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123 results on '"Platzbecker U"'

1. Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial

Author: Zeidan, A, Ando, K, Rauzy, O, Turgut, M, Wang, M, Cairoli, R, Hou, H, Kwong, Y, Arnan, M, Meers, S, Pullarkat, V, Santini, V, Malek, K, Kiertsman, F, Niolat, J, Ramos, P, Menssen, H, Fenaux, P, Miyazaki, Y, Platzbecker, U, Zeidan A. M., Ando K., Rauzy O., Turgut M., Wang M. -C., Cairoli R., Hou H. -A., Kwong Y. -L., Arnan M., Meers S., Pullarkat V., Santini V., Malek K., Kiertsman F., Niolat J., Ramos P. M., Menssen H. D., Fenaux P., Miyazaki Y., Platzbecker U., Zeidan, A, Ando, K, Rauzy, O, Turgut, M, Wang, M, Cairoli, R, Hou, H, Kwong, Y, Arnan, M, Meers, S, Pullarkat, V, Santini, V, Malek, K, Kiertsman, F, Niolat, J, Ramos, P, Menssen, H, Fenaux, P, Miyazaki, Y, Platzbecker, U, Zeidan A. M., Ando K., Rauzy O., Turgut M., Wang M. -C., Cairoli R., Hou H. -A., Kwong Y. -L., Arnan M., Meers S., Pullarkat V., Santini V., Malek K., Kiertsman F., Niolat J., Ramos P. M., Menssen H. D., Fenaux P., Miyazaki Y., and Platzbecker U.
Abstract: Background: Sabatolimab is an immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), an immuno-myeloid regulator expressed on immune cells and leukaemic stem cells. In this trial, we compared the efficacy and safety of sabatolimab plus hypomethylating agent with placebo plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes. Methods: STIMULUS-MDS1 was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study done at 54 investigational sites in 17 countries. Adult patients (aged ≥18 years) with intermediate-risk, high-risk, and very high-risk myelodysplastic syndromes (according to Revised International Prognostic Scoring System criteria) who had not received previous treatment were included. Patients were randomly assigned (1:1) to intravenous sabatolimab (400 mg on day 8 and 22) or placebo plus a hypomethylating agent (intravenous decitabine 20 mg/m2 on day 1–5 or intravenous or subcutaneous azacitidine 75 mg/m2 on day 1–7 or day 1–5 and day 8 and 9) every 28 days until treatment discontinuation. The two primary endpoints were complete response rate and progression-free survival, assessed in the full analysis set, which included all randomly assigned patients. Complete response was analysed, as prespecified, 7 months after the last patient was randomly assigned. All other analyses presented, including progression-free survival, were done at the final data cutoff prespecified via a protocol amendment on Sept 2, 2021. Safety was assessed in in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03946670, and is ongoing. Findings: Between July 29, 2019, and Aug 10, 2020, 127 patients were randomly assigned to sabatolimab plus a hypomethylating agent group (sabatolimab group; n=65) or placebo plus a hypomethylating agent (placebo group; n=62). The median age of participants was 73 years (IQR 69–77), of whom 86 (68%
Published: 2024

2. Improving post-cellular therapy care with an interdisciplinary, cross-regional, cross-sectoral, digital-aided approach

Author: Schneider, M, Egger-Heidrich, K, Müller, G, Schmädig, R, Schmidt, F, Leppla, L, Geest, SD, Teynor, A, Wolfien, M, Sedlmayr, M, Hänel, M, Vucinic, V, Schmitt, J, Platzbecker, U, Schetelig, J, Bornhäuser, M, Middeke, JM, Schneider, M, Egger-Heidrich, K, Müller, G, Schmädig, R, Schmidt, F, Leppla, L, Geest, SD, Teynor, A, Wolfien, M, Sedlmayr, M, Hänel, M, Vucinic, V, Schmitt, J, Platzbecker, U, Schetelig, J, Bornhäuser, M, and Middeke, JM
Published: 2024

3. EFFICACY AND SAFETY OF LUSPATERCEPT VERSUS EPOETIN ALFA IN ERYTHROPOIESIS-STIMULATING AGENT (ESA)-NAIVE PATIENTS WITH TRANSFUSION-DEPENDENT LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS): FULL ANALYSIS OF THE COMMANDS TRIAL

Author: Garcia-Manero, G, Platzbecker, U, Santini, V, Zeidan, A, Fenaux, P, Komrokji, R, Shortt, J, Valcarcel, D, Jonasova, A, Dimicoli-Salazar, S, Tiong, IS, Lin, C-C, Li, J, Zhang, J, Giuseppi, AC, Kreitz, S, Pozharskaya, V, Keeperman, K, Rose, S, Prebet, T, Degulys, A, Paolini, S, Cluzeau, T, Porta, MD, Garcia-Manero, G, Platzbecker, U, Santini, V, Zeidan, A, Fenaux, P, Komrokji, R, Shortt, J, Valcarcel, D, Jonasova, A, Dimicoli-Salazar, S, Tiong, IS, Lin, C-C, Li, J, Zhang, J, Giuseppi, AC, Kreitz, S, Pozharskaya, V, Keeperman, K, Rose, S, Prebet, T, Degulys, A, Paolini, S, Cluzeau, T, and Porta, MD
Published: 2024

4. Outcomes of CMML patients undergoing allo-HCT are significantly worse compared to MDS-a study of the CMWP of the EBMT

Author: Rovó, A, Gras, L, Piepenbroek, B, Kroeger, N, Reinhardt, HC, Radujkovic, A, Blaise, D, Kobbe, G, Niityvuopio, R, Platzbecker, U, Sockel, K, Hunault-Berger, M, Cornelissen, JJ, Forcade, E, Bourhis, JH, Chalandon, Y, Kinsella, F, Nguyen-Quoc, S, Maertens, J, Elmaagacli, A, Mordini, N, Hayden, P, Raj, K, Drozd-Sokolowska, J, de Wreede, LC, Mclornan, DP, Robin, M, Yakoub-Agha, I, Onida, F, Rovó, A, Gras, L, Piepenbroek, B, Kroeger, N, Reinhardt, HC, Radujkovic, A, Blaise, D, Kobbe, G, Niityvuopio, R, Platzbecker, U, Sockel, K, Hunault-Berger, M, Cornelissen, JJ, Forcade, E, Bourhis, JH, Chalandon, Y, Kinsella, F, Nguyen-Quoc, S, Maertens, J, Elmaagacli, A, Mordini, N, Hayden, P, Raj, K, Drozd-Sokolowska, J, de Wreede, LC, Mclornan, DP, Robin, M, Yakoub-Agha, I, and Onida, F
Abstract: Although CMML since long has been separated from MDS, many studies continue to evaluate the outcomes of both diseases after hematopoietic cell transplantation (allo-HCT) together. Data evaluating outcomes of a large CMML cohort after allo-HCT compared to MDS are limited. We aim to compare outcomes of CMML to MDS patients who underwent allo-HCT between 2010 and 2018. Patients ≥18 years with CMML and MDS undergoing allo-HCT reported to the EBMT registry were analyzed. Progression to AML before allo-HCT was an exclusion criterion. Overall survival (OS), progression/relapse-free survival (PFS), relapse incidence (including progression) (REL), and non-relapse mortality (NRM) were evaluated in univariable and multivariable (MVA) Cox proportional hazard models including interaction terms between disease and confounders. In total, 10832 patients who underwent allo-HCT were included in the study, there were a total of 1466 CMML, and 9366 MDS. The median age at time of allo-HCT in CMML (median 60.5, IQR 54.3–65.2 years) was significantly higher than in the MDS cohort (median 58.8, IQR 50.2–64.5 years; p < .001). A significantly higher percentage of CMML patients were male (69.4%) compared to MDS (61.2%; p < .001). There were no clinically meaningful differences in the distribution of Karnofsky score, Sorror HCT-CI score at allo-HCT, and donor type, between the CMML and MDS patients. RIC platforms were utilized in 63.9% of CMML allo-HCT, and in 61.4% of MDS patients (p = .08). In univariable analyses, we found that OS, PFS, and REL were significantly worse in CMML when compared with MDS (all p < .0001), whereas no significant difference was observed in NRM (p = .77). In multivariable analyses, the HR comparing MDS versus CMML for OS was 0.81 (95% CI, 0.74–0.88, p < .001), PFS 0.76 (95% CI 0.70–0.82, p < .001), relapse 0.66 (95% CI 0.59–0.74, p < .001), and NRM 0.87 (95% CI 0.78–0.98, p = .02), respectively. The association between baseline variables and outco
Published: 2024

5. Impact of post-transplant cyclophosphamide (PTCy)-based prophylaxis in matched sibling donor allogeneic haematopoietic cell transplantation for patients with myelodysplastic syndrome: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT

Author: Salas, M. Q., Eikema, D. -J., Koster, L., Maertens, J., Passweg, J., Finke, J., Broers, A. E. C., Koc, Y., Kroger, N., Ozkurt, Z. N., Pascual-Cascon, M. J., Platzbecker, U., Van Gorkom, G., Schroeder, T., Lopez-Lorenzo, J. L., Martino, Michelangelo, Chiusolo, Patrizia, Kaufmann, M., Onida, F., Gurnari, C., Scheid, C., Drozd-Sokolowska, J., Raj, K., Robin, M., Mclornan, D. P., Martino M., Chiusolo P. (ORCID:0000-0002-1355-1587), Salas, M. Q., Eikema, D. -J., Koster, L., Maertens, J., Passweg, J., Finke, J., Broers, A. E. C., Koc, Y., Kroger, N., Ozkurt, Z. N., Pascual-Cascon, M. J., Platzbecker, U., Van Gorkom, G., Schroeder, T., Lopez-Lorenzo, J. L., Martino, Michelangelo, Chiusolo, Patrizia, Kaufmann, M., Onida, F., Gurnari, C., Scheid, C., Drozd-Sokolowska, J., Raj, K., Robin, M., Mclornan, D. P., Martino M., and Chiusolo P. (ORCID:0000-0002-1355-1587)
Abstract: We retrospectively compared outcomes of 404 MDS patients undergoing 1st matched sibling donor allo-HCT receiving either PTCy-based (n = 66) or other “conventional prophylaxis” (n = 338; mostly calcineurin inhibitor + methotrexate or MMF). Baseline characteristics were balanced, except for higher use of myeloablative regimens in the PTCy group (52.3% vs. 38.2%, p = 0.047). Incidences of neutrophil (Day +28: 89% vs. 97%, p = 0.011) and platelet (Day +100: 89% vs. 97%, p < 0.001) engraftment were lower for PTCy-based. Day +100 cumulative incidences of grade II–IV and III–IV aGVHD, and 5-year CI of extensive cGVHD were 32%, 18% and 18% for PTCy-based and 25% (p = 0.3), 13% (p = 0.4) and 31% (p = 0.09) for the conventional cohort. Five-year OS (51% vs. 52%, p = 0.6) and GRFS (33% vs. 25%, p = 0.6) were similar between groups. Patients receiving PTCy had a trend to a lower cumulative incidence of relapse (20% vs. 33%, p = 0.06), not confirmed on multivariable analysis (p = 0.3). Although higher NRM rates were observed in patients receiving PTCy (32% vs. 21%, p = 0.02) on univariate analysis, this was not confirmed on multivariate analysis (HR 1.46, p = 0.18), and there was no resultant effect on OS (HR 1.20, p = 0.5). Based on these data, PTCy prophylaxis appears to be an attractive option for patients with MDS undergoing MSD allo-HCT.
Published: 2024

6. Synthetic Data Generation by Artificial Intelligence to Accelerate Research and Precision Medicine in Hematology

Author: D'Amico, S, Dall'Olio, D, Sala, C, Dall'Olio, L, Sauta, E, Zampini, M, Asti, G, Lanino, L, Maggioni, G, Campagna, A, Ubezio, M, Russo, A, Bicchieri, M, Riva, E, Tentori, C, Travaglino, E, Morandini, P, Savevski, V, Santoro, A, Prada-Luengo, I, Krogh, A, Santini, V, Kordasti, S, Platzbecker, U, Diez-Campelo, M, Fenaux, P, Haferlach, T, Castellani, G, Della Porta, M, D'Amico S., Dall'Olio D., Sala C., Dall'Olio L., Sauta E., Zampini M., Asti G., Lanino L., Maggioni G., Campagna A., Ubezio M., Russo A., Bicchieri M. E., Riva E., Tentori C. A., Travaglino E., Morandini P., Savevski V., Santoro A., Prada-Luengo I., Krogh A., Santini V., Kordasti S., Platzbecker U., Diez-Campelo M., Fenaux P., Haferlach T., Castellani G., Della Porta M. G., D'Amico, S, Dall'Olio, D, Sala, C, Dall'Olio, L, Sauta, E, Zampini, M, Asti, G, Lanino, L, Maggioni, G, Campagna, A, Ubezio, M, Russo, A, Bicchieri, M, Riva, E, Tentori, C, Travaglino, E, Morandini, P, Savevski, V, Santoro, A, Prada-Luengo, I, Krogh, A, Santini, V, Kordasti, S, Platzbecker, U, Diez-Campelo, M, Fenaux, P, Haferlach, T, Castellani, G, Della Porta, M, D'Amico S., Dall'Olio D., Sala C., Dall'Olio L., Sauta E., Zampini M., Asti G., Lanino L., Maggioni G., Campagna A., Ubezio M., Russo A., Bicchieri M. E., Riva E., Tentori C. A., Travaglino E., Morandini P., Savevski V., Santoro A., Prada-Luengo I., Krogh A., Santini V., Kordasti S., Platzbecker U., Diez-Campelo M., Fenaux P., Haferlach T., Castellani G., and Della Porta M. G.
Abstract: PURPOSE: Synthetic data are artificial data generated without including any real patient information by an algorithm trained to learn the characteristics of a real source data set and became widely used to accelerate research in life sciences. We aimed to (1) apply generative artificial intelligence to build synthetic data in different hematologic neoplasms; (2) develop a synthetic validation framework to assess data fidelity and privacy preservability; and (3) test the capability of synthetic data to accelerate clinical/translational research in hematology. METHODS: A conditional generative adversarial network architecture was implemented to generate synthetic data. Use cases were myelodysplastic syndromes (MDS) and AML: 7,133 patients were included. A fully explainable validation framework was created to assess fidelity and privacy preservability of synthetic data. RESULTS: We generated MDS/AML synthetic cohorts (including information on clinical features, genomics, treatment, and outcomes) with high fidelity and privacy performances. This technology allowed resolution of lack/incomplete information and data augmentation. We then assessed the potential value of synthetic data on accelerating research in hematology. Starting from 944 patients with MDS available since 2014, we generated a 300% augmented synthetic cohort and anticipated the development of molecular classification and molecular scoring system obtained many years later from 2,043 to 2,957 real patients, respectively. Moreover, starting from 187 MDS treated with luspatercept into a clinical trial, we generated a synthetic cohort that recapitulated all the clinical end points of the study. Finally, we developed a website to enable clinicians generating high-quality synthetic data from an existing biobank of real patients. CONCLUSION: Synthetic data mimic real clinical-genomic features and outcomes, and anonymize patient information. The implementation of this technology allows to increase the scientific
Published: 2023

7. Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation

Author: Ruggeri, A, de Wreede, L, Muller, C, Crivello, P, Bonneville, E, Petersdorf, E, Socie, G, Dubois, V, Niittyvuopio, R, Perasaari, J, Yakoub-Agha, I, Cornelissen, J, Wieten, L, Gedde-Dahl, T, Forcade, E, Crawley, C, Marsh, S, Gandemer, V, Tholouli, E, Bulabois, C, Huynh, A, Choi, G, Deconinck, E, Itala-Remes, M, Lenhoff, S, Bengtsson, M, Johansson, J, van Gorkom, G, Hoogenboom, J, Vago, L, Rocha, V, Bonini, C, Chabannon, C, Fleischhauer, K, Clausen, J, Holter, W, Kalhs, P, Beguin, Y, Bron, D, Deeren, D, Lung, W, Kerre, T, Poire, X, Selleslag, D, Schroyens, W, Jindra, P, Mayer, J, Vydra, J, Zak, P, Nielsen, B, Sengeloev, H, Kaare, A, Partanen, A, Bay, J, Bertrand, Y, Blaise, D, Bourhis, J, Chevallier, P, Cluzeau, T, Damaj, G, Fegueux, N, Guyotat, D, Hunault-Berger, M, Labussiere-Wallet, H, Leleu, X, Lioure, B, Maury, S, Michel, G, Mohty, M, Rubio, M, Tilly, H, Turlure, P, Bethge, W, Casper, J, Einsele, H, Ganser, A, Kroger, N, Martin, S, Platzbecker, U, Reinhardt, C, Schafer-Eckart, K, Thurner, L, Valerius, T, Wulf, G, Karakasis, D, Spyridonidis, A, Hauser, P, Remenyi, P, Reykdal, S, Mousavi, A, Angelucci, E, Arcese, W, Benedetti, F, Bernasconi, P, Biondi, A, Bonifazi, F, Carella, A, Carluccio, P, Casini, M, Cavanna, L, Ciceri, F, Cimino, G, Corradini, P, Fanin, R, Galieni, P, Grillo, G, Iori, A, La Nasa, G, Locatelli, F, Marotta, G, Martino, M, Mazza, P, Mordini, N, Musso, M, Olivieri, A, Pavone, V, Pane, F, Petrini, M, Pioltelli, P, Rambaldi, A, Ruggeri, M, Saccardi, R, Santarone, S, Scime, R, Sica, S, Tarella, C, Velardi, A, Visani, G, Zecca, M, Tanase, A, Kulagin, A, Savchenko, V, Lopez, C, Amor, A, Lopez, J, Caballero, D, Duarte, R, Cascon, M, Porras, R, Perez-Simon, J, Rovira, M, Sanz, J, Carrete, J, Cammenga, J, Isaksson, C, Mielke, S, Chalandon, Y, Passweg, J, Schanz, U, Meijer, E, Kuball, J, Veelken, J, Apperley, J, Bloor, A, Byrne, J, Carpenter, B, Clark, A, Collin, M, Craddock, C, Gibson, B, Khan, A, Martin, M, Medd, P, Nicholson, E, Orchard, K, Patel, A, Peniket, A, Potter, V, Snowden, J, Wilson, K, Ruggeri A., de Wreede L. C., Muller C. R., Crivello P., Bonneville E. F., Petersdorf E. W., Socie G., Dubois V., Niittyvuopio R., Perasaari J., Yakoub-Agha I., Cornelissen J. J., Wieten L., Gedde-Dahl T., Forcade E., Crawley C. R., Marsh S. G. E., Gandemer V., Tholouli E., Bulabois C. -E., Huynh A., Choi G., Deconinck E., Itala-Remes M., Lenhoff S., Bengtsson M., Johansson J. -E., van Gorkom G., Hoogenboom J. D., Vago L., Rocha V., Bonini C., Chabannon C., Fleischhauer K., Clausen J., Holter W., Kalhs P., Beguin Y., Bron D., Deeren D., Lung W. K., Kerre T., Poire X., Selleslag D., Schroyens W., Jindra P., Mayer J., Vydra J., Zak P., Nielsen B., Sengeloev H., Kaare A., Partanen A., Bay J., Bertrand Y., Blaise D., Bourhis J. H., Chevallier P., Cluzeau T., Damaj G., Fegueux N., Guyotat D., Hunault-Berger M., Labussiere-Wallet H., Leleu X., Lioure B., Maury S., Michel G., Mohty M., Rubio M. T., Tilly H., Turlure P., Bethge W., Casper J., Einsele H., Ganser A., Kroger N., Martin S., Platzbecker U., Reinhardt C., Schafer-Eckart K., Thurner L., Valerius T., Wulf G. G., Karakasis D., Spyridonidis A., Hauser P., Remenyi P., Reykdal S., Mousavi A., Angelucci E., Arcese W., Benedetti F., Bernasconi P., Biondi A., Bonifazi F., Carella A. M., Carluccio P., Casini M., Cavanna L., Ciceri F., Cimino G., Corradini P., Fanin R., Galieni P., Grillo G., Iori A. P., La Nasa G., Locatelli F., Marotta G., Martino M., Mazza P., Mordini N., Musso M., Olivieri A., Pavone V., Pane F., Petrini M., Pioltelli P., Rambaldi A., Ruggeri M., Saccardi R., Santarone S., Scime R., Sica S., Tarella C., Velardi A., Visani G., Zecca M., Tanase A., Kulagin A., Savchenko V., Lopez C. A., Amor A. A., Lopez J. L. B., Caballero D., Duarte R., Cascon M. J. P., Porras R. P., Perez-Simon J. A., Rovira M., Sanz J., Carrete J. P. T., Cammenga J., Isaksson C., Mielke S., Chalandon Y., Passweg J., Schanz U., Meijer E., Kuball J., Veelken J. H., Apperley J., Bloor A., Byrne J., Carpenter B., Clark A., Collin M., Craddock C., Gibson B. E., Khan A., Martin M., Medd P., Nicholson E., Orchard K., Patel A., Peniket A., Potter V., Snowden J., Wilson K. M. O., Ruggeri, A, de Wreede, L, Muller, C, Crivello, P, Bonneville, E, Petersdorf, E, Socie, G, Dubois, V, Niittyvuopio, R, Perasaari, J, Yakoub-Agha, I, Cornelissen, J, Wieten, L, Gedde-Dahl, T, Forcade, E, Crawley, C, Marsh, S, Gandemer, V, Tholouli, E, Bulabois, C, Huynh, A, Choi, G, Deconinck, E, Itala-Remes, M, Lenhoff, S, Bengtsson, M, Johansson, J, van Gorkom, G, Hoogenboom, J, Vago, L, Rocha, V, Bonini, C, Chabannon, C, Fleischhauer, K, Clausen, J, Holter, W, Kalhs, P, Beguin, Y, Bron, D, Deeren, D, Lung, W, Kerre, T, Poire, X, Selleslag, D, Schroyens, W, Jindra, P, Mayer, J, Vydra, J, Zak, P, Nielsen, B, Sengeloev, H, Kaare, A, Partanen, A, Bay, J, Bertrand, Y, Blaise, D, Bourhis, J, Chevallier, P, Cluzeau, T, Damaj, G, Fegueux, N, Guyotat, D, Hunault-Berger, M, Labussiere-Wallet, H, Leleu, X, Lioure, B, Maury, S, Michel, G, Mohty, M, Rubio, M, Tilly, H, Turlure, P, Bethge, W, Casper, J, Einsele, H, Ganser, A, Kroger, N, Martin, S, Platzbecker, U, Reinhardt, C, Schafer-Eckart, K, Thurner, L, Valerius, T, Wulf, G, Karakasis, D, Spyridonidis, A, Hauser, P, Remenyi, P, Reykdal, S, Mousavi, A, Angelucci, E, Arcese, W, Benedetti, F, Bernasconi, P, Biondi, A, Bonifazi, F, Carella, A, Carluccio, P, Casini, M, Cavanna, L, Ciceri, F, Cimino, G, Corradini, P, Fanin, R, Galieni, P, Grillo, G, Iori, A, La Nasa, G, Locatelli, F, Marotta, G, Martino, M, Mazza, P, Mordini, N, Musso, M, Olivieri, A, Pavone, V, Pane, F, Petrini, M, Pioltelli, P, Rambaldi, A, Ruggeri, M, Saccardi, R, Santarone, S, Scime, R, Sica, S, Tarella, C, Velardi, A, Visani, G, Zecca, M, Tanase, A, Kulagin, A, Savchenko, V, Lopez, C, Amor, A, Lopez, J, Caballero, D, Duarte, R, Cascon, M, Porras, R, Perez-Simon, J, Rovira, M, Sanz, J, Carrete, J, Cammenga, J, Isaksson, C, Mielke, S, Chalandon, Y, Passweg, J, Schanz, U, Meijer, E, Kuball, J, Veelken, J, Apperley, J, Bloor, A, Byrne, J, Carpenter, B, Clark, A, Collin, M, Craddock, C, Gibson, B, Khan, A, Martin, M, Medd, P, Nicholson, E, Orchard, K, Patel, A, Peniket, A, Potter, V, Snowden, J, Wilson, K, Ruggeri A., de Wreede L. C., Muller C. R., Crivello P., Bonneville E. F., Petersdorf E. W., Socie G., Dubois V., Niittyvuopio R., Perasaari J., Yakoub-Agha I., Cornelissen J. J., Wieten L., Gedde-Dahl T., Forcade E., Crawley C. R., Marsh S. G. E., Gandemer V., Tholouli E., Bulabois C. -E., Huynh A., Choi G., Deconinck E., Itala-Remes M., Lenhoff S., Bengtsson M., Johansson J. -E., van Gorkom G., Hoogenboom J. D., Vago L., Rocha V., Bonini C., Chabannon C., Fleischhauer K., Clausen J., Holter W., Kalhs P., Beguin Y., Bron D., Deeren D., Lung W. K., Kerre T., Poire X., Selleslag D., Schroyens W., Jindra P., Mayer J., Vydra J., Zak P., Nielsen B., Sengeloev H., Kaare A., Partanen A., Bay J., Bertrand Y., Blaise D., Bourhis J. H., Chevallier P., Cluzeau T., Damaj G., Fegueux N., Guyotat D., Hunault-Berger M., Labussiere-Wallet H., Leleu X., Lioure B., Maury S., Michel G., Mohty M., Rubio M. T., Tilly H., Turlure P., Bethge W., Casper J., Einsele H., Ganser A., Kroger N., Martin S., Platzbecker U., Reinhardt C., Schafer-Eckart K., Thurner L., Valerius T., Wulf G. G., Karakasis D., Spyridonidis A., Hauser P., Remenyi P., Reykdal S., Mousavi A., Angelucci E., Arcese W., Benedetti F., Bernasconi P., Biondi A., Bonifazi F., Carella A. M., Carluccio P., Casini M., Cavanna L., Ciceri F., Cimino G., Corradini P., Fanin R., Galieni P., Grillo G., Iori A. P., La Nasa G., Locatelli F., Marotta G., Martino M., Mazza P., Mordini N., Musso M., Olivieri A., Pavone V., Pane F., Petrini M., Pioltelli P., Rambaldi A., Ruggeri M., Saccardi R., Santarone S., Scime R., Sica S., Tarella C., Velardi A., Visani G., Zecca M., Tanase A., Kulagin A., Savchenko V., Lopez C. A., Amor A. A., Lopez J. L. B., Caballero D., Duarte R., Cascon M. J. P., Porras R. P., Perez-Simon J. A., Rovira M., Sanz J., Carrete J. P. T., Cammenga J., Isaksson C., Mielke S., Chalandon Y., Passweg J., Schanz U., Meijer E., Kuball J., Veelken J. H., Apperley J., Bloor A., Byrne J., Carpenter B., Clark A., Collin M., Craddock C., Gibson B. E., Khan A., Martin M., Medd P., Nicholson E., Orchard K., Patel A., Peniket A., Potter V., Snowden J., and Wilson K. M. O.
Published: 2023

8. Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes.

Author: Zeidan, A.M., Platzbecker, U., Bewersdorf, J.P., Stahl, M., Adès, L., Borate, U., Bowen, D., Buckstein, R., Brunner, A., Carraway, H.E., Daver, N., Díez-Campelo, M., Witte, T.J. de, DeZern, A.E., Efficace, F., Garcia-Manero, G., Garcia, J.S., Germing, U., Giagounidis, A., Griffiths, E.A., Hasserjian, R.P., Hellström-Lindberg, E., Iastrebner, M., Komrokji, R., Kulasekararaj, A.G., Malcovati, L., Miyazaki, Y., Odenike, O., Santini, V., Sanz, G., Scheinberg, P., Stauder, R., Loosdrecht, A.A. van de, Wei, A.H., Sekeres, M.A., Fenaux, P., Zeidan, A.M., Platzbecker, U., Bewersdorf, J.P., Stahl, M., Adès, L., Borate, U., Bowen, D., Buckstein, R., Brunner, A., Carraway, H.E., Daver, N., Díez-Campelo, M., Witte, T.J. de, DeZern, A.E., Efficace, F., Garcia-Manero, G., Garcia, J.S., Germing, U., Giagounidis, A., Griffiths, E.A., Hasserjian, R.P., Hellström-Lindberg, E., Iastrebner, M., Komrokji, R., Kulasekararaj, A.G., Malcovati, L., Miyazaki, Y., Odenike, O., Santini, V., Sanz, G., Scheinberg, P., Stauder, R., Loosdrecht, A.A. van de, Wei, A.H., Sekeres, M.A., and Fenaux, P.
Abstract: Item does not contain fulltext, Myelodysplastic syndromes/myelodysplastic neoplasms (MDS) are associated with variable clinical presentations and outcomes. The initial response criteria developed by the International Working Group (IWG) in 2000 have been used in clinical practice, clinical trials, regulatory reviews, and drug labels. Although the IWG criteria were revised in 2006 and 2018 (the latter focusing on lower-risk disease), limitations persist in their application to higher-risk MDS (HR-MDS) and their ability to fully capture the clinical benefits of novel investigational drugs or serve as valid surrogates for longer-term clinical end points (eg, overall survival). Further, issues related to the ambiguity and practicality of some criteria lead to variability in interpretation and interobserver inconsistency in reporting results from the same sets of data. Thus, we convened an international panel of 36 MDS experts and used an established modified Delphi process to develop consensus recommendations for updated response criteria that would be more reflective of patient-centered and clinically relevant outcomes in HR-MDS. Among others, the IWG 2023 criteria include changes in the hemoglobin threshold for complete remission (CR), the introduction of CR with limited count recovery and CR with partial hematologic recovery as provisional response criteria, the elimination of marrow CR, and specific recommendations for the standardization of time-to-event end points and the derivation and reporting of responses. The updated criteria should lead to a better correlation between patient-centered outcomes and clinical trial results in an era of multiple emerging new agents with novel mechanisms of action.
Published: 2023

9. 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

10. Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation

Author: Ruggeri, A., de Wreede, L. C., Muller, C. R., Crivello, P., Bonneville, E. F., Petersdorf, E. W., Socie, G., Dubois, V., Niittyvuopio, R., Perasaari, J., Yakoub-Agha, I., Cornelissen, J. J., Wieten, L., Gedde-Dahl, T., Forcade, E., Crawley, C. R., Marsh, S. G. E., Gandemer, V., Tholouli, E., Bulabois, C. -E., Huynh, A., Choi, G., Deconinck, E., Itala-Remes, M., Lenhoff, S., Bengtsson, M., Johansson, J. -E., van Gorkom, G., Hoogenboom, J. D., Vago, L., Rocha, V., Bonini, C., Chabannon, C., Fleischhauer, K., Clausen, J., Holter, W., Kalhs, P., Beguin, Y., Bron, D., Deeren, D., Lung, W. K., Kerre, T., Poire, X., Selleslag, D., Schroyens, W., Jindra, P., Mayer, J., Vydra, J., Zak, P., Nielsen, B., Sengeloev, H., Kaare, A., Partanen, A., Bay, J., Bertrand, Y., Blaise, D., Bourhis, J. H., Chevallier, P., Cluzeau, T., Damaj, G., Fegueux, N., Guyotat, D., Hunault-Berger, M., Labussiere-Wallet, H., Leleu, X., Lioure, B., Maury, S., Michel, G., Mohty, M., Rubio, M. T., Tilly, H., Turlure, P., Bethge, W., Casper, J., Einsele, H., Ganser, A., Kroger, N., Martin, S., Platzbecker, U., Reinhardt, C., Schafer-Eckart, K., Thurner, L., Valerius, T., Wulf, G. G., Karakasis, D., Spyridonidis, A., Hauser, P., Remenyi, P., Reykdal, S., Mousavi, A., Angelucci, E., Arcese, W., Benedetti, F., Bernasconi, P., Biondi, A., Bonifazi, F., Carella, A. M., Carluccio, P., Casini, M., Cavanna, L., Ciceri, F., Cimino, G., Corradini, P., Fanin, R., Galieni, P., Grillo, G., Iori, A. P., La Nasa, G., Locatelli, Franco, Marotta, G., Martino, M., Mazza, P., Mordini, N., Musso, M., Olivieri, A., Pavone, V., Pane, F., Petrini, M., Pioltelli, P., Rambaldi, A., Ruggeri, M., Saccardi, R., Santarone, S., Scime, R., Sica, S., Tarella, C., Velardi, A., Visani, G., Zecca, M., Tanase, A., Kulagin, A., Savchenko, V., Lopez, C. A., Amor, A. A., Lopez, J. L. B., Caballero, D., Duarte, R., Cascon, M. J. P., Porras, R. P., Perez-Simon, J. A., Rovira, M., Sanz, J., Carrete, J. P. T., Cammenga, J., Isaksson, C., Mielke, S., Chalandon, Y., Passweg, J., Schanz, U., Meijer, E., Kuball, J., Veelken, J. H., Apperley, J., Bloor, A., Byrne, J., Carpenter, B., Clark, A., Collin, M., Craddock, C., Gibson, B. E., Khan, A., Martin, M., Medd, P., Nicholson, E., Orchard, K., Patel, A., Peniket, A., Potter, V., Snowden, J., Wilson, K. M. O., Locatelli F. (ORCID:0000-0002-7976-3654), Ruggeri, A., de Wreede, L. C., Muller, C. R., Crivello, P., Bonneville, E. F., Petersdorf, E. W., Socie, G., Dubois, V., Niittyvuopio, R., Perasaari, J., Yakoub-Agha, I., Cornelissen, J. J., Wieten, L., Gedde-Dahl, T., Forcade, E., Crawley, C. R., Marsh, S. G. E., Gandemer, V., Tholouli, E., Bulabois, C. -E., Huynh, A., Choi, G., Deconinck, E., Itala-Remes, M., Lenhoff, S., Bengtsson, M., Johansson, J. -E., van Gorkom, G., Hoogenboom, J. D., Vago, L., Rocha, V., Bonini, C., Chabannon, C., Fleischhauer, K., Clausen, J., Holter, W., Kalhs, P., Beguin, Y., Bron, D., Deeren, D., Lung, W. K., Kerre, T., Poire, X., Selleslag, D., Schroyens, W., Jindra, P., Mayer, J., Vydra, J., Zak, P., Nielsen, B., Sengeloev, H., Kaare, A., Partanen, A., Bay, J., Bertrand, Y., Blaise, D., Bourhis, J. H., Chevallier, P., Cluzeau, T., Damaj, G., Fegueux, N., Guyotat, D., Hunault-Berger, M., Labussiere-Wallet, H., Leleu, X., Lioure, B., Maury, S., Michel, G., Mohty, M., Rubio, M. T., Tilly, H., Turlure, P., Bethge, W., Casper, J., Einsele, H., Ganser, A., Kroger, N., Martin, S., Platzbecker, U., Reinhardt, C., Schafer-Eckart, K., Thurner, L., Valerius, T., Wulf, G. G., Karakasis, D., Spyridonidis, A., Hauser, P., Remenyi, P., Reykdal, S., Mousavi, A., Angelucci, E., Arcese, W., Benedetti, F., Bernasconi, P., Biondi, A., Bonifazi, F., Carella, A. M., Carluccio, P., Casini, M., Cavanna, L., Ciceri, F., Cimino, G., Corradini, P., Fanin, R., Galieni, P., Grillo, G., Iori, A. P., La Nasa, G., Locatelli, Franco, Marotta, G., Martino, M., Mazza, P., Mordini, N., Musso, M., Olivieri, A., Pavone, V., Pane, F., Petrini, M., Pioltelli, P., Rambaldi, A., Ruggeri, M., Saccardi, R., Santarone, S., Scime, R., Sica, S., Tarella, C., Velardi, A., Visani, G., Zecca, M., Tanase, A., Kulagin, A., Savchenko, V., Lopez, C. A., Amor, A. A., Lopez, J. L. B., Caballero, D., Duarte, R., Cascon, M. J. P., Porras, R. P., Perez-Simon, J. A., Rovira, M., Sanz, J., Carrete, J. P. T., Cammenga, J., Isaksson, C., Mielke, S., Chalandon, Y., Passweg, J., Schanz, U., Meijer, E., Kuball, J., Veelken, J. H., Apperley, J., Bloor, A., Byrne, J., Carpenter, B., Clark, A., Collin, M., Craddock, C., Gibson, B. E., Khan, A., Martin, M., Medd, P., Nicholson, E., Orchard, K., Patel, A., Peniket, A., Potter, V., Snowden, J., Wilson, K. M. O., and Locatelli F. (ORCID:0000-0002-7976-3654)
Abstract: NO ABSTRACT
Published: 2023

11. 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

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. -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

13. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial

Author: Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.
Published: 2020

14. Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.

Author: Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L.R., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Campelo M.D., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Fianchi L., Torre I.L., Zhong J., Laille E., De Menezes D.L., Skikne B., Beach C.L., Giagounidis A., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L.R., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Campelo M.D., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Fianchi L., Torre I.L., Zhong J., Laille E., De Menezes D.L., Skikne B., Beach C.L., and Giagounidis A.
Abstract: PURPOSE Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia. METHODS Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). RESULTS Two hundred sixteen patients received CC-486 (n 5 107) or placebo (n 5 109). The median age was 74 years, median platelet count was 25 3 109/L, and absolute neutrophil count was 1.3 3 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI (P5.0002), with median durations of 11.1 and 5.0 months. Reductions of $ 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months, and more CC-486 patients had $ 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC- 486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P 5 .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC- 486, n 5 16; placebo, n 5 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 3 109/L. CONCLUSION CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further evaluation of
Published: 2022

15. Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.

Author: Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L.R., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Campelo M.D., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Fianchi L., Torre I.L., Zhong J., Laille E., De Menezes D.L., Skikne B., Beach C.L., Giagounidis A., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L.R., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Campelo M.D., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Fianchi L., Torre I.L., Zhong J., Laille E., De Menezes D.L., Skikne B., Beach C.L., and Giagounidis A.
Abstract: PURPOSE Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia. METHODS Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). RESULTS Two hundred sixteen patients received CC-486 (n 5 107) or placebo (n 5 109). The median age was 74 years, median platelet count was 25 3 109/L, and absolute neutrophil count was 1.3 3 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI (P5.0002), with median durations of 11.1 and 5.0 months. Reductions of $ 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months, and more CC-486 patients had $ 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC- 486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P 5 .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC- 486, n 5 16; placebo, n 5 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 3 109/L. CONCLUSION CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further evaluation of
Published: 2022

16. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

Author: Khoury, J.D., Solary, E., Abla, O., Akkari, Y., Alaggio, R., Apperley, J.F., Bejar, R., Berti, E., Busque, L., Chan, J.K.C., Chen, Weina, Chen, Xueyan, Chng, W.J., Choi, J.K., Colmenero, I., Coupland, S.E., Cross, N.C., Jong, Daphne de, Elghetany, M.T., Takahashi, E., Emile, J.F., Ferry, J., Fogelstrand, L., Fontenay, M., Germing, U., Gujral, S., Haferlach, T, Harrison, C., Hodge, J.C., Hu, S., Jansen, J.H., Kanagal-Shamanna, R., Kantarjian, H.M., Kratz, C.P., Li, X.Q., Lim, M.S.C., Loeb, K., Loghavi, S., Marcogliese, A., Meshinchi, S., Michaels, P., Naresh, K.N., Natkunam, Y., Nejati, R., Ott, G., Padron, E., Patel, K.P., Patkar, N., Picarsic, J., Platzbecker, U., Roberts, I., Schuh, A., Sewell, W., Siebert, R., Tembhare, P., Tyner, J., Verstovsek, S., Wang, W., Wood, B., Xiao, W., Yeung, C., Hochhaus, A., Khoury, J.D., Solary, E., Abla, O., Akkari, Y., Alaggio, R., Apperley, J.F., Bejar, R., Berti, E., Busque, L., Chan, J.K.C., Chen, Weina, Chen, Xueyan, Chng, W.J., Choi, J.K., Colmenero, I., Coupland, S.E., Cross, N.C., Jong, Daphne de, Elghetany, M.T., Takahashi, E., Emile, J.F., Ferry, J., Fogelstrand, L., Fontenay, M., Germing, U., Gujral, S., Haferlach, T, Harrison, C., Hodge, J.C., Hu, S., Jansen, J.H., Kanagal-Shamanna, R., Kantarjian, H.M., Kratz, C.P., Li, X.Q., Lim, M.S.C., Loeb, K., Loghavi, S., Marcogliese, A., Meshinchi, S., Michaels, P., Naresh, K.N., Natkunam, Y., Nejati, R., Ott, G., Padron, E., Patel, K.P., Patkar, N., Picarsic, J., Platzbecker, U., Roberts, I., Schuh, A., Sewell, W., Siebert, R., Tembhare, P., Tyner, J., Verstovsek, S., Wang, W., Wood, B., Xiao, W., Yeung, C., and Hochhaus, A.
Abstract: Contains fulltext : 282922.pdf (Publisher’s version ) (Open Access)
Published: 2022

17. Primary Results of Stimulus-MDS1: A Randomized, Double-Blind, Placebo-Controlled Phase II Study of TIM-3 Inhibition with Sabatolimab Added to Hypomethylating Agents (HMAs) in Adult Patients with Higher-Risk Myelodysplastic Syndromes (MDS)

Author: Zeidan, A, Ando, K, Rauzy, O, Turgut, M, Wang, M, Cairoli, R, Hou, H, Kwong, Y, Sangerman, M, Meers, S, Pullarkat, V, Santini, V, Malek, K, Kiertsman, F, Lyu, J, Ramos, P, Fenaux, P, Miyazaki, Y, Platzbecker, U, Zeidan, AM, Wang, MC, Hou, HA, Kwong, YL, Sangerman, MA, Pullarkat, VA, Lyu, JY, Ramos, PM, Zeidan, A, Ando, K, Rauzy, O, Turgut, M, Wang, M, Cairoli, R, Hou, H, Kwong, Y, Sangerman, M, Meers, S, Pullarkat, V, Santini, V, Malek, K, Kiertsman, F, Lyu, J, Ramos, P, Fenaux, P, Miyazaki, Y, Platzbecker, U, Zeidan, AM, Wang, MC, Hou, HA, Kwong, YL, Sangerman, MA, Pullarkat, VA, Lyu, JY, and Ramos, PM
Published: 2022

18. VERY LONG-TERM RESULTS OF ALL-TRANS RETINOIC ACID AND ARSENIC TRIOXIDE IN NON-HIGH RISK ACUTE PROMYELOCYTIC LEUKEMIA: LATEST UPDATE OF THE ITALIAN-GERMAN APL0406 RANDOMIZED TRIAL

Author: Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.
Published: 2019

19. Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party

Author: Hayden, P.J., Eikema, D.J., Wreede, L.C. de, Koster, L, Kröger, N., Einsele, H., Minnema, M., Dominietto, A., Potter, M., Passweg, J., Bermúdez, A., Nguyen-Quoc, S., Platzbecker, U., Tischer, J., Ciceri, F., Veelken, J.H., Ljungman, P., Schaap, N.P., Forcade, E., Carella, A.M., Gandemer, V., Arcese, W., Bloor, A., Olivieri, A., Vincent, L., Beksac, M., Schönland, S., Yakoub-Agha, I., Hayden, P.J., Eikema, D.J., Wreede, L.C. de, Koster, L, Kröger, N., Einsele, H., Minnema, M., Dominietto, A., Potter, M., Passweg, J., Bermúdez, A., Nguyen-Quoc, S., Platzbecker, U., Tischer, J., Ciceri, F., Veelken, J.H., Ljungman, P., Schaap, N.P., Forcade, E., Carella, A.M., Gandemer, V., Arcese, W., Bloor, A., Olivieri, A., Vincent, L., Beksac, M., Schönland, S., and Yakoub-Agha, I.
Abstract: Contains fulltext : 244085.pdf (Publisher’s version ) (Open Access), The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30-46%) at 2 years and 25% (17-32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24-46%); Others 9% (0-17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33-67%); Other 22% (8-36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21-40%) vs. 10% (1-20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24-0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.
Published: 2021

20. Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.

Author: Skikne B., Lopes de Menezes D., Beach C.L., Giagounidis A., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L.R., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Diez Campelo M., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Fianchi L., La Torre I., Zhong J., Laille E., Skikne B., Lopes de Menezes D., Beach C.L., Giagounidis A., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L.R., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Diez Campelo M., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Fianchi L., La Torre I., Zhong J., and Laille E.
Abstract: PURPOSE: Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia. METHOD(S): Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). RESULT(S): Two hundred sixteen patients received CC-486 (n = 107) or placebo (n = 109). The median age was 74 years, median platelet count was 25 x 109/L, and absolute neutrophil count was 1.3 x 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI (P = .0002), with median durations of 11.1 and 5.0 months. Reductions of >= 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months, and more CC-486 patients had >= 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC-486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P = .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC-486, n = 16; placebo, n = 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 x 109/L. CONCLUSION(S): CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further e
Published: 2021

21. Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.

Author: Skikne B., Lopes de Menezes D., Beach C.L., Giagounidis A., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L.R., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Diez Campelo M., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Fianchi L., La Torre I., Zhong J., Laille E., Skikne B., Lopes de Menezes D., Beach C.L., Giagounidis A., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L.R., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Diez Campelo M., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Fianchi L., La Torre I., Zhong J., and Laille E.
Abstract: PURPOSE: Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia. METHOD(S): Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). RESULT(S): Two hundred sixteen patients received CC-486 (n = 107) or placebo (n = 109). The median age was 74 years, median platelet count was 25 x 109/L, and absolute neutrophil count was 1.3 x 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI (P = .0002), with median durations of 11.1 and 5.0 months. Reductions of >= 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months, and more CC-486 patients had >= 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC-486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P = .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC-486, n = 16; placebo, n = 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 x 109/L. CONCLUSION(S): CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further e
Published: 2021

22. Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes

Author: Garcia-Manero, G, Santini, V, Almeida, A, Platzbecker, U, Jonasova, A, Silverman, LR, Falantes, J, Reda, G, Buccisano, F, Fenaux, P, Buckstein, R, Campelo, MD, Larsen, S, Valcarcel, D, Vyas, P, Giai, V, Oliva, EN, Shortt, J, Niederwieser, D, Mittelman, M, Fianchi, L, La Torre, I, Zhong, J, Laille, E, de Menezes, DL, Skikne, B, Beach, CL, Giagounidis, A, Garcia-Manero, G, Santini, V, Almeida, A, Platzbecker, U, Jonasova, A, Silverman, LR, Falantes, J, Reda, G, Buccisano, F, Fenaux, P, Buckstein, R, Campelo, MD, Larsen, S, Valcarcel, D, Vyas, P, Giai, V, Oliva, EN, Shortt, J, Niederwieser, D, Mittelman, M, Fianchi, L, La Torre, I, Zhong, J, Laille, E, de Menezes, DL, Skikne, B, Beach, CL, and Giagounidis, A
Abstract: PURPOSE: Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia. METHODS: Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). RESULTS: Two hundred sixteen patients received CC-486 (n = 107) or placebo (n = 109). The median age was 74 years, median platelet count was 25 × 109/L, and absolute neutrophil count was 1.3 × 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI (P = .0002), with median durations of 11.1 and 5.0 months. Reductions of ≥ 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months, and more CC-486 patients had ≥ 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC-486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P = .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC-486, n = 16; placebo, n = 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 × 109/L. CONCLUSION: CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further evaluation
Published: 2021

23. Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party

Author: Hayden, P.J., Eikema, D.J., Wreede, L.C. de, Koster, L, Kröger, N., Einsele, H., Minnema, M., Dominietto, A., Potter, M., Passweg, J., Bermúdez, A., Nguyen-Quoc, S., Platzbecker, U., Tischer, J., Ciceri, F., Veelken, J.H., Ljungman, P., Schaap, N.P., Forcade, E., Carella, A.M., Gandemer, V., Arcese, W., Bloor, A., Olivieri, A., Vincent, L., Beksac, M., Schönland, S., Yakoub-Agha, I., Hayden, P.J., Eikema, D.J., Wreede, L.C. de, Koster, L, Kröger, N., Einsele, H., Minnema, M., Dominietto, A., Potter, M., Passweg, J., Bermúdez, A., Nguyen-Quoc, S., Platzbecker, U., Tischer, J., Ciceri, F., Veelken, J.H., Ljungman, P., Schaap, N.P., Forcade, E., Carella, A.M., Gandemer, V., Arcese, W., Bloor, A., Olivieri, A., Vincent, L., Beksac, M., Schönland, S., and Yakoub-Agha, I.
Abstract: Contains fulltext : 244085.pdf (Publisher’s version ) (Open Access), The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30-46%) at 2 years and 25% (17-32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24-46%); Others 9% (0-17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33-67%); Other 22% (8-36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21-40%) vs. 10% (1-20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24-0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.
Published: 2021

24. Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party

Author: Hayden, P.J., Eikema, D.J., Wreede, L.C. de, Koster, L, Kröger, N., Einsele, H., Minnema, M., Dominietto, A., Potter, M., Passweg, J., Bermúdez, A., Nguyen-Quoc, S., Platzbecker, U., Tischer, J., Ciceri, F., Veelken, J.H., Ljungman, P., Schaap, N.P., Forcade, E., Carella, A.M., Gandemer, V., Arcese, W., Bloor, A., Olivieri, A., Vincent, L., Beksac, M., Schönland, S., Yakoub-Agha, I., Hayden, P.J., Eikema, D.J., Wreede, L.C. de, Koster, L, Kröger, N., Einsele, H., Minnema, M., Dominietto, A., Potter, M., Passweg, J., Bermúdez, A., Nguyen-Quoc, S., Platzbecker, U., Tischer, J., Ciceri, F., Veelken, J.H., Ljungman, P., Schaap, N.P., Forcade, E., Carella, A.M., Gandemer, V., Arcese, W., Bloor, A., Olivieri, A., Vincent, L., Beksac, M., Schönland, S., and Yakoub-Agha, I.
Abstract: Contains fulltext : 244085.pdf (Publisher’s version ) (Open Access), The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30-46%) at 2 years and 25% (17-32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24-46%); Others 9% (0-17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33-67%); Other 22% (8-36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21-40%) vs. 10% (1-20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24-0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.
Published: 2021

25. Clinical relevance of clonal hematopoiesis in persons aged ≥80 years

Author: Rossi, M, Meggendorfer, M, Zampini, M, Tettamanti, M, Riva, E, Travaglino, E, Bersanelli, M, Mandelli, S, Galbussera, A, Mosca, E, Saba, E, Chiereghin, C, Manes, N, Milanesi, C, Ubezio, M, Morabito, L, Peano, C, Soldà, G, Asselta, R, Duga, S, Selmi, C, De Santis, M, Malik, K, Maggioni, G, Bicchieri, M, Campagna, A, Tentori, C, Russo, A, Civilini, E, Allavena, P, Piazza, R, Corrao, G, Sala, C, Termanini, A, Giordano, L, Detoma, P, Malabaila, A, Sala, L, Rosso, S, Zanetti, R, Saitta, C, Condorelli, G, Passamonti, F, Santoro, A, Sole, F, Platzbecker, U, Fenaux, P, Bolli, N, Castellani, G, Kern, W, Vassiliou, G, Haferlach, T, Lucca, U, Della Porta, M, Rossi, Marianna, Meggendorfer, Manja, Zampini, Matteo, Tettamanti, Mauro, Riva, Emma, Travaglino, Erica, Bersanelli, Matteo, Mandelli, Sara, Galbussera, Alessia Antonella, Mosca, Ettore, Saba, Elena, Chiereghin, Chiara, Manes, Nicla, Milanesi, Chiara, Ubezio, Marta, Morabito, Lucio, Peano, Clelia, Soldà, Giulia, Asselta, Rosanna, Duga, Stefano, Selmi, Carlo, De Santis, Maria, Malik, Karolina, Maggioni, Giulia, Bicchieri, Maria Elena, Campagna, Alessia, Tentori, Cristina Astrid, Russo, Antonio, Civilini, Efrem, Allavena, Paola, Piazza, Rocco, Corrao, Giovanni, Sala, Claudia, Termanini, Alberto, Giordano, Laura, Detoma, Paolo, Malabaila, Aurelio, Sala, Luca, Rosso, Stefano, Zanetti, Roberto, Saitta, Claudia, Riva, Elena, Condorelli, Gianluigi, Passamonti, Francesco, Santoro, Armando, Sole, Francesc, Platzbecker, Uwe, Fenaux, Pierre, Bolli, Niccolo, Castellani, Gastone, Kern, Wolfgang, Vassiliou, George, Haferlach, Torsten, Lucca, Ugo, Della Porta, Matteo G, Rossi, M, Meggendorfer, M, Zampini, M, Tettamanti, M, Riva, E, Travaglino, E, Bersanelli, M, Mandelli, S, Galbussera, A, Mosca, E, Saba, E, Chiereghin, C, Manes, N, Milanesi, C, Ubezio, M, Morabito, L, Peano, C, Soldà, G, Asselta, R, Duga, S, Selmi, C, De Santis, M, Malik, K, Maggioni, G, Bicchieri, M, Campagna, A, Tentori, C, Russo, A, Civilini, E, Allavena, P, Piazza, R, Corrao, G, Sala, C, Termanini, A, Giordano, L, Detoma, P, Malabaila, A, Sala, L, Rosso, S, Zanetti, R, Saitta, C, Condorelli, G, Passamonti, F, Santoro, A, Sole, F, Platzbecker, U, Fenaux, P, Bolli, N, Castellani, G, Kern, W, Vassiliou, G, Haferlach, T, Lucca, U, Della Porta, M, Rossi, Marianna, Meggendorfer, Manja, Zampini, Matteo, Tettamanti, Mauro, Riva, Emma, Travaglino, Erica, Bersanelli, Matteo, Mandelli, Sara, Galbussera, Alessia Antonella, Mosca, Ettore, Saba, Elena, Chiereghin, Chiara, Manes, Nicla, Milanesi, Chiara, Ubezio, Marta, Morabito, Lucio, Peano, Clelia, Soldà, Giulia, Asselta, Rosanna, Duga, Stefano, Selmi, Carlo, De Santis, Maria, Malik, Karolina, Maggioni, Giulia, Bicchieri, Maria Elena, Campagna, Alessia, Tentori, Cristina Astrid, Russo, Antonio, Civilini, Efrem, Allavena, Paola, Piazza, Rocco, Corrao, Giovanni, Sala, Claudia, Termanini, Alberto, Giordano, Laura, Detoma, Paolo, Malabaila, Aurelio, Sala, Luca, Rosso, Stefano, Zanetti, Roberto, Saitta, Claudia, Riva, Elena, Condorelli, Gianluigi, Passamonti, Francesco, Santoro, Armando, Sole, Francesc, Platzbecker, Uwe, Fenaux, Pierre, Bolli, Niccolo, Castellani, Gastone, Kern, Wolfgang, Vassiliou, George, Haferlach, Torsten, Lucca, Ugo, and Della Porta, Matteo G
Abstract: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of cancers and inflammation-related diseases. This phenomenon becomes common in persons aged ≥80 years, in whom the implications of CHIP are not well defined. We performed a mutational screening in 1794 persons aged ≥80 years and investigated the relationships between CHIP and associated pathologies. Mutations were observed in one-third of persons aged ≥80 years and were associated with reduced survival. Mutations in JAK2 and splicing genes, multiple mutations (DNMT3A, TET2, and ASXL1 with additional genetic lesions), and variant allele frequency ≥0.096 had positive predictive value for myeloid neoplasms. Combining mutation profiles with abnormalities in red blood cell indices improved the ability of myeloid neoplasm prediction. On this basis, we defined a predictive model that identifies 3 risk groups with different probabilities of developing myeloid neoplasms. Mutations in DNMT3A, TET2, ASXL1, or JAK2 were associated with coronary heart disease and rheumatoid arthritis. Cytopenia was common in persons aged ≥80 years, with the underlying cause remaining unexplained in 30% of cases. Among individuals with unexplained cytopenia, the presence of highly specific mutation patterns was associated with myelodysplastic-like phenotype and a probability of survival comparable to that of myeloid neoplasms. Accordingly, 7.5% of subjects aged ≥80 years with cytopenia had presumptive evidence of myeloid neoplasm. In summary, specific mutational patterns define different risk of developing myeloid neoplasms vs inflammatory-associated diseases in persons aged ≥80 years. In individuals with unexplained cytopenia, mutational status may identify those subjects with presumptive evidence of myeloid neoplasms.
Published: 2021

26. Trends in allogeneic haematopoietic cell transplantation for myelofibrosis in Europe between 1995 and 2018:a CMWP of EBMT retrospective analysis

Author: McLornan, D., Eikema, D. J., Czerw, T., Kröger, N., Koster, L., Reinhardt, Hans Christian, Angelucci, E., Robin, M., Bornhäuser, M., Passweg, J., Clark, A., Vydra, J., Blau, I. E., Niittyvuopio, R., Platzbecker, U., Cornelissen, J. J., Chevallier, P., Srour, M., Stamatovic, D., Martinez-Lopez, J., de Wreede, L., Hayden, P., Hernández-Boluda, J. C., Yakoub-Agha, I., McLornan, D., Eikema, D. J., Czerw, T., Kröger, N., Koster, L., Reinhardt, Hans Christian, Angelucci, E., Robin, M., Bornhäuser, M., Passweg, J., Clark, A., Vydra, J., Blau, I. E., Niittyvuopio, R., Platzbecker, U., Cornelissen, J. J., Chevallier, P., Srour, M., Stamatovic, D., Martinez-Lopez, J., de Wreede, L., Hayden, P., Hernández-Boluda, J. C., and Yakoub-Agha, I.
Abstract: We performed a retrospective assessment of patient- and transplant-specific characteristics and outcomes for 4142 patients undergoing allogeneic haematopoietic cell transplant for myelofibrosis between 1995 and 2018 across 278 centres. Activity increased steadily across the four analysed eras (<2006, 2006–2010, 2011–2014 and 2015–2018). Median recipient age increased over time between the earliest and most recent cohort (49.4 years (range, 20.1–68) versus 59.3 years (range, 18.1–78.1). Increasing number of patients with a Karnofsky performance status <90 underwent transplant over time. Increased utilisation of matched unrelated donors was apparent (<2006, 22.5% versus 2015–18, 45.2%; p < 0.001). Decreased use of myeloablative conditioning, increased use of busulphan-based platforms and anti-thymocyte globulin was evident. Of note, rates of acute (a)GVHD grade II-IV by day +100 decreased over time (p = 0.027) as did rates of chronic (c) GVHD, predominantly extensive cGVHD (<2006, 36% (31–41%) versus 2015–18, 23% (21–25%); p = 0.001). Overall, significant factors associated with worse overall survival and non-relapse mortality (NRM) remained older age, use of donors other than matched sibling, recipient CMV seropositivity and a lower Karnofsky performance status (<90). Multivariable analysis demonstrated improvements in overall survival and reductions in relapse risk over time with stable NRM rates despite increasing numbers of older, less fit patients and use of unrelated donors.
Published: 2021

27. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Author: Bernard, E., Nannya, Y., Hasserjian, R.P., Devlin, S.M., Tuechler, H., Medina-Martinez, J.S., Yoshizato, T., Shiozawa, Y., Saiki, R., Malcovati, L., Levine, M.F., Arango, J.E., Zhou, Y, Solé, F., Cargo, C.A., Haase, D., Creignou, M., Germing, U., Zhang, Y., Gundem, G., Sarian, A., Loosdrecht, A.A. van de, Jädersten, M., Tobiasson, M., Kosmider, O., Follo, M.Y., Thol, F., Pinheiro, R.F., Santini, V., Kotsianidis, I., Boultwood, J., Santos, F.P.S., Schanz, J., Kasahara, S., Ishikawa, T., Tsurumi, H., Takaori-Kondo, A., Kiguchi, T., Polprasert, C., Bennett, J.M., Klimek, V.M., Savona, M.R., Belickova, M., Ganster, C., Palomo, L., Sanz, G., Ades, L., Porta, M.G. Della, Smith, A.G., Werner, Y., Patel, M., Viale, A., Vanness, K., Neuberg, D.S., Stevenson, K.E., Menghrajani, K., Bolton, K.L., Fenaux, P., Pellagatti, A., Platzbecker, U., Heuser, M., Valent, P., Chiba, S., Miyazaki, Y., Finelli, C., Voso, M.T., Shih, L.Y., Fontenay, M., Jansen, J.H., Cervera, J., Atsuta, Y., Gattermann, N., Ebert, B.L., Bejar, R., Greenberg, P.L., Cazzola, M., Hellström-Lindberg, E., Ogawa, S., Papaemmanuil, E., Bernard, E., Nannya, Y., Hasserjian, R.P., Devlin, S.M., Tuechler, H., Medina-Martinez, J.S., Yoshizato, T., Shiozawa, Y., Saiki, R., Malcovati, L., Levine, M.F., Arango, J.E., Zhou, Y, Solé, F., Cargo, C.A., Haase, D., Creignou, M., Germing, U., Zhang, Y., Gundem, G., Sarian, A., Loosdrecht, A.A. van de, Jädersten, M., Tobiasson, M., Kosmider, O., Follo, M.Y., Thol, F., Pinheiro, R.F., Santini, V., Kotsianidis, I., Boultwood, J., Santos, F.P.S., Schanz, J., Kasahara, S., Ishikawa, T., Tsurumi, H., Takaori-Kondo, A., Kiguchi, T., Polprasert, C., Bennett, J.M., Klimek, V.M., Savona, M.R., Belickova, M., Ganster, C., Palomo, L., Sanz, G., Ades, L., Porta, M.G. Della, Smith, A.G., Werner, Y., Patel, M., Viale, A., Vanness, K., Neuberg, D.S., Stevenson, K.E., Menghrajani, K., Bolton, K.L., Fenaux, P., Pellagatti, A., Platzbecker, U., Heuser, M., Valent, P., Chiba, S., Miyazaki, Y., Finelli, C., Voso, M.T., Shih, L.Y., Fontenay, M., Jansen, J.H., Cervera, J., Atsuta, Y., Gattermann, N., Ebert, B.L., Bejar, R., Greenberg, P.L., Cazzola, M., Hellström-Lindberg, E., Ogawa, S., and Papaemmanuil, E.
Abstract: Contains fulltext : 229615.pdf (Publisher’s version ) (Closed access)
Published: 2020

28. A phase iii placebo-controlled trial of CC-486 in patients with red blood cell transfusiondependent (RBC-TD) anemia and thrombocytopenia due to IPSS lower-risk myelodysplastic syndromes (LR-MDS).

Author: Laille E., Fianchi L., Zhong J., La Torre I., Giagounidis A., Beach C., Skikne B., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Diez Campelo M., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Laille E., Fianchi L., Zhong J., La Torre I., Giagounidis A., Beach C., Skikne B., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Diez Campelo M., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., and Mittelman M.
Abstract: Background: MDS is characterized by bone marrow dysplasia and peripheral cytopenias of variable severity. Treatment (Tx) options are limited for LR-MDS patients (pts) with low blast counts but high-risk disease features (eg, RBC-TD anemia and thrombocytopenia). The phase III placebo (PBO)-controlled QUAZAR Lower-risk MDS trial (NCT01566695) assessed CC-486, an oral hypomethylating agent, in pts who were RBC-TD and thrombocytopenic at study entry. Aim(s): Describe clinical outcomes from the QUAZAR Lower-risk MDS trial. Method(s): Eligible pts were age >=18 yrs, with IPSS LR-MDS, average RBC transfusion requirement of >=2 units (U)/28 days (d) for 56d, and 2 platelet (PLT) counts <=75 x 109/L taken >=21d apart. Pts were randomized 1:1 to CC-486 300 mg or PBO QD for 21d per 28d Tx cycle (C). The primary endpoint was RBC transfusion independence (TI) lasting >=56d (IWG 2006). Key secondary endpoints were overall survival (OS), >=84d RBC-TI, and hematologic improvement in erythroid and PLT lineages (HI-E, HI-P). Planned enrollment was 386 pts. An imbalance of early deaths in the CC-486 arm led to a decision to close enrollment; the final sample size (N = 216) allowed comparison of RBC-TI between Tx arms with ~99% power. Result(s): At data cutoff all pts (CC-486 n = 107; PBO n = 109) completed >=12 mo of Tx or discontinued before 12 mo. Baseline (BL) characteristics were similar between Tx arms. Median age was 74 yrs (30-89), Hgb 8.1 g/dL (5.4-10.9), PLT count 25x109/L (5-73), ANC 1.3x109/L (0.1-25), and transfusion requirement 6.7 U/56d. All pts had IPSS INT-1 MDS. Significantly more pts in the CC-486 arm achieved RBC-TI for >=56d (31%, vs. 11% with PBO; P = 0.0002) (Table 1). Median RBC-TI durations in the CC-486 and PBO arms were 11.1 and 5.0 mo, respectively (P = 0.42). In the CC-486 and PBO arms, 42% and 31%, respectively, had RBC transfusion reductions of >=4 U from BL, sustained for a median of 10.0 and 2.3 mo (P = 0.0001). While HI-E rates were comparable (P = 0.1
Published: 2020

29. A phase iii placebo-controlled trial of CC-486 in patients with red blood cell transfusiondependent (RBC-TD) anemia and thrombocytopenia due to IPSS lower-risk myelodysplastic syndromes (LR-MDS).

Author: Laille E., Fianchi L., Zhong J., La Torre I., Giagounidis A., Beach C., Skikne B., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Diez Campelo M., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., Mittelman M., Laille E., Fianchi L., Zhong J., La Torre I., Giagounidis A., Beach C., Skikne B., Garcia-Manero G., Santini V., Almeida A., Platzbecker U., Jonasova A., Silverman L., Falantes J., Reda G., Buccisano F., Fenaux P., Buckstein R., Diez Campelo M., Larsen S., Valcarcel D., Vyas P., Giai V., Oliva E.N., Shortt J., Niederwieser D., and Mittelman M.
Abstract: Background: MDS is characterized by bone marrow dysplasia and peripheral cytopenias of variable severity. Treatment (Tx) options are limited for LR-MDS patients (pts) with low blast counts but high-risk disease features (eg, RBC-TD anemia and thrombocytopenia). The phase III placebo (PBO)-controlled QUAZAR Lower-risk MDS trial (NCT01566695) assessed CC-486, an oral hypomethylating agent, in pts who were RBC-TD and thrombocytopenic at study entry. Aim(s): Describe clinical outcomes from the QUAZAR Lower-risk MDS trial. Method(s): Eligible pts were age >=18 yrs, with IPSS LR-MDS, average RBC transfusion requirement of >=2 units (U)/28 days (d) for 56d, and 2 platelet (PLT) counts <=75 x 109/L taken >=21d apart. Pts were randomized 1:1 to CC-486 300 mg or PBO QD for 21d per 28d Tx cycle (C). The primary endpoint was RBC transfusion independence (TI) lasting >=56d (IWG 2006). Key secondary endpoints were overall survival (OS), >=84d RBC-TI, and hematologic improvement in erythroid and PLT lineages (HI-E, HI-P). Planned enrollment was 386 pts. An imbalance of early deaths in the CC-486 arm led to a decision to close enrollment; the final sample size (N = 216) allowed comparison of RBC-TI between Tx arms with ~99% power. Result(s): At data cutoff all pts (CC-486 n = 107; PBO n = 109) completed >=12 mo of Tx or discontinued before 12 mo. Baseline (BL) characteristics were similar between Tx arms. Median age was 74 yrs (30-89), Hgb 8.1 g/dL (5.4-10.9), PLT count 25x109/L (5-73), ANC 1.3x109/L (0.1-25), and transfusion requirement 6.7 U/56d. All pts had IPSS INT-1 MDS. Significantly more pts in the CC-486 arm achieved RBC-TI for >=56d (31%, vs. 11% with PBO; P = 0.0002) (Table 1). Median RBC-TI durations in the CC-486 and PBO arms were 11.1 and 5.0 mo, respectively (P = 0.42). In the CC-486 and PBO arms, 42% and 31%, respectively, had RBC transfusion reductions of >=4 U from BL, sustained for a median of 10.0 and 2.3 mo (P = 0.0001). While HI-E rates were comparable (P = 0.1
Published: 2020

30. Evaluation of pregnancies after allogeneic stem cell transplantation during the last 15years in Germany

Author: Sockel, K., Frank, S., Neu, A., Ditschkowski, M., Hilgendorf, I., Goeckenjan, M., Stoelzel, F., Middeke, J. M., Kroeger, N., Ayuketang, Ayuk F., Eder, M., Bethge, W., Finke, J., Bertz, H., Kobbe, G., Kaufmann, M., Platzbecker, U., Beverungen, D., Schmid, C., von Bonin, M., Heberling, L., Teipel, R., Bug, G., Fraccaroli, A., Tischer, J., Holler, B., Wolff, D., Luft, T., Roesler, W., Schaefer-Eckart, K., Dressler, S., Scheid, C., Holtick, U., Klein, S., Blau, I. -W., Burchert, A., Wulf, G., Hasenkamp, J., Kaun, S., Wittke, C., Wortmann, F., Bornhaeuser, M., Schetelig, J., Sockel, K., Frank, S., Neu, A., Ditschkowski, M., Hilgendorf, I., Goeckenjan, M., Stoelzel, F., Middeke, J. M., Kroeger, N., Ayuketang, Ayuk F., Eder, M., Bethge, W., Finke, J., Bertz, H., Kobbe, G., Kaufmann, M., Platzbecker, U., Beverungen, D., Schmid, C., von Bonin, M., Heberling, L., Teipel, R., Bug, G., Fraccaroli, A., Tischer, J., Holler, B., Wolff, D., Luft, T., Roesler, W., Schaefer-Eckart, K., Dressler, S., Scheid, C., Holtick, U., Klein, S., Blau, I. -W., Burchert, A., Wulf, G., Hasenkamp, J., Kaun, S., Wittke, C., Wortmann, F., Bornhaeuser, M., and Schetelig, J.
Published: 2020

31. Changes in the burden of disease in treated and untreated patients in the German cohort of the International Registry of Paroxysmal Nocturnal Hemoglobinuria (PNH) - a 2020 Update

Author: Roeth, A., Raiser, C., Panse, J., Steinbach, Cicalo F., Sockel, K., Haferlach, T., Huebel, K., Blau, I. W., Casper, J., Platzbecker, U., Ganser, A., Hoechsmann, B., Schrezenmeier, H., Roeth, A., Raiser, C., Panse, J., Steinbach, Cicalo F., Sockel, K., Haferlach, T., Huebel, K., Blau, I. W., Casper, J., Platzbecker, U., Ganser, A., Hoechsmann, B., and Schrezenmeier, H.
Published: 2020

32. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Author: Bernard, E., Nannya, Y., Hasserjian, R.P., Devlin, S.M., Tuechler, H., Medina-Martinez, J.S., Yoshizato, T., Shiozawa, Y., Saiki, R., Malcovati, L., Levine, M.F., Arango, J.E., Zhou, Y, Solé, F., Cargo, C.A., Haase, D., Creignou, M., Germing, U., Zhang, Y., Gundem, G., Sarian, A., Loosdrecht, A.A. van de, Jädersten, M., Tobiasson, M., Kosmider, O., Follo, M.Y., Thol, F., Pinheiro, R.F., Santini, V., Kotsianidis, I., Boultwood, J., Santos, F.P.S., Schanz, J., Kasahara, S., Ishikawa, T., Tsurumi, H., Takaori-Kondo, A., Kiguchi, T., Polprasert, C., Bennett, J.M., Klimek, V.M., Savona, M.R., Belickova, M., Ganster, C., Palomo, L., Sanz, G., Ades, L., Porta, M.G. Della, Smith, A.G., Werner, Y., Patel, M., Viale, A., Vanness, K., Neuberg, D.S., Stevenson, K.E., Menghrajani, K., Bolton, K.L., Fenaux, P., Pellagatti, A., Platzbecker, U., Heuser, M., Valent, P., Chiba, S., Miyazaki, Y., Finelli, C., Voso, M.T., Shih, L.Y., Fontenay, M., Jansen, J.H., Cervera, J., Atsuta, Y., Gattermann, N., Ebert, B.L., Bejar, R., Greenberg, P.L., Cazzola, M., Hellström-Lindberg, E., Ogawa, S., Papaemmanuil, E., Bernard, E., Nannya, Y., Hasserjian, R.P., Devlin, S.M., Tuechler, H., Medina-Martinez, J.S., Yoshizato, T., Shiozawa, Y., Saiki, R., Malcovati, L., Levine, M.F., Arango, J.E., Zhou, Y, Solé, F., Cargo, C.A., Haase, D., Creignou, M., Germing, U., Zhang, Y., Gundem, G., Sarian, A., Loosdrecht, A.A. van de, Jädersten, M., Tobiasson, M., Kosmider, O., Follo, M.Y., Thol, F., Pinheiro, R.F., Santini, V., Kotsianidis, I., Boultwood, J., Santos, F.P.S., Schanz, J., Kasahara, S., Ishikawa, T., Tsurumi, H., Takaori-Kondo, A., Kiguchi, T., Polprasert, C., Bennett, J.M., Klimek, V.M., Savona, M.R., Belickova, M., Ganster, C., Palomo, L., Sanz, G., Ades, L., Porta, M.G. Della, Smith, A.G., Werner, Y., Patel, M., Viale, A., Vanness, K., Neuberg, D.S., Stevenson, K.E., Menghrajani, K., Bolton, K.L., Fenaux, P., Pellagatti, A., Platzbecker, U., Heuser, M., Valent, P., Chiba, S., Miyazaki, Y., Finelli, C., Voso, M.T., Shih, L.Y., Fontenay, M., Jansen, J.H., Cervera, J., Atsuta, Y., Gattermann, N., Ebert, B.L., Bejar, R., Greenberg, P.L., Cazzola, M., Hellström-Lindberg, E., Ogawa, S., and Papaemmanuil, E.
Abstract: Contains fulltext : 229615.pdf (Publisher’s version ) (Closed access)
Published: 2020

33. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Author: Bernard, E., Nannya, Y., Hasserjian, R.P., Devlin, S.M., Tuechler, H., Medina-Martinez, J.S., Yoshizato, T., Shiozawa, Y., Saiki, R., Malcovati, L., Levine, M.F., Arango, J.E., Zhou, Y, Solé, F., Cargo, C.A., Haase, D., Creignou, M., Germing, U., Zhang, Y., Gundem, G., Sarian, A., Loosdrecht, A.A. van de, Jädersten, M., Tobiasson, M., Kosmider, O., Follo, M.Y., Thol, F., Pinheiro, R.F., Santini, V., Kotsianidis, I., Boultwood, J., Santos, F.P.S., Schanz, J., Kasahara, S., Ishikawa, T., Tsurumi, H., Takaori-Kondo, A., Kiguchi, T., Polprasert, C., Bennett, J.M., Klimek, V.M., Savona, M.R., Belickova, M., Ganster, C., Palomo, L., Sanz, G., Ades, L., Porta, M.G. Della, Smith, A.G., Werner, Y., Patel, M., Viale, A., Vanness, K., Neuberg, D.S., Stevenson, K.E., Menghrajani, K., Bolton, K.L., Fenaux, P., Pellagatti, A., Platzbecker, U., Heuser, M., Valent, P., Chiba, S., Miyazaki, Y., Finelli, C., Voso, M.T., Shih, L.Y., Fontenay, M., Jansen, J.H., Cervera, J., Atsuta, Y., Gattermann, N., Ebert, B.L., Bejar, R., Greenberg, P.L., Cazzola, M., Hellström-Lindberg, E., Ogawa, S., Papaemmanuil, E., Bernard, E., Nannya, Y., Hasserjian, R.P., Devlin, S.M., Tuechler, H., Medina-Martinez, J.S., Yoshizato, T., Shiozawa, Y., Saiki, R., Malcovati, L., Levine, M.F., Arango, J.E., Zhou, Y, Solé, F., Cargo, C.A., Haase, D., Creignou, M., Germing, U., Zhang, Y., Gundem, G., Sarian, A., Loosdrecht, A.A. van de, Jädersten, M., Tobiasson, M., Kosmider, O., Follo, M.Y., Thol, F., Pinheiro, R.F., Santini, V., Kotsianidis, I., Boultwood, J., Santos, F.P.S., Schanz, J., Kasahara, S., Ishikawa, T., Tsurumi, H., Takaori-Kondo, A., Kiguchi, T., Polprasert, C., Bennett, J.M., Klimek, V.M., Savona, M.R., Belickova, M., Ganster, C., Palomo, L., Sanz, G., Ades, L., Porta, M.G. Della, Smith, A.G., Werner, Y., Patel, M., Viale, A., Vanness, K., Neuberg, D.S., Stevenson, K.E., Menghrajani, K., Bolton, K.L., Fenaux, P., Pellagatti, A., Platzbecker, U., Heuser, M., Valent, P., Chiba, S., Miyazaki, Y., Finelli, C., Voso, M.T., Shih, L.Y., Fontenay, M., Jansen, J.H., Cervera, J., Atsuta, Y., Gattermann, N., Ebert, B.L., Bejar, R., Greenberg, P.L., Cazzola, M., Hellström-Lindberg, E., Ogawa, S., and Papaemmanuil, E.
Abstract: Contains fulltext : 229615.pdf (Publisher’s version ) (Closed access)
Published: 2020

34. Changes in the burden of disease in treated and untreated patients in the German cohort of the International Registry of Paroxysmal Nocturnal Hemoglobinuria (PNH) - a 2020 Update

Author: Roeth, A., Raiser, C., Panse, J., Steinbach, Cicalo F., Sockel, K., Haferlach, T., Huebel, K., Blau, I. W., Casper, J., Platzbecker, U., Ganser, A., Hoechsmann, B., Schrezenmeier, H., Roeth, A., Raiser, C., Panse, J., Steinbach, Cicalo F., Sockel, K., Haferlach, T., Huebel, K., Blau, I. W., Casper, J., Platzbecker, U., Ganser, A., Hoechsmann, B., and Schrezenmeier, H.
Published: 2020

35. Evaluation of pregnancies after allogeneic stem cell transplantation during the last 15years in Germany

Author: Sockel, K., Frank, S., Neu, A., Ditschkowski, M., Hilgendorf, I., Goeckenjan, M., Stoelzel, F., Middeke, J. M., Kroeger, N., Ayuketang, Ayuk F., Eder, M., Bethge, W., Finke, J., Bertz, H., Kobbe, G., Kaufmann, M., Platzbecker, U., Beverungen, D., Schmid, C., von Bonin, M., Heberling, L., Teipel, R., Bug, G., Fraccaroli, A., Tischer, J., Holler, B., Wolff, D., Luft, T., Roesler, W., Schaefer-Eckart, K., Dressler, S., Scheid, C., Holtick, U., Klein, S., Blau, I. -W., Burchert, A., Wulf, G., Hasenkamp, J., Kaun, S., Wittke, C., Wortmann, F., Bornhaeuser, M., Schetelig, J., Sockel, K., Frank, S., Neu, A., Ditschkowski, M., Hilgendorf, I., Goeckenjan, M., Stoelzel, F., Middeke, J. M., Kroeger, N., Ayuketang, Ayuk F., Eder, M., Bethge, W., Finke, J., Bertz, H., Kobbe, G., Kaufmann, M., Platzbecker, U., Beverungen, D., Schmid, C., von Bonin, M., Heberling, L., Teipel, R., Bug, G., Fraccaroli, A., Tischer, J., Holler, B., Wolff, D., Luft, T., Roesler, W., Schaefer-Eckart, K., Dressler, S., Scheid, C., Holtick, U., Klein, S., Blau, I. -W., Burchert, A., Wulf, G., Hasenkamp, J., Kaun, S., Wittke, C., Wortmann, F., Bornhaeuser, M., and Schetelig, J.
Published: 2020

36. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: Final results of the randomized Italian-German APL0406 trial

Author: Platzbecker, U, Avvisati, G, Cicconi, L, Thiede, C, Paoloni, F, Vignetti, M, Ferrara, F, Divona, M, Albano, F, Efficace, F, Fazi, P, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Wattad, M, Lübbert, M, Brandts, C, Hänel, M, Röllig, C, Schmitz, N, Link, H, Frairia, C, Pogliani, E, Fozza, C, D'Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Döhner, K, Ganser, A, Döhner, H, Amadori, S, Mandelli, F, Ehninger, G, Schlenk, R, Lo-Coco, F, Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F., Platzbecker, U, Avvisati, G, Cicconi, L, Thiede, C, Paoloni, F, Vignetti, M, Ferrara, F, Divona, M, Albano, F, Efficace, F, Fazi, P, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Wattad, M, Lübbert, M, Brandts, C, Hänel, M, Röllig, C, Schmitz, N, Link, H, Frairia, C, Pogliani, E, Fozza, C, D'Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Döhner, K, Ganser, A, Döhner, H, Amadori, S, Mandelli, F, Ehninger, G, Schlenk, R, Lo-Coco, F, Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, and Lo-Coco F.
Abstract: Purpose: The initial results of the APL0406 trial showed that the combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods: The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 109/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results: Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively (P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively (P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion: These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.
Published: 2017

37. Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials

Author: Platzbecker, U., Fenaux, P., Ades, L., Giagounidis, A., Santini, V., Loosdrecht, A.A. van de, Witte, T.J.M. de, Steensma, D.P., Gloaguen, S., Platzbecker, U., Fenaux, P., Ades, L., Giagounidis, A., Santini, V., Loosdrecht, A.A. van de, Witte, T.J.M. de, Steensma, D.P., and Gloaguen, S.
Abstract: Contains fulltext : 202124.pdf (publisher's version ) (Open Access)
Published: 2019

38. Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials

Author: Platzbecker, U., Fenaux, P., Ades, L., Giagounidis, A., Santini, V., Loosdrecht, A.A. van de, Witte, T.J.M. de, Steensma, D.P., Gloaguen, S., Platzbecker, U., Fenaux, P., Ades, L., Giagounidis, A., Santini, V., Loosdrecht, A.A. van de, Witte, T.J.M. de, Steensma, D.P., and Gloaguen, S.
Abstract: Contains fulltext : 202124.pdf (publisher's version ) (Open Access)
Published: 2019

39. The Evolving Landscape of Biomarkers for Anti-PD-1 or Anti-PD-L1 Therapy

Author: Tunger, A., Sommer, U., Wehner, R., Kubasch, A. S., Grimm, M.-O., (0000-0002-8029-5755) Bachmann, M., Platzbecker, U., Bornhaeuser, M., Baretton, G., Schmitz, M., Tunger, A., Sommer, U., Wehner, R., Kubasch, A. S., Grimm, M.-O., (0000-0002-8029-5755) Bachmann, M., Platzbecker, U., Bornhaeuser, M., Baretton, G., and Schmitz, M.
Abstract: The administration of antibodies blocking the immune checkpoint molecules programmed cell death protein 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) has evolved as a very promising treatment option for cancer patients. PD-1/PD-L1 inhibition has significantly enhanced expansion, cytokine secretion, and cytotoxic activity of CD4(+) and CD8(+) T lymphocytes, resulting in enhanced antitumor responses. Anti-PD-1 or anti-PD-L1 therapy has induced tumor regression and improved clinical outcome in patients with different tumor entities, including melanoma, non-small-cell lung cancer, and renal cell carcinoma. These findings led to the approval of various anti-PD-1 or anti-PD-L1 antibodies for the treatment of tumor patients. However, the majority of patients have failed to respond to this treatment modality. Comprehensive immune monitoring of clinical trials led to the identification of potential biomarkers distinguishing between responders and non-responders, the discovery of modes of treatment resistance, and the design of improved immunotherapeutic strategies. In this review article, we summarize the evolving landscape of biomarkers for anti-PD-1 or anti-PD-L1 therapy.
Published: 2019

40. Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials.

Author: Platzbecker, U. and Platzbecker, U.
Subjects: All institutes and research themes of the Radboud University Medical Center., Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life Sciences.
Published: 2019

41. The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort

Author: Stahl, M., DeVeaux, M., Witte, T.J. de, Neukirchen, J., Sekeres, M.A., Brunner, A.M., Roboz, G.J., Steensma, D.P., Bhatt, V.R., Platzbecker, U., Cluzeau, T., Prata, P.H., Itzykson, R., Fenaux, P., Fathi, A.T., Smith, A., Germing, U., Ritchie, E.K., Verma, V., Nazha, A., Maciejewski, J.P., Podoltsev, N.A., Prebet, T., Santini, V., Gore, S.D., Komrokji, R.S., Zeidan, A.M., Stahl, M., DeVeaux, M., Witte, T.J. de, Neukirchen, J., Sekeres, M.A., Brunner, A.M., Roboz, G.J., Steensma, D.P., Bhatt, V.R., Platzbecker, U., Cluzeau, T., Prata, P.H., Itzykson, R., Fenaux, P., Fathi, A.T., Smith, A., Germing, U., Ritchie, E.K., Verma, V., Nazha, A., Maciejewski, J.P., Podoltsev, N.A., Prebet, T., Santini, V., Gore, S.D., Komrokji, R.S., and Zeidan, A.M.
Abstract: Item does not contain fulltext, Most studies of immunosuppressive therapy (IST) in myelodysplastic syndromes (MDS) are limited by small numbers and their single-center nature, and report conflicting data regarding predictors for response to IST. We examined outcomes associated with IST and predictors of benefit in a large international cohort of patients with MDS. Data were collected from 15 centers in the United States and Europe. Responses, including red blood cell (RBC) transfusion independence (TI), were assessed based on the 2006 MDS International Working Group criteria, and overall survival (OS) was estimated by Kaplan-Meier methods. Logistic regression models estimated odds for response and TI, and Cox Proportional Hazard models estimated hazards ratios for OS. We identified 207 patients with MDS receiving IST, excluding steroid monotherapy. The most common IST regimen was anti-thymocyte globulin (ATG) plus prednisone (43%). Overall response rate (ORR) was 48.8%, including 11.2% (95% confidence interval [CI], 6.5%-18.4%) who achieved a complete remission and 30% (95% CI, 22.3%-39.5%) who achieved RBC TI. Median OS was 47.4 months (95% CI, 37-72.3 months) and was longer for patients who achieved a response or TI. Achievement of RBC TI was associated with a hypocellular bone marrow (cellularity < 20%); horse ATG plus cyclosporine was more effective than rabbit ATG or ATG without cyclosporine. Age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST. IST leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows.
Published: 2018

42. The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort

Author: Stahl, M., DeVeaux, M., Witte, T.J. de, Neukirchen, J., Sekeres, M.A., Brunner, A.M., Roboz, G.J., Steensma, D.P., Bhatt, V.R., Platzbecker, U., Cluzeau, T., Prata, P.H., Itzykson, R., Fenaux, P., Fathi, A.T., Smith, A., Germing, U., Ritchie, E.K., Verma, V., Nazha, A., Maciejewski, J.P., Podoltsev, N.A., Prebet, T., Santini, V., Gore, S.D., Komrokji, R.S., Zeidan, A.M., Stahl, M., DeVeaux, M., Witte, T.J. de, Neukirchen, J., Sekeres, M.A., Brunner, A.M., Roboz, G.J., Steensma, D.P., Bhatt, V.R., Platzbecker, U., Cluzeau, T., Prata, P.H., Itzykson, R., Fenaux, P., Fathi, A.T., Smith, A., Germing, U., Ritchie, E.K., Verma, V., Nazha, A., Maciejewski, J.P., Podoltsev, N.A., Prebet, T., Santini, V., Gore, S.D., Komrokji, R.S., and Zeidan, A.M.
Abstract: Item does not contain fulltext, Most studies of immunosuppressive therapy (IST) in myelodysplastic syndromes (MDS) are limited by small numbers and their single-center nature, and report conflicting data regarding predictors for response to IST. We examined outcomes associated with IST and predictors of benefit in a large international cohort of patients with MDS. Data were collected from 15 centers in the United States and Europe. Responses, including red blood cell (RBC) transfusion independence (TI), were assessed based on the 2006 MDS International Working Group criteria, and overall survival (OS) was estimated by Kaplan-Meier methods. Logistic regression models estimated odds for response and TI, and Cox Proportional Hazard models estimated hazards ratios for OS. We identified 207 patients with MDS receiving IST, excluding steroid monotherapy. The most common IST regimen was anti-thymocyte globulin (ATG) plus prednisone (43%). Overall response rate (ORR) was 48.8%, including 11.2% (95% confidence interval [CI], 6.5%-18.4%) who achieved a complete remission and 30% (95% CI, 22.3%-39.5%) who achieved RBC TI. Median OS was 47.4 months (95% CI, 37-72.3 months) and was longer for patients who achieved a response or TI. Achievement of RBC TI was associated with a hypocellular bone marrow (cellularity < 20%); horse ATG plus cyclosporine was more effective than rabbit ATG or ATG without cyclosporine. Age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST. IST leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows.
Published: 2018

43. The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort

Author: Stahl, M., DeVeaux, M., Witte, T.J. de, Neukirchen, J., Sekeres, M.A., Brunner, A.M., Roboz, G.J., Steensma, D.P., Bhatt, V.R., Platzbecker, U., Cluzeau, T., Prata, P.H., Itzykson, R., Fenaux, P., Fathi, A.T., Smith, A., Germing, U., Ritchie, E.K., Verma, V., Nazha, A., Maciejewski, J.P., Podoltsev, N.A., Prebet, T., Santini, V., Gore, S.D., Komrokji, R.S., Zeidan, A.M., Stahl, M., DeVeaux, M., Witte, T.J. de, Neukirchen, J., Sekeres, M.A., Brunner, A.M., Roboz, G.J., Steensma, D.P., Bhatt, V.R., Platzbecker, U., Cluzeau, T., Prata, P.H., Itzykson, R., Fenaux, P., Fathi, A.T., Smith, A., Germing, U., Ritchie, E.K., Verma, V., Nazha, A., Maciejewski, J.P., Podoltsev, N.A., Prebet, T., Santini, V., Gore, S.D., Komrokji, R.S., and Zeidan, A.M.
Abstract: Item does not contain fulltext, Most studies of immunosuppressive therapy (IST) in myelodysplastic syndromes (MDS) are limited by small numbers and their single-center nature, and report conflicting data regarding predictors for response to IST. We examined outcomes associated with IST and predictors of benefit in a large international cohort of patients with MDS. Data were collected from 15 centers in the United States and Europe. Responses, including red blood cell (RBC) transfusion independence (TI), were assessed based on the 2006 MDS International Working Group criteria, and overall survival (OS) was estimated by Kaplan-Meier methods. Logistic regression models estimated odds for response and TI, and Cox Proportional Hazard models estimated hazards ratios for OS. We identified 207 patients with MDS receiving IST, excluding steroid monotherapy. The most common IST regimen was anti-thymocyte globulin (ATG) plus prednisone (43%). Overall response rate (ORR) was 48.8%, including 11.2% (95% confidence interval [CI], 6.5%-18.4%) who achieved a complete remission and 30% (95% CI, 22.3%-39.5%) who achieved RBC TI. Median OS was 47.4 months (95% CI, 37-72.3 months) and was longer for patients who achieved a response or TI. Achievement of RBC TI was associated with a hypocellular bone marrow (cellularity < 20%); horse ATG plus cyclosporine was more effective than rabbit ATG or ATG without cyclosporine. Age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST. IST leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows.
Published: 2018

44. Eltrombopag In Combination With Azacitidine For First-Line Treatment Of Mds Patients With Thrombocytopenia : The Randomized, Placebo-Controlled, Phase Iii, Support Study

Author: Dickinson, M., Cherif, Honar, Fenaux, P., Mittelman, M., Verma, A., Portella, M. S. O., Burgess, P., Platzbecker, U., Dickinson, M., Cherif, Honar, Fenaux, P., Mittelman, M., Verma, A., Portella, M. S. O., Burgess, P., and Platzbecker, U.
Published: 2017

45. Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel

Author: Witte, T.J.M. de, Bowen, D., Robin, M., Malcovati, L., Niederwieser, D., Yakoub-Agha, I., Mufti, G.J., Fenaux, P., Sanz, G., Martino, R., Alessandrino, E.P., Onida, F., Symeonidis, A., Passweg, J., Kobbe, G., Ganser, A., Platzbecker, U., Finke, J., Gelder, M. van, Loosdrecht, A.A. van de, Ljungman, P., Stauder, R., Volin, L., Deeg, H.J., Cutler, C., Saber, W., Champlin, R., Giralt, S., Anasetti, C., Kroger, N., Witte, T.J.M. de, Bowen, D., Robin, M., Malcovati, L., Niederwieser, D., Yakoub-Agha, I., Mufti, G.J., Fenaux, P., Sanz, G., Martino, R., Alessandrino, E.P., Onida, F., Symeonidis, A., Passweg, J., Kobbe, G., Ganser, A., Platzbecker, U., Finke, J., Gelder, M. van, Loosdrecht, A.A. van de, Ljungman, P., Stauder, R., Volin, L., Deeg, H.J., Cutler, C., Saber, W., Champlin, R., Giralt, S., Anasetti, C., and Kroger, N.
Abstract: Item does not contain fulltext, An international expert panel, active within the European Society for Blood and Marrow Transplantation, European LeukemiaNet, Blood and Marrow Transplant Clinical Trial Group, and the International Myelodysplastic Syndromes Foundation developed recommendations for allogeneic hematopoietic stem cell transplantation (HSCT) in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Disease risks scored according to the revised International Prognostic Scoring System (IPSS-R) and presence of comorbidity graded according to the HCT Comorbidity Index (HCT-CI) were recognized as relevant clinical variables for HSCT eligibility. Fit patients with higher-risk IPSS-R and those with lower-risk IPSS-R with poor-risk genetic features, profound cytopenias, and high transfusion burden are candidates for HSCT. Patients with a very high MDS transplantation risk score, based on combination of advanced age, high HCT-CI, very poor-risk cytogenetic and molecular features, and high IPSS-R score have a low chance of cure with standard HSCT and consideration should be given to treating these patients in investigational studies. Cytoreductive therapy prior to HSCT is advised for patients with >/=10% bone marrow myeloblasts. Evidence from prospective randomized clinical trials does not provide support for specific recommendations on the optimal high intensity conditioning regimen. For patients with contraindications to high-intensity preparative regimens, reduced intensity conditioning should be considered. Optimal timing of HSCT requires careful evaluation of the available effective nontransplant strategies. Prophylactic donor lymphocyte infusion (DLI) strategies are recommended in patients at high risk of relapse after HSCT. Immune modulation by DLI strategies or second HSCT is advised if relapse occurs beyond 6 months after HSCT.
Published: 2017

46. Allogeneic Stem Cell Transplantation for Patients Age >/= 70 Years with Myelodysplastic Syndrome: A Retrospective Study of the MDS Subcommittee of the Chronic Malignancies Working Party of the EBMT

Author: Heidenreich, S., Ziagkos, D., Wreede, L.C. de, Biezen, A. van, Finke, J., Platzbecker, U., Niederwieser, D., Einsele, H., Bethge, W., Schleuning, M., Beelen, D.W., Tischer, J., Nagler, A., Glass, B., Maertens, J., Yanez, L., Beguin, Y., Sill, H., Scheid, C., Stelljes, M., Ganser, A., Zachee, P., Selleslag, D., Witte, T.J.M. de, Robin, M., Kroger, N., Heidenreich, S., Ziagkos, D., Wreede, L.C. de, Biezen, A. van, Finke, J., Platzbecker, U., Niederwieser, D., Einsele, H., Bethge, W., Schleuning, M., Beelen, D.W., Tischer, J., Nagler, A., Glass, B., Maertens, J., Yanez, L., Beguin, Y., Sill, H., Scheid, C., Stelljes, M., Ganser, A., Zachee, P., Selleslag, D., Witte, T.J.M. de, Robin, M., and Kroger, N.
Abstract: Item does not contain fulltext, In this retrospective analysis we evaluated the outcome of 313 patients aged >/= 70 years in the registry of the European Group for Blood and Marrow Transplantation with myelodysplastic syndrome (MDS; n = 221) and secondary acute myeloid leukemia (n = 92) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from related (n = 79) or unrelated (n = 234) donors. Median age at HSCT was 72 years (range, 70 to 78). Conditioning regimen was nonmyeloablative (n = 54), reduced intensity (n = 207), or standard intensity (n = 52). Allogeneic HSCT for MDS patients >/= 70 years was increasingly performed over time. Although during 2000 to 2004 only 16 patients received HSCT, during 2011 to 2013 the number of transplantations increased to 181. The cumulative incidence of nonrelapse mortality at 1 year and relapse at 3 years was 32% and 28%, respectively, with a 3-year overall survival rate of 34%. Good performance, determined by Karnofsky performance status, and recipients' seronegativity for cytomegalovirus was associated with 3-year estimated overall survival rates of 43% (P = .01) and 46% (P = .002), respectively. Conditioning intensity did not impact survival. After careful patient selection, allogeneic HSCT can be offered to patients older than 70 years with MDS.
Published: 2017

47. Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial)

Author: Kroger, N., Iacobelli, S., Franke, G.N., Platzbecker, U., Uddin, R., Hubel, K., Scheid, C., Weber, T., Robin, M., Stelljes, M., Afanasyev, B., Heim, D., Deliliers, G.L., Onida, F., Dreger, P., Pini, M., Guidi, S., Volin, L., Gunther, A., Bethge, W., Poire, X., Kobbe, G., Os, M. van, Brand, R., Witte, T.J. de, Kroger, N., Iacobelli, S., Franke, G.N., Platzbecker, U., Uddin, R., Hubel, K., Scheid, C., Weber, T., Robin, M., Stelljes, M., Afanasyev, B., Heim, D., Deliliers, G.L., Onida, F., Dreger, P., Pini, M., Guidi, S., Volin, L., Gunther, A., Bethge, W., Poire, X., Kobbe, G., Os, M. van, Brand, R., and Witte, T.J. de
Abstract: Item does not contain fulltext, Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. Results Engraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC ( P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC ( P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC ( P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC ( P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC ( P = .58 and P = .08, respectively). Conclusion This prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.
Published: 2017

48. Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel

Author: Witte, T.J.M. de, Bowen, D., Robin, M., Malcovati, L., Niederwieser, D., Yakoub-Agha, I., Mufti, G.J., Fenaux, P., Sanz, G., Martino, R., Alessandrino, E.P., Onida, F., Symeonidis, A., Passweg, J., Kobbe, G., Ganser, A., Platzbecker, U., Finke, J., Gelder, M. van, Loosdrecht, A.A. van de, Ljungman, P., Stauder, R., Volin, L., Deeg, H.J., Cutler, C., Saber, W., Champlin, R., Giralt, S., Anasetti, C., Kroger, N., Witte, T.J.M. de, Bowen, D., Robin, M., Malcovati, L., Niederwieser, D., Yakoub-Agha, I., Mufti, G.J., Fenaux, P., Sanz, G., Martino, R., Alessandrino, E.P., Onida, F., Symeonidis, A., Passweg, J., Kobbe, G., Ganser, A., Platzbecker, U., Finke, J., Gelder, M. van, Loosdrecht, A.A. van de, Ljungman, P., Stauder, R., Volin, L., Deeg, H.J., Cutler, C., Saber, W., Champlin, R., Giralt, S., Anasetti, C., and Kroger, N.
Abstract: Item does not contain fulltext, An international expert panel, active within the European Society for Blood and Marrow Transplantation, European LeukemiaNet, Blood and Marrow Transplant Clinical Trial Group, and the International Myelodysplastic Syndromes Foundation developed recommendations for allogeneic hematopoietic stem cell transplantation (HSCT) in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Disease risks scored according to the revised International Prognostic Scoring System (IPSS-R) and presence of comorbidity graded according to the HCT Comorbidity Index (HCT-CI) were recognized as relevant clinical variables for HSCT eligibility. Fit patients with higher-risk IPSS-R and those with lower-risk IPSS-R with poor-risk genetic features, profound cytopenias, and high transfusion burden are candidates for HSCT. Patients with a very high MDS transplantation risk score, based on combination of advanced age, high HCT-CI, very poor-risk cytogenetic and molecular features, and high IPSS-R score have a low chance of cure with standard HSCT and consideration should be given to treating these patients in investigational studies. Cytoreductive therapy prior to HSCT is advised for patients with >/=10% bone marrow myeloblasts. Evidence from prospective randomized clinical trials does not provide support for specific recommendations on the optimal high intensity conditioning regimen. For patients with contraindications to high-intensity preparative regimens, reduced intensity conditioning should be considered. Optimal timing of HSCT requires careful evaluation of the available effective nontransplant strategies. Prophylactic donor lymphocyte infusion (DLI) strategies are recommended in patients at high risk of relapse after HSCT. Immune modulation by DLI strategies or second HSCT is advised if relapse occurs beyond 6 months after HSCT.
Published: 2017

49. Allogeneic Stem Cell Transplantation for Patients Age >/= 70 Years with Myelodysplastic Syndrome: A Retrospective Study of the MDS Subcommittee of the Chronic Malignancies Working Party of the EBMT

Author: Heidenreich, S., Ziagkos, D., Wreede, L.C. de, Biezen, A. van, Finke, J., Platzbecker, U., Niederwieser, D., Einsele, H., Bethge, W., Schleuning, M., Beelen, D.W., Tischer, J., Nagler, A., Glass, B., Maertens, J., Yanez, L., Beguin, Y., Sill, H., Scheid, C., Stelljes, M., Ganser, A., Zachee, P., Selleslag, D., Witte, T.J.M. de, Robin, M., Kroger, N., Heidenreich, S., Ziagkos, D., Wreede, L.C. de, Biezen, A. van, Finke, J., Platzbecker, U., Niederwieser, D., Einsele, H., Bethge, W., Schleuning, M., Beelen, D.W., Tischer, J., Nagler, A., Glass, B., Maertens, J., Yanez, L., Beguin, Y., Sill, H., Scheid, C., Stelljes, M., Ganser, A., Zachee, P., Selleslag, D., Witte, T.J.M. de, Robin, M., and Kroger, N.
Abstract: Item does not contain fulltext, In this retrospective analysis we evaluated the outcome of 313 patients aged >/= 70 years in the registry of the European Group for Blood and Marrow Transplantation with myelodysplastic syndrome (MDS; n = 221) and secondary acute myeloid leukemia (n = 92) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from related (n = 79) or unrelated (n = 234) donors. Median age at HSCT was 72 years (range, 70 to 78). Conditioning regimen was nonmyeloablative (n = 54), reduced intensity (n = 207), or standard intensity (n = 52). Allogeneic HSCT for MDS patients >/= 70 years was increasingly performed over time. Although during 2000 to 2004 only 16 patients received HSCT, during 2011 to 2013 the number of transplantations increased to 181. The cumulative incidence of nonrelapse mortality at 1 year and relapse at 3 years was 32% and 28%, respectively, with a 3-year overall survival rate of 34%. Good performance, determined by Karnofsky performance status, and recipients' seronegativity for cytomegalovirus was associated with 3-year estimated overall survival rates of 43% (P = .01) and 46% (P = .002), respectively. Conditioning intensity did not impact survival. After careful patient selection, allogeneic HSCT can be offered to patients older than 70 years with MDS.
Published: 2017

50. Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial)

Author: Kroger, N., Iacobelli, S., Franke, G.N., Platzbecker, U., Uddin, R., Hubel, K., Scheid, C., Weber, T., Robin, M., Stelljes, M., Afanasyev, B., Heim, D., Deliliers, G.L., Onida, F., Dreger, P., Pini, M., Guidi, S., Volin, L., Gunther, A., Bethge, W., Poire, X., Kobbe, G., Os, M. van, Brand, R., Witte, T.J. de, Kroger, N., Iacobelli, S., Franke, G.N., Platzbecker, U., Uddin, R., Hubel, K., Scheid, C., Weber, T., Robin, M., Stelljes, M., Afanasyev, B., Heim, D., Deliliers, G.L., Onida, F., Dreger, P., Pini, M., Guidi, S., Volin, L., Gunther, A., Bethge, W., Poire, X., Kobbe, G., Os, M. van, Brand, R., and Witte, T.J. de
Abstract: Item does not contain fulltext, Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. Results Engraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC ( P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC ( P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC ( P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC ( P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC ( P = .58 and P = .08, respectively). Conclusion This prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.
Published: 2017

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