Cytogenetic Features and Prognosis of 943 South American Patients with De Novo Myelodysplastic Syndromes: A Multicenter Study
Authors: Belli Carolina , Feitosa Pinheiro Ronald , Magalhaes Silvia M. M. , Gonzalez Jacqueline , Iastrebner Marcelo , Prates Maria Virginia , Benasayag Silvia , Bestach Yesica , Cordeiro Juliana , Cavalcante de Andrade Silva Marcela , da Silva Tanizawa Roberta , Bengió Raquel M , Lang Cecilia , Nucifora Elsa , Larripa Irene B , Velloso Elvira RP 
Published: October 2019

Abstract
Recently, the IPSS-R has proposed five cytogenetic groups of risk (CGR) based on Schanz et al, 2011, proposal. Nevertheless, nearly 70% of patients belong to lower CGR. Our aim was to characterize the cytogenetic profile of South American (SA) MDS population trying to find differences among Argentine (A) and Brazil (B), both with diverse ethnicity, to evaluate CGR, and to define the impact of more frequent aberrations and of monosomal karyotype (MK) in our population.
This is a multicenter retrospective study of 943 SA (634 from A and 309 from B) de novo MDS patients (pts) evaluated from 1981 to 2014. Pts were classified following FAB and WHO criteria. The median age was 69 (15-99) years old with a male/female ratio of (533/410) 1.3. During the follow-up, censored up to receiving a disease modifying therapy (median: 21 months), 159 (17%) evolve to AML and 351 (37%) died. Regarding 130 pts (14%) who received hypomethylating therapy (HMT), 46 (35%) evolved to AML, and 61 (47%) died.
Although A population was larger than B series, no differences were observed concerning to: CGR distribution according to the IPSS (p=0.565) and to the IPSS-R (p=0.343), percentage of abnormal karyotypes (42%-A vs 40%-B; p=0.499), and presence of deletions and/or monosomies (77%-A vs 80%-B, p=0.700). B showed a higher proportion of karyotypes involving, at least, one chromosome Y, 5, 7, 8 and/or 20 (83% vs 73%-A, p=0.039), mostly due to a higher proportion of 5q- (39% vs 22%-A, p<0.001).
Karyotypes were classified as Very Good/Good (72%), Intermediate-Int (17%), Poor (5%), and Very Poor CGR (6%), with median survival of 68, 32, 18 and 12 months (p<0.001), and time to AML progression (25%) of 72, 26, 10, and 4 months, respectively (p<0.001). In order to find the prognostic value of certain cytogenetic findings, we evaluated the presence of 5q-, chr 7 alterations and +8 as isolated or accompanied by one (noncomplex- non CK) or more alterations (complex-CK). Our results were consistent with previous data. Interestingly +8 non CK showed better outcome than +8 isolated (p<0.001), in agreement with Haase et al, 2007. We also evaluated the presence of MK in the context of CK or non CK. MK non CK, that included 3 Good, 6 Int and 4 Poor karyotypes according to the IPSS-R, showed similar survival than CK, MK CK and other Poor risk findings (p=0.629). Therefore, MK non CK might be considered, at least, as a Poor risk finding, as proposed for primary Myelofibrosis by Teffery et al, 2011. In order to identify karyotypes with diverse outcome within the Int CGR, we applied different grouping criteria. The presence of a trisomy or of a deletion accompanied by other alteration (both excluding patients with +8), were associated with short survival (p=0.019 and p=0.092, respectively).
We also evaluated the impact of CGR on the outcome of patients under HMT. Patients with Int CGR (23%) showed similar median survival to the Very Good/Good (57%) group and a better outcome than the Poor/Very Poor (20%) (25 m vs 24 m vs 10 m, p=0.001), and a longer time to evolve to AML (22 m vs 12 m vs 6 m, p=0.005).
Cytogenetic findings had a clear impact in our population, and except for a higher incidence of 5q- in B, both series showed a high concordance of cytogenetic findings. Our results are in agreement with previously reported data from European and North American series. Also, our data suggest that MK are indicators of poor prognosis, not different from CK, and that the heterogeneous Int CGR might be further clarified taking into account the nature of different cytogenetic alterations. However, the wide spectrum of low frequency aberrations and the highly variant combinatory of aberrations stress the importance of large study groups to stablish a consensus in the way of grouping Int CGR findings.

Disclosures
No relevant conflicts of interest to declare.