title: Time-dependent changes in mortality and transformation risk in MDS.
abstract: In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower- and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making.
authors.affiliation: Hanusch Hospital and L. Boltzmann Cluster Oncology, Vienna, Austria;
authors.forename: Michael
authors.initials: M
authors.lastname: Pfeilstöcker
authors.affiliation: L. Boltzmann Institute for Leukemia Research, Vienna, Austria;
authors.forename: Heinz
authors.initials: H
authors.lastname: Tuechler
authors.affiliation: Hospital Universitario La Fe, Valencia, Spain;
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanz
authors.affiliation: Georg August Universität, Göttingen, Germany;
authors.forename: Julie
authors.initials: J
authors.lastname: Schanz
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Institut de Recerca contra la Leucèmia Josep Carreras, Barcelona, Spain;
authors.forename: Francesc
authors.initials: F
authors.lastname: Solé
authors.affiliation: James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY;
authors.forename: John M
authors.initials: JM
authors.lastname: Bennett
authors.affiliation: St James's University Hospital, Leeds, United Kingdom;
authors.forename: David
authors.initials: D
authors.lastname: Bowen
authors.affiliation: Hopital Avicenne, Assistance Publique-Hopitaux de Paris (AP-HP)/University of Paris XIII, Bobigny, France;
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.affiliation: Hopital Cochin, AP-HP, University of Paris V, Paris, France;
authors.forename: Francois
authors.initials: F
authors.lastname: Dreyfus
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Heinrich-Heine University Hospital, Düsseldorf, Germany;
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuendgen
authors.affiliation: Fondazione Istituti di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy;
authors.forename: Luca
authors.initials: L
authors.lastname: Malcovati
authors.affiliation: Fondazione Istituti di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy;
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.affiliation: Institute of Hematology and Blood Transfusion, Praha, Czech Republic;
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cermak
authors.affiliation: Medical University of Vienna, Vienna, Austria;
authors.forename: Christa
authors.initials: C
authors.lastname: Fonatsch
authors.affiliation: University of Chicago Comprehensive Cancer Research Center, Chicago, IL;
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Le Beau
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM;
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Slovak
authors.affiliation: Antonio e Biagio e Cesare Arrigo Hospital, Alessandria, Italy;
authors.forename: Alessandro
authors.initials: A
authors.lastname: Levis
authors.affiliation: University of Freiburg Medical Center, Freiburg, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Luebbert
authors.affiliation: Cleveland Clinic, Cleveland, OH;
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Maciejewski
authors.affiliation: Elisabethinen Hospital, Linz, Austria;
authors.forename: Sigrid
authors.initials: S
authors.lastname: Machherndl-Spandl
authors.affiliation: Federal University of Ceara, Fortaleza, Brazil;
authors.forename: Silvia M M
authors.initials: SM
authors.lastname: Magalhaes
authors.affiliation: Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Cleveland Clinic, Cleveland, OH;
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.affiliation: Division of Hematology, Medical University of Vienna, Vienna, Austria;
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.affiliation: University Hospital of Innsbruck, Innsbruck, Austria;
authors.forename: Reinhard
authors.initials: R
authors.lastname: Stauder
authors.affiliation: University of Dundee, Dundee, United Kingdom;
authors.forename: Sudhir
authors.initials: S
authors.lastname: Tauro
authors.affiliation: Division of Hematology, Medical University of Vienna and L. Boltzmann Cluster Oncology, Vienna, Austria;
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Hospital Universitario Vall d'Hebron, Barcelona, Spain;
authors.forename: Teresa
authors.initials: T
authors.lastname: Vallespi
authors.affiliation: Vrije Universiteit Medical Center, Amsterdam, The Netherlands; and.
authors.forename: Arjan A
authors.initials: AA
authors.lastname: van de Loosdrecht
authors.affiliation: Heinrich-Heine University Hospital, Düsseldorf, Germany;
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.affiliation: Georg August Universität, Göttingen, Germany;
authors.forename: Detlef
authors.initials: D
authors.lastname: Haase
authors.affiliation: Stanford Cancer Institute, Stanford, CA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Greenberg
mesh_terms: D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009190:Myelodysplastic Syndromes / Q000401:mortality*; D012307:Risk Factors; D013997:Time Factors; D014944:World Health Organization