Prognostic Impact of Rare Single Abnormalities in Myelodysplastic Syndromes

Konference: 2015 57th ASH Annual Meeting - účast ČR

Kategorie: Myelodysplastický syndrom

Téma: 637. Myelodysplastic Syndromes – Clinical Studies: Poster II

Číslo abstraktu: 2879

Autoři: M.D. Julie Schanz; Heinz Tüchler (Tuechler); M.D. Francesc Solé, Ph.D.; MD Guillermo F Sanz, PhD; M.D. Guillermo Garcia Manero; Michelle Lebeau (LeBeau), Ph.D.; Prof. M.D. John M. Bennett; Marilyn L. Slovak, Ph.D.; MD Pierre Fenaux, PhD; MD Luca Malcovati; M.D. Mario Cazzola; Prof. Dr. Peter Valent; MD Kazuma Ohyashiki, PhD; M.D. Alessandro Levis; M.D. Mikkael A. Sekeres, M.S.; Dr. Sudhir Tauro, PhD, FRCPath; M.D. Silvia M. M. Magalhaes; M.D. Arjan A. van de Loosdrecht, Ph.D.; Doc.MUDr. Jaroslav Čermák, CSc.; Prof. Dr. Michael Luebbert (Lübbert), Ph.D.; MD Reinhard Stauder; MD Eva Hellström-Lindberg; MD Tatjana Gindina; MD Ulrich Germing; Prof. M.D. Peter L. Greenberg; M.D. Detlef Haase, Ph.D.

Introduction: Since its implementation in 2012, the IPSS-R (Greenberg et al., 2012), defines the latest standard in risk stratification of patients with Myelodysplastic Syndromes (MDS). However, the prognostic impact of rare abnormalities remains unclear as yet because the number of these aberrations was too low to allow a valid statistical analysis. Hence, rare abnormalities were coalesced in one group in the IPSS and IPSS-R and, due to the unknown prognosis of these abnormalities, classified as prognostically intermediate. The main goal of the study presented here was to analyse the type, frequency and prognosis of rare single abnormalities in a large cohort of patients with primary, untreated MDS and integrate them in the existing IPSS-R in order to refine its predictive power.

Methods: The data set analyzed was derived from the IPSS-R database and extended by additional data  from European centers. In total, 7245 patients with primary, untreated MDS were included. Of these, we identified 410 (6%) pts. with rare single abnormalities. An aberration was defined as rare when it occurred in less than 10 patients in the cytogenetic scoring system that was the basis for the IPSS-R (Schanz et al., 2012). Additionally, further cytogenetic abnormalities not considered in this score were detected. A specific cytogenetic subgroup was defined as having at least n=5 cases with the same abnormality. Survival analyses was performed in cytogenetic subgroups with a minimum number of n=10 exclusively. The participating centers (in numerical order) were: Spain (n=110; 26.8%), MD Anderson Cancer Center (69; 16.8%), Düsseldorf (44; 10.8%), IMRAW (41; 10.0%), France (32; 7.8%), Pavia (21; 5.1%), Vienna (19; 4.6%), Japan (13; 3.2%), Vienna Medical University (12; 2.9%) Italy (11; 2.7%), Cleveland (10; 2.4%), Dundee (9; 2.2%), Brazil (8; 2.0%), Netherlands (5; 1.2%), Czech (2, 0.5%), Freiburg (1; 0.2%), Innsbruck (1; 0.2%), Sweden (1; 0.2%), and Russia (1; 0.2%). The median overall- (OS) and AML-free survival (AFS) was calculated for any specific cytogenetic subgroup.

Results: Rare single abnormalities detected were: der(1;7)(n=24; 5.9%), partial or total monosomy 13 (22; 5.4%), partial or total monosomy 9 (22; 5.4%), +21 (20; 4.9%), +mar (14; 3.4%), del(3p) (12; 2.9%), total or partial monosomy 21 (11; 2.7%), total or partial monosomy X (11; 2.7%), total or partial monosomy 18 (10; 2.4%), +1/+1q (10; 2.4%), del(17p) (9; 2.2%), total or partial monosomy 14 (9; 2.2%), total or partial monosomy 16 (9; 2.2%), total or partial monosomy 6 (9; 2.2%), total or partial monosomy 1 (8; 2.0%), t(11q23;varia) (7; 1.7%), total or partial monosomy 19 (6; 1.5%), +11/+11q (6; 1.5%), +13 (6; 1.5%), +14 (6; 1.5%), del(5p) (5; 1.2%), total or partial monosomy 2 (5; 1.2%), +15 (5; 1.2%) and +X (5; 1.2%) The remaining 159 patients (38.7%) showed very rare abnormalities occurring in less than 5 patients each. The median overall survival as well as the AML-free survival in each category will be presented in detail. Furthermore, a multivariate model including all relevant confounders and a  proposal to integrate these abnormalities in the cytogenetic module of the IPSS-R will be suggested.

Conclusions: In order to overcome the problem of their extremely low frequency, knowledge about rare single abnormalities in MDS can only be gained by large, international cooperative projects. The present study was performed to identify and comprehensively analyze rare abnormalities occurring in MDS, uninfluenced by therapy or additional abnormalities. The results will lead to a further refinement of the cytogenetic prognostic classification in patients with MDS.

The study was supported by a grant from the European Leukemia Net (ELN)

Disclosures: Schanz: Novartis: Honoraria , Other: Travel Grant ; Celgene: Honoraria , Research Funding ; Alexion:Other: Travel Grant ; Lilly: Other: Travel Grant . Sole: Celgene: Honoraria , Membership on an entity’s Board of Directors or advisory committees . Fenaux: Amgen: Honoraria , Research Funding ; Celgene Corporation:Honoraria , Research Funding ; Janssen: Honoraria , Research Funding ; Novartis: Honoraria , Research Funding .Valent: Novartis: Consultancy , Honoraria , Research Funding ; Ariad: Honoraria , Research Funding ; Bristol-Myers Squibb: Honoraria ; Pfizer: Honoraria ; Celgene: Honoraria . Ohyashiki: Kyowa Kirin KK: Honoraria ; Novartis Pharma KK: Honoraria , Research Funding , Speakers Bureau ; Celegen KK: Consultancy , Honoraria , Research Funding , Speakers Bureau ; Jansen Pharma KK: Honoraria , Research Funding , Speakers Bureau ; Chugai Pharna KK: Research Funding ; Bristol Meyer Squib KK: Research Funding ; Taiho Yakuhin KK: Research Funding ;Asahikasei: Research Funding ; Teijin Pharma KK: Research Funding ; Alexion Pharma KK: Research Funding ;Asteras: Research Funding ; Shinbaio Pharma KK: Honoraria ; Toyama Kagaku KK: Speakers Bureau ; MSD KK:Honoraria ; Nippo Shinyaku KK: Speakers Bureau ; Sumitomo Dainippon: Membership on an entity’s Board of Directors or advisory committees . Sekeres: TetraLogic: Membership on an entity’s Board of Directors or advisory committees ; Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees ;Amgen: Membership on an entity’s Board of Directors or advisory committees .

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Datum přednesení příspěvku: 6. 12. 2015