. Kuijper, P. Madry, K. Camara, M. Almeida, A. Vulkan, G. Stanca Ciocan, O. Tatic, A. Savic, A. Pedro, C. Xicoy, B. Leiva, P. Munoz, J. Betes, V. Benavente, C. Lozano, M. Martinez, M. Iniesta, P. Bernal, T. Diez Campelo, M. Tormo, D. Andreu Lapiedra, R. Sanz, G. Hesse Sundin, E. Garelius, H. Karlsson, C. Antunovic, P. Jönsson, A. Brandefors, L. Nilsson, L. Kozlowski, P. Hellstrom-Lindberg, E. Grövdal, M. Larsson, K. Wallvik, J. Lorenz, F. Ejerblad, E. Culligan, D. Craddock, C. Kolade, S. Cahalin, P. Killick, S. Ackroyd, S. Wong, C. Warren, A. Drummond, M. Hall, C. Rothwell, K. Green, S. Ali, S. Karakantza, M. Dennis, M. Jones, G. Parker, J. Bowen, A. Radia, R. Das-Gupta, E. Vyas, P. Nga, E. Creagh, D. Ashcroft, J. Mills, J. Bond, L. the EUMDS Registry Participants

Published
2021

48. Outcome of older (>= 70 years) APL patients frontline treated with or without arsenic trioxide-an International Collaborative Study

Author

Kayser S, Rahme R, Martinez-Cuadron D, Ghiaur G, Thomas X, Sobas M, Guerci-Bresler A, Garrido A, Pigneux A, Gil C, Raffoux E, Tormo M, Vey N, de la Serna J, Salamero O, Lengfelder E, Levis M, Fenaux P, Sanz M, Platzbecker U, Schlenk R, Ades L, and Montesinos P

Subjects
organic chemicals, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, neoplasms, biological factors
Abstract

Data on outcome in older (>= 70 years) patients with acute promyelocytic leukemia after treatment with arsenic trioxide (ATO) compared with standard chemotherapy (CTX) is scarce. We evaluated 433 patients (median age, 73.4 years) treated either with ATO+ all-trans retinoic acid (ATO/ATRA; n = 26), CTX/ATRA + ATO during consolidation (CTX/ATRA/ATO; n = 148), or with CTX/ATRA (n = 259). Median follow-up for overall survival (OS) was 4.8 years. Complete remissions (CR) were achieved in 92% with ATO/ATRA and 82% with CTX/ATRA; induction death rates were 8% and 18%, respectively. For analysis of postremission outcomes we combined the ATO/ATRA and CTX/ATRA/ATO groups (ATO/ATRA +/- CTX). Cumulative incidence of relapse (CIR) was significantly lower after ATO/ATRA +/- CTX compared with CTX/ATRA (P < 0.001). The same held true when restricting the analysis according to the treatment period after the year 2000. OS of patients in CR1 was not different between ATO/ATRA +/- CTX compared with CTX/ATRA (P = 0.20). High (>10 x 10(9)/l) white blood cell (WBC) counts at diagnosis were associated with higher CIR (P < 0.001) compared with lower WBC in the CTX/ATRA group, but not in the ATO/ATRA +/- CTX group (P = 0.48). ATO, when added to ATRA or CTX/ATRA is feasible and effective in elderly patients for remission induction and consolidation, particularly in patients with high WBC at diagnosis.

Published
2020

49. Implications ofTP53allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Author

Bernard, E, Nannya, Y, Hasserjian, RP, Devlin, SM, Tuechler, H, Medina-Martinez, JS, Yoshizato, T, Shiozawa, Y, Saiki, R, Malcovati, L, Levine, MF, Arango, JE, Zhou, YY, Sole, F, Cargo, CA, Haase, D, Creignou, M, Germing, U, Zhang, YM, Gundem, G, Sarian, A, van de Loosdrecht, AA, Jadersten, M, Tobiasson, M, Kosmider, O, Follo, MY, Thol, F, Pinheiro, RF, Santini, V, Kotsianidis, I, Boultwood, J, Santos, FPS, Schanz, J, Kasahara, S, Ishikawa, T, Tsurumi, H, Takaori-Kondo, A, Kiguchi, T, Polprasert, C, Bennett, JM, Klimek, VM, Savona, MR, Belickova, M, Ganster, C, Palomo, L, SANZ, G, Ades, L, Della Porta, MG, Smith, AG, Werner, Y, Patel, M, Viale, A, Vanness, K, Neuberg, DS, Stevenson, KE, Menghrajani, K, Bolton, KL, Fenaux, P, Pellagatti, A, Platzbecker, U, Heuser, M, Valent, P, Chiba, S, Miyazaki, Y, Finelli, C, Voso, MT, Shih, LY, Fontenay, M, Jansen, JH, Cervera, J, Atsuta, Y, Gattermann, N, Ebert, BL, Bejar, R, Greenberg, PL, Cazzola, M, Hellstrom-Lindberg, E, Ogawa, S, and Papaemmanuil, E

Abstract

Clinical sequencing across a large prospective cohort of patients with myelodysplasic syndrome uncovers distinct associations between the mono- and biallelic states ofTP53and clinical presentation Tumor protein p53 (TP53) is the most frequently mutated gene in cancer(1,2). In patients with myelodysplastic syndromes (MDS),TP53mutations are associated with high-risk disease(3,4), rapid transformation to acute myeloid leukemia (AML)(5), resistance to conventional therapies(6-8)and dismal outcomes(9). Consistent with the tumor-suppressive role ofTP53, patients harbor both mono- and biallelic mutations(10). However, the biological and clinical implications ofTP53allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS forTP53mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third ofTP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only.TP53multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)(11). Surprisingly, monoallelic patients did not differ fromTP53wild-type patients in outcomes and response to therapy. This study shows that consideration ofTP53allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results