Time-dependent changes in mortality and transformation risk in MDS

Michael Pfeilstocker (Lead / Corresponding author), Heinz Tuechler, Guillermo Sanz, Julie Schanz, Guillermo Garcia-Manero, Françesc Solé, John M. Bennett, David Bowen, Pierre Fenaux, Francois Dreyfus, Hagop Kantarjian, Andrea Kuendgen, Luca Malcovati, Mario Cazzola, Jaroslav Cermak, Alessandro Levis, Michael Luebbert, Jaroslaw Maciejewski, Sigrid Machherndl-Spandl, Silvia M.M. Magalhaes & 11 others Yasushi Miyazaki, Mikkael A. Sekeres, Wolfgang R. Sperr, Reinhard Stauder, Sudhir Tauro, Peter Valent, Teresa Vallespi, Arjan A. Van De Loosdrecht, Ulrich Germing, Detlef Haase, Peter L. Greenberg

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Abstract

In myelodysplastic syndromes (MDS) 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 describe changes in risk over time, the consequences for basal prognostic scores and their potential clinical implications. Major MDS prognostic risk scoring systems (IPSS, IPSS-R, WPSS, LRPSS) and their constituent individual predictors were analyzed in 7,212 primary untreated MDS patients from the IWG-PM database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. In higher risk MDS, hazards regarding mortality and AML transformation diminished over time from diagnosis, whereas they remained stable in lower risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and essentially equivalent after five years. This fact led to loss of prognostic power of different scoring systems considered 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 cut-off 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 “constant lower risk", while "initially high risk" patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making.
Original languageEnglish
Pages (from-to)902-910
Number of pages9
JournalBlood
Volume128
Issue number7
Early online date22 Jun 2016
DOIs
Publication statusPublished - 18 Aug 2016

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Myelodysplastic Syndromes
Mortality
Hazards
Survival
Multicenter Studies

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Pfeilstocker, M., Tuechler, H., Sanz, G., Schanz, J., Garcia-Manero, G., Solé, F., ... Greenberg, P. L. (2016). Time-dependent changes in mortality and transformation risk in MDS. Blood, 128(7), 902-910. https://doi.org/10.1182/blood-2016-02-700054
Pfeilstocker, Michael ; Tuechler, Heinz ; Sanz, Guillermo ; Schanz, Julie ; Garcia-Manero, Guillermo ; Solé, Françesc ; Bennett, John M. ; Bowen, David ; Fenaux, Pierre ; Dreyfus, Francois ; Kantarjian, Hagop ; Kuendgen, Andrea ; Malcovati, Luca ; Cazzola, Mario ; Cermak, Jaroslav ; Levis, Alessandro ; Luebbert, Michael ; Maciejewski, Jaroslaw ; Machherndl-Spandl, Sigrid ; Magalhaes, Silvia M.M. ; Miyazaki, Yasushi ; Sekeres, Mikkael A. ; Sperr, Wolfgang R. ; Stauder, Reinhard ; Tauro, Sudhir ; Valent, Peter ; Vallespi, Teresa ; Van De Loosdrecht, Arjan A. ; Germing, Ulrich ; Haase, Detlef ; Greenberg, Peter L. / Time-dependent changes in mortality and transformation risk in MDS. In: Blood. 2016 ; Vol. 128, No. 7. pp. 902-910.
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title = "Time-dependent changes in mortality and transformation risk in MDS",
abstract = "In myelodysplastic syndromes (MDS) 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 describe changes in risk over time, the consequences for basal prognostic scores and their potential clinical implications. Major MDS prognostic risk scoring systems (IPSS, IPSS-R, WPSS, LRPSS) and their constituent individual predictors were analyzed in 7,212 primary untreated MDS patients from the IWG-PM database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. In higher risk MDS, hazards regarding mortality and AML transformation diminished over time from diagnosis, whereas they remained stable in lower risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and essentially equivalent after five years. This fact led to loss of prognostic power of different scoring systems considered 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 cut-off 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 “constant lower risk{"}, while {"}initially high risk{"} patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making.",
author = "Michael Pfeilstocker and Heinz Tuechler and Guillermo Sanz and Julie Schanz and Guillermo Garcia-Manero and Fran{\cc}esc Sol{\'e} and Bennett, {John M.} and David Bowen and Pierre Fenaux and Francois Dreyfus and Hagop Kantarjian and Andrea Kuendgen and Luca Malcovati and Mario Cazzola and Jaroslav Cermak and Alessandro Levis and Michael Luebbert and Jaroslaw Maciejewski and Sigrid Machherndl-Spandl and Magalhaes, {Silvia M.M.} and Yasushi Miyazaki and Sekeres, {Mikkael A.} and Sperr, {Wolfgang R.} and Reinhard Stauder and Sudhir Tauro and Peter Valent and Teresa Vallespi and {Van De Loosdrecht}, {Arjan A.} and Ulrich Germing and Detlef Haase and Greenberg, {Peter L.}",
note = "This work was in part supported by the MDS Foundation, Inc.",
year = "2016",
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language = "English",
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Pfeilstocker, M, Tuechler, H, Sanz, G, Schanz, J, Garcia-Manero, G, Solé, F, Bennett, JM, Bowen, D, Fenaux, P, Dreyfus, F, Kantarjian, H, Kuendgen, A, Malcovati, L, Cazzola, M, Cermak, J, Levis, A, Luebbert, M, Maciejewski, J, Machherndl-Spandl, S, Magalhaes, SMM, Miyazaki, Y, Sekeres, MA, Sperr, WR, Stauder, R, Tauro, S, Valent, P, Vallespi, T, Van De Loosdrecht, AA, Germing, U, Haase, D & Greenberg, PL 2016, 'Time-dependent changes in mortality and transformation risk in MDS', Blood, vol. 128, no. 7, pp. 902-910. https://doi.org/10.1182/blood-2016-02-700054

Time-dependent changes in mortality and transformation risk in MDS. / Pfeilstocker, Michael (Lead / Corresponding author); Tuechler, Heinz ; Sanz, Guillermo ; Schanz, Julie ; Garcia-Manero, Guillermo; Solé, Françesc; Bennett, John M.; Bowen, David; Fenaux, Pierre; Dreyfus, Francois; Kantarjian, Hagop; Kuendgen, Andrea; Malcovati, Luca; Cazzola, Mario; Cermak, Jaroslav ; Levis, Alessandro; Luebbert, Michael ; Maciejewski, Jaroslaw; Machherndl-Spandl, Sigrid; Magalhaes, Silvia M.M.; Miyazaki, Yasushi; Sekeres, Mikkael A. ; Sperr, Wolfgang R.; Stauder, Reinhard; Tauro, Sudhir; Valent, Peter; Vallespi, Teresa; Van De Loosdrecht, Arjan A. ; Germing, Ulrich ; Haase, Detlef ; Greenberg, Peter L.

In: Blood, Vol. 128, No. 7, 18.08.2016, p. 902-910.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Time-dependent changes in mortality and transformation risk in MDS

AU - Pfeilstocker, Michael

AU - Tuechler, Heinz

AU - Sanz, Guillermo

AU - Schanz, Julie

AU - Garcia-Manero, Guillermo

AU - Solé, Françesc

AU - Bennett, John M.

AU - Bowen, David

AU - Fenaux, Pierre

AU - Dreyfus, Francois

AU - Kantarjian, Hagop

AU - Kuendgen, Andrea

AU - Malcovati, Luca

AU - Cazzola, Mario

AU - Cermak, Jaroslav

AU - Levis, Alessandro

AU - Luebbert, Michael

AU - Maciejewski, Jaroslaw

AU - Machherndl-Spandl, Sigrid

AU - Magalhaes, Silvia M.M.

AU - Miyazaki, Yasushi

AU - Sekeres, Mikkael A.

AU - Sperr, Wolfgang R.

AU - Stauder, Reinhard

AU - Tauro, Sudhir

AU - Valent, Peter

AU - Vallespi, Teresa

AU - Van De Loosdrecht, Arjan A.

AU - Germing, Ulrich

AU - Haase, Detlef

AU - Greenberg, Peter L.

N1 - This work was in part supported by the MDS Foundation, Inc.

PY - 2016/8/18

Y1 - 2016/8/18

N2 - In myelodysplastic syndromes (MDS) 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 describe changes in risk over time, the consequences for basal prognostic scores and their potential clinical implications. Major MDS prognostic risk scoring systems (IPSS, IPSS-R, WPSS, LRPSS) and their constituent individual predictors were analyzed in 7,212 primary untreated MDS patients from the IWG-PM database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. In higher risk MDS, hazards regarding mortality and AML transformation diminished over time from diagnosis, whereas they remained stable in lower risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and essentially equivalent after five years. This fact led to loss of prognostic power of different scoring systems considered 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 cut-off 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 “constant lower risk", while "initially high risk" patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making.

AB - In myelodysplastic syndromes (MDS) 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 describe changes in risk over time, the consequences for basal prognostic scores and their potential clinical implications. Major MDS prognostic risk scoring systems (IPSS, IPSS-R, WPSS, LRPSS) and their constituent individual predictors were analyzed in 7,212 primary untreated MDS patients from the IWG-PM database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. In higher risk MDS, hazards regarding mortality and AML transformation diminished over time from diagnosis, whereas they remained stable in lower risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and essentially equivalent after five years. This fact led to loss of prognostic power of different scoring systems considered 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 cut-off 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 “constant lower risk", while "initially high risk" patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making.

U2 - 10.1182/blood-2016-02-700054

DO - 10.1182/blood-2016-02-700054

M3 - Article

VL - 128

SP - 902

EP - 910

JO - Blood

JF - Blood

SN - 0006-4971

IS - 7

ER -

Pfeilstocker M, Tuechler H, Sanz G, Schanz J, Garcia-Manero G, Solé F et al. Time-dependent changes in mortality and transformation risk in MDS. Blood. 2016 Aug 18;128(7):902-910. https://doi.org/10.1182/blood-2016-02-700054