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1. The new WHO 2022 and ICC proposals for the classification of myelodysplastic neoplasms. Validation based on the Düsseldorf MDS Registry and proposals for a merged classification

Author

Nachtkamp, K., Strupp, C., Vukelja, M., Kasprzak, A., Haase, D., Ganster, C., Hildebrandt, B., Betz, B., Giagounidis, A., Aul, C., Blum, S., Hofmann, W. K., Pfeilstöcker, M., Valent, P., Lübbert, M., Seidl, M., Rudelius, M., Stauder, R., Krieger, O., Götze, K. S., Bobak, J., Kündgen, A., Schulz, F., Dietrich, S., Kobbe, G., Gattermann, N., and Germing, U.

Published
2024
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2. Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification—an approach to classification of patients with t-MDS

Author

Kuendgen, A., Nomdedeu, M., Tuechler, H., Garcia-Manero, G., Komrokji, R. S., Sekeres, M. A., Della Porta, M. G., Cazzola, M., DeZern, A. E., Roboz, G. J., Steensma, D. P., Van de Loosdrecht, A. A., Schlenk, R. F., Grau, J., Calvo, X., Blum, S., Pereira, A., Valent, P., Costa, D., Giagounidis, A., Xicoy, B., Döhner, H., Platzbecker, U., Pedro, C., Lübbert, M., Oiartzabal, I., Díez-Campelo, M., Cedena, M. T., Machherndl-Spandl, S., López-Pavía, M., Baldus, C. D., Martinez-de-Sola, M., Stauder, R., Merchan, B., List, A., Ganster, C., Schroeder, T., Voso, M. T., Pfeilstöcker, M., Sill, H., Hildebrandt, B., Esteve, J., Nomdedeu, B., Cobo, F., Haas, R., Sole, F., Germing, U., Greenberg, P. L., Haase, D., and Sanz, G.

Published
2021
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5. ESMO Consensus Conference on malignant lymphoma: general perspectives and recommendations for the clinical management of the elderly patient with malignant lymphoma

Author

Buske, Christian, Dreyling, Martin, Ferreri, Andrés J M, Fields, Paul, Gaidano, Gianluca, Goede, Valentin, Hutchings, Martin, Ladetto, Marco, Le Gouill, Steven, Luminari, Stefano, Mey, Ulrich, de Nully Brown, Peter, Pfreundschuh, Michael, Pott, Christiane, Schmitz, Norbert, Soubeyran, Pierre, Spina, Michele, Stauder, Reinhard, Balari, Anna Sureda, Trněný, Marek, van Imhoff, Gustaaf, Walewski, Jan, Wedding, Ulrich, Zamò, Alberto, Zucca, Emanuele, Buske, C., Hutchings, M., Ladetto, M., Goede, V., Mey, U., Soubeyran, P., Spina, M., Stauder, R., Trněný, M., Wedding, U., and Fields, P.

Published
2018
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7. Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment: IMPROVED PROGNOSIS OF PATIENTS WITH MDS OVER FOUR DECADES: ANALYSIS FROM THE GERMAN MDS REGISTRY

Author

Kasprzak, A., primary, Strupp, C., additional, Haase, D., additional, Ganster, C., additional, Pfeilstöcker, M., additional, Blum, S., additional, Hofmann, W.-K., additional, Platzbecker, U., additional, Valent, P., additional, Beier, F., additional, Götze, K., additional, Parmentier, S., additional, Lübbert, M., additional, Stauder, R., additional, Thol, F., additional, Giagounidis, A., additional, Tüchler, H., additional, Lauseker, M., additional, Gattermann, N., additional, Kobbe, G., additional, Nachtkamp, K., additional, and Germing, U., additional

Published
2023
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8. Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment: A STEP TOWARDS IDENTIFICATION AND CAUSAL INTERPRETATION OF THERAPY-RELATED MDS (T-MDS)

Author

Kuendgen, A., primary, Nomdedeu, M., additional, Tuechler, H., additional, Garcia-Manero, G., additional, Komrokji, R., additional, Sekeres, M., additional, Della Porta, M., additional, Cazzola, M., additional, Dezern, A., additional, Roboz, G., additional, Steensma, D., additional, Van De Loosdrecht, A., additional, Malcovati, L., additional, Schlenk, R., additional, Grau, J., additional, Calvo, X., additional, Blum, S., additional, Pereira, A., additional, Valent, P., additional, Costa, D., additional, Giagounidis, A., additional, Xicoy, B., additional, Döhner, H., additional, Platzbecker, U., additional, Pedro, C., additional, Lübbert, M., additional, Oiartzabal, I., additional, Diez-Campelo, M., additional, Cedena, M.T., additional, Machherndl-Spandl, S., additional, Lopez-Pavia, M., additional, Martinez-De-Sola, M., additional, Stauder, R., additional, Merchan, B., additional, Ganster, C., additional, Schroeder, T., additional, Voso, M.T., additional, Pfeilstöcker, M., additional, Sill, H., additional, Hildebrandt, B., additional, Esteve, J., additional, Cobo, F., additional, Solé, F., additional, Germing, U., additional, Greenberg, P., additional, Haase, D., additional, and Sanz, G., additional

Published
2023
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12. Cause of death and excess mortality in patients with lower-risk myelodysplastic syndromes (MDS): A report from the European MDS registry.

Author

Mądry, K., Lis, K., Fenaux, P., Bowen, D., Symeonidis, A., Mittelman, M., Stauder, R., Čermák, J., Sanz, G., Hellström-Lindberg, E., Langemeijer, S.M.C., Malcovati, L., Germing, U., Holm, M.S., Guerci-Bresler, A., Culligan, D., Sanhes, L., Kotsianidis, I., Marrewijk, C. van, Crouch, S., Witte, T.J. de, Smith, A, Mądry, K., Lis, K., Fenaux, P., Bowen, D., Symeonidis, A., Mittelman, M., Stauder, R., Čermák, J., Sanz, G., Hellström-Lindberg, E., Langemeijer, S.M.C., Malcovati, L., Germing, U., Holm, M.S., Guerci-Bresler, A., Culligan, D., Sanhes, L., Kotsianidis, I., Marrewijk, C. van, Crouch, S., Witte, T.J. de, and Smith, A

Abstract

01 februari 2023, Item does not contain fulltext, Information on causes of death (CoDs) and the impact of myelodysplastic syndromes (MDS) on survival in patients with lower-risk MDS (LR-MDS) is limited. A better understanding of the relationship between disease characteristics, clinical interventions and CoDs may improve outcomes of patients with LR-MDS. We prospectively collected data on patients with LR-MDS in the European MDS registry from 2008 to 2019. Clinical, laboratory and CoDs data were obtained. To examine MDS-specific survival, relative survival (RS) was estimated using national life tables. Of 2396 evaluated subjects, 900 died (median overall survival [OS]: 4.7 years; median follow-up: 3.5 years). The most common CoDs were acute myeloid leukaemia/MDS (20.1%), infection (17.8%) and cardiovascular disease (CVD; 9.8%). Patients with isolated del(5q) and with red cell transfusion needed during the disease course, had a higher risk of fatal CVD. The 5-year OS was 47.3% and the 5-year RS was 59.6%, indicating that most patients died due to their underlying MDS. Older patients (aged >80 years) and the lowest-risk patients were more likely to die from competing causes. This study shows that MDS and its related complications play crucial role in the outcome of patients with LR-MDS.

Published
2023

13. 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

14. Raising the standards of patient-centered outcomes research in myelodysplastic syndromes: Clinical utility and validation of the subscales of the QUALMS from the MDS-RIGHT project.

Author

Efficace, F., Koinig, K., Cottone, F., Bowen, D., Mittelman, M., Sommer, K., Langemeijer, S.M., Culligan, D., Filanovsky, K., Storck, M., Smith, A, Marrewijk, C. van, Dugas, M., Stojkov, I., Siebert, U., Witte, T.J. de, Stauder, R., Efficace, F., Koinig, K., Cottone, F., Bowen, D., Mittelman, M., Sommer, K., Langemeijer, S.M., Culligan, D., Filanovsky, K., Storck, M., Smith, A, Marrewijk, C. van, Dugas, M., Stojkov, I., Siebert, U., Witte, T.J. de, and Stauder, R.

Abstract

Item does not contain fulltext, BACKGROUND: Clinical decision-making for patients with myelodysplastic syndromes (MDS) is challenging, and both disease and treatment effects heavily impact health-related quality of life (HRQoL) of these patients. Therefore, disease-specific HRQoL measures can be critical to harness the patient voice in MDS research. METHODS: We report a prospective international validation study of the Quality of Life in Myelodysplasia Scale (QUALMS) with a main focus on providing information on the psychometric characteristics of its three subscales: physical burden (QUALMS-P), emotional burden (QUALMS-E), and benefit finding (QUALMS-BF). The analysis is based on patients enrolled from three European countries and Israel, participating to the MDS-RIGHT Project. The scale structure and psychometric properties of the QUALMS were assessed. RESULTS: Overall, 270 patients with a median age of 74 years were analyzed and the majority of them (60.3%) had a low MDS-Comorbidity Index score. Results of the confirmatory factor analysis supported the underlying scale structure of the QUALMS, which, in addition to a total score, includes three subscales: QUALMS-P, QUALMS-E, and the QUALMS-BF. The QUALMS-P exhibited the highest Cronbach's alpha coefficients. Discriminant validity analysis indicated good results with the QUALMS-P and QUALMS-E distinguishing between patients with different performance status, comorbidity, anemia, and transfusion dependency status. No floor and ceiling effects were observed. Responsiveness to change analysis supported the validity of the measure. Patients with a hemoglobin (Hb) level of <11 g/dL at study entry, who subsequently showed an improvement in their Hb levels, also reported a mean score change of 9 and 8 points (scales ranging between 0 and 100) in the expected direction of the QUALMS-E and QUALMS-P, respectively. CONCLUSIONS: Our study provides additional validation data on the QUALMS from the international MDS-RIGHT Project. The use of this disease-spec

Published
2023

15. Accuracy of physician assessment of treatment preferences and health status in elderly patients with higher-risk myelodysplastic syndromes

Author

Caocci, G., Voso, M.T., Angelucci, E., Stauder, R., Cottone, F., Abel, G., Nguyen, K., Platzbecker, U., Beyne-Rauzy, O., Gaidano, G., Invernizzi, R., Molica, S., Criscuolo, M., Breccia, M., Lübbert, M., Sanpaolo, G., Buccisano, F., Ricco, A., Palumbo, G.A., Niscola, P., Zhang, H., Fenu, S., La Nasa, G., Mandelli, F., and Efficace, F.

Published
2015
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17. P091 - Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment: A STEP TOWARDS IDENTIFICATION AND CAUSAL INTERPRETATION OF THERAPY-RELATED MDS (T-MDS)

Author

Kuendgen, A., Nomdedeu, M., Tuechler, H., Garcia-Manero, G., Komrokji, R., Sekeres, M., Della Porta, M., Cazzola, M., Dezern, A., Roboz, G., Steensma, D., Van De Loosdrecht, A., Malcovati, L., Schlenk, R., Grau, J., Calvo, X., Blum, S., Pereira, A., Valent, P., Costa, D., Giagounidis, A., Xicoy, B., Döhner, H., Platzbecker, U., Pedro, C., Lübbert, M., Oiartzabal, I., Diez-Campelo, M., Cedena, M.T., Machherndl-Spandl, S., Lopez-Pavia, M., Martinez-De-Sola, M., Stauder, R., Merchan, B., Ganster, C., Schroeder, T., Voso, M.T., Pfeilstöcker, M., Sill, H., Hildebrandt, B., Esteve, J., Cobo, F., Solé, F., Germing, U., Greenberg, P., Haase, D., and Sanz, G.

Published
2023
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18. P089 - Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment: IMPROVED PROGNOSIS OF PATIENTS WITH MDS OVER FOUR DECADES: ANALYSIS FROM THE GERMAN MDS REGISTRY

Author

Kasprzak, A., Strupp, C., Haase, D., Ganster, C., Pfeilstöcker, M., Blum, S., Hofmann, W.-K., Platzbecker, U., Valent, P., Beier, F., Götze, K., Parmentier, S., Lübbert, M., Stauder, R., Thol, F., Giagounidis, A., Tüchler, H., Lauseker, M., Gattermann, N., Kobbe, G., Nachtkamp, K., and Germing, U.

Published
2023
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20. Determinants of low health-related quality of life in patients with myelodysplastic syndromes: EUMDS registry study

Author

Stojkov, I., Conrads-Frank, A., Rochau, U., Arvandi, M., Koinig, K.A., Schomaker, M., Mittelman, M., Fenaux, P., Bowen, D., Sanz, G.F., Malcovati, L., Langemeijer, S.M.C., Germing, U., Madry, K., Guerci-Bresler, A., Culligan, D.J., Kotsianidis, I., Sanhes, L., Mills, J., Puntscher, S., Schmid, D., Marrewijk, C.J. van, Smith, A, Efficace, F., Witte, T.J. de, Stauder, R., and Siebert, U.

Subjects
Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], All institutes and research themes of the Radboud University Medical Center, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Abstract

Item does not contain fulltext Patients with myelodysplastic syndromes (MDS) frequently experience a significant symptom burden, which reduces health-related quality of life (HRQoL). We aimed to identify determinants of low HRQoL in patients recently diagnosed with MDS, for guiding early intervention strategies. We evaluated longitudinal data in 2205 patients with MDS during their first year after diagnosis. Median values of EQ-5D 3-level (EQ-5D-3L) index (0.78) and visual analog scale (VAS) score (0.70) were used as thresholds for low HRQoL. In addition, the 5 dimensions of EQ-5D-3L were analyzed for impairments (any level vs "no problem" category). After multiple imputation of missing values, we used generalized estimating equations (GEE) to estimate odds ratios (OR) for univariable determinant screening (P < .15), and to subsequently derive multivariable models for low HRQoL with 95% confidence intervals (CI). Multivariable GEE analysis showed the following independent determinants (OR, 95% CI) for low EQ-5D index: increased age (60-75 years: 1.33, 1.01-1.75; >75: 1.84, 1.39-2.45), female sex (1.70, 1.43-2.03), high serum ferritin level (≥1000 vs ≤300 μg/L: 1.41, 1.06-1.87), comorbidity burden (per unit: 1.11, 1.02-1.20), and reduced Karnofsky performance status (KPS, per 10 units: 0.62, 0.58-0.67). For low VAS score, additional determinants were transfusion dependence (1.53, 1.03-2.29), low hemoglobin

Published
2022

25. Erythropoietin stimulation agents significantly improves outcome in lower risk MDS

Author

Garelius, H K G, Smith, Alexandra Gwen, Bagguley, Timothy Charles, Taylor, Adele, Fenaux, Pierre, Bowen, D., Symeonidis, Argyris, MIttelmann, M, Stauder, R, Čermák, Jaroslav, Sanz, Guillermo, Langemeijer, Saskia, Malcovati, Luca, Germing, Ulrich, Itzykson, Raphael, Guerci-Bresler, Agnès, Culligan, Dominic, Kotsianidis, Ioannis, Koinig, Karin A., van Marrewijk, Corine, Crouch, Simon, de Witte, Theo, and Hellstrom-Lindberg, E

Abstract

The EUMDS Registry started in 2008 as a prospective, non-interventional longitudinal study, enrolling newly diagnosed patients with IPSS low or intermediate-1 MDS from 16 European countries and Israel.

Published
2022

26. Prevalence and possible causes of anemia in the elderly: a cross-sectional analysis of a large European university hospital cohort

Author

Bach V, Schruckmayer G, Sam I, Kemmler G, and Stauder R

Subjects
Anemia, elderly, anemia prevalence, causes of anemia, MDS, Geriatrics, RC952-954.6
Abstract

Veronika Bach,1 Guenter Schruckmayer,1 Ines Sam,1 Georg Kemmler,2 Reinhard Stauder11Department of Internal Medicine V (Hematology and Oncology), 2Department of Biological Psychiatry, Innsbruck Medical University, Innsbruck, AustriaBackground: Anemia in later life is associated with increased morbidity and mortality. The purpose of this study was to evaluate the prevalence and possible causes of anemia in the elderly in a well defined hospital cohort.Methods: Participants in this cross-sectional, retrospective analysis included all inpatients and outpatients aged ≥64 years with complete blood counts treated at Innsbruck Medical University Hospital between October 1, 2004 and September 29, 2005 (n=19,758, median age 73 years).Results: According to World Health Organization criteria, 21.1% of these patients were anemic, ie, 30.7% and 37.0% at 80+ years and 90+ years, respectively. The prevalence of anemia was significantly correlated with advanced age (r=0.21; P

Published
2014

27. S168: ERYTHROPOIETIN STIMULATION AGENTS SIGNIFICANTLY IMPROVES OUTCOME IN LOWER RISK MDS.

Author

Garelius, H., primary, Smith, A., additional, Bagguley, T., additional, Taylor, A., additional, Fenaux, P., additional, Bowen, D., additional, Symeonidis, A., additional, Mittelmann, M., additional, Stauder, R., additional, Čermák, J., additional, Sanz, G., additional, Langemeijer, S., additional, Malcovati, L., additional, Germing, U., additional, Itzykson, R., additional, Guerci-Bresler, A., additional, Culligan, D., additional, Kotsianidis, I., additional, Koinig Mag, K., additional, van Marrewijk, C., additional, Crouch, S., additional, de Witte, T., additional, and Hellström-Lindberg, E., additional

Published
2022
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28. Erythropoiesis‐stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower‐risk myelodysplastic syndrome

Author

Garelius, H. K. G., Johnston, W. T., Smith, A. G., Park, S., de Swart, L., Fenaux, P., Symeonidis, A., Sanz, G., Čermák, J., Stauder, R., Malcovati, L., Mittelman, M., van de Loosdrecht, A. A., van Marrewijk, C. J., Bowen, D., Crouch, S., de Witte, T. J. M., and Hellström‐Lindberg, E.

Published
2017
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29. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM)

Author

Della Porta, M G, Tuechler, H, Malcovati, L, Schanz, J, Sanz, G, Garcia-Manero, G, Solé, F, Bennett, J M, Bowen, D, Fenaux, P, Dreyfus, F, Kantarjian, H, Kuendgen, A, Levis, A, Cermak, J, Fonatsch, C, Le Beau, M M, Slovak, M L, Krieger, O, Luebbert, M, Maciejewski, J, Magalhaes, S M M, Miyazaki, Y, Pfeilstöcker, M, Sekeres, M A, Sperr, W R, Stauder, R, Tauro, S, Valent, P, Vallespi, T, van de Loosdrecht, A A, Germing, U, Haase, D, Greenberg, P L, and Cazzola, M

Published
2015
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32. Treatment of Centroblastic-Centrocytic and Centrocytic Lymphomas at Advanced Stages — Results of the German Low-Grade Lymphoma Study Group

Author

Hiddemann, W., Unterhalt, M., Herrmann, R., Tiemann, M., Parwaresch, R., Stein, H., Trümper, L., Nahler, M., Reuss-Borst, M., Tirier, C., Neubauer, A., Freund, M., Kreuser, E.-D., Dietzfelbinger, H., Bodenstein, H., Engert, A., Stauder, R., Eimermacher, H., Landys, K., Hiddemann, W., editor, Büchner, T., editor, Wörmann, B., editor, Ritter, J., editor, Creutzig, U., editor, Keating, M., editor, and Plunkett, W., editor

Published
1998
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33. Therapie der zentroblastisch-zentrozytischen und zentrozytischen Lymphome in fortgeschrittenen Stadien — Ergebnisse der Deutschen Studiengruppe zur Behandlung niedrigmaligner Lymphome

Author

Hiddemann, W., Unterhalt, M., Herrmann, R., Tiemann, M., Parwaresch, R., Stein, H., Trümper, L., Nahler, M., Reuss-Borst, M., Tirier, C., Neubauer, A., Freund, M., Kreuser, E.-D., Dietzfelbinger, H., Bodenstein, H., Engert, A., Stauder, R., Eimermacher, H., Landys, K., HÖffkes, Heinz-Gert, editor, and Uppenkamp, Michael, editor

Published
1997
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37. Alemtuzumab in chronic lymphocytic leukemia: final results of a large observational multicenter study in mostly pretreated patients

Author

Fiegl, M., Stauder, R., Steurer, M., Mian, M., Hopfinger, G., Brychtova, Y., Skrabs, C., Zabernigg, A., Schmid, F., Haslbaur, F., Winder, G., Walder, A., Lang, A., Voskova, D., Greil, R., Mayer, J., Gastl, G., and for The Austrian Collaborative Study Group on Alemtuzumab in Chronic Lymphocytic Leukemia, in cooperation with The Czech Leukemia Study Group for Life, CELL

Published
2014
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38. O29 - Topic: AS02-Epidemiology: COMPARISON OF CYTOGENETIC ABERRATIONS IN 1590 PATIENTS WITH THERAPY-RELATED MDS (T-MDS) AND 4738 PATIENTS FROM THE REVISED INTERNATIONAL PROGNOSTIC SCORING SYSTEM DATABASE WITH PRIMARY-MDS (P-MDS)

Author

Kuendgen, A., Nomdedeu, M., Tuechler, H., Garcia-Manero, G., Komrokji, R., Sekeres, M., Della Porta, M., Cazzola, M., Malcovati, L., Dezern, A., Roboz, G., Steensma, D., Haase, D., Stauder, R., Cedena, M.T., Van De Loosdrecht, A., Schlenk, R., Blum, S., Grau, J., Calvo, X., Valent, P., Costa, D., Pereira, A., Xicoy, B., Döhner, H., Platzbecker, U., Giagounidis, A., Pedro, C., Lübbert, M., Oiartzabal, I., Díez-Campelo, M., Machherndl-Spandl, S., Lopez-Pavia, M., Martinez-De-Sola, M., Merchan, B., Ganster, C., Schroeder, T., Voso, M.T., Hildebrandt, B., Esteve, J., Nomdedeu, B., Cobo, F., Haas, R., Sole, F., Germing, U., Greenberg, P., Sill, H., Pfeilstöcker, M., and Sanz, G.

Published
2021
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39. O08 - Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment: LYMPHOPENIA IS HIGHLY PREVALENT IN MDS AND PROVIDES ADDITIONAL PROGNOSTIC INFORMATION FOR IPSS-R VERY-LOW AND LOW-RISK PATIENTS. AN ANALYSIS FROM THE EU-MDS REGISTRY

Author

Silzle, T., Taylor, A., De Witte, T., Malcovati, L., Fenaux, P., Bowen, D., Symeonidis, A., Mittelman, M., Stauder, R., Cermak, J., Sanz, G., Hellström-Lindberg, E., Langemeijer, S., Holm, M. Skov, Madry, K., Tatic, A., Almeida, A. Medina, Savic, A., Rogulj, I. Mandac, Germing, U., and Smith, A.

Published
2021
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40. Non-Hodgkin-Lymphome

Author

Huber, H., Fasching, B., Pohl, P., Nachbaur, D., Pastner, D., Stauder, R., Faber, V., Müller-Hermelink, H. K., Huber, Heinz, editor, Löffler, Helmut, editor, and Pastner, Dorothea, editor

Published
1992
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43. Toxic iron species in lower-risk myelodysplastic syndrome patients : course of disease and effects on outcome

Author

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

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

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

Published
2021

44. Topic: AS02-Epidemiology

Author

Kuendgen, A., primary, Nomdedeu, M., additional, Tuechler, H., additional, Garcia-Manero, G., additional, Komrokji, R., additional, Sekeres, M., additional, Della Porta, M., additional, Cazzola, M., additional, Malcovati, L., additional, Dezern, A., additional, Roboz, G., additional, Steensma, D., additional, Haase, D., additional, Stauder, R., additional, Cedena, M.T., additional, Van De Loosdrecht, A., additional, Schlenk, R., additional, Blum, S., additional, Grau, J., additional, Calvo, X., additional, Valent, P., additional, Costa, D., additional, Pereira, A., additional, Xicoy, B., additional, Döhner, H., additional, Platzbecker, U., additional, Giagounidis, A., additional, Pedro, C., additional, Lübbert, M., additional, Oiartzabal, I., additional, Díez-Campelo, M., additional, Machherndl-Spandl, S., additional, Lopez-Pavia, M., additional, Martinez-De-Sola, M., additional, Merchan, B., additional, Ganster, C., additional, Schroeder, T., additional, Voso, M.T., additional, Hildebrandt, B., additional, Esteve, J., additional, Nomdedeu, B., additional, Cobo, F., additional, Haas, R., additional, Sole, F., additional, Germing, U., additional, Greenberg, P., additional, Sill, H., additional, Pfeilstöcker, M., additional, and Sanz, G., additional

Published
2021
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45. Topic: AS06-Prognosis/AS06a-Prognostic factors of outcome and risk assessment

Author

Silzle, T., primary, Taylor, A., additional, De Witte, T., additional, Malcovati, L., additional, Fenaux, P., additional, Bowen, D., additional, Symeonidis, A., additional, Mittelman, M., additional, Stauder, R., additional, Cermak, J., additional, Sanz, G., additional, Hellström-Lindberg, E., additional, Langemeijer, S., additional, Holm, M. Skov, additional, Madry, K., additional, Tatic, A., additional, Almeida, A. Medina, additional, Savic, A., additional, Rogulj, I. Mandac, additional, Germing, U., additional, and Smith, A., additional

Published
2021
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46. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM)

Author

Porta, Della MG, Tuechler, H, Malcovati, L, Schanz, J, Sanz, G, Garcia-Manero, G, Solé, F, Bennett, J M, Bowen, D, Fenaux, P, Dreyfus, F, Kantarjian, H, Kuendgen, A, Levis, A, Cermak, J, Fonatsch, C, Le Beau, M M, Slovak, M L, Krieger, O, Luebbert, M, Maciejewski, J, Magalhaes, S MM, Miyazaki, Y, Pfeilstöcker, M, Sekeres, M A, Sperr, W R, Stauder, R, Tauro, S, Valent, P, Vallespi, T, van de Loosdrecht, A A, Germing, U, Haase, D, Greenberg, P L, and Cazzola, M

Published
2015
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48. Monosomal karyotype in MDS: explaining the poor prognosis?

Author

Schanz, J, Tüchler, H, Solé, F, Mallo, M, Luño, E, Cervera, J, Grau, J, Hildebrandt, B, Slovak, M L, Ohyashiki, K, Steidl, C, Fonatsch, C, Pfeilstöcker, M, Nösslinger, T, Valent, P, Giagounidis, A, Aul, C, Lübbert, M, Stauder, R, Krieger, O, Le Beau, M M, Bennett, J M, Greenberg, P, Germing, U, and Haase, D

Published
2013
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49. Toxic iron species in lower-risk myelodysplastic syndrome patients: course of disease and effects on outcome

Author

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

Published
2021

50. The anemia-independent impact of myelodysplastic syndromes on health-related quality of life

Author

Wouters, H, Conrads-Frank, A., Koinig, Karin A., Smith, A, Yu, G., Witte, T.J. de, Wolffenbuttel, B.H.R., Huls, G., Siebert, U., Stauder, R., Klauw, M.M. van der, Wouters, H, Conrads-Frank, A., Koinig, Karin A., Smith, A, Yu, G., Witte, T.J. de, Wolffenbuttel, B.H.R., Huls, G., Siebert, U., Stauder, R., and Klauw, M.M. van der

Abstract

Contains fulltext : 244105.pdf (Publisher’s version ) (Open Access), Myelodysplastic syndromes (MDS) are in the majority of cases characterized by anemia. Both anemia and MDS per se may directly contribute to impairments in health-related quality of life (HRQoL). In this study, we aimed to investigate the anemia-independent impact of MDS on HRQoL. We evaluated participants (≥ 50 years) from the large population-based Lifelines cohort (N = 44,694, mean age 59.0 ± 7.4 years, 43.6% male) and the European MDS Registry (EUMDS) (N = 1538, mean age 73.4 ± 9.0 years, 63.0% male), which comprises a cohort of lower-risk MDS patients. To enable comparison concerning HRQoL, SF-36 scores measured in Lifelines were converted to EQ-5D-3L index (range 0-1) and dimension scores. Lower-risk MDS patients had significantly lower HRQoL than those from the Lifelines cohort, as illustrated in both the index score and in the five different dimensions. Multivariable linear regression analysis demonstrated that MDS had an adjusted total impact on the EQ-5D index score (B = - 0.12, p < 0.001) and an anemia-independent "direct" impact (B = - 0.10, p < 0.001). Multivariable logistic regression analysis revealed an anemia-independent impact of MDS in the dimension mobility, self-care, usual activities, and anxiety/depression (all except pain/discomfort). This study demonstrates that the major part of the negative impact of lower-risk MDS on HRQoL is not mediated via anemia. Thus, the therapeutic focus should include treatment strategies directed at underlying pathogenic mechanisms to improve HRQoL, rather than aiming predominantly at increasing hemoglobin levels.

Published
2021

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